The most common presenting sign for patients with malignancy of the periampullary region is obstructive jaundice. While a significant proportion of these patients will be asymptomatic, the deleterious systemic consequences of uncontrolled hyperbilirubinemia may still occur. Furthermore, symptoms such as pruritus can be debilitating and have a significant impact on the quality of life. Thus, some have advocated preoperative drainage of the biliary system in patients with resectable periampullary malignancies, given widespread availability of endoscopic retrograde cholangiopancreatography and its perceived safety profile. On the other hand, the purported benefits of routine preoperative drainage in this patient population (namely, resolution of symptoms in symptomatic patients while awaiting surgery, restoration of the enterohepatic cycle, and a potential decrease in postoperative morbidity) have proven to be largely theoretical, and now there are high-quality phase III data that demonstrate the deleterious effects of routine stenting. A seminal study originating from the Netherlands in 2010 evaluated this issue in the only modern randomized controlled trial to date evaluating preoperative endoscopic biliary decompression for these patients. In their multicenter study, they randomized 202 patients with newly diagnosed pancreatic head cancer and bilirubin levels between 2.3 and 14.6 mg/dL to preoperative biliary drainage for 4–6 weeks vs. immediate surgery which was to be performed within a week of enrollment. The primary endpoint was the development of serious complications within 120 days after randomization. Serious complications were defined as complications related to the drainage procedure or the surgical intervention that required additional medical, endoscopic, or surgical management, and that resulted in prolongation of the hospital stay, readmission to the hospital, or death. The reported overall rate of serious complications in this study favored the immediate surgery group (39 vs. 74%; RR 0.54–95% [CI], 0.41–0.71; P < 0.001), complications related to surgery were equivalent (37 vs. 47%; P = 0.14), and there was no difference in mortality rates or length of hospital stay. The observed drainage-related complications included a 15% rate of stent occlusion, 30% need for exchange, and 26% incidence of cholangitis.
“Based on these results, the authors concluded that the morbidity associated with the drainage procedure itself had an additive effect on the postoperative morbidity of patients undergoing pancreatic head resection for cancer and recommended against its routine use in this population.“
A Cochrane systematic review of all available randomized studies (including the abovementioned study by van der Gaag et al.) evaluating preoperative biliary drainage was published in 2012. In this study, Fang et al. assessed the impact of this intervention on survival, serious morbidity (defined as Clavien-Dindo grade 3 or 4), and quality of life. Furthermore, they sought to assess differences in total length of hospital stay and cost. They identified six randomized trials of which four used percutaneous transhepatic biliary drainage and the remaining two used endoscopic sphincterotomy and stenting. The pooled analysis of 520 patients (of which 51% underwent preoperative biliary drainage) showed no difference in mortality, but importantly, it showed a significantly higher incidence of serious morbidity in the preoperative drainage group with a rate ratio (RaR) of 1.66 (95% CI 1.28–2.16;P = 0.002). There was no difference in length of hospital stay and not enough data reported for analysis of cost or quality of life.
“Based on the available level 1 data, the authors concluded that there was no evidence to support or refute routine preoperative biliary drainage in patients with obstructive jaundice.“
However, this review also underscored the fact that preoperative biliary drainage may be associated with an increased rate of adverse events and thus questioned the safety of this practice. This Cochrane review included old studies that evaluated patients undergoing percutaneous drainage, a technique used less frequently today for periampullary malignancies. Furthermore, several of these trials included patients with hilar and other types of biliary obstruction. However, the concept of preoperative decompression, as well as its purported benefits and observed results, may be reasonably extrapolated to patients with periampullary lesions.
Liver cancer is the sixth most common cancer and, in 2018, was the fourth leading cause of cancer-related death worldwide. The rates of incidence and mortality are approximately 2 to 3 times higher for men than for women. Hepatocellular carcinoma (HCC) is the most common primary liver cancer and accounts for 75% to 85% of diagnoses, followed by intrahepatic cholangiocarcinoma (10%–15%), and other rare liver histologies. The improvement and safety of surgical techniques for liver resection and transplant, and advancements in ablation, transarterial chemoembolization (TACE), and systemic therapies have expanded the treatment options for patients with HCC. Liver transplant is the ideal treatment option for patients with HCC and poorly compensated liver disease because it removes both HCC and damaged liver and reduces the risk for early recurrence. However, shortages in donor liver and long waiting times to transplant are significant barriers to this treatment approach. As such, liver resection remains an effective treatment option for patients with HCC. The use of a multidisciplinary approach and the knowledge of each therapeutic option is critical in the management of patients with HCC.
Minimal future liver remnant requirements
Liver resection remains the treatment of choice for HCC. Two major preoperative considerations for HCC resection are the patient’s liver function and the predicted future liver remnant (FLR). The intrinsic liver function of patients with HCC is often impaired because this patient population generally has chronic liver disease, including viral hepatitis, alcoholic hepatitis, and nonalcoholic steatohepatitis. As such, studies report that more FLR is needed for patients undergoing resection for HCC than for patients undergoing resection of secondary liver cancer (ie, metastatic disease). The minimal requirement of FLR/standardized liver volume (standardized liver volume 5 x 794 1 1267.28 x body surface area) is 30% in patients with hepatic injury and fibrosis and 40% in patients with cirrhosis, whereas it is 20% to 25% for patients with normal liver.
Anatomic resection versus nonanatomic resection
Anatomic resection of Couinaud segment for small HCC was reported in 1981 by Makuuchi and colleagues. HCC frequently invades to the intrahepatic vascular structures and spreads through the portal vein. As such, the complete removal of tumor-bearing portal territory was reported to be theoretically superior to nonanatomic resection. The technique proposed by Makuuchi and colleagues is detailed as follows: (1) under the guidance of intraoperative ultrasonography, the portal vein of interest is identified and punctured using a 22-gauge needle; (2) blue dye is injected into the portal vein; (3) the territory of the dyed surface is marked using electrocautery; and (4) liver resection is performed using ultrasonography guidance and intersegmental hepatic veins are exposed. This technique was recently refined using fluorescence imaging. By using transportal injection or systemic intravenous injection of indocyanine green, the portal vein territory was more clearly visualized on the liver surface compared with the traditional method. Many retrospective studies reported that anatomic resection was associated with better survival and lower recurrence than nonanatomic resection. In contrast, other studies showed that survival did not differ significantly between patients undergoing anatomic resection and those undergoing nonanatomic resection. Therefore, this clinical question remains unanswered and needs to be further elucidated.
Laparoscopic liver resection
Laparoscopic liver resection (LLR) has been increasingly used worldwide. In their systemic review, Nguyen and colleagues reported on the safety of LLR with low rates of morbidity and mortality for both major and minor resections, as well as appropriate oncologic results compared with open liver resection (OLR). These results are most likely caused by patient selection and the advantages of the laparoscopic approach, including a magnified view and the hemostatic effect caused by pneumoperitoneum. Three retrospective studies including more than 200 patients showed that the 5-year overall survival (OS) was not significantly different between patients undergoing LLR for HCC and those undergoing OLR for HCC. However, no randomized controlled trials (RCTs) comparing long-term outcomes in patients undergoing LLR versus OLR for HCC have been reported. For patients with colorectal liver metastases, a recent RCT (Oslo-CoMet study) showed that median OS in patients undergoing LLR was similar to those undergoing OLR: 80 months versus 81 months.
Liver Resection Versus Ablation
It remains unclear whether liver resection or ablation is the most effective treatment of small HCC lesions. To answer this clinical question, 5 RCTs have been reported. Two of these studies showed that liver resection was associated with better survival than radiofrequency ablation and 3 showed that survival did not differ significantly between patients undergoing resection and those undergoing ablation. The shortcomings of these RCTs include insufficient patient follow-up; unclear treatment allocation; and different inclusion criteria, including tumor number, tumor diameter, and Child-Pugh grade. Nonetheless, for patients with small HCCs (ie,<3 cm), the current evidence shows that both resection and ablation can be recommended.
Liver Resection Versus Transarterial Chemoembolization
There has been 1 RCT comparing the outcomes of patients undergoing resection for HCC with those undergoing TACE. For patients outside of Milan criteria, resection was associated with better survival than TACE. The authors found 8 cohort studies comparing outcomes after resection with TACE using the propensity score adjustment. Although the studies had different inclusion criteria, the data show that resection is associated with better survival than TACE in selected patients who have multiple HCCs.
Liver Resection Versus Liver Transplant
Liver transplant is an established treatment option for patients who have early-stage HCC and poorly compensated cirrhosis and/or portal hypertension. However, the preferred treatment of patients who have early-stage HCC and wellcompensated cirrhosis is not established. Several retrospective studies have evaluated outcomes after liver resection for HCC in this setting, comparing them with those of transplant. However, most are limited by small sample sizes and low statistical power. No prospective studies have been performed on this topic given the inability to randomize patients to liver resection versus transplant. The authors found 2 studies including more than 200 patients. They both suggest that transplant is associated with better survival than liver resection in patients within Milan criteria and Child-Pugh A or B. Nonetheless, it should be noted that graft availability and waiting times for transplant differ between countries, which greatly influences the selection of liver resection versus transplant for patients with early-stage HCC.
The current evidence suggests that, for patients with small HCC lesions (<3 cm), OS is likely to be similar for patients undergoing liver resection versus ablation. For selected patients with multiple HCCs, liver resection may be associated with better OS than TACE. For the past 10 years, sorafenib has been the only effective medical therapy available for unresectable HCC. Recently, several promising new therapies, including multikinase inhibitors and immunotherapies, have been reported. Perioperative use of these new therapies may further improve outcomes in patients undergoing liver resection for HCC and potentially change the current treatment guidelines.
Com imensa satisfação é realizada a 3ª Edição da JORNADA MARANHENSE DE CIRURGIA DIGESTIVA, com abordagem de temas inovadores sobre a cirurgia digestiva, os avanços na medicina em relação a essa especialidade e procedimentos de mínima invasibilidade a fim de atualização e aprendizado da comunidade médica maranhense. Para isso, contamos com grandes nomes da área de Cirurgia do Aparelho Digestivo da região meio-norte brasileiro que trouxeram para a Jornada palestras enriquecedoras e discussões de casos.