The absence of oxygen and nutrients during ischaemia affects all tissues with aerobic metabolism. Ischaemia of these tissues creates a condition which upon the restoration of circulation results in further inflammation and oxidative damage (reperfusion injury). Restoration of blood flow to an ischaemic organ is essential to prevent irreversible tissue injury, however reperfusion of the organ or tissues may result in a local and systemic inflammatory response augmenting tissue injury in excess of that produced by ischaemia alone. This process of organ damage with ischaemia being exacerbated by reperfusion is called ischaemia-reperfusion (IR). Regardless of the disease process, severity of IR injury depends on the length of ischaemic time as well as size and pre-ischaemic condition of the affected tissue. The liver is the largest solid organ in the body, hence liver IR injury can have profound local and systemic consequences, particularly in those with pre-existing liver disease. Liver IR injury is common following liver surgery and transplantation and remains the main cause of morbidity and mortality.
The liver has a dual blood supply from the hepatic artery (20%) and the portal vein (80%). A temporary reduction in blood supply to the liver causes IR injury. This can be due to a systemic reduction or local cessation and restoration of blood flow. Liver resections are performed for primary or secondary tumours of the liver and carry a substantial risk of bleeding especially in patients with chronic liver disease. Significant blood loss is associated with increased transfusion requirements, tumour recurrence, complications and increased morbidity and mortality. Several methods of hepatic vascular control have been described in order to minimise blood loss during elective liver resection. The simplest and most common method is inflow occlusion by applying a tape or vascular clamp across the hepatoduodenal ligament (Pringle Manoeuvre). This occludes both the arterial and portal vein inflow to the liver and leads to a period of warm ischaemia (37 °C) to the liver parenchyma resulting in ‘warm’ IR injury when the temporary inflow occlusion is relieved. In major liver surgery, extensive mobilisation of the liver itself without inflow occlusion results in a significant reduction in hepatic oxygenation.
3. PATOPHYSIOLOGY and RISK FACTORS
A complex cellular and molecular network of hepatocytes, Kupffer cells, liver sinusoidal endothelial cells (LSEC), leukocytes and cytokines play a role in the pathogenesis of IR injury. In general, both warm and cold ischaemia share similar mechanisms of injury. Hepatocyte injury is a predominant feature of warm ischaemia, whilst endothelial cells are more susceptible to cold ischaemic injury. There are currently no proven treatments for liver IR injury. Understanding this complex network is essential in developing therapeutic strategies in prevention and treatment of IR injury. Identifying risk factors for IR injury are extremely important in patient selection for liver surgery and transplantation. The main factors are the donor or patient age, the duration of organ ischaemia, presence or absence of liver steatosis and in transplantation whether the donor organ has been retrieved from a brain dead or cardiac death donor.
4. PREVENTION and TREATMENT
There is currently no accepted treatment for liver IR injury. Several pharmacological agents and surgical techniques have been beneficial in reducing markers of hepatocyte injury in experimental liver IR, however, they are yet to show clinical benefit in human trials. The following is an outline of current and future strategies which may be effective in reducing the detrimental effects of liver IR injury in liver surgery and transplantation.
4.1 SURGICAL STRATEGIES
Inflow occlusion or portal triad clamping (PTC) can be continuous or intermittent; alternating between short periods of inflow occlusion and reperfusion. Intermittent clamping (IC) increases parenchymal tolerance to ischaemia. Hence, prolonged continuous inflow occlusion rather than short intermittent periods results in greater degree of post-operative liver dysfunction. IC permits longer total ischaemia times for more complex resections. Alternating between 15 min of inflow occlusion and 5 min reperfusion cycles can be performed safely for up to 120 min total ischaemia time. There is a potential risk of increased blood loss during the periods of no inflow occlusion. However, these intervals provide an opportunity for the surgeon to check for haemostasis and control small bleeding areas from the cut surface of the liver. The optimal IC cycle times are not clear, although intermittent cycles of up to 30 min inflow occlusion have also been reported with no increase in morbidity, blood loss or liver dysfunction compared to 15 min cycles. IC is particularly beneficial in reducing post-operative liver dysfunction in patients with liver cirrhosis or steatosis.
In liver surgery, IPC ( Ischaemic Preconditioning) involves a short period of ischaemia (10 min) and reperfusion (10 min) intraoperatively by portal triad clamping prior to parenchymal transection during which a longer continuous inflow occlusion is applied to minimise blood loss. It allows continuous ischaemia times of up to 40 min without significant liver dysfunction. However, the protective effect of IPC decreases with increasing age above 60 years old and compared to IC it is less effective in steatotic livers. Moreover, IPC may impair liver regeneration capacity and may not be tolerated by the small remnant liver in those with more complex and extensive liver resections increasing the risk of post-operative hepatic insufficiency.
In order to avoid direct ischaemic insult to the liver by inflow occlusion, remote ischaemic preconditioning (RIPC) has been used. RIPC involves preconditioning a remote organ prior to ischaemia of the target organ. It has been shown to be reduce warm IR injury to the liver in experimental studies. A recent pilot randomised trial of RIPC in patients undergoing major liver resection for colorectal liver metastasis used a tourniquet applied to the right thigh with 10 min cycles of inflation-deflation to induce IR injury to the leg for 60 min. This was performed after general anaesthesia prior to skin incision. A reduction in post-operative transaminases and improved liver function was shown without the use of liver inflow occlusion. These results are promising but require validation in a larger trial addressing clinical outcomes.
5. FUTURE PERSPECTIVES
Hepatic IR injury remains the main cause of morbidity and mortality in liver surgery and transplantation. Despite over two decades of research in this area, therapeutic options to treat or prevent liver IR are limited. This is primarily due to the difficulties in translation of promising agents into human clinical studies. Recent advances in our understanding of the immunological responses and endothelial dysfunction in the pathogenesis of liver IR injury may pave the way for the development of new and more effective and targeted pharmacological agents.
Chronic pancreatitis (CP) is a progressive, destructive, inflammatory process that ends in total destruction of the pâncreas and results in malabsorption, diabetes mellitus, and severe pain. The incidence and prevalence of CP are increasing in the worldwide and incidence is between 1.6 and 23 per 100 000 with increasing prevalence. The treatment of CP is complex; in the majority of cases na interdisciplinary approach is indicated that includes conservative, endoscopic, and surgical therapy. The surgical treatment of CP is based on two main concepts:preservation of tissue via drainage aims to protect against further loss of pancreatic function, and pancreatic resection is performed for nondilated pancreatic ducts, pancreatic head enlargement,or if a pancreatic carcinoma is suspected in the setting of CP.
The vast majority of patients are seen with a ductal obstruction in the pancreatic head, frequently associated with an inflammatory mass. In these patients, pancreatic head resection is the procedure of choice; The partial pancreatoduodenectomy (PD) or Kausch-Whipple procedure, in its classic or pylorus-preserving variant, has been the procedure of choice for pancreatic head resection in CP for many years (Jimenez et al, 2003). The duodenum-preserving pancreatic head resections and its variants—the Beger (1985), Frey (1987), and Bern procedures (Gloor et al, 2001)—represent less invasive, organsparing techniques with equal long-term results. Only very few patients come to medical attention with smallduct disease (diameter of the pancreatic duct ❤ mm) and no mass in the pancreatic head. Possibly, a large majority of those patients from former series had unknown autoimmune pancreatitis. In these cases, a V-shaped excision of the anterior aspect of the pancreas is a safe approach, with effective pain management (Yekebas et al, 2006). In the rare case of a patient seen with segmental CP in the pancreatic body or tail, such as that seen as a result of posttraumatic ductal stenosis, a middle segment pancreatectomy or a pancreatic left resection may be the best approach.
The adequate therapy of CP is adjusted to the symptoms of the patient, the stage of the disease, and the morphology of pathologic changes of the pancreas. The surgical technique must be adjusted to the pathomorphologic changes of the pancreas. For patients with CP and an inflammatory mass in the head of the pancreas, the DPPHR is less invasive than a PD and is associated with comparable long-term results. The Bern modification of the DPPHR represents a technical variation that is equally effective but technically less demanding. Whether total pancreatectomy with islet cell transplantation is a viable therapy of CP remains to be proved by further studies. Surgical therapy provides effective long-term pain relief and improvement of quality of life, but it may not stop the decline of endocrine or exocrine pancreatic function. Strategies to improve or maintain endocrine and exocrine function in CP remain an interesting field of research.
Laparoscopic distal pancreatectomy has become a relatively standard operation and has been approached by a similar technique by multiple groups since its original description. Generally, four or five trocars are used to gain entrance to the abdominal cavity, but three-trocar LPD has been described. A “clockwise” technique results in an efficient, reliable, and uniform approach for removing the vast majority of lesions that are located to the left of the neck of the pancreas (Asbun & Stauffer, 2011). The technique begins with the positioning of the patient in a modified right lateral decubitus position. The degree of lateral positioning depends on the patient’s body habitus and the location of the lesion, as well as the tilting capabilities of the operative bed. The use of gravity assisted retraction with the patient in a reverse Trendelenburg position with the left flank elevated is a key component to successful exposure of the tail of the pancreas and the spleen. Four mid- to left-sided abdominal trocars are placed in a semicircle around the body and tail of the pancreas, including two 12 mm and two 5 mm trocars, and a five step clockwise method is used.
Step 1: Mobilization of the splenic flexure of the colon
and exposure of the pancreas
The first step is mobilization of the splenic flexure of the colon. The lateral attachments, splenocolic ligament, and gastrocolic ligament are succes-sively transected to allow access to the lesser sac. If the spleen is to be removed, the dissection proceeds cranially, and the short gastric vessels are transected up to the superior pole of the spleen. Sufficient mobilization of the colon allows for gravity-assisted retraction of the colon, and the stomach is completely freed from the anterior aspect of the body and tail of the pancreas. Infrequently, an additional trocar or tacking stitch is required to elevate the stomach to the anterior abdominal wall off the pancreas and out of the operative field.
Step 2: Dissection along the inferior edge of the pancreas
and choosing the site for pancreatic division
The second step is to identify the inferior border of the pancreas and create a window in the fibroadipose tissue plane between the retroperitoneum and the pancreas. This dissection is carried medially toward the lesion of interest. Intraoperative ultrasound is performed to clearly identify the lesion and the planned site of division of the pancreas.
Step 3: Pancreatic parenchymal division and ligation
of the splenic vein and artery
The third step is pancreatic parenchymal division and ligation of the splenic artery and vein. After dissecting around the pancreas in 360 degrees, a Penrose drain or suture is placed around the proposed site of division of the pancreas and is used to elevate the pancreas from the retroperitoneum. A band passer instrument is helpful for this part of the procedure. For distal pancreatectomy, the splenic vessels will often be dissected, ligated, and divided en bloc with the parenchyma. For subtotal resections with division of the pancreas at the neck, the underlying superior mesenteric vein and splenic vein are dissected away from the posterior aspect of the pancreas, and the celiac trunk is identified individually and dissected free from the neck and proximal body of the pancreas. Parenchymal transection is performed with a linear stapling device by using a slow, gradual, and stepwise compression technique. Thick tissue staples (open staple height of approximately 4 mm) with staple line reinforcement is preferred for almost any pancreas consistency, and the stapler is gradually closed in a stepwise manner over the course of several minutes to allow for parenchymal compression. Parenchymal transection and splenic vessel division are done individually for subtotal pancreatectomy for lesions located between the gastroduodenal artery and the celiac trunk.
Step 4: Dissection along the superior edge of the pancreas
The fourth step is to sweep the pancreas inferiorly and anteriorly off the retroperitoneum toward the splenic hilum. A deeper dissection plane that includes Gerota fascia and the left adrenal gland may be chosen for malig-nancies that appear to have posterior invasion from the pancreas.
Step 5: Mobilization of the spleen and specimen removal
The fifth step is the mobilization of the spleen from its diaphragmatic and retroperitoneal attachments and placement of the specimen within a bag for exteriorization. Major complications were seen in less than 10% of patients, and both the conversion rate and the clinically significant pancreatic fistula (grade B/C) rate by using the gradual stepwise compression stapled technique was seen in fewer than 5%. Operative drains were rarely placed.
The minimally invasive approach to resection of the left-sided pancreas by distal or subtotal pancreatectomy has gained acceptance and been used with an increasing frequency worldwide during the past decade. Multiple systematic reviews have demonstrated the safety of LDP and its superiority versus open distal pancreatectomy (ODP) for selected outcomes, such as blood loss, transfusion rates, and hospital stays; it must be remembered, however, that all these studies are retrospective in nature and therefore severely limited by significant selection bias. All studies showed similar reoperation rates and mortality, but most found a lower overall morbidity for the laparoscopic approach. Some studies identified lower rates of specific complications, such as wound infection and even pancreatic fistula. Although oncologic clearance was similar, most studies have shown that ODP is often the surgery of choice for larger tumors.
INTRODUCTION: Few other surgical procedures adversely affect a patient’s quality of life as much as a poorly functioning stoma. An ideal stoma meets two criteria: (1) The site is optimally matched to a patient’s variability in body form, physical ability and activities. (2) The construction minimises complications that relate to the use of stomal appliances and minimises technical failings such as parastomal hernia or prolapse.
1.The Skin and Subcutaneous Incision
A circular stomal opening is generally preferred, though for temporary stomata a linear incision minimises skin loss and may improve cosmesis after closure. We favour making a cruciate incision with cutting electrocautery, each quadrant being excised in a curved fashion with electrocautery or curved (Mayo) scissors to prevent charring.
A cruciate incision of the muscle fascia is generally used, mirroring that for the skin incision but without excision. It is common practice during laparotomy to align the muscle fasciotomy and skin incision by medial retraction of the rectus sheath using tissue-grasping forceps (e.g. Lanes’). This may reduce angulation of the bowel through the abdominal wall, though is unlikely to affect the duration of paralytic ileus in the post-operative phase and has little effect on eventual function.
A muscle-splitting incision through rectus abdominis is advocated, though this may simply be a necessary anatomical consequence reflecting the preference for an anterior stoma distant from the umbilicus, iliac crest and midline wounds. Stomal formation lateral to rectus abdominis does not actually seem to increase the risk of para-stomal hernia formation. This is unsurprising, since muscle division and correct closure at apppendicectomy rarely leads to hernia formation.
4.Choice of Bowel for the Construction of a Stoma
The principles of good anastamotic healing apply equally to stomal construction. Attention to tissue handling, vascularity and lack of tension encourage primary healing at the muco-cutaneous junction. Poor technique risks separation of the muco-cutaneous junction and prolonged healing by granulation, leading to stenosis. Tension may worsen stomal or spout retraction and can lead to difficulties in attaching stomal appliances to a concave stoma, particularly if a tight limb of the stoma gives a skin fold crease. Similarly, impaired vascularity can turn stomata a worrying colour, particularly if inotropes are required for a critically ill patient, and although frank necrosis is rare, stenosis may result in the longer term.
“Patients often judge a surgeon’s technical ability by the external appearance of scars, and may also judge a surgeon’s care and precision by the appearance and function of an abdominal stoma.”
The “ideal” tumor marker is economical, easy to estimate in easily accessible body fluids like blood or urine, has high sensitivity and specificity, can be used to screen for a cancer, has prognostic and predictive value at diagnosis, and is reliable during treatment and follow-up. It does not exist as of now. Commonly used tumor markers in gastrointestinal, liver, biliary tract, and pancreatic cancers are alpha fetoprotein (AFP), CA19.9, carcinoembryonic antigen (CEA), and chromogranin A (CgA).
Alpha Fetoprotein (AFP)
Alpha fetoprotein (AFP) is a glycoprotein that is produced in the yolk sac and the fetal liver. It is the most commonly used tumor marker for hepatocellular carcinoma (HCC). AFP may be raised in gonadal tumors, gastric cancer, and benign states like pregnancy, viral hepatitis, and cirrhosis caused by hepatitis C. The normal range is 10–20 ng/ml. Values above 400 ng/ml or a steady rise in serial estimation (even if lower than 400 ng/ml) is highly suggestive of HCC in a patient at risk of developing HCC. Persistent elevation of AFP is more significant than fluctuating levels. AFP levels are usually normal in the fibrolamellar variety of HCC. AFP is a heterogeneous molecule with respect to the carbohydrate moiety. Different AFP glycoforms can be separated and characterized by their affinity for lectins. Lectins are carbohydrate-binding proteins.
AFP level >500 ng/ml predicts high recurrence rate after transplantation, and such patients are not listed in the USA. Rise of AFP while on the wait list is also a poor prognostic factor. AFP >1000 ng/ml appears to be related to poor prognostic factors like microvascular invasion, portal vein invasion, bile duct invasion, and intrahepatic metastasis. In 2012 a French paper reported a model that added AFP to Milan criteria which improved prediction of recurrence and survival after liver transplantation for HCC.
CA 19-9 is the abbreviation for carbohydrate antigen or cancer antigen 19-9. This tumor marker belongs to the family of mucinous markers. These have a transmembrane protein skeleton and an extracellular side that has glycosylated oligosaccharides. It is a sialylated Lewis blood group antigen. Mucus glands in the pancreas, biliary tree, salivary glands, stomach, colon, and endometrium physiologically secrete CA 19-9, and this is present in small quantities in serum. Higher levels are observed in inflammatory conditions of the pancreas and biliary tree like acute pancreatitis, biliary obstruction, and cholangitis. Overall mean sensitivity and specificity of serum CA 19-9 for diagnosis of pancreatic cancer are 81% and 90% according to one recent review. This study reported these results using 37 KU/l as cutoff of CA 19-9. Serum CA 19-9 seems to fare very poorly and is unsuitable as a screening modality for pancreatic cancer.
In one of the largest reviews of data, positive predictive value for diagnosis of pancreatic cancer was only 0.9%. Another study from Mumbai used CA 19-9 to predict operability in 49 patients with pancreatic cancer. When CA 19-9 was more than twice the normal (37 U/l), 88% were unresectable. Out of the 29 patients considered resectable after contrast-enhanced CT scan of abdomen, 5 patients were found unresectable at operation due to subcentimeter liver or peritoneal metastasis. All these five patients had CA 19-9 level more than three times the normal limit. These investigators suggest that diagnostic/ staging laparoscopy should be used to avoid a non-therapeutic laparotomy if CA 19-9 is more than thrice the normal limit.
Chromogranin A (CgA)
CgA is an acidic glycoprotein that is ubiquitously present in almost all endocrine and neuroendocrine cells of the human body. They are synthesized in these cells, stored along with other hormones /neurotransmitters in vesicles and released from the cells by exocytosis along with other hormones. The granin family consists of eight different substances of which chromogranin A is the best known and the one in clinical use for several decades now. CgA is thus a universal marker for neuroendocrine cell differentiation and activity. Testing its serum level is a marker of neuroendocrine secretory activity in the body. There are numerous limitations for the use of serum chromogranin A for diagnosis or follow-up of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, it still remains the preferred tumor marker in these conditions, as it is widely available and less cumbersome to perform and retains a reasonable sensitivity and specificity provided the clinician applies all necessary recommended precautions in performance of the test and interpretation of the results.
Highest levels of CgA in GEP-NETs are obtained in midgut neuroendocrine tumors, previously termed as “carcinoid tumors.” In ileal carcinoids with liver metastasis, level as high as 200 times upper normal limit is reported. GEP-NETs in MEN-1 syndrome could result in chromogranin A values of about 150 times the upper normal limit. CgA levels in pancreatic NETs are about 60–80 times upper normal limit. CgA is elevated in 100% of gastrinomas and 70% of pancreatic NETs. In gastrinoma, very high levels are reported even in the absence of liver metastasis. CgA level of more than 5000 μg/l was found to be an independent prognostic factor for midgut NETs. Median survival was 33 and 57 months below and above the 5000 μg/l cutoff, respectively. This interpretation of CgA level cannot be generalized to all GEP-NETs. Typical exception of high level without any metastatic disease is gastrinoma as mentioned earlier. CgA level does not correlate with the degree of differentiation of GEP-NETs. Diagnostic accuracy of CgA was 73% in well-differentiated NETs and 50% in poorly differentiated NETs. This is probably related to loss of secretory function of poorly differentiated NETs, where this tumor marker is less reliable. CgA level has been reported to fall after all forms of therapy for GEP-NETs. This could be resection of the tumor, liver transplantation for metastatic disease, radionuclide therapy, or treatment with receptor blockade like everolimus.
Neuroendocrine tumours (NETs) are neoplasia that can exhibit a range of features such as the production of neuropeptides, the presence of large dense-core secretory vesicles, and the lack of neural structures. NETs can be found in many body regions including the head, neck, lungs, and abdomen. Gastroenteropancreatic (GEP) NETs can be functioning or nonfunctioning, depending on whether hormones are secreted. While the majority of NETs are sporadic, a smaller portion can be related to genetic syndromes such as multiple endocrine neoplasia (MEN), von Hippel-Lindau (VHL), and neurofibromatosis (NF). Compared with their epithelial counterparts, NETs have usually better outcomes. Surgical resections, ranging from enucleation to standard pancreatectomy and lymphadenectomy, play a key role in the management of these lesions, even in advanced disease. Long-term outcomes are correlated with the grading of the disease. Among GEP-NETs, small intestinal NETs (Si-NETs) have a higher incidence than pancreatic neuroendocrine tumours (PanNETs).
Along with incidental diagnosis, tumour size and tumour grading are the most powerful predictors of long-term survival and recurrence. Based on this data, the ENETS guidelines suggested active surveillance rather than surgery for patients with incidental NF-PanNETs that are <2 cm. A recent systematic review demonstrated that surveillance of asymptomatic small NF-PanNETs is safe at least in selected patients although the quality of available studies is still too low to draw firm conclusions. Regardless the size of the primary tumour and the absence of symptoms, a G2 or G3 PanNET/Cs should be treated with resection. Surgery still remains the gold standard in patients with NF-PanNET >2 cm.
The type of resection depends on the location of the lesion. In the presence of head lesions, Whipple’s procedure is the treatment of choice, while distal pancreatectomy and splenectomy is recommended in body-tail lesions. Regardless the type of surgery, a standard lymphadenectomy should be performed. The role of lymphadenectomy during surgical resection for PanNETs is still unclear; however, several authors have shown that the presence of lymph node metastases is associated with poor prognosis; therefore, lymphadenectomy is very helpful in the staging of the disease, but there is no evidence to support an extended lymphadenectomy. The risk of lymph node metastases increases with the increasing size of the primary lesion. Therefore, a standard lymphadenectomy which consists of peripancreatic lymph node dissection along major pancreatic vessels, should always be performed. Recent evidence on the role of conservative management of small PanNETs and the risk of node involvement in PanNETs >2 cm have now significantly limited the role of PSP in NF-PanNETs. These procedures that include enucleation and MP are now limited to patients with small, asymptomatic PanNETs in whom a conservative approach is contraindicated because of young age or for patient’s willingness. Despite a clear benefit in terms of long-term risk of developing pancreatic insufficiency, PSP has a similar morbidity and mortality to standard pancreatic resections.
Liver resection offers the only chance of cure in patients with a variety of primary and secondary liver tumors. For breast cancer, the natural history of this condition is poorly defined and the management remains controversial. Most physicians view liver metastases from breast cancer with resignation or attempt palliation with hormones and chemotherapy. Proper patient selection is crucial to ensure favorable long-term results. Although results of hepatic resection for metastatic colorectal cancer have been reported extensively, the experience with liver resection of metastases from breast cancer is limited. In 1991, the first series reporting hepatectomy for breast cancer patients was published.
A large series by Adam et al. reported the experience of 41 French centers regarding liver resection for noncolorectal, nonendocrine liver metastases. Among the 1452 patients who were studied, 454 (32%) were breast cancer patients. Mean age was 52 years (range 27–80 years). Most patients received adjuvant chemotherapy (58%), as few were downstaged by neoadjuvant chemotherapy. Delay between the treatment of the primary breast tumor and metastases was 54 months, with metachronous metastases in more than 90% of cases. There was a single metastasis in 56% of cases and less than three metastases in 84%. Only 8% were nonresectable. Most patients (77% of cases) underwent anatomical major resections (>3 segments). Negative margins were obtained in 82% of cases. Operative mortality was 0.2% during the 2 months following surgery. Fewer than 10% of the patients developed a local or systemic complication. With a median follow-up of 31 months, the overall survival was 41% at 5 years and 22% at 10 years, with a median of 45 months. Five- and 10-year recurrencefree survival rates were 14% and 10%, respectively.
Poor survival was associated with four factors determined by multivariate analysis: time to metastases, extrahepatic location, progression under chemotherapy treatment, and incomplete resection. At the UTMDACC, breast cancer patients who present with isolated synchronous liver metastases are treated initially with systemic chemotherapy. In responders,
hepatic resection is only contemplated if no other disease becomes evident during initial systemic treatment. Most candidates for hepatic resection undergo treatment for metachronous disease and only undergo resection for metastatic disease confined to the liver.
The incidence of HCC is increasing in the worldwide. Surgery in the form of liver resection or transplantation remains the mainstay of curative treatment for HCC, even though selected patients with small tumours may also be cured with ablation. Liver resection and transplantation are not necessarily two binary choices in most patients and, despite all the debates, are often complementary treatment modalities ideally suited to different patient groups. Thus characterisation of patient and tumour characteristics to guide decision making is vital to achieve the best outcome for patients.
1.Anatomical Resection or Not?
The aim of liver resection in patients with HCC and CLD is that it should be curative with resection of tumour vascular territories and also preserve as much liver volume as possible to prevent postoperative liver failure. EASL guidelines recommend anatomical resection of HCC, whereby the lines of resection match the limits of one or more functional segments of the liver. This is based on evidence suggesting superior oncological outcomes in addition to a reduction in the risk of bleeding and biliary fistula. Although there are no randomised data, a meta-analysis including 2000 patients from 12 non-randomised comparative trials did not show any benefit of anatomical compared with non-anatomical resection in 1-, 3- and 5-year survival, recurrence rate, postoperative morbidity or blood loss . It is practice to perform an anatomical resection for tumours >2 cm, and for smaller tumours in anatomically favourable positions, a wedge with adequate margin is often sufficient. Modifying techniques to maximise parenchymal preservation preserving adequate margins are often the key in these patients.
2. Anterior Approach
The anterior approach, as described by Professor Belghiti , has been advocated for large right-sided tumours. This technique involves transection of the liver parenchyma to the IVC without mobilisation of the liver with the theoretical advantage of less tumour seeding. A prospective randomised controlled trial compared the anterior and conventional approach on 120 patients with large (>5 cm) HCCs. The anterior approach group had less blood transfusion requirements and a significantly longer overall survival (68.1 v 22.6 months; p = 0.006).
As in liver resection for other indications, there is no good evidence to indicate that a single method of parenchymal transection, application of fibrin sealants or intermittent inflow occlusion is beneficial in surgery for HCC. There is also no evidence to suggest that using special equipment for liver resection is of any benefit in decreasing the mortality, morbidity, or blood transfusion requirements. Surgeons should use techniques in which they have been trained and can demonstrate acceptable outcomes.
4. Laparoscopic Approach
Laparoscopic HCC resections are gaining popularity as the approach is more widely adopted across centres. It is important that patients for laparoscopic resection are selected based on the technical capabilities of the surgeon and centre, and the proper mentoring takes place during the learning curve. A summary of published metaanalyses concluded that the laparoscopic approach was associated with improved short-term outcomes (blood loss, complication rates and hospital length of stay) without compromising long-term oncological outcomes. It is worth noting that there are no randomised data; however a number of trials are in progress. Furthermore,their analysis suggested that the incidence of postoperative ascites and liver failure is decreased in the selected group of laparoscopic liver resections . A further metaanalysis of cirrhotic patients up to Child-Pugh B undergoing laparoscopic compared with open liver resection for HCC confirmed these perioperative benefits .
5. Robotic Approach
Although still very much in its infancy, the application of robotic surgery to HCC resection can theoretically yield similar advantages in short-term outcomes to the laparoscopic technique. The only comparative study between robotic and open liver resection for HCC included 183 patients undergoing robotic hepatectomy who were compared using propensity scoring with a cohort of 275 open resections. The robotic group required longer operating time (343 vs 220 min), shorter hospital stays (7.5 vs 10.1 days) and lower dosages of postoperative patient-controlled analgesia (350 vs 554 ng/kg). The 3-year disease-free survival of the robotic group was comparable with that of the open group (72.2% vs 58.0%; p = 0.062), as was the 3-year overall survival (92.6 vs 93.7%; p = 0.431). The associated financial costs of robotic surgery still pose a limitation to its adoption, and it is unclear if this approach is associated with any significant advantages over laparoscopic rather than open resection.
6. Associating Liver Partition with Portal Vein Ligation for Staged
ALPPS is still considered an experimental technique in which a first-stage procedure consisting of physical liver splitting and portal vein ligation is followed by a second stage of resection of the HCC and associated liver segments. The advantage seen in colorectal liver metastases is that of rapid hypertrophy for the FLR. There are only limited data describing outcomes of ALPPS for HCC; however an analysis of 35 patients in the international ALPPS registry showed an impressive FLR hypertrophy of 47% following the first stage of the procedure that was associated with a 31% perioperative mortality rate. The majority of these patients were in the intermediate-stage category of the BCLC algorithm. Further evaluation is required prior to routine use of ALPPS for HCC resection, and it is the view of the authors that ALPPS may be a procedure best reserved for carefully selected patients who have bilateral disease.
7. Combined Resection with RFA for Bilobar HCC
For patients with multiple or bilobar HCC in whom resection is contraindicated due to inadequate FLR, combined resection and radiofrequency ablation (RFA) may yield better results than alternative treatments. A single-centre study compared patients with bilobar liver HCCs who underwent resection (n = 89), combination of resection and RFA (n = 114) and TACE (n = 161). The results showed that 1-, 3- and 5-year survival was better in both resection and combined resection, and RFA groups compared with TACE and survival and disease-free survival were comparable between both surgical groups. They concluded that resection combined with RFA provided a chance for cure in patients with bilobar HCC, and provided liver function is preserved, aggressive treatment can improve prognosis.
The most critical component of the treatment of Retroperitineal Sarcoma (RPS) remains the surgical excision, and the best chance for cure is at the time of primary surgery. Surgery should achieve a macroscopically complete excision of the tumor (R0 or R1), minimizing marginality, ideally through an en-bloc resection of all potentially involved structures as determined by careful preoperative imaging in combination with intraoperative findings.
Operative planning also includes the functional assessment of critical organs—eg, the function of each kidney. Contraindications to primary resection are believed to be bilateral renal involvement; encasement of the superior mesenteric artery, celiac axis, and porta hepatis; and spinal cord involvement.
When planning for surgery, it is paramount to take into consideration the histology of the RPS as well as its predicted behavior pattern, as these differ widely. Indeed, the largest transatlantic multi-institutional series identified histologic subtype as a predictor of patterns of local and distant recurrence. Moreover, analysis of a large, single-institution database demonstrated that histologic subtype is the strongest predictor of disease-specific death and affects both local and distant recurrence. Of greater interest, the patterns of contiguous organ involvement are also heavily dependent on histologic subtype.
In light of these data, surgeons oncologists should decide the extent of surgical resection in a multidisciplinary setting at a specialized center after review of imaging and pathology, given that the pattern of growth and prognostic risks vary broadly among the different histologic subtypes. For example, liposarcoma is the histologic subtype with the highest recurrence rate. In addition, it is the one with the least clear separation from normal retroperitoneal fat, given that the well-differentiated component of liposarcoma is virtually undistinguishable from normal fat. As a consequence, the extent of surgery should be aimed at removing all ipsilateral retroperitoneal fat en bloc with the mass at the price of sacrificing at least the ipsilateral kidney and colon and part of or the entire psoas muscle.
A staged approach can be followed in virtually all cases. The stages include:
A. Generous laparotomy, exploration, and retraction.
B. Division of the gastrocolic ligament, division of the transverse colon (plus distal ileum if on the right side), and assessment of the duodenum/head of the pancreas if on the right side, or body/tail of the pancreas and spleen if on the left side.
C. Liberation of duodenum/head of the pancreas if on the right side or body/tail of the pancreas and spleen and duodenojejunal junction if on the left side (when possible) and partial duodenal resection or pancreaticoduodenectomy (< 5% of right-sided retroperitoneal sarcomas) if on the right side or distal pancreatectomy and splenectomy if on the left (40%–50% of left-sided retroperitoneal sarcomas), when too adherent/invaded by the tumor.
D. Dissection of the inferior vena cava (IVC) if on the right side or aorta if on the left side, ligating ipsilateral renal vessels and other collaterals and dissection of the iliac vessels.
E. Peritonectomy, resection of the psoas muscle in the pelvis (plus rectal resection if on the left side) after identification and liberation of the femoral nerve (unless directly invaded) and possibly of the femoral cutaneous branch, while the genitofemoralis and ilioinguinal nerves are usually resected, as these lie between the tumor and the psoas fascia.
F. Section of the origin of the psoas major from the spine, sparing the roots of the femoral nerve and possibly the iliohypogastric nerve, liberation/resection of the costodiaphragmatic fold, and removal of the specimen.
Subcapsular liver dissection or partial hepatectomy are rarely needed for tumors located on the right side, whereas a complete liberation of the right liver lobe is usually of help. Similarly, sleeve gastrectomy or proximal gastrectomy is rarely required for tumors located on the left side. Finally, vascular resections (predominantly iliac vessels on either side and IVC on the right side) are required in 4% of cases.
Leiomyosarcoma and other rarer histologic subtypes such as solitary fibrous tumor are much more well-defined tumors. Their border can be clearly separated from retroperitoneal fat/structures. A wide resection is still required but not necessarily involving the adjacent organs if these are not clearly invaded.
Extended surgery may raise concern for added morbidity. A recent multi-institutional collaboration, however, found that a radical resection is safe and is associated with low 30-day mortality (1.8%). Severe complications were associated with increased age, transfusion requirements, and organ resection score, with a more pronounced risk in patients undergoing splenectomy and pancreatectomy and Whipple procedure.
Although major vascular resection (MVR) is associated with higher morbidity, vascular involvement does not preclude resection because it can be safely performed in specialized centers. MVR may be necessary either due to the origin of the RPS, as is the case for leiomyosarcoma of the IVC, or due to local invasion and involvement. Whereas multiple strategies for approaching MVR can be used, a good understanding of the vasculature and collaterals is critical prior to attempting resection and reconstruction, given that IVC resections are well tolerated if a good network of collaterals is present.
In essence, resection of RPS requires technical expertise in multiple sites throughout the abdominal and pelvic cavity, including the handling of large vessels. Single organ/site expertise is not sufficient. The ability to orchestrate a team of complementary surgical experts is critical to successful management of RPS patients. To minimize the risk of intraoperative and perioperative morbidity, RPS resection should be undertaken by surgical teams with expertise in specific aspects of the anatomy of the retroperitoneal space—for example, expertise in retroperitoneal autonomic and somatic nerves, the lymphatic system, paravertebral vessels, and organs of the gastrointestinal tract.
Required expertise also includes experience with additional procedures, such as full-thickness thoracoabdominal wall resection and reconstruction, diaphragmatic resection and reconstruction, major vascular resection and reconstruction, and bone resection. Surgical teams with these abilities, which may accrue from prior participation in multidisciplinary surgical teams, can achieve macroscopically complete tumor resection in the majority of patients.
Laparoscopic versus Open gastrectomy
Surgery is the only curative therapy for gastric cancer but most operable gastric cancer presents in a locally advanced stage characterized by tumor infiltration of the serosa or the presence of regional lymph node metastases. Surgery alone is no longer the standard treatment for locally advanced gastric cancer as the prognosis is markedly improved by perioperative chemotherapy. The decisive factor for optimum treatment is the multidisciplinary team specialized in gastric cancer. However, despite multimodal therapy and adequate surgery only 30% of gastric cancer patients are alive at 3 years.
The same principles that govern open surgery is applied to laparoscopic surgery. To ensure the same effectiveness of laparoscopic gastrectomy (LG) as conventional open gastrectomy, all the basic principles such as properly selected patients, sufficient surgical margins, standardized D2 lymphadenectomy, no-touch technique, etc., should be followed.
LG may be considered as a safe procedure with better short-term and comparable long-term oncological results compared with open gastrectomy. In addition, there is HRQL advantages to minimal access surgery. There is a general agreement that a laparoscopic approach to the treatment of gastric cancer should be chosen only by surgeons already highly skilled in gastric surgery and other advanced laparoscopic interventions. Furthermore, the first procedures should be carried out during a tutoring program. Diagnostic laparoscopy is strongly recommended as the first step of laparoscopic as well as open gastrectomies. The advantage of early recovery because of reduced surgical trauma would allow earlier commencement of adjuvant chemotherapy and the decreased hospital stay and early return to work may offset the financial costs of laparoscopic surgery.
The first description of LG was given by Kitano, Korea in 1994 and was initially indicated only for early gastric cancer patients with a low-risk lymph node metastasis. As laparoscopic experience has accumulated, the indications for LG have been broadened to patients with advanced gastric cancer. However, the role of LG remains controversial, because studies of the long-term outcomes of LG are insufficient. The Japanese Gastric Cancer Association guidelines in 2004 suggested endoscopic mucosal resection or endoscopic submucosal dissection for stage 1a (cT1N0M0) diagnosis; patients with stage 1b (cT1N1M0) and cT2N0M0) were referred for LG. Totally laparoscopic D2 radical distal gastrectomy using Billroth II anastomosis with laparoscopic linear staplers for early gastric cancer is considered to be safe and feasible. Laparoscopy-assisted total gastrectomy shows better short-term outcomes compared with open total gastrectomy in eligible patients with gastric cancer.
There was a significant reduction of intraoperative blood loss, a reduced risk of postoperative complications, and a shorter hospital stay. Western patients are relatively obese and there is an increased risk of bleeding if lymphadenectomy is performed. LG is technically difficult in the obese than in the normal weight due to reduced visibility, difficulty retracting tissues, dissection plane hindered by adipose tissue, and difficulty with anastomosis. Open gastrectomy is thus preferable for the obese. However, obesity is not a risk factor for survival of patients but it is independently predictive of postoperative complications. Careful approach is being needed, especially for male patients with high body mass index.
Robotic surgery will become an additional option in minimally invasive surgery. The importance of performing effective extended lymph node dissection may provide the advantage of using robotic systems. Such developments will improve the quality of life of patients following gastric cancer surgery. A multicenter study with a large number of patients is needed to compare the safety, efficacy, value (efficacy/cost ratio) as well as the long-term outcomes of robotic surgery, traditional laparoscopy, and the open approach.
There has been significant improvement in the perioperative results following liver resection, mainly due to techniques that help reduce blood loss during the operation. Extent of liver resection required in HCC for optimal oncologic results is still controversial. On this basis, the rationale for anatomically removing the entire segment or lobe bearing the tumor, would be to remove undetectable tumor metastases along with the primary tumor.
SIZE OF TUMOR VERSUS TUMOR FREE-MARGIN
Several retrospective studies and meta-analyses have shown that anatomical resections are safe in patients with HCC and liver dysfunction, and may offer a survival benefit. It should be noted, that most studies are biased, as non-anatomical resections are more commonly performed in patients with more advanced liver disease, which affects both recurrence and survival. It therefore remains unclear whether anatomical resections have a true long-term survival benefit in patients with HCC. Some authors have suggested that anatomical resections may provide a survival benefit in tumors between 2 and 5 cm. The rational is that smaller tumors rarely involve portal structures, and in larger tumors presence of macrovascular invasion and satellite nodules would offset the effect of aggressive surgical approach. Another important predictor of local recurrence is margin status. Generally, a tumor-free margin of 1 cm is considered necessary for optimal oncologic results. A prospective randomized trial on 169 patients with solitary HCC demonstrated that a resection margin aiming at 2 cm, safely decreased recurrence rate and improved long-term survival, when compared to a resection margin aiming at 1 cm. Therefore, wide resection margins of 2 cm is recommended, provided patient safety is not compromised.
Intraoperative ultrasound (IOUS) is an extremely important tool when performing liver resections, specifically for patients with HCC and compromised liver function. IOUS allows for localization of the primary tumor, detection of additional tumors, satellite nodules, tumor thrombus, and define relationship with bilio-vascular structures within the liver. Finally, intraoperative US-guided injection of dye, such as methylene-blue, to portal branches can clearly define the margins of the segment supplied by the portal branch and facilitate safe anatomical resection.
The anterior approach to liver resection is a technique aimed at limiting tumor manipulation to avoid tumoral dissemination, decrease potential for blood loss caused by avulsion of hepatic veins, and decrease ischemia of the remnant liver caused by rotation of the hepatoduodenal ligament. This technique is described for large HCCs located in the right lobe, and was shown in a prospective, randomized trial to reduce frequency of massive bleeding, number of patients requiring blood transfusions, and improve overall survival in this setting. This approach can be challenging, and can be facilitated by the use of the hanging maneuver.
Multiple studies have demonstrated that blood loss and blood transfusion administration are significantly associated with both short-term perioperative, and long-term oncological results in patients undergoing resection for HCC. This has led surgeons to focus on limiting operative blood loss as a major objective in liver resection. Transfusion rates of <20 % are expected in most experienced liver surgery centers. Inflow occlusion, by the use of the Pringle Maneuver represents the most commonly performed method to limit blood loss. Cirrhotic patients can tolerate total clamping time of up to 90 min, and the benefit of reduced blood loss outweighs the risks of inflow occlusion, as long as ischemia periods of 15 min are separated by at least 5 min of reperfusion. Total ischemia time of above 120 min may be associated with postoperative liver dysfunction. Additional techniques aimed at reducing blood loss include total vascular isolation, by occluding the inferior vena cava (IVC) above and below the liver, however, the hemodynamic results of IVC occlusion may be significant, and this technique has a role mainly in tumors that are adjacent to the IVC or hepatic veins.
Anesthesiologists need to assure central venous pressure is low (below 5 mmHg) by limiting fluid administration, and use of diuretics, even at the expense 470 N. Lubezky et al. of low systemic pressure and use of inotropes. After completion of the resection, large amount of crystalloids can be administered to replenish losses during parenchymal dissection.
Laparoscopic liver resections were shown to provide benefits of reduced surgical trauma, including a reduction in postoperative pain, incision-related morbidity, and shorten hospital stay. Some studies have demonstrated reduced operative bleeding with laparoscopy, attributed to the increased intra-abdominal pressure which reduces bleeding from the low-pressured hepatic veins. Additional potential benefits include a decrease in postoperative ascites and ascites-related wound complications, and fewer postoperative adhesions, which may be important in patients undergoing salvage liver transplantation. There has been a delay with the use of laparoscopy in the setting of liver cirrhosis, due to difficulties with hemostasis in the resection planes, and concerns for possible reduction of portal flow secondary to increased intraabdominal pressure. However, several recent studies have suggested that laparoscopic resection of HCC in patients with cirrhosis is safe and provides improved outcomes when compared to open resections.
Resections of small HCCs in anterior or left lateral segments are most amenable for laparoscopic resections. Larger resections, and resection of posterior-sector tumors are more challenging and should only be performed by very experienced surgeons. Long-term oncological outcomes of laparoscopic resections was shown to be equivalent to open resections on retrospective studies , but prospective studies are needed to confirm these findings. In recent years, robotic-assisted liver resections are being explored. Feasibility and safety of robotic-assisted surgery for HCC has been demonstrated in small non-randomized studies, but more experience is needed, and long-term oncologic results need to be studied, before widespread use of this technique will be recommended.
ALPPS: Associating Liver Partition with Portal vein ligation for Staged hepatectomy
The pre-operative options for inducing atrophy of the resected part and hypertrophy of the FLR, mainly PVE, were described earlier. Associating Liver Partition with Portal vein ligation for Staged hepatectomy (ALPPS) is another surgical option aimed to induce rapid hypertrophy of the FLR in patients with HCC. This technique involves a 2-stage procedure. In the first stage splitting of the liver along the resection plane and ligation of the portal vein is performed, and in the second stage, performed at least 2 weeks following the first stage, completion of the resection is performed. Patient safety is a major concern, and some studies have reported increased morbidity and mortality with the procedure. Few reports exist of this procedure in the setting of liver cirrhosis. Currently, the role of ALPPS in the setting of HCC and liver dysfunction needs to be better delineated before more widespread use is recommended.
After the first major hepatic resection, a left hepatic resection, carried out in 1888 by Carl Langenbuch, it took another 20 years before the first right hepatectomy was described by Walter Wendel in 1911. Three years before, in 1908, Hogarth Pringle provided the first description of a technique of vascular control, the portal triad clamping, nowadays known as the Pringle maneuver. Liver surgery has progressed rapidly since then. Modern surgical concepts and techniques, together with advances in anesthesiological care, intensive care medicine, perioperative imaging, and interventional radiology, together with multimodal oncological concepts, have resulted in fundamental changes. Perioperative outcome has improved significantly, and even major hepatic resections can be performed with morbidity and mortality rates of less than 45% and 4% respectively in highvolume liver surgery centers. Many liver surgeries performed routinely in specialized centers today were considered to be high-risk or nonresectable by most surgeons less than 1–2 decades ago.Interestingly, operative blood loss remains the most important predictor of postoperative morbidity and mortality, and therefore vascular control remains one of the most important aspects in liver surgery.
“Bleeding control is achieved by vascular control and optimized and careful parenchymal transection during liver surgery, and these two concepts are cross-linked.”
First described by Pringle in 1908, it has proven effective in decreasing haemorrhage during the resection of the liver tissue. It is frequently used, and it consists in temporarily occluding the hepatic artery and the portal vein, thus limiting the flow of blood into the liver, although this also results in an increased venous pressure in the mesenteric territory. Hemodynamic repercussion during the PM is rare because it only diminishes the venous return in 15% of cases. The cardiovascular system slightly increases the systemic vascular resistance as a compensatory response, thereby limiting the drop in the arterial pressure. Through the administration of crystalloids, it is possible to maintain hemodynamic stability.
In the 1990s, the PM was used continuously for 45 min and even up to an hour because the depth of the potential damage that could occur due to hepatic ischemia was not yet known. During the PM, the lack of oxygen affects all liver cells, especially Kupffer cells which represent the largest fixed macrophage mass. When these cells are deprived of oxygen, they are an endless source of production of the tumour necrosis factor (TNF) and interleukins 1, 6, 8 and 10. IL 6 has been described as the cytokine that best correlates to postoperative complications. In order to mitigate the effects of continuous PM, intermittent clamping of the portal pedicle has been developed. This consists of occluding the pedicle for 15 min, removing the clamps for 5 min, and then starting the manoeuvre again. This intermittent passage of the hepatic tissue through ischemia and reperfusion shows the development of hepatic tolerance to the lack of oxygen with decreased cell damage. Greater ischemic tolerance to this intermittent manoeuvre increases the total time it can be used.
Gallbladder cancer is uncommon disease, although it is not rare. Indeed, gallbladder cancer is the fifth most common gastrointestinal cancer and the most common biliary tract cancer in the United States. The incidence is 1.2 per 100,000 persons per year. It has historically been considered as an incu-rable malignancy with a dismal prognosis due to its propensity for early in-vasion to liver and dissemination to lymph nodes and peritoneal surfaces. Patients with gallbladder cancer usually present in one of three ways: (1) advanced unresectable cancer; (2) detection of suspicious lesion preoperatively and resectable after staging work-up; (3) incidental finding of cancer during or after cholecystectomy for benign disease.
Although, many studies have suggested improved survival in patients with early gallbladder cancer with radical surgery including en bloc resection of gallbladder fossa and regional lymphadenectomy, its role for those with advanced gallbladder cancer remains controversial. First, patients with more advanced disease often require more extensive resections than early stage tumors, and operative morbidity and mortality rates are higher. Second, the long-term outcomes after resection, in general, tend to be poorer; long-term survival after radical surgery has been reported only for patients with limited local and lymph node spread. Therefore, the indication of radical surgery should be limited to well-selected patients based on thorough preoperative and intra-operative staging and the extent of surgery should be determined based on the area of tumor involvement.
Surgical resection is warranted only for those who with locoregional disease without distant spread. Because of the limited sensitivity of current imaging modalities to detect metastatic lesions of gallbladder cancer, staging laparoscopy prior to proceeding to laparotomy is very useful to assess the
abdomen for evidence of discontinuous liver disease or peritoneal metastasis and to avoid unnecessary laparotomy. Weber et al. reported that 48% of patients with potentially resectable gallbladder cancer on preoperative imaging work-up were spared laparotomy by discovering unresectable disease by laparoscopy. Laparoscopic cholecystectomy should be avoided when a preoperative cancer is suspected because of the risk of violation of the plane between tumor and liver and the risk of port site seeding.
The goal of resection should always be complete extirpation with microscopic negative margins. Tumors beyond T2 are not cured by simple cholecystectomy and as with most of early gallbladder cancer, hepatic resection is always required. The extent of liver resection required depends upon whether involvement of major hepatic vessels, varies from segmental resection of segments IVb and V, at minimum to formal right hemihepatectomy or even right trisectionectomy. The right portal pedicle is at particular risk for advanced tumor located at the neck of gallbladder, and when such involvement is suspected, right hepatectomy is required. Bile duct resection and reconstruction is also required if tumor involved in bile duct. However, bile duct resection is associated with increased perioperative morbidity and it should be performed only if it is necessary to clear tumor; bile duct resection does not necessarily increase the lymph node yield.
Portal vein Embolizations (PVE) is commonly used in the patients requiring extensive liver resection but have insufficient Future Liver Remanescent (FLR) volume on preoperative testing. The procedure involves occluding portal venous flow to the side of the liver with the lesion thereby redirecting portal flow to the contralateral side, in an attempt to cause hypertrophy and increase the volume of the FLR prior to hepatectomy.
PVE was first described by Kinoshita and later reported by Makuuchi as a technique to facilitate hepatic resection of hilar cholangiocarcinoma. The technique is now widely used by surgeons all over the world to optimize FLR volume before major liver resections.
PVE works because the extrahepatic factors that induce liver hypertrophy are carried primarily by the portal vein and not the hepatic artery. The increase in FLR size seen after PVE is due to both clonal expansion and cellular hypertrophy, and the extent of post-embolization liver growth is generally proportional to the degree of portal flow diversion. The mechanism of liver regeneration after PVE is a complex phenomenon and is not fully understood. Although the exact trigger of liver regeneration remains unknown, several studies have identified periportal inflammation in the embolized liver as an important predictor of liver regeneration.
PVE is technically feasible in 99% of the patients with low risk of complications. Studies have shown the FLR to increase by a median of 40–62% after a median of 34–37 days after PVE, and 72.2–80% of the patients are able to undergo resection as planned. It is generally indicated for patients being considered for right or extended right hepatectomy in the setting of a relatively small FLR. It is rarely required before extended left hepatectomy or left trisectionectomy, since the right posterior section (segments 6 and 7) comprises about 30% of total liver volume.
PVE is usually performed through percutaneous transhepatic access to the portal venous system, but there is considerable variability in technique between centers. The access route can be ipsilateral (portal access at the same side being resected) with retrograde embolization or contralateral (portal access through FLR) with antegrade embolization. The type of approach selected depends on a number of factors including operator preference, anatomic variability, type of resection planned, extent of embolization, and type of embolic agent used. Many authors prefer ipsilateral approach especially for right-sided tumors as this technique allows easy catheterization of segment 4 branches when they must be embolized and also minimizes the theoretic risk of injuring the FLR vasculature or bile ducts through a contralateral approach and potentially making a patient ineligible for surgery.
However, majority of the studies on contralateral PVE show it to be a safe technique with low complication rate. Di Stefano et al. reported a large series of contralateral PVE in 188 patients and described 12 complications (6.4%) only 6 of which could be related to access route and none precluded liver resection. Site of portal vein access can also change depending on the choice of embolic material selected which can include glue, Gelfoam, n-butyl-cyanoacrylate (NBC), different types and sizes of beads, alcohol, and nitinol plus. All agents have similar efficacy and there are no official recommendations for a particular type of agent.
Proponents of PVE believe that there should be very little or no tumor progression during the 4–6 week wait period for regeneration after PVE. Rapid growth of the FLR can be expected within the first 3–4 weeks after PVE and can continue till 6–8 weeks. Results from multiple studies suggest that 8–30% hypertrophy over 2–6 weeks can be expected with slower rates in cirrhotic patients. Most studies comparing outcomes after major hepatectomy with and without preoperative PVE report superior outcomes with PVE. Farges et al. demonstrated significantly less risk of postoperative complications, duration of intensive care unit, and hospital stay in patients with cirrhosis who underwent right hepatectomy after PVE compared to those who did not have preoperative PVE. The authors also reported no benefit of PVE in patients with a normal liver and FLR >30%. Abulkhir et al. reported results from a meta-analysis of 1088 patients undergoing PVE and showed a markedly lower incidence of Post Hepatectomy Liver Failure (PHLF) and death compared to series reporting outcomes after major hepatectomy in patients who did not undergo PVE. All patients had FLR volume increase, and 85% went on to have liver resection after PVE with a PHLF incidence of 2.5% and a surgical mortality of 0.8%. Several studies looking at the effect of systemic neoadjuvant chemotherapy on the degree of hypertrophy after PVE show no significant impact on liver regeneration and growth.
The volumetric response to PVE is also a very important factor in understanding the regenerative capacity of a patient’s liver and when used together with FLR volume can help identify patients at risk of poor postsurgical outcome. Ribero et al. demonstrated that the risk of PHLF was significantly higher not only in patients with FLR ≤ 20% but also in patients with normal liver who demonstrated ≤5% of FLR hypertrophy after PVE. The authors concluded that the degree of hypertrophy >10% in patients with severe underlying liver disease and >5% in patients with normal liver predicts a low risk of PHLF and post-resection mortality. Many authors do not routinely offer resection to patients with borderline FLR who demonstrate ≤5% hypertrophy after PVE.
Careful analysis of outcome based on liver remnant volume stratified by underlying liver disease has led to recommendations regarding the safe limits of resection. The liver remnant to be left after resection is termed the future liver remnant (FLR). For patients with normal underlying liver, complications, extended hospital stay, admission to the intensive care unit, and hepatic insufficiency are rare when the standardized FLR is >20% of the TLV. For patients with tumor-related cholestasis or marked underlying liver disease, a 40% liver remnant is necessary to avoid cholestasis, fluid retention, and liver failure. Among patients who have been treated with preoperative systemic chemotherapy for more than 12 weeks, FLR >30% reduces the rate of postoperative liver insufficiency and subsequent mortality.
When the liver remnant is normal or has only mild disease, the volume of liver remnant can be measured directly and accurately with threedimensional computed tomography (CT) volumetry. However, inaccuracy may arise because the liver to be resected is often diseased, particularly in patients with cirrhosis or biliary obstruction. When multiple or large tumors occupy a large volume of the liver to be resected, subtracting tumor volumes from liver volume further decreases accuracy of CT volumetry. The calculated TLV, which has been derived from the association between body surface area (BSA) and liver size, provides a standard estimate of the TLV. The following formula is used:
TLV (cm3) = –794.41 + 1267.28 × BSA (square meters)
Thus, the standardized FLR (sFLR) volume calculation uses the measured FLR volume from CT volumetry as the numerator and the calculated TLV as the denominator: Standardized FLR (sFLR) = measured FLR volume/TLV Calculating the standardized TLV corrects the actual liver volume to the individual patient’s size and provides an individualized estimate of that patient’s postresection liver function. In the event of an inadequate FLR prior to major hepatectomy, preoperative liver preparation may include portal vein embolization (PVE).
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Cholangiocarcinoma (CCA) is a rare but lethal cancer arising from the bile duct epithelium. As a whole, CCA accounts for approximately 3 % of all gastrointestinal cancers. It is an aggressive disease with a high mortality rate. Unfortunately, a significant proportion of patients with CCA present with either unresectable or metastatic disease. In a retrospective review of 225 patients with hilar cholangiocarcinoma, Jarnagin et al. reported that 29 % of patients had either unresectable disease were unfit for surgery. Curative resection offers the best chance for longterm survival. Whereas palliation with surgical bypass was once the preferred surgical procedure even for resectable disease, aggressive surgical resection is now the standard.
The abdomen is the lower part of the trunk below the diaphragm. Its walls surround a large cavity called the abdominal cavity. The abdominal cavity is much more extensive than what it appears from the outside. It extends upward deep to the costal margin up to the diaphragm and downward within the bony pelvis. Thus, a considerable part of the abdominal cavity is overlapped by the lower part of the thoracic cage above and by the bony pelvis below. The abdominal cavity is subdivided by the plane of the pelvic inlet into a larger upper part, i.e., the abdominal cavity proper, and a smaller lower part, i.e., the pelvic cavity. Clinically the importance of the abdomen is manifold. To the physician, the physical examination of the patient is never complete until he/she thoroughly examines the abdomen. To the surgeon, the abdomen remains an enigma because in number of cases the cause of abdominal pain and nature of abdominal lump remains inconclusive even after all possible investigations. To summarize, many branches of medicine such as general surgery and gastroenterology are all confined to the abdomen.
IPMNs were first recognized in 1982 by Ohashi, but the term IPMN was not officially used until 1993. IPMNs are defined in the WHO Classification of Tumors of the Digestive System as an intraductal, grossly visible epithelial neoplasm of mucin-producing cells. Using imaging and histology, IPMNs can be classified into three types based on duct involvement:
1. Main-duct IPMN (approximately 25% of IPMNs): Segmental or diffuse dilation of the main pancreatic duct (>5 mm) in the absence of other causes of ductal obstruction.
2. Branch-duct IPMN (approximately 57% of IPMNs): Pancreatic cysts (>5 mm) that communicate with the main pancreatic duct.
3. Mixed type IPMN (approximately 18% of IPMNs): Meets criteria for both main and branch duct.
Due to the asymptomatic nature of the disease, the overall incidence of IPMNs is difficult to define but is thought to account for approximately 3% to 5% of all pancreatic tumors. Most IPMNs are discovered as incidental lesions from the workup of an unrelated process by imaging or endoscopy. IPMNs are slightly more prevalent in males than in females, with a peak incidence of 60 to 70 years of age. Branch-duct IPMNs tend to occur in a slightly younger population and are less associated with malignancy compared with main-duct or mixed variants.
Because a majority of IPMNs are discovered incidentally, most are asymptomatic. When symptoms do occur, they tend to be nonspecific and include unexplained weight loss, anorexia, abdominal pain, and back pain. Jaundice can occur with mucin obstructing the ampulla or with an underlying invasive carcinoma. The obstruction of the pancreatic duct can also lead to pancreatitis. IPMNs may represent genomic instability of the entire pancreas. This concept, known as a “field defect,” has been described as a theoretical risk of developing a recurrent IPMN or pancreatic adenocarcinoma at a site remote from the original IPMN. The three different types of IPMNs, main duct, branch duct, and mixed duct, dictate different treatment algorithms.
MAIN DUCT IPMNs
Main-duct IPMNs should be resected in all patients unless the risks of existing comorbidities outweigh the benefits of resection. The goal of operative management of IPMNs is to remove all adenomatous or potentially malignant epithelium to minimize recurrence in the pancreas remnant. There are two theories on the pathophysiologic basis of IPMNs. The first groups IPMNs into a similar category as an adenocarcinoma, a localized process involving only a particular segment of the pancreas. The thought is that removal of the IPMN is the only treatment necessary. In contrast, some believe IPMNs to represent a field defect of the pancreas. All of the ductal epithelium remains at risk of malignant degeneration despite removal of the cyst. Ideally, a total pancreatectomy would eliminate all risk, but this is a radical procedure that is associated with metabolic derangements and exocrine insufficiency. Total pancreatectomy should be limited to the most fit patients, with a thorough preoperative assessment and proper risk stratification prior to undertaking this surgery.
There is less uncertainty with treatment of main-duct IPMNs. The high incidence of underlying malignancy associated with the IPMNs warrants surgical resection. IPMNs localized to the body and tail (approximately 33%) can undergo a distal pancreatectomy with splenectomy. At the time of surgery, a frozen section of the proximal margin should be interpreted by a pathologist to rule out high-grade dysplasia. A prospective study identified a concordance rate of 94% between frozen section and final pathologic examination. If the margin is positive (high-grade dysplasia, invasion) additional margins may be resected from the pancreas until no evidence of disease is present. However, most surgeons will proceed to a total pancreatectomy after two subsequent margins demonstrate malignant changes. This more extensive procedure should be discussed with the patient prior to surgery, and the patient should be properly consented regarding the risks of a total pancreatectomy.
IPMNs localized to the head or uncinate process of the pancreas should undergo a pancreaticoduodenectomy. A frozen section of the distal margin should be analyzed by pathology for evidence of disease. As mentioned before, after two additional margins reveal malignant changes, a total pancreatectomy is usually indicated (approximately 5%). The absence of abnormal changes in frozen sections does not equate to negative disease throughout the pancreas remnant. Rather, skip lesions involving the remainder of the pancreas can exist and thus patients ultimately still require imaging surveillance after successful resection. A prophylactic total pancreatectomy is rarely performed because the subsequent pancreatic endocrine (diabetes mellitus) and exocrine deficits (malnutrition) carry an increased morbidity.
BRANCH DUCT IPMNs
Localized branch-duct IPMN can be treated with a formal anatomic pancreatectomy, pancreaticoduodenectomy, or distal pancreatectomy, depending on the location of the lesion. However, guidelines were established that allow for nonoperative management with certain branch- type IPMN characteristics.
These include asymptomatic patients with a cyst size less than 3 cm and lack of mural nodules. The data to support this demonstrate a very low incidence of malignancy (approximately 2%) in this patient group. Which nearly matches the anticipated mortality of undergoing a formal anatomic resection. In approximately 20% to 30% of patients with branch- duct IPMNs, there is evidence of multifocality. The additional IPMNs can be visualized on high-resolution CT or MRI imaging. Ideally, patients with multifocal branch-duct IPMNs should undergo a total pancreatectomy. However, as previously mentioned, the increased morbidity and lifestyle alterations associated with a total pancreatectomy allows for a more conservative approach. This would include removing the most suspicious or dominant of the lesions in an anatomic resection and follow-up imaging surveillance of the remaining pancreas remnant. If subsequent imaging demonstrates malignant charac- teristics, a completion pancreatectomy is usually indicated.
Recurrence rates with IPMNs are variable. An anatomic resection of a branch-duct IPMN with negative margins has been shown to be curative. The recurrence of a main- duct IPMN in the remnant gland is anywhere from 0% to 10% if the margins are negative and there is no evidence of invasion. Most case series cite a 5-year survival rate of at least 70% after resection of noninvasive IPMNs. In contrast, evidence of invasive disease, despite negative margins, decreases 5-year survival to 30% to 50%. The recurrence rate in either the pancreatic remnant or distant sites approaches 50% to 90% in these patients. Histopathologic subtype of the IPMN is correlated with survival. The aggressive tubular subtype has a 5-year survival ranging from 37% to 55% following surgical resection, whereas the colloid subtype has 5-year survival ranging from 61% to 87% post resection. Factors associated with decreased survival include tubular subtype, lymph node metastases, vascular invasion, and positive margins. IPMNs with evidence of invasion should be treated similar to pancreatic adenocarcinomas. Studies show that IPMNs tend to have better survival than pancreatic adenocarcinoma. This survival benefit may be secondary to the less aggressive tumor biology or the earlier diagnosis of IPMNs.
All patients who have a resected IPMN should undergo imaging surveillance. There is continual survival benefit with further resection if an IPMN does recur. International Consensus Guidelines published in 2017 offer recom- mendations for the frequency and modality of imaging surveillance after resection. Routine serum measurement of CEA and CA 19-9 has a limited role for detection of an IPMN recurrence. Of note, a new pancreatic lesion discovered on imaging after resection could represent a postoperative pseudocyst, a recurrence of the IPMN from inadequate resection, a new IPMN, or an unrelated new neoplastic process. IPMNs may also be associated with extrapancreatic neoplasms (stomach, colon, rectum, lung, breast) and pancreatic ductal adenocarcinoma. It is unclear if this represents a true genetic syndrome. However, patients with IPMNs should have a discussion about the implications of their disease with their physician and are encouraged to undergo colonoscopy to exclude a synchronous neoplastic process.
The incidence of PANCREATIC CYSTIC LESIONS will continue to increase as imaging technology improves. EUS, cytology, and molecular panels have made differentiating the type of PCN less problematic. The importance of an accurate preoperative diagnosis ensures that operative management is selectively offered to those with high-risk lesions. Management beyond surgery, including adjuvant therapy and surveillance, continue to be active areas of research.
Surgery and anesthesia profoundly alter the normal physiologic and metabolic states. Estimating the patient’s ability to respond to these stresses in the postoperative period is the task of the preoperative evaluation. Perioperative complications are often the result of failure, in the preoperative period, to identify underlying medical conditions, maximize the patient’s preoperative health, or accurately assess perioperative risk. Sophisticated laboratory studies and specialized testing are no substitute for a thoughtful and careful history and physical examination. Sophisticated technology has merit primarily in confirming clinical suspicion.
Hepatocellular carcinoma is the second most common cause of cancer mortality worldwide and its incidence is rising in North America, with an estimated 35,000 cases in the U.S. in 2014. The best chance for cure is surgical resection in the form of either segmental removal or whole organ transplantation although recent survival data on radiofrequency ablation approximates surgical resection and could be placed under the new moniker of “thermal resection”. The debate between surgical resection and transplantation focuses on patients with “within Milan criteria” tumors, single tumors, and well compensated cirrhosis who can safely undergo either procedure. Although transplantation historically has had better survival outcomes, early diagnosis, reversal of liver disease, and innovations in patient selection and neo-adjuvant therapies have led to similar 5-year survival. Transplantation clearly has less risk of tumor recurrence but exposes recipients to long term immunosuppression and its side effects. Liver transplantation is also limited by the severe global limit on the supply of organ donors whereas resection is readily available. The current data does not favor one treatment over the other for patients with minimal or no portal hypertension and normal synthetic function. Instead, the decision to resect or transplant for HCC relies on multiple factors including tumor characteristics, biology, geography, co-morbidities, location, organ availability, social support and practice preference.
Resection Versus Transplantation
The debate between resection and transplantation revolves around patients who have well compensated cirrhosis with Milan criteria resectable tumors. Patients within these criteria represent a very small proportion of those who initially present with HCC. This is especially true in western countries where hepatitis C is the most common cause of liver failure and HCC is a result of the progressive and in most cases advanced cirrhosis.
Given the need for a large number of patients to show statistical significance, it would be difficult to perform a high-quality prospective randomized controlled trial comparing resection and transplantation. In fact the literature revealed that no randomized controlled trials addressing this issue exist. Instead, outcomes of surgical treatment for HCC stem from retrospective analyses that have inherent detection, selection and attrition biases.
Given the numerous articles available on this subject, several meta-analyses have been published to delineate the role of transplantation and resection for treatment of HCC. However, there is reason to be wary of these meta-analyses because they pool data from heterogeneous populations with variable selection criteria and treatment protocols. One such meta-analysis by Dhir et al. focused their choice of articles to strict criteria which excluded studies with non-cirrhotic patients, fibrolamellar HCC and hepato-cholangiocarcinomas but included those with HCC within Milan criteria and computation of 5-year survival; between 1990 and 2011 they identified ten articles that fit within these criteria, of which six were ITT analyses, six included only well-compensated cirrhotics (Child-Pugh Class A without liver dysfunction) and three were ITT analyses of well-compensated cirrhotics.
Analysis of the six ITT studies that included all cirrhotics (n = 1118) (Child-Pugh Class A through C) showed no significant difference in survival at 5 years (OR = 0.600, 95 % CI 0.291– 1.237 l; p=0.166) but ITT analysis of only well-compensated cirrhotics (Child- Pugh Class A) revealed that patients undergoing transplant had a significantly higher 5-year survival as compared to those with resection (OR=0.521, 95 % CI 0.298–0.911; p=0.022).
A more recent ITT retrospective analysis from Spain assessed long-term survival and tumor recurrence following resection or transplant for tumors <5 cm in 217 cirrhotics (Child-Pugh Class A, B and C) over the span of 16 years. Recurrence at 5 years was significantly higher in the resection group (71.6 % vs. 16 % p<0.001) but survival at 4 years was similar (60 % vs. 62 %) which is likely explained by the evolving role of adjuvant therapies to treat post-resection recurrence.
- Patients with anatomically resectable single tumors and no cirrhosis or Child-Pugh Class A cirrhosis with normal bilirubin, HVPG (<10 mmHg), albumin and INR can be offered resection (evidence quality moderate; strong recommendation).
- Patients with Milan criteria tumors in the setting of Child- Pugh Class A with low platelets and either low albumin or high bilirubin or Child-Pugh Class B and C cirrhosis, especially those with more than one tumor, should be offered liver transplantation over resection (evidence quality moderate; strong recommendation).
- Those with Milan criteria tumors and Child-Pugh Class A cirrhosis without liver dysfunction should be considered for transplantation over resection (evidence quality low; weak recommendation).
- No recommendation can be made in regard to transplanting tumors beyond Milan criteria (evidence quality low) except to follow regional review board criteria.
- Pre-transplant therapies such as embolic or thermal ablation are safe and by expert opinion considered to be effective in decreasing transplant waitlist dropout and bridging patients to transplant (evidence quality low, weak recommendation). These interventions should be considered for those waiting longer than 6 months (evi- dence quality low, moderate recommendation).
- Living donor liver transplantation is a safe and effective option for treatment of HCC that are within and exceed Milan criteria (evidence quality moderate, weak recommendation).
Minimally invasive surgery, a widely adopted tool for most domains of gastrointestinal surgery, has been relatively slow to evolve in the field of pancreatic surgery. The reasons include proximity to the great vessels, retroperitoneal location, need for advanced intracorporeal suturing skills and increased risk of complications associated with these procedures. With enormous development in surgical technology coupled with improved anatomical knowledge and refined skills, minimally invasive pancreatic surgery has grown out of its infancy and is an established specialty in hepato-pancreato-biliary surgery today. As a result, the initial scepticism and reluctance associated with minimally invasive pancreatic resections has decreased and many surgeons are attempting to enter this difficult terrain. Recent publications highlight potential advantages of minimally invasive pancreatic resection (MIPR) over open pancreatic resection (OPR). These include reduced pain, decreased blood loss and need for transfusion, an earlier return of bowel function, decreased wound infection rates and shorter intensive care unit and overall hospital stays. Though the number of minimally invasive pancreatic resections performed for benign and malignant diseases of the pancreas has increased in recent years, cost considerations and financial implications of these new approaches need to be well defined. Clear guidelines and standardization of surgical technique are paramount for the safe and steady expansion of this novel surgical approach.
Minimally Invasive Pancreaticoduodenectomy
Gagner and Pomp reported the first LPD in 1994. They felt that laparoscopy was not useful for such a major resection and reconstruction. However, their initial patients included those with chronic pancreatitis, where LPD is considered difficult to do even at present. With this background, we began doing LPD after sufficient experience had been gained in other major laparoscopic procedures such as colectomy, gastrectomy and choledochal cyst excision. During the initial phase, LPD was attempted in only periampullary tumours or small pancreatic head masses. With increasing experience, the indications for LPD were expanded to include carcinoma head of the pancreas and larger tumours.
Over the years, numerous technical modifications in terms of surgeon comfort, use of energy source, radicality of surgery, type of reconstruction and specimen extraction were made. These refinements resulted in better outcomes as was evident in the next publication in 2009 which included 75 patients. Oncologically, the resection status and lymph nodal yield were comparable with the open approach and would translate to equal survival outcomes. Recently, Asbun et al. compared their open PDs and LPDs and found that LPD had better perioperative outcomes in terms of blood loss and ICU and hospital stays.
In 2015, Palanivelu reported that the pathological radicality of LPD was comparable to that of the open approach when performed by experienced minimal access surgeons. And analysed yours long-term outcomes following LPD in 130 patients with pancreatic and periampullary cancers. This study, one of the largest published series so far, showed excellent short-term results and acceptable long-term survival. The pancreatic fistula rate was 8.5%, mean (SD) operating time was 310 (34) min, and mean blood loss was 110 (22) ml with a mean hospital stay of 8 (2.6) days. The resected margins were positive in 9.2% with an overall 5-year actuarial survival of 29.4% and a median survival of 33 months.
Published outcomes of LPD have shown that it is feasible and safe when done in high-volume institutions by expert surgeons. In a recent systematic review of LPD, Boggi et al. identified 25 articles with 746 patients who had LPD for both malignant and benign indications. The mean operative time and estimated blood loss were 464 min and 321 ml, respectively. Conversion to open surgery was required in 9% of patients. The average hospital stay was 14 days. The overall morbidity, mortality and pancreatic fistula rates were 41.2, 1.9 and 22.3%, respectively. The majority of surgeons did a pancreaticojejunostomy (84%), whereas a small number did pancre- aticogastrostomy (9.8%) or duct occlusion (6.8%). A slight majority did pylorus preservation (55%) instead of hemigastrectomy (45%). No major differences in outcomes were seen for laparoscopic, robotic, laparoscopic-assisted or hand-assisted methods.
Similarly, no significant differences were seen between high-volume (>30 cases) and low-volume centres other than longer operative times and higher estimated blood loss in the low-volume ones. The average number of lymph nodes recovered was 14.4 and the negative margin rate was 95.6%. Although the data were heterogeneous with a high likelihood for selection bias, the results for LPD appear to be at least comparable to those in patients undergoing open PD.
In general, LPD was associated with reduced blood loss and hospital stay; however, operative times tend to be longer. The longer operative times associated with LPD tend to reduce with increasing experience. In a series by Kim et al., the median operative time for LPD was 7.9 h and decreased with accumulating experience of the surgeon doing this procedure from 9.8 h for the first 33 cases to 6.6 h for the last 34 cases.
Hepatic resection had an impressive growth over time. It has been widely performed for the treatment of various liver diseases, such as malignant tumors, benign tumors, calculi in the intrahepatic ducts, hydatid disease, and abscesses. Management of hepatic resection is challenging. Despite technical advances and high experience of liver resection of specialized centers, it is still burdened by relatively high rates of postoperative morbidity and mortality. Especially, complex resections are being increasingly performed in high risk and older patient population. Operation on the liver is especially challenging because of its unique anatomic architecture and because of its vital functions. Common post-hepatectomy complications include venous catheter-related infection, pleural effusion, incisional infection, pulmonary atelectasis or infection, ascites, subphrenic infection, urinary tract infection, intraperitoneal hemorrhage, gastrointestinal tract bleeding, biliary tract hemorrhage, coagulation disorders, bile leakage, and liver failure. These problems are closely related to surgical manipulations, anesthesia, preoperative evaluation and preparation, and postoperative observation and management. The safety profile of hepatectomy probably can be improved if the surgeons and medical staff involved have comprehensive knowledge of the expected complications and expertise in their management.
The era of hepatic surgery began with a left lateral hepatic lobectomy performed successfully by Langenbuch in Germany in 1887. Since then, hepatectomy has been widely performed for the treatment of various liver diseases, such as malignant tumors, benign tumors, calculi in the intrahepatic ducts, hydatid disease, and abscesses. Operation on the liver is especially challenging because of its unique anatomic architecture and because of its vital functions. Despite technical advances and high experience of liver resection of specialized centers, it is still burdened by relatively high rates of postoperative morbidity (4.09%-47.7%) and mortality (0.24%-9.7%). This review article focuses on the major postoperative issues after hepatic resection and presents the current management.
The first postgastrectomy syndrome was noted not long after the first gastrectomy was performed: Billroth reported a case of epigastric pain associated with bilious vomiting as a sequel of gastric surgery in 1885. Several classic treatises exist on the subject; we cannot improve on them and merely provide a few references for the interested reader.
However, the indications for gastric resection have changed dramatically over the past 4 decades, and the overall incidence of gastric resection has decreased. The most marked reduction in the frequency of gastric resection has occurred among patients with peptic ulcer disease. For example, in Olmstead County, Minnesota, the incidence of elective operations on previously unoperated patients declined 8-fold during the 30-year study period between 1956 and 1985 and undoubtedly has declined even further since.
One population-based study concluded that elective surgery for ulcer disease had “virtually disappeared by 1992–1996.” Whereas emergency operations for bleeding and perforation are still encountered, acid-reducing procedures are being performed less frequently in these situations in favor of a damage control approach. Even for gastric cancer, resection rates decreased approximately 20% from 1988 to 2000 in the United States.
An estimated 21,000 new cases of stomach cancer occurred in the United States in 2010, so that the number of cases of gastric resection for cancer is probably less than 15,000 per year in the United States. The virtual disappearance of elective surgery for peptic ulcer has also changed the demographic profile of the postgastrectomy patient: patients who have gastric cancer tend to be older and there is only a slight male preponderance.
These significant changes in the gastric surgery population make it worthwhile to revisit postgastrectomy syndromes. The frequency with which postgastrectomy symptoms/syndromes are found can depend on how hard they are looked for. Loffeld, in a survey of 124 postgastrectomy patients, most of whom had undergone surgery more than 15 years earlier, found that 75% suffered from upper abdominal symptoms, and 1 or more symptoms that indicate dumping were found in 70% of patients who had undergone Billroth-II (B-II) reconstruction.
However, the lack of age-matched and sex-matched controls in this study may have overstated the frequency of symptoms caused by the surgical procedure. Mine and colleagues conducted a large survey of 1153 patients after gastrectomy for cancer and found that 67% reported early dumping and 38% late dumping. By contrast, Pedrazzani and colleagues surveyed 195 patients who underwent subtotal gastrectomy and B-II reconstruction for gastric adenocarcinoma for up to 5 years postoperatively, and concluded that “the incidence of late complications was low and the majority of them recovered within one year after surgery.”
This article focuses on the small proportion of patients with severe, debilitating symptoms; these symptoms can challenge the acumen of the surgeon who is providing the patient’s long-term follow-up and care.
The creation of a stoma is a technical exercise. Like most undertakings, if done correctly, the stoma will usually function well with minimal complications for the remainder of the ostomate’s life. Conversely, if created poorly, stoma complications are common and can lead to years of misery. Intestinal stomas are in fact enterocutaneous anastomoses and all the principles that apply to creation of any anastomosis (i.e., using healthy intestine, avoiding ischemia and undue tension) are important in stoma creation.
Colon surgery represents a high number of patients treated at a department of gastrointestinal surgery and is not limited to colon cancer. It includes other non-neoplastic pathologies such as inflammatory bowel disease, diverticular disease or colonic volvulus. As with any major procedure, colon surgery patients may present serious or even fatal complications. The incidence of postoperative complications from colon surgery has been estimated at between 10% and 30% according to selected series. Preventive measures against surgical complications include selection of an appropriate procedure for the patient as well as good preoperative care, appropriate surgical technique and good postoperative management. When diagnosis has been established, risks for patient should be assessed according to patient’s health conditions and type of surgery accomplished. When the patient meets the surgical requirements, an appropriate course of preoperative care should be carried out including colon wash antibiotics and antithrombotic prophylaxis. Postoperative period will be equivalent to any major abdominal surgery. Typically, it was considered appropriate to wait a few days before initiating feeding in order to protect anastomosis; however, some authors agree that an early oral diet hours after intervention is not associated with a higher risk of anastomotic dehiscence and other complications.
Extent of lymph node dissection has been an area of controversy in gastric adenocarcinoma for many years. Some surgeons believe that cancer metastasizes through a stepwise progression, and an extensive lymphadenectomy is necessary to improve survival and/or cure the patient. Other physicians argue that extensive ly-mphadenectomies only add pe-rioperative morbidity and mor-tality and do not improve survival. Asian countries have been performing extended lymphadenectomies routinely for many years with promising survival data, although Western countries have not been able to reproduce those results. Much of the controversy surrounding lymphadenectomies started in the 1980s when Japanese studies reported superior survival rates matched stage for stage, compared to the United States. This was theorized to be secondary to the more extensive lymphadenectomy performed in Japan compared to the United States.
A United Kingdom study randomized 400 patients to either a D1 or a D2 lymph node dissection. Those patients with tumors in the upper or middle third of the stomach underwent a distal pancreaticosplenectomy to obtain retropancreatic and splenic hilar nodes. While the 5-year survival rates were not statistically significant between the two groups, on multivariate analyses it was noted that those patients in the D2 group that did not undergo the distal pancreaticosplenectomy had an increased survival compared with the D1 group. A trial in the Netherlands randomized 380 gastric cancer patients to a D1 lymphadenectomy and 331 patients to a D2 lymphadenectomy. Similar to the United Kingdom study, there was not a significant difference in survival between the two groups, even when followed out to 11 years. There was a significant increase in postoperative complications in the D2 group compared with the D1 group (43 % vs. 25 %, respectively) as well as mortality (10 % vs. 4 %, respectively).
The data from these two studies suggest that a pancreaticosplenectomy performed to harvest lymph nodes seems to only add morbidity and mortality while not improving survival. One concern raised about the prior two studies was the variation in surgical technique and lack of standardization of surgeon experience. A Taiwanese study accounted for this by performing the study at a single institution with three surgeons, each of whom had completed at least 25 D3 lymph node dissections prior to the study. Patients with gastric cancer were randomized to a D1 lymph node dissection (defined as resection of perigastric lymph nodes along the lesser and greater curves of the stomach) or a D3 lymph node dissection (defined as resection of additional lymph nodes surrounding the splenic, common hepatic, left gastric arteries, nodes in the hepatoduodenal ligament, and retropancreatic lymph nodes). There was an overall 5-year survival benefit with the D3 group of 60 % compared with the D1 group of 54 %. A Japanese study evaluated a more aggressive lymph node dissection and randomized patients to a D2 dissection or a para-aortic lymph node dissection (PAND). There was no significant difference in 5-year survival between the two groups with a trend toward an increase in complications in the PAND group. Multiple studies have shown that the number of positive lymph nodes is a significant predictor of survival. Current AJCC guidelines stipulate that at least 15 lymph nodes are needed for pathologic examination to obtain adequate staging.
Laparoscopic techniques have become an integral part of surgical practice over the past several decades. For gastric cancer, multiple retrospective studies have reported the advantages of laparoscopic gastrectomy (LG) over open gastrectomy (OG). A recent meta-analysis of 15 nonrandomized comparative studies has also shown that although LG had a longer operative time than OG, it was associated with lower intraoperative blood loss, overall complication rate, fewer wound-related complications, quicker recovery of gastrointestinal motility with shorter time to first flatus and oral intake, and shorter hospital stay. A randomized prospective trial comparing laparoscopic assisted with open subtotal gastrectomy reported that LG had a significantly lower blood loss (229 ± 144 ml versus 391 ± 136 ml; P< 0.001), shorter time to resumption of oral intake (5.1 ± 0.5 days versus 7.4 ± 2 days; P< 0.001), and earlier discharge from hospital (10.3 ± 3.6 days versus 14.5 ± 4.6 days; P< 0.001).
Cancer of the rectum is the fifth most common form of cancer in adults worldwide. In 2012, an estimated 40,300 new rectal cancers will be diagnosed in the US with a median age 69 years. Five-year survival rates for rectal cancer are high for early stage disease (90% for Stage I disease) but drop significantly with worsening stage (7% for metastatic Stage IV disease). Recently, advances in neoadjuvant and adjuvant therapy have decreased the rate of local recurrence and improved long-term survival for some patients. Although the treatment for rectal cancer has become increasingly multimodal, surgical excision of the primary tumor remains essential for eradication of disease.
For a long time there has been a debate about the best surgical approach to early stage rectal cancer, whether treatment should involve radical excision (excision of the rectum) or local excision (tumor alone). Proponents of radical surgery argue that excision of the rectum with its surrounding lymphatic drainage offers the best chance for cure. On the other hand, advocates of local excision feel that a less-aggressive approach can avoid the potential ramifications of major pelvic surgery such as sepsis, poor anorectal function, sexual dysfunction, and difficulty with urination and can eliminate the potential need for a permanent stoma. Although the debate has gone back and forth on the adequacy of local excision, there is a growing body of scientific data that suggests that local excision can be sufficient in patients with early rectal cancer of the mid and distal rectum with good histologic features and preoperative imaging (computed tomography, magnetic resonance imaging, and endorectal ultrasound) that shows no evidence of lymph node involvement.
Traditionally, transanal excision has been performed with the conventional technique using traditional equipment. Although this conventional technique can give surgeons operative access to most distal rectal lesions, it can be difficult to conduct on mid-rectal tumors or in large patients with a deep buttock cleft. The technical difficulties experienced under such circumstances can lead to poor visualization, inadequate margins, or specimen fragmentation. In response to the technical limitations of conventional transanal excision, in the 1980s Professor Gehard Buess from Tubingen, Germany, began to develop the technique of transanal endoscopic microsurgery (TEM).
In collaboration with the Richard Wolf Company in Germany, Dr Buess developed the specialized instruments necessary to perform endoscopic surgery transanally. TEM was introduced into clinical practice in 1983, and was gradually implemented in several European countries and eventually introduced in North America and Asia. The last decade has witnessed international growth in the application of TEM yielding a significant amount of scientific data to support its clinical merits and advantages and also shedding some light on its limitations.
É o tipo de câncer mais associada a quem faz uso de bebidas alcoólicas e é adepto do tabagismo. Mas pode ocorrer também em quem tem refluxo acido do estômago para o esôfago (hérnia hiato e/ou doença do refluxo gastro esofágico). Como todo câncer, seu diagnóstico é tardio, pois não causa dor nem incomodo nas suas fases mais iniciais, e por isso, pedimos aos pacientes, que façam o exame de controle regularmente (endoscopia digestiva alta). O tratamento é um a combinação de radioterapia, quimioterapia e cirurgia, mas que vai ter variações conforme localização no esôfago (medindo entre 26 e 30 centímetros) e o estagio da doença. O esôfago é um tubo musculomembranoso, longo e delgado, que comunica a garganta ao estômago. Ele permite a passagem do alimento ou líquido ingerido até o interior do sistema digestivo, através de contrações musculares. O câncer de esôfago mais freqüente é o carcinoma epidermóide escamoso, responsável por 96% dos casos. Outro tipo de câncer de esôfago, o adenocarcinoma, vem tendo um aumento significativo principalmente em indivíduos com esôfago de Barrett, quando há crescimento anormal de células do tipo colunar para dentro do esôfago.
O câncer de esôfago apresenta uma alta taxa de incidência em países como a China, Japão, Cingapura e Porto Rico. No Brasil, consta entre os dez mais incidentes, segundo dados obtidos dos Registros de Base Populacional existentes, e em 2000 foi o sexto tipo mais mortal, com 5.307 óbitos. De acordo com a Estimativa de Incidência de Câncer no Brasil para 2006, devem ocorrer cerca de 10.580 casos novos deste câncer (7.970 entre os homens e 2.610 entre as mulheres) este ano.
Fatores de Risco/Prevenção
O câncer de esôfago está associado ao alto consumo de bebidas alcoólicas e de produtos derivados do tabaco (tabagismo). Outras condições que podem ser predisponentes para a maior incidência deste tumor são a tilose (espessamento nas palmas das mãos e na planta dos pés), a acalasia, o esôfago de Barrett, lesões cáusticas no esôfago, Síndrome de Plummer-Vinson (deficiência de ferro), agentes infecciosos (papiloma vírus – HPV) e história pessoal de câncer de cabeça e pescoço ou pulmão. Para prevenir o câncer de esôfago é importante adotar uma dieta rica em frutas e legumes, evitar o consumo freqüente de bebidas quentes, alimentos defumados, bebidas alcoólicas e produtos derivados do tabaco. A detecção precoce do câncer de esôfago torna-se muito difícil, pois essa doença não apresenta sintomas específicos. Indivíduos que sofrem de acalasia, tilose, refluxo gastro-esofageano, síndrome de Plummer-Vinson e esôfago de Barrett possuem mais chances de desenvolver o tumor, e por isso devem procurar o médico regularmente para a realização de exames.
O câncer de esôfago na sua fase inicial não apresenta sintomas. Porém, alguns sintomas são característicos como a dificuldade ou dor ao engolir, dor retroesternal, dor torácica, sensação de obstrução à passagem do alimento, náuseas, vômitos e perda do apetite. Na maioria das vezes, a dificuldade de engolir (disfagia) já demonstra a doença em estado avançado. A disfagia progride geralmente de alimentos sólidos até alimentos pastosos e líquidos. A perda de peso pode chegar até 10% do peso corporal.
O diagnóstico é feito através da endoscopia digestiva, de estudos citológicos e de métodos com colorações especiais (azul de toluidina e lugol) para que seja possível se fazer o diagnóstico precoce, fazendo com que as chances de cura atinjam 98%. Na presença de disfagia para alimentos sólidos é necessária a realização de um estudo radiológico contrastado, e também de uma endoscopia com biópsia ou citologia para confirmação. A extensão da doença é muito importante em função do prognóstico, já que esta tem uma agressividade biológica devido ao fato do esôfago não possuir serosa e, com isto, haver infiltração local das estruturas adjacentes, disseminação linfática, cau-sando metástases hematogênicas com grande freqüência.
O paciente pode receber como formas de tratamento a cirurgia, radioterapia, quimioterapia ou a combinação destes três tipos. Para os tumores iniciais pode ser indicada a ressecção endoscópica, no entanto este tipo de tratamento é bastante raro. Na maioria dos casos, a cirurgia é o tratamento utilizado. Dependendo da extensão da doença, o tratamento pode passar a ser unicamente paliativo, através de quimioterapia ou radioterapia. Nos casos de cuidados paliativos, também dispõe-se de dilatações com endoscopia, colocação de próteses auto-expansivas, assim como uso da braquiterapia.
The operative conduct of the biliary-enteric anastomosis centers around three technical steps: 1) identification of healthy bile duct mucosa proximal to the site of obstruction; 2) preparation of a segment of alimentary tract, most often a Roux-en-Y jejunal limb; and 3) construction of a direct mucosa-to-mucosa anastomosis between these two. Selection of the proper anastomosis is dictated by the indication for biliary decompression and the anatomic location of the biliary obstruction. A right subcostal incision with or without an upper midline extension or left subcostal extension provides adequate exposure for construction of the biliary-enteric anastomosis. Use of retractors capable of upward elevation and cephalad retraction of the costal edges are quite valuable for optimizing visual exposure of the relevant hilar anatomy.
Division of the ligamentum teres and mobilization of the falciform ligament off the anterior surface of the liver also facilitate operative exposure; anterocephalad retraction of the ligamentum teres and division of the bridge of tissue overlying the umbilical fissure are critical for optimal visualization of the vascular inflow and biliary drainage of segments II, III, and IV. Cholecystectomy also exposes the cystic plate, which runs in continuity with the hilar plate. Lowering of the hilar plate permits exposure of the left hepatic duct as it courses along the base of segment IVb. In cases of unilateral hepatic atrophy as a result of long-standing biliary obstruction or preoperative portal vein embolization, it is critical to understand that the normal anatomic relationships of the portal structures are altered. In the more common circumstance of right-sided atrophy, the portal and hilar structures are rotated posteriorly and to the right; as a result, the portal vein, which is typically most posterior, is often encountered first; meticulous dissection is necessary to identify the common bile duct and hepatic duct deep within the porta hepatis.
GIST, da sigla em inglês gastrointestinal stromal tumors, pertence a um grupo de tumores chamados sarcoma de partes moles. Essa neoplasia se diferencia dos outros tipos de tumores por iniciar-se na parede dos órgãos, junto às camadas musculares do trato gastrointestinal, mais especificamente, nas células do plexo mioenterico, chamadas células de Cajal. Tais células são responsáveis pela motilidade intestinal, sendo consideradas o marca-passo do trato gastrointestinal.
O tumor de GIST é relativamente raro, com estudos atuais mostrando uma prevalência anual em torno de 20 a 40 casos por milhão de habitantes. É mais comum entre pessoas de 50 a 60 anos de idade, sendo extremamente raros até os 20 anos. Por representar um tumor raro, recomenda-se que seja tratado por serviços especializados com cirurgiões do aparelho digestivo, que tenham experiência multidisciplinar na condução e no tratamento dos pacientes com este tumor.
O GIST pode se originar em qualquer local do trato gastrointestinal, do esôfago ao ânus. Em relação à distribuição, 50% a 60% das lesões são provenientes do estômago, 20% a 30% do intestino delgado, 10% do intestino grosso, 5% do esôfago e 5% de outros locais da cavidade abdominal.
A apresentação clínica dos pacientes portadores de GIST não é especifica e depende da localização e do tamanho do tumor. O GIST tem uma característica biológica que é uma mutação genética, com ativação do proto-oncogene Kit e a superexpressão do receptor tirosina quinase (c-Kit). Geralmente, o diagnóstico é feito por uma biópsia da lesão, que a depender da localização, pode ser feita por endoscopia, colonoscopia, ou ecoendoscopia. A tomografia computadorizada do abdômen é importante para avaliação da extensão do tumor e também pode ser utilizada em alguns casos para realização de biópsia do tumor. Não apresentam sinais e/ou sintomas específicos. Podem causar náuseas, vômitos, hemorragias intestinais (vômitos com sangue ou evacuações com sangue ou fezes enegrecidas), sensação de plenitude após alimentação, dor e distensão abdominal, ou presença de uma massa ou tumor palpável no abdômen.
O tratamento padrão para pacientes com GIST não metastático, ou seja, não provenientes de outros órgãos, é a ressecção cirúrgica completa da lesão. Muitas vezes é necessária a cirurgia radical e de grande porte, com a retirada de estruturas e órgãos aderidos, oferecendo a maior chance de cura. O tratamento com imatinib, e mais atualmente ao sunitinib, é utilizado para doença metastática ou irressecável, com intuito de diminuir o tamanho da lesão para que a cirurgia possa ser realizada em melhores condições locais. Tais drogas também podem ser utilizadas após a cirurgia. Para o tratamento sistêmico pode ser necessário estudo genético específico para saber qual a mutação presente no tumor, com intuito de guiar a terapia em relação à dose e tipo de medicação utilizada.
FATORES DE RISCO
Não há fatores de risco diretamente relacionados a essa neoplasia. Manter hábitos de vida saudáveis, uma alimentação balanceada e a prática de exercícios físicos ajudam, de maneira geral, na prevenção do câncer.
PARA MAIS INFORMAÇÕES: http://www.gistsupport.org/
A existência de cistos e tumores primários do mediastino tem vindo a ser relatada com uma incidência crescente. Os avanços das técnicas radiológicas, incluindo a TC e a RM, aumentaram singularmente a capa-cidade de avaliar pré – operatoriamente a natureza e a extensão das lesões do mediastino. Por outro lado, os progressos terapêuticos têm sido relacionados com um diagnóstico mais precoce e com uma maior efetividade dos regimes de radioterapia e de quimioterapia.
Tromboembolismo venoso é complicação frequente após tratamento cirúrgico em geral e, de um modo especial, na condução terapêutica do câncer. A cirurgia do aparelho digestivo tem sido referida como potencialmente indutora desta complicação. Ela tem maior representatividade em determinados segmentos anatômicos e nas condições em que se associam fatores de risco dos pacientes. A prevenção do tromboembolismo é tema de grande importância na prática diária dos cirurgiões. Várias são as formas físicas e medicamentosas que podem ser utilizadas. Nos últimos anos abordagens novas, tanto em relação às manobras físicas como em posologia medicamentosa, têm sido estudadas com boa metodologia. Estes novos enfoques ainda são pouco divulgados e talvez pouco conhecidos pela maioria dos cirurgiões. No câncer a importância desse tema é ainda maior que nas doenças benignas. A Medicina Baseada em Evidências incorpora dados obtidos com base nas mais recentes revisões sistemáticas disponíveis na literatura originando várias formas de contribuições científicas. BOM ESTUDO.