Recent standardization of treatment strategy for pancreatic neuroendocrine tumors

Recent advances in localization techniques,such as the selective arterial secretagogue injection test(SASI test) and somatostatin receptor scintigraphy have promoted curative resection surgery for patients with pancreatic neuroendocrine tumors(PNET).For patients with sporadic functioning PNET,curative resection surgery has been established by localization with the SASI test using secretin or calcium.For curative resection of functioning PNET associated with multiple endocrine neoplasia type 1(MEN 1) which are usually multiple and sometimes numerous,resection surgery of the pancreas and/or the duodenum has to be performed based on localization by the SASI test.As resection surgery of PNET has increased,several important pathological features of PNET have been revealed.For example,in patients with Zollinger-Ellison syndrome(ZES),duodenal gastrinoma has been detected more frequently than pancreatic gastrinoma,and in patients with MEN 1 and ZES,gastrinomas have been located mostly in the duodenum,and pancreatic gastrinoma has been found to co-exist in 13% of patients.Nonfunctioning PNET in patients with MEN 1 becomes metastatic to the liver when it is more than 1 cm in diameter and should be resected after careful observation.The most important prognos-tic factor in patients with PNET is the development of hepatic metastases.The treatment strategy for hepatic metastases of PNET has not been established and aggressive resection with chemotherapy and trans-arterial chemoembolization have been performed with significant benefit.The usefulness of octreotide treatment and other molecular targeting agents are currently being assessed.     

Diagnosis and treatment of Zollinger-Ellison syndrome

A diagnostic and therapeutic strategy for the management of patients with Zollinger-Ellison syndrome has been developed, based on the review of a large personal experience and the most recent literature. The mainstay of a modern ZES management is the eradication of tumoral processes whenever feasible. Diagnosis is centred upon gastric acid and gastrin secretion measurements both in basal conditions and on secretin stimulation. Recognition of other endocrine involvement and familial inheritance is of the utmost importance in distinguishing sporadic ZES patients from those who have the condition known as multiple endocrine neoplasia type I. Blood calcium and phosphorus levels, parathyroid hormone concentration, combined if necessary with urinary cyclic AMP excretion measurement, should be performed routinely once ZES diagnosis is established or highly suspected. Localization of the tumour is the next essential step, and this has been considerably facilitated by the recent development in imaging techniques: it involves computerized axial tomography and selective abdominal angiography, a combination of which allows tumour detection in 60-70% of sporadic gastrinoma patients, with a maximal sensitivity for well-developed hepatic metastases. In sporadic ZES exploratory laparotomy is legitimate when preoperative localization of the tumour has failed; this laparotomy will allow further detection and then eradication of gastrinomas in a significant number of patients. Control of gastric acid secretion is mandatory throughout the work-up period; modern antisecretory agents are efficacious in most cases; total gastrectomy, when control of acid hypersecretion has failed, is now exceptional. Eradication of the tumour should be attempted in cases of sporadic ZES in the absence of recognizable liver involvement. The chance of a definite cure provided by surgery when performed by an experienced surgeon varies from 20% to 60% in pancreatic and ectopic gastrinomas respectively. In ZES patients with MEN I, exploratory laparotomy is seldom indicated (other than for symptomatic associated endocrine secretion), as the chance of a definite cure by surgery is very rare. Parathyroid surgery is often indicated and should take place before any form of abdominal surgery. In cases of hepatic metastases, chemotherapy with streptozocin and fluorouracil is indicated and soon, perhaps, chemo-embolization.     

Repeat hepatic resection for recurrent metastatic melanoma

We present an unusual case of a recurrent metastatic hepatic melanoma that had undergone a repeat hepatic resection. A 62 year-old female patient was diagnosed with a plantar melanoma and was managed with resection and regional lymphadenectomy. Eight months later, a solitary liver metastasis was diagnosed and a right hepatectomy performed. Sixteen months later, a recurrent solitary metastasis was diagnosed in the caudate lobe and resection was performed. She has since been asymptomatic with no evidence of recurrence of the disease at a 2-year follow up. We recommend surgical removal of hepatic metastatic melanoma in selected cases where the disease is confined to the liver and surgery can be performed without unacceptable risk.     

Laparoscopic liver surgery: Shifting the management of liver tumors

Laparoscopic liver surgery has evolved rapidly over the past 5 years in a select number of centers. The growing experience with these procedures has resulted in a shift in the diagnostic and therapeutic approach to common liver tumors. The fact that resection of benign and malignant hepatic masses can now be accomplished laparoscopically with relatively low morbidity has influenced the decision-making process for physicians involved in the diagnosis and management of these lesions. For example, should a gastroenterologist or hepatologist seeing a 32-year-old woman with an asymptomatic 4 cm hepatic lesion that is radiologically indeterminate for adenoma or focal nodular hyperplasia (FNH): (1) continue to observe with annual computed tomography/magnetic resonance imaging (CT/MRI) scans, (2) subject the patient to a liver biopsy, or (3) refer for laparoscopic resection? For a solitary malignant liver tumor in the left lateral segment, should laparoscopic resection be considered the new standard of care, assuming the surgeon can perform the operation safely? We present current data and representative case studies on the use of laparoscopic liver resection at 2 major medical centers in the United States. We propose that surgical engagement defined by the managing physician's decision to proceed with a surgical intervention is increasingly affected by the availability of, and experience with, laparoscopic liver resection.     

Treatment of Zollinger-Ellison syndrome

In this article, we have reviewed the main therapeutic measures for the treatment of Zollinger-Ellison syndrome (ZES). Review of the literature was based on computer searches (Pub-Med, Index Medicus) and personal experiences. We have evaluated all the measures now available for treating patients with sporadic gastrinomas or gastrinomas associated with Multiple Endocrine Neoplasia Type 1, (MEN 1) including medical therapy such as antisecretory drugs and somatostatin analogs (SST), chemotherapy and chemoembolization, and surgical procedures. In ZES patients, the best therapeutic procedure is surgery which, if radical, can be curative. Medical treatment can be the best palliative therapy and should be used, when possible, in association with surgery, in a multimodal therapeutic approach.     

Successful en bloc resection of primary hepatocellular carcinoma directly invading the stomach and pancreas

Multivisceral surgical resection for cure was successfully performed in a 70-year-old man suffering from a primary hepatocellular carcinoma （HCC） associated with direct invasion to the stomach and pancreas. The patient presented with gastric outlet obstruction, upper abdominal pain and a history of chronic liver disease due to hepatitis B virus （HBV） infection. Upper gastrointestinal （GI） endoscopy revealed an infiltrating tumor protruding through the gastric wall and obliterating the lumen. Computer tomograghy （CT） and magnetic resonance imaging （MRI） scan demonstrated a 15-cm tumor in the left lateral segment of the liver with invasion to the stomach and pancreas. Alpha-foetoprotein （AFP） levels and liver function tests were normal. The patient underwent an en bloc left hepatectomy, total gastrectomy, distal pancreatectomy with splenectomy and radical lymphadenectomy. Pathology revealed a poorly differentiated, giant cell HCC involving the stomach and pancreas. Disease-free margins of resection were achieved. The patient＇s postoperative course was uneventful. Sixteen months after surgery, he has no recurrence or distal metastasis. Direct invasion of HCC into the GI tract is rarely encountered. Complete surgical resection should be considered in selected patients with an appropriate hepatic functional reserve.     

Tailoring the area of hepatic resection using inflow and outflow modulation

The performance of hepatic surgery without a parenchyma-sparing strategy carries significant risks for patient survival because of the not negligible occurrence of postoperative liver failure.The key factor of modern hepatic surgery is the use of the intraoperative ultrasound(IOUS),not only to stage the disease,but more importantly to guide resection with the specific aim to maximize the sparing of the functional parenchyma.Whether in patients with hepatocellular carcinoma and underlying liver cirrhosis,or in patients with colorectal liver metastasis,IOUS allows the performance of the so-called "radical but conservative surgery",which is the pivotal factor to offer a chance of cure to an increasing proportion of patients,who until few years ago were considered only for palliative care.Using some new IOUS-guided surgical maneuvers,which are based on the liver inflow and outflow modulations,more precise anatomically subsegmental-and segmentaloriented resections can be effectively performed.The present work describes the rationale and the surgical technique for a precise tailoring of the area of hepatic resection using the most recent attainments in IOUS.Such important technical achievements should be a fundamental part of the surgical armamentarium of the modern liver surgeon.     

Sporadic versus hereditary gastrinomas of the duodenum and pancreas： Distinct clinico-pathological and epidemiological features

INTRODUCTION Gastrinomas are de?ned as gastrin-producing tumors that are associated with Zollinger-Ellison syndrome (ZES) due to inappropriate gastrin secretion. ZES is characterized by elevated fasting gastrin serum levels, positive gastrin secretin stim…     

Surgical treatment and prognosis of gastrinoma

Zollinger-Ellison syndrome (ZES) is a clinical syndrome with severe peptic ulcer disease and diarrhea caused by gastric acid hypersecretion secondary to a neuroendocrine tumour that secretes excessive amounts of the hormone gastrin (gastrinoma). Gastrinomas occur in a familial and a sporadic form. Patients with gastrinoma in the familial setting of Multiple Endocrine Neoplasia type 1 (MEN-1) are seldom, if ever, cured of Zollinger-Ellison syndrome by the current non-Whipple operations to remove duodenal and pancreatic gastrinoma. Surgery is currently used in these patients to deal with the malignant nature of pancreatic or duodenal neuroendocrine tumours. Malignant potential is best determined by tumour size. Tumours that are greater than 2 cm in size should be excised. In the sporadic setting, cure occurs in a significant proportion of patients (50%) by surgical resection of gastrinoma. Duodenotomy has improved both the tumour detection rate and the cure rate and should be routinely done. Whipple pancreaticoduodenectomy results in the highest probability of cure in both sporadic and MEN-1 gastrinoma patients as it removes the entire gastrinoma triangle. However, the excellent long-term survival of these patients with lesser operations and the increased operative mortality and long-term morbidity of Whipple make its current role unclear until further studies are done.     

Role of surgery in colorectal cancer liver metastases

Colorectal carcinoma (CRC) is the third most common cancer, and approximately 35%-55% of patients with CRC will develop hepatic metastases during the course of their disease. Surgical resection represents the only chance of long-term survival. The goal of surgery should be to resect all metastases with negative histological margins while preserving sufficient functional hepatic parenchyma. Although resection remains the only chance of long-term survival, management strategies should be tailored for each case. For patients with extensive metastatic disease who would otherwise be unresectable, the combination of advances in medical therapy, such as systemic chemotherapy (CTX), and the improvement in surgical techniques for metastatic disease, have enhanced prognosis with prolongation of the median survival rate and cure. The use of portal vein embolization and preoperative CTX may also increase the number of patients suitable for surgical treatment. Despite current treatment options, many patients still experience a recurrence after hepatic resection. More active systemic CTX agents are being used increasingly as adjuvant therapy either before or after surgery. Local tumor ablative therapies, such as microwave coagulation therapy and radiofrequency ablation therapy, should be considered as an adjunct to hepatic resection, in which resection cannot deal with all of the tumor lesions. Formulation of an individualized plan, which combines surgery with systemic CTX, is a necessary task of the multidisciplinary team. The aim of this paper is to discuss different approaches for patients that are treated due to CRC liver metastasis.     

Determinants of surgical resection for pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (pNETs) include functioning and non‐functional tumors. Functioning tumors consist of tumors that produce a variety of hormones and their clinical effects. Therefore, determinants of resection of pNETs should be discussed for each group of tumors. Less than 10% of insulinomas are malignant, therefore more than 90% of the cases can be cured by surgical resection. Lymphadenectomy is generally not necessary in insulinoma operation. If preoperative localization of the insulinoma is completed, enucleation from the pancreatic body or tail, and distal pancreatectomy can be performed safely by laparoscopy. When preoperative localization of a sporadic insulinoma is not confirmed, surgical exploration is needed. Intraoperative localization of a tumor, intraoperative insulin sampling and frozen section are required. The crucial purpose of surgical resection is to control inappropriate insulin secretion by removing all insulinomas. Gastrinomas are usually located in the duodenum or pancreas, which secrete gastrin and cause Zollinger‐Ellison syndrome (ZES). Duodenal gastrinomas are usually small, therefore they are not seen on preoperative imaging studies or endoscopic ultrasound, and can be found only at surgery if a duodenotomy is performed. In addition, lymph node metastasis is found in 40–60% of cases. Therefore, the experienced surgeons should direct operation for gastrinomas. Surgical exploration with duodenotomy should be performed at a laparotomy. Other functioning pNETs can occur in the pancreas or in other locations. Curative resection is always recommended whenever possible after optimal symptomatic control of the clinical syndrome by medical treatment. Indications for surgery depend on clinical symptom control, tumor size, location, extent, malignancy and presence of metastasis. A lot of non‐functioning pNETs are found incidentally according to the quality improvement of imaging techniques. Localized, small, malignant non‐functioning pNETs should be operated on aggressively, while in possibly benign tumors smaller than 2 cm the surgical risk‐benefit ratio should be carefully weighted. Surgical liver resection is generally proposed in curative intent to all patients with operable metastases from G1 or G2 pNET. The benefits of surgical resection of liver metastases have been demonstrated in terms of overall survival and quality of life. Complete resection is associated with better long‐term survival.     

Hepatic encephalopathy caused by congenital extrahepatic portosystemic venous shunt

Congenital portosystemic venous shunt is a relatively rare disease. Recently, a 60-year-old woman was admitted to our hospital for hepatic encephalopathy caused by congenital extrahepatic portocaval shunt. She had been in good health until the onset of this event, with no liver damage and no experience of abdominal surgery or history of abdominal trauma. In May 1993, hepatic encephalopathy manifested suddenly, with the chief complaint of orthostatic disturbance. Although conservative treatment was administered during the subsequent 5 years, on admission, liver damage and slight splenomegaly were shown, for which complete resection of the shunt vessel and splenectomy were performed. Postoperatively, the patient's symptoms have been alleviated. Hepatic encephalopathy caused by congenital portosystemic venous shunt requires long-term conservative treatment, and the patient's quality of life is reduced. For this reason, surgical intervention or embolization with interventional radiology should be considered, and the maintenance of hepatic blood flow should also be considered.     

Laparoscopic liver resection in the treatment of hepatocellular carcinoma

Laparoscopic liver resection is an emerging technique in liver surgery. Although?laparoscopy is well established for several abdominal procedures and is considered by some the preferred approach, laparoscopic hepatic resection has been introduced into clinical practice more widely since 2000. These procedures are performed only in experienced centers and only in a select group of patients. While initially performed only for benign hepatic lesions, the indications for laparoscopic resection have gradually broadened to encompass all kinds of malignant hepatic lesions, including hepatocellular carcinoma in patients with cirrhosis, for whom the advantages of the minimally invasive approach may be most evident.     

Biliary tree gastrinomas in multiple endocrine neoplasia type 1 syndrome

AIM:To describe our patients affected with ectopic biliary tree gastrinoma and review the literature on this topic.METHODS:Between January 1992 and June 2012,28 patients affected by duodenopancreatic endocrine tumors in multiple endocrine neoplasia type 1(MEN1)syndrome underwent surgery at our institution.This retrospective review article analyzes our experience regarding seventeen of these patients subjected to duodenopancreatic surgery for Zollinger-Ellison syndrome(ZES).Surgical treatment consisted of duodenopancreatectomy(DP)or total pancreatectomy(TP).Regional lymphadenectomy was always performed.Any hepatic tumoral lesions found were removed during surgery.In MEN1 patients,removal of duodenal lesions can sometimes lead to persistence or recurrence of hypergastrinemia.One possible explanation for this unfavorable outcome could be unrecognized ectopic localization of gastrin-secreting tumors.This study described three cases among the seventeen patients who were found to have an ectopic gastrinoma located in the biliary tree.RESULTS:Seventeen MEN1 patients affected with ZES were analyzed.The mean age was 40 years.Fifteen patients underwent DP and two TP.On histopathological examination,duodeno pancreatic endocrine tumors were found in all 17 patients.Eighty-one gastrinomas were detected in the first three portions of the duodenum.Only one gastrinoma was found in the pancreas.The mean number of gastrinomas per patient was 5(range 1-16).Malignancy was established in 12 patients(70.5%)after lymph node,liver and omental metastases were found.Three patients exhibited biliary tree gastrinomas as well as duodenal gastrinoma(s).In two cases,the ectopic gastrinoma was removed at the same time as pancreatic surgery,while in the third case,the biliary tree gastrinoma was resected one year after DP because of recurrence of ZES.CONCLUSION:These findings suggest the importance of checking for the presence of ectopic gastrinomas in the biliary tree in MEN1 patients undergoing ZES surgery.     

From minimal to maximal surgery in the treatment of hepatocarcinoma:A review

Hepatocellular carcinoma represents one of the most challenging frontiers in liver surgery. Surgeons have to face a broad spectrum of aspects,from the underlying liver disease to the new surgical techniques. Safe liver resection can be performed in patients with portal hypertension and well-compensated liver function witha 5-year survival rate of 50%,offering good longterms results in selected patients. With the advances in laparoscopic surgery,major liver resections can be performed with minimal harm,avoiding the wound and leak complications related to the laparotomies. Studies have shown that oncological margins are the same as in open surgery. In patients submitted to liver resection(either laparoscopic or open) who experience recurrence,re-resection or salvage liver transplantation has been showing to be an alternative approach in well selected cases. The decision making approach to the cirrhotic patient is becoming more complex and should involve hepatologists,liver surgeons,radiologists and oncologists. Better understanding of the different risk factors for recurrence and survival should be aimed in these multidisciplinary discussions. We here in discuss the hot topics related to surgical risk factors regarding the surgical treatment of hepatocellular carcinoma: anatomical resection,margin status,macrovascular tumor invasion,the place of laparoscopy,salvage liver transplantation and liver transplantation.     

Surgery and prognosis of duodenal gastrinoma as a duodenal neuroendocrine tumor

It has become increasingly clear that duodenal gastrinomas are the most common cause of Zollinger-Ellison syndrome (ZES). However, attempts to find these tumors before and during surgery for ZES have had limited success until duodenotomy (opening the duodenum) was described. The routine use of duodenotomy in patients with non-familial gastrinoma increases the number of duodenal tumors found, and the immediate and long-term cure-rate. The increase in cure-rate appears to be secondary to increased detection of small, previously undetectable duodenal gastrinomas. Duodenotomy detects small tumors (<1 cm) in the proximal duodenum. It does not detect more duodenal gastrinomas per patient, nor does it detect tumors in unusual duodenal locations. Duodenotomy decreases the death-rate associated with these tumors. However, it has not affected the rate of development of liver metastases. Duodenotomy is a critical method to find duodenal gastrinomas. It should be routinely performed in all surgery to find and remove gastrinoma for cure of ZES.     

Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies

Zollinger-Ellison syndrome (ZES) associated with pancreatic or duodenal gastrinoma is characterized by gastric acid hypersecretion, which typically leads to gastroesophageal reflux disease, recurrent peptic ulcers, and chronic diarrhea. As symptoms of ZES are nonspecific and overlap with other gastrointestinal disorders, the diagnosis is often delayed with an average time between the onset of symptoms and final diagnosis longer than 5 years. The critical step for the diagnosis of ZES is represented by the initial clinical suspicion. Hypergastrinemia is the hallmark of ZES; however, hypergastrinemia might recognize several causes, which should be ruled out in order to make a final diagnosis. Gastrin levels > 1000 pg/mL and a gastric pH below 2 are considered to be diagnostic for gastrinoma; some specific tests, including esophageal pH-recording and secretin test, might be useful in selected cases, although they are not widely available. Endoscopic ultrasound is very useful for the diagnosis and the local staging of the primary tumor in patients with ZES, particularly in the setting of multiple endocrine neoplasia type 1. Some controversies about the management of these tumors also exist. For the localized stage, the combination of proton pump inhibitory therapy, which usually resolves symptoms, and surgery, whenever feasible, with curative intent represents the hallmark of gastrinoma treatment. The high expression of somatostatin receptors in gastrinomas makes them highly responsive to somatostatin analogs, supporting their use as anti-proliferative agents in patients not amenable to surgical cure. Other medical options for advanced disease are super-imposable to other neuroendocrine neoplasms, and studies specifically focused on gastrinomas only are scant and often limited to case reports or small retrospective series. The multidisciplinary approach remains the cornerstone for the proper management of this composite disease. Herein, we reviewed available literature about gastrinoma-associated ZES with a specific focus on differential diagnosis, providing potential diagnostic and therapeutic algorithms.     

Laparoscopic management of benign liver diseases: where are we?

BACKGROUND: The role of laparoscopic surgery in the management of benign cystic and solid liver tumours appears to differ according to each tumour type. As regards congenital liver cysts, laparoscopic treatment is now the gold standard for treating selected, huge, accessible, highly symptomatic or complicated cysts. In contrast, the laparoscopic approach is not useful for patients suffering from adult polycystic liver disease (PLD), except for type I PLD with large multiple hepatic cysts. For benign hepatocellular tumours, the surgical management has recently benefited from a better knowledge of the natural history of each type of tumour and from the improvement of imaging techniques in assuring a precise diagnosis of tumour nature. Thus the general tendency has led to a progressive restriction and tailoring of indications for resection in benign liver tumours, selecting only patients with huge, specifically symptomatic or compressive benign tumours or patients suffering from liver cell adenoma. Despite the enthusiastic use of the laparoscopic approach, selective indications for resection of benign liver tumours should indeed remain unchanged. For all types of benign liver tumours, the best indication remains small, superficial lesions, located in the anterior or the lateral segments of the liver. Deep, centrally located lesions or tumours in contact with major vascular or biliary trunks are not ideal candidates for laparoscopic liver resections. When performed by expert liver and laparoscopic surgeons using an adequate surgical technique, the laparoscopic approach is safe for performing minor liver resections and is accompanied by the usual postoperative benefits of laparoscopic surgery. When applied in selected patients and tumours, laparoscopic management of benign liver diseases appears to be a promising technique for hepatobiliary surgeons.     

Assessment of hepatic reserve for indication of hepatic resection: how I do it

The perioperative outcome of hepatic resection has improved remarkably in recent years with improved surgical techniques and perioperative care. As a result, the indications of hepatic resection have been extended to include patients with borderline liver function, especially those with associated cirrhosis. For such patients, proper preoperative assessment of liver function reserve is essential to ensure a low incidence of postoperative liver failure and mortality. In our center, routine preoperative assessment of hepatic function reserve in all patients includes clinical assessment, liver biochemistry, coagulation profile, platelet count, and Child-Pugh classification. The indocyanine green clearance test is routinely performed for patients with chronic liver disease. For patients with cirrhosis undergoing major hepatectomy, computed tomography volumetry and laparoscopy are helpful in evaluating whether the remnant liver volume is adequate. In selected patients with small remnant liver, preoperative portal vein embolization can be employed to induce hypertrophy of the remnant liver even in the presence of chronic hepatitis and mild cirrhosis. Careful assessment of comorbid conditions of patients and meticulous surgical techniques to reduce bleeding and hypoxic injury to the remnant liver are complementary to the selection of patients with adequate liver function reserve, to minimize operative mortality.     

Pancreatic ductal adenocarcinoma and paraaortic lymph nodes metastases: The accuracy of intraoperative frozen section

BackgroundPancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) with paraaortic lymph nodes metastases (PALN +) is associated with poor survival. Still, there are no current guidelines advocating systematic detection of PALN+.MethodsAll consecutive patients who underwent surgical exploration/resection with concurrent paraaortic (group 16) lymphadenectomy for PDAC between 2009 and 2016 were considered for inclusion. Resection was systematically aborted in case of intraoperative PALN + detection. Diagnostic performance of preoperative imaging upon blind review and intraoperative PALN dissection with frozen section (FS) for PALN detection were evaluated. Additionally, the prognostic significance of PALN + on overall survival (OS) was analyzed.ResultsOver the study period, among 129 patients undergoing surgery for PDAC, 113 had intraoperative PALN dissection with FS analysis. Median number of resected PALN was 3 (range, 1–15). Overall, PALN+ was found in 19 patients (16.8%). Upon blind review, preoperative imaging performed poorly for PALN + detection with a low agreement between imaging and final pathology (Kappa-Cohen index<0.2). In contrast, PALN FS showed high detection performances and strong agreement with final pathology (Kappa-Cohen index = 0.783, 95%CI 0.779–0.867, p < 0.001). Regarding survival outcomes, there was no difference between patients with PALN+ and patients not resected in the setting of liver metastases or locally unresectable disease found at exploration (p = 0.708).ConclusionsBefore PD for PDAC, intraoperative PALN dissection and FS analysis yields accurate PALN assessment and allows appropriate patient selection. This should be routinely performed and aborting resection should be strongly considered in case of PALN+.