Pancreatic Neuroendocrine Tumours
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.
For non-functioning pancreatic tumors, a surgical procedure is usually recommended. Exception occurs in patients with MEN-1 and who have tumors <2 cm, when the operation is not consensually recommended. For some authors and societies, observation and follow-up should be performed when the tumor is <1 cm, asymptomatic and incidental. The decision for surgical treatment should be made based on the estimated surgical risk, tumor location and comorbidities. The surgical choice may vary between enucleation, distal pancreatectomy and duodenopancreatectomy always associated with regional nodal resection due to the real chances of lymph node metastasis, even in tumors with a size between 1-2 cm. For patients with tumors >2 cm, the choice is tumor cell excision. The location is indicative for the choice of technique, which may range from duodenopancreatectomy to the distal pancreatectomy associated with splenectomy. Both should be accompanied by lymph node resection due to the risk of metastases. Complete resection R0 should always be the primary endpoint. Regardless of tumor size, there is no evidence to support adjuvant systemic therapy for pNET and optimal follow-up of patients undergoing surgical treatment remains unknown.
Surgery for Breast Cancer Liver Metastases
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.