'IHPBA-APHPBA clinical practice guidelines': international Delphi consensus recommendations for gallbladder cancer.

BACKGROUND: The Delphi consensus study was carried out under the auspices of the International and Asia-Pacific Hepato-Pancreato-Biliary Associations (IHPBA-APHPBA) to develop practice guidelines for management of gallbladder cancer (GBC) globally. METHOD: GBC experts from 17 countries, spanning 6 continents, participated in a hybrid four-round Delphi consensus development process. The methodology involved email, online consultations, and in-person discussions. Sixty eight clinical questions (CQs) covering various domains related to GBC, were administered to the experts. A consensus recommendation was accepted only when endorsed by more than 75% of the participating experts. RESULTS: Out of the sixty experts invited initially to participate in the consensus process 45 (75%) responded to the invitation. The consensus was achieved in 92.6% (63/68) of the CQs. Consensus covers epidemiological aspects of GBC, early, incidental and advanced GBC management, definitions for radical GBC resections, the extent of liver resection, lymph node dissection, and definitions of borderline resectable and locally advanced GBC. CONCLUSIONS: This is the first international Delphi consensus on GBC. These recommendations provide uniform terminology and practical clinical guidelines on the current management of GBC. Unresolved contentious issues like borderline resectable/locally advanced GBC need to be addressed by future clinical studies.

Long-term outcomes and survival analysis of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei at a newly established peritoneal malignancy centre in Japan.

Background: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is established in the management of pseudomyxoma peritonei (PMP), selected cases of peritoneal mesothelioma, and resectable colorectal or ovarian peritoneal metastases in Western countries. However, the efficacy and feasibility of these techniques are not well established in the Asian population, and little has been reported on long-term survival outcomes for surgically resected PMP patients. Materials and Methods: Retrospective analysis of a prospective database of short- and longer-term outcomes of consecutive patients who underwent CRS and HIPEC for PMP in a newly established peritoneal malignancy unit in Japan between 2010 and 2016. Results: A total of 105 patients underwent CRS and HIPEC and 57 maximal tumor debulking (MTD) for pseudomyxoma peritonei. In the CRS group, the primary tumor was appendiceal in 94 patients (90%) followed by ovarian and colorectal. Major postoperative complications occurred in 22/105 patients (21%) with one in-hospital mortality (0.9%). The 5-year overall and disease-free survival rates for the CRS group were 74.2% and 50.1%, respectively. Multivariate analysis revealed unfavorable histology to be the significant predictor of reduced overall and disease-free survival. Completeness of cytoreduction, CA19-9, and CA125 were also associated with disease-free survival. Conclusions: This is the first report on long-term outcomes and survival analysis of CRS and HIPEC for PMP in the Asian population. CRS and HIPEC can be conducted with reasonable safety and favorable survival in a new center. Complete tumor removal and histological type are the strongest prognostic factors for both overall and disease-free survival.

Role of liver resection in the era of advanced systemic therapy for hepatocellular carcinoma.

The recent dramatic progress in systemic therapy for hepatocellular carcinoma (HCC) provides the possibility of a combination of surgery and systemic therapy including adjuvant, neoadjuvant, or conversion settings. Since the turn of the century, at least three negative studies have tested adjuvant therapies after curative resection or ablation, including uracil-tegafur, which is an oral chemotherapeutic drug, sorafenib, and peretinoin, which a synthetic retinoid that may induce the apoptosis and differentiation of liver cancer cells. Using more potent immuno-checkpoint inhibitors (ICIs), at least 4 phase III trials of adjuvant immunotherapy are ongoing: nivolumab, durvalumab/ bevacizumab, pembrolizumab, and atezolizumab+bevacizumab. Very recently, the last trial indicated a significantly better recurrence-free survival (RFS) for adjuvant atezolizumab+bevacizumab. Another promising combination of surgery and systemic therapy is neoadjuvant therapy for potentially resectable cases or a conversion strategy for oncologically unresectable cases. There are 2 neoadjuvant trials for technically or oncologically unresectable HCCs ongoing in Japan: the LENS-HCC trial using lenvatinib and the RACB study using atezolizumab+bevacizumab. A longer follow-up may be needed, but the overall survival (OS) in resected cases seems much higher than that in unresectable cases. Recently, the Japan Liver Cancer Association (JLCA) and the Japanese Society of HPB Surgery (JSHPBS) created a joint working group on "so-called borderline resectable HCC". They obtained a Japanese consensus on this issue that has been published on the websites of JLCA and JSHPBS. The definition of resectability or borderline resectability provides a common language regarding advanced HCC for investigators and is a useful tool for future clinical trials.

A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma (LENS-HCC Trial).

Introduction: The phase III REFLECT trial demonstrated that lenvatinib was superior to sorafenib in terms of progression-free survival (PFS), time to progression, and objective response rate (ORR) for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of preoperative lenvatinib therapy for patients with oncologically or technically unresectable HCC. Methods: In this multicenter single-arm phase II trial, patients with advanced HCC and factors suggestive of a poor prognosis (macroscopic vascular invasion, extrahepatic metastasis, or multinodular tumors) were enrolled. Patients with these factors, even with technically resectable HCC, were defined as oncologically unresectable because of the expected poor prognosis after surgery. After 8 weeks of lenvatinib therapy, the patients were assessed for resectability, and tumor resection was performed if the tumor was considered technically resectable. The primary endpoint was the surgical resection rate. The secondary endpoints were the macroscopic curative resection rate, overall survival (OS), ORR, PFS, and the change in the indocyanine green retention rate at 15 min as measured before and after lenvatinib therapy. The trial was registered with the Japan Registry of Clinical Trials (s031190057). Results: Between July 2019 and January 2021, 49 patients (42 oncologically unresectable patients and 7 technically unresectable patients) from 11 centers were enrolled. The ORR was 37.5% based on mRECIST and 12.5% based on RECIST version 1.1. Thirty-three patients underwent surgery (surgical resection rate: 67.3%) without perioperative mortality. The surgical resection rate was 76.2% for oncologically unresectable patients and 14.3% for technically unresectable patients. The 1-year OS rate and median PFS were 75.9% and 7.2 months, respectively, with a median follow-up period of 9.3 months. Conclusions: The relatively high surgical resection rate seen in this study suggests the safety and feasibility of lenvatinib therapy followed by surgical resection for patients with oncologically or technically unresectable HCC.

A successful complete resection for multidrug-resistant giant gastrointestinal stromal tumor invading the transverse colon with multiple liver metastases in a young female: a case report.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare in young people and are often detected after becoming symptomatic or at an advanced stage. Herein, we report a case of complete reduction surgery for a substantially large malignant gastric GIST with multiple liver metastases in a young woman who successfully resulted in R0 surgery. CASE PRESENTATION: An 18-year-old woman presented to our hospital with anorexia and vomiting, and was diagnosed with a 17 cm gastric GIST with transverse colon invasion and multiple liver metastases. Due to being considered unresectable, tyrosine and multi-kinase inhibitor therapy were administered up to the fourth line yielding no response. After careful discussion at a multidisciplinary team conference, pancreatoduodenectomy or distal gastrectomy, transverse colectomy, and resection of the liver metastases were planned. Consequently, distal gastrectomy, transverse colectomy, resection of the liver metastases, and incidental peritoneal metastases were performed. Although the primary goal of the surgery was to reduce the volume of the tumor as much as possible, the results revealed that the complete removal of all detectable tumors was achieved. No recurrence was observed after surgery for 27 months with long-term adjuvant imatinib therapy. CONCLUSIONS: Even for highly advanced GISTs, aggressive surgery followed by adjuvant drug therapy may prolong survival in young patients.

Middle-segment preserving pancreatectomy: a literature review and case report.

PURPOSE: Middle segment-preserving pancreatectomy (MSPP) is a relatively new parenchymal-sparing surgery that has been introduced as an alternative to total pancreatectomy (TP) for multicentric benign and borderline pancreatic diseases. To date, only 36 cases have been reported in English. METHODS: We reviewed 22 published articles on MSPP and reported an additional case. RESULTS: Our patient was a 49-year-old Japanese man diagnosed with Zollinger-Elison syndrome (ZES) caused by duodenal and pancreatic gastrinoma associated with multiple endocrine neoplasia syndrome type 1. We avoided TP and chose MSPP as the operative technique due to his relatively young age. The patient developed a grade B postoperative pancreatic fistula (POPF), which improved with conservative treatment. He was discharged without further treatment. To date, no tumor has recurred, and pancreatic function seems to be maintained. According to a literature review, the morbidity rate of MSPP is as high as 54%, mainly due to the high incidence of POPF (32%). In contrast, there was no perioperative mortality, and postoperative pancreatic function was comparable to that after conventional pancreatectomy. CONCLUSIONS: Despite the high incidence of POPF, MSPP appears to be safe, with low perioperative mortality and good postoperative pancreatic sufficiency.

Secondary ileal lymph node metastases from rectal cancer: a case report.

BACKGROUND: Colorectal cancer can invade adjacent organs, but rarely metastasizes to the regional lymph nodes (LNs) of the invaded organ. Herein, we report a case of rectal cancer invading the ileum and metastasized to the regional ileal LNs. CASE PRESENTATION: A 77-year-old male presented abdominal pain and anorexia, diagnosed with rectal cancer invading the small intestine and concurrently metastasized to the regional LN of the intestine and liver. High anterior resection and partial resection of the small intestine was performed, then, the patient was referred to our hospital for chemotherapy. We performed 17 cycles of systemic chemotherapy that achieved a partial reduction in size of the LN, followed by an ileocecal resection with ileal mesentery resection for regional LNs removal. Histopathological analysis of the resected ileal LNs and six liver lesions revealed a moderately differentiated tubular adenocarcinoma. The patient was discharged on postoperative day 18. Cancer recurrences developed in the lungs 5 months after the surgery, then to the liver and peritoneum, and further surgery and chemotherapy were performed. Despite the challenging presentation, the patient survived for 40 months after the first surgery. CONCLUSIONS: We report a rare case of a surgical resection of a secondary ileal LN metastasis from rectal cancer. The patient survives for a relatively long time after surgical resection. When colorectal cancer invades the small intestine, clinicians should consider the possibility of secondary LN metastasis in the invaded site.

Pancreaticoduodenectomy after bilirubin adsorption for distal cholangiocarcinoma with severe obstructive jaundice refractory to repeat preoperative endoscopic biliary drainage: a case report.

The necessity of biliary drainage before pancreaticoduodenectomy remains controversial in cases involving malignant obstructive jaundice; however, the benefits of biliary drainage have been reported in cases with severe hyperbilirubinemia. Herein, we present the case of a 61-year-old man suffering from jaundice due to distal cholangiocarcinoma. In this case, obstructive jaundice was refractory to repeat endoscopic drainage and bilirubin adsorption. Hyperbilirubinemia persisted despite successful implementation of biliary endoscopic sphincterotomy and two rounds of plastic stent placements. Stent occlusion and migration were unlikely and oral cholagogues proved ineffective. Owing to the patient's surgical candidacy and his aversion to nasobiliary drainage due to discomfort, bilirubin adsorption was introduced as an alternative therapeutic intervention. Following repeated adsorption sessions, a gradual decline in serum total bilirubin levels was observed and pancreaticoduodenectomy was scheduled. The patient successfully underwent pancreaticoduodenectomy with portal vein resection and reconstruction and D2 lymph node dissection. After the surgery, the serum bilirubin levels gradually decreased and the patient remained alive, with no recurrence at 26 months postoperatively. Therefore, this case highlights the feasibility and safety of performing pancreaticoduodenectomy in patients with severe, refractory jaundice who have not responded to repeated endoscopic interventions and have partially responded to bilirubin adsorption.

A case of gastric adenocarcinoma with pyloric gland-type infiltrating submucosa.

BACKGROUND: The development of immunohistochemical staining has revealed that gastric adenocarcinoma with the gastric phenotype can be divided into the foveolar, fundic gland, and pyloric gland phenotypes. Gastric adenocarcinoma of the pyloric gland type is difficult to diagnose using biopsy because of its low atypia and rarity. Herein, we describe a case of gastric adenocarcinoma of the pyloric gland type that was diagnosed immunohistochemically after endoscopic resection. CASE PRESENTATION: A 67-year-old man was referred to our hospital for the diagnosis and treatment of a 30-mm elevated lesion on the lesser curvature side of the middle of the gastric body. Although four biopsies were performed, it was difficult to determine whether the lesion was benign or malignant. Therefore, endoscopic submucosal dissection was performed, and the presence of tumor cells infiltrating the submucosa with venous invasions was identified. Immunohistochemical staining revealed that the tumor cells were positive for MUC5AC and MUC6 and negative for Pepsinogen I and H + /K + -ATPase. From the above findings, he was diagnosed as having gastric adenocarcinoma with pyloric gland type. The patient underwent a laparoscopic distal gastrectomy and was discharged without any adverse events. CONCLUSIONS: Gastric adenocarcinoma of the pyloric gland type is a rare disease, and endoscopic resection can serve as a viable diagnostic option for this condition when it is difficult to diagnose using biopsy. Immunohistochemical pathology images can aid in the diagnosis of gastric adenocarcinoma of the pyloric gland type.

A unique case of a typical pancreatic ductal adenocarcinoma that initially presented with a cystic component but underwent morphological changes.

A 66-year-old man was initially suspected of having a microcystic serous cystic neoplasm based on magnetic resonance imaging findings of a multifocal mass measuring 46 mm in the pancreatic head, with a cystic component showing a high signal on T2-weighted images. The tumor marker levels were within normal limits. However, contrast-enhanced computed tomography revealed thick cyst walls with delayed staining, which was atypical for serous cystic neoplasms; therefore, the patient was followed up closely. Twenty-two months later, the delayed contrast area was enlarged, carbohydrate antigen 19-9 levels were elevated, and 18 F-fluorodeoxyglucose-positron emission tomography revealed increased accumulation, indicating a potentially malignant lesion. Pancreatoduodenectomy was performed and histopathological examination confirmed the diagnosis of normal-type pancreatic carcinoma with predominantly poorly differentiated cells. Based on the pathological findings and a literature review, it is highly likely that this case represents pancreatic ductal adenocarcinoma with a cystic structure from the beginning. While distinguishing pancreatic ductal adenocarcinoma from other pancreatic cystic tumors, such as serous cystic neoplasms, is critical owing to differing treatments and prognoses, caution is warranted as they may exhibit similar imaging features, as observed in our patient.

International survey on opinions and use of robot-assisted and laparoscopic minimally invasive pancreatic surgery: 5-year follow up.

BACKGROUND: Evidence on the value of minimally invasive pancreatic surgery (MIPS) has been increasing but it is unclear how this has influenced the view of pancreatic surgeons on MIPS. METHODS: An anonymous survey was sent to members of eight international Hepato-Pancreato-Biliary Associations. Outcomes were compared with the 2016 international survey. RESULTS: Overall, 315 surgeons from 47 countries participated. The median volume of pancreatic resections per center was 70 (IQR 40-120). Most surgeons considered minimally invasive distal pancreatectomy (MIDP) superior to open (ODP) (94.6%) and open pancreatoduodenectomy (OPD) superior to minimally invasive (MIPD) (67.9%). Since 2016, there has been an increase in the number of surgeons performing both MIDP (79%-85.7%, p = 0.024) and MIPD (29%-45.7%, p < 0.001), and an increase in the use of the robot-assisted approach for both MIDP (16%-45.6%, p < 0.001) and MIPD (23%-47.9%, p < 0.001). The use of laparoscopy remained stable for MIDP (91% vs. 88.1%, p = 0.245) and decreased for MIPD (51%-36.8%, p = 0.024). CONCLUSION: This survey showed considerable changes of MIPS since 2016 with most surgeons considering MIDP superior to ODP and an increased use of robot-assisted MIPS. Surgeons prefer OPD and therefore the value of MIPD remains to be determined in randomized trials.

How to do it: rescue duct-to-duct biliary reconstruction techniques to avoid severe biliary complications of hepatic resection for hepatocellular carcinoma.

There are few reports on duct-to-duct biliary reconstruction for complex liver resection with limited bile duct resection. We performed duct-to-duct biliary reconstruction in two patients undergoing limited bile duct resection where Roux-en-Y hepaticojejunostomy (HJ) was difficult. An external biliary drainage tube was placed routinely at the anastomotic site to prevent stenosis. In case 1, the tumor-infiltrated part of the left hepatic duct (LHD) was resected and the LHD was repaired using duct-to-duct reconstruction with interrupted sutures. In case 2, after the tumor-infiltrated part of the LHD and posterior hepatic duct (PHD) were resected, T-tube reconstruction was performed on the PHD, and the LHD was anastomosed using interrupted sutures for the posterior wall and a round ligament patch for the anterior wall. Our literature review suggests that an external biliary drainage tube with stenting over the anastomosis may reduce the risk of biliary complications.

A case of pseudomyxoma peritonei arising from a perforated intraductal papillary mucinous neoplasm that underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Pseudomyxoma peritonei (PMP) of pancreatic origin arising from an intraductal papillary mucinous neoplasm (IPMN) is rare. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been established as the optimal treatment for PMP. However, the benefits and safety of CRS with HIPEC for treating PMP of pancreatic origin remain unclear. Herein, we describe a case of PMP of pancreatic origin that was treated with CRS and HIPEC without postoperative complications. A 75-year-old woman was referred to our department. Computed tomography (CT) revealed a multilocular cystic tumor in the pancreatic tail, notable mucinous ascites in the abdominal cavity, and scalloping of the liver and spleen. CT did not reveal the appendix, and the ovaries were normal in size. The patient was diagnosed with PMP of pancreatic origin, and CRS and HIPEC were performed. Intraoperatively, the pancreatic tumor was perforated, and there was a large amount of mucinous ascites. We performed distal pancreatectomy in addition to CRS and HIPEC, with no intraoperative complications. The postoperative course was uneventful, and the patient survived after 6 months without recurrence. CRS with HIPEC may be a feasible treatment option for PMP of pancreatic origin.

Questionnaire survey of Japanese board-certified expert hepatobiliary and pancreatic surgeons and instructors on the surgical indications for hepatocellular carcinoma.

BACKGROUND: Recent advancements in systemic therapy for hepatocellular carcinoma (HCC) necessitate the establishment of resectability criteria for advanced HCC. METHODS: A questionnaire survey sought to clarify the perspectives of Japanese expert hepatobiliary surgeons regarding surgical indications for HCC. Thirty-one questions were used to determine when surgery is strongly recommended (resectable: R) or not recommended (unresectable: UR). RESULTS: A total of 351 responses were obtained. While 64.7% of the respondents considered solitary tumors as being R, irrespective of size, opinions diverged on the upper limit of the number of tumors/tumor size for R: (1) up to three nodules with no size limit (27.9%), (2) up to three nodules ≤5 cm in diameter each (21.4%) and (3) up to three nodules ≤3 cm in diameter each (19.4%). Vp1, Vp2, Vp3, and Vp4 were considered as being R by 90.9%, 70.7%, 39.0%, and 8.0% of respondents, respectively. Half of the respondents indicated they would consider resection even for cases with extrahepatic spread under limited conditions. CONCLUSIONS: The current views of Japanese expert surgeons on the resectability criteria for HCC were clarified for the first time. The findings could serve as a basis for preparing expert consensus statements on the resectability criteria for HCC.

Refractory gastrocutaneous fistula treated by two-stage surgery: a case report.

BACKGROUND: Gastrocutaneous fistulas are a rare complication of enterocutaneous fistulas and can be caused by intestinal injury, infection, and anastomotic leakage. They are typically treated conservatively or endoscopically; however, for large or difficult-to-treat gastrocutaneous fistulas, surgical intervention is required. Herein, we present a case of a huge gastrocutaneous fistula that was successfully treated with a two-stage surgery performed using open abdomen management. CASE PRESENTATION: A 61-year-old man with a perforated gastric ulcer underwent omental filling as an emergency surgery. Post-operative leakage led the development of a 10-cm gastrocutaneous fistula. He was transferred to our hospital for the treatment of gastrocutaneous fistula. Furthermore, nutritional therapy was administered for dehydration, electrolyte abnormalities, metabolic acidosis, and acute kidney injury due to the high-output nature of the fistula. Moreover, owing to the intraperitoneal severe adhesion and poor nutritional status, two-stage surgery was planned. In the first stage, extensive dissection of the adhesions, distal gastrectomy reconstruction with Roux-en-Y anastomosis, and jejunostomy were performed. Furthermore, open abdomen management was conducted to check for the presence of unexpected complications due to extensive dissection of the adhesion and anastomotic leakage. Subsequently, in the second stage of the surgery, abdominal closure was performed on the 9th day after gastrectomy. CONCLUSION: Open abdomen management may be effective for huge gastrocutaneous fistulas with extensive adhesions that require surgical intervention.

A multicenter validation study for determining the condition of nonanatomical or minor anatomical hepatectomies satisfying technical difficulty of current high-level hepatectomy certificated by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

BACKGROUND: The current high-level hepatectomy (HLH) is certified by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS), comprising only anatomical hepatectomies above Couinaud's segmentectomy. This multicenter study aimed to identify the conditions of non-HLH that satisfy equivalent technical difficulties to HLH. METHODS: Between 2018 and 2021, 595 first open hepatectomies without biliary reconstruction (374 HLHs and 221 non-HLHs) were performed in the five institutions. Non-HLHs belonging to at least one of the three conditions; depth of hepatectomy ≥5 cm, number of resections ≥3 locations and at least one location with a depth of hepatectomy ≥3 cm, and hepatectomy involving the paracaval portion of the caudate lobe was proposed as the candidate for difficult non-HLH. The technical difficulty was estimated by the operative time and blood loss. RESULTS: Difficult non-HLHs were neither associated with shorter operative time (373 min vs. 354 min, p = .184) nor lesser blood loss than those with HLHs (503 mL vs. 436 mL, p = .126). Postoperative complications such as Clavien-Dindo classification grade III or more were not significant between the two groups (18.6% vs. 13.4%, p = 0212). CONCLUSIONS: Difficult non-HLHs were associated with no lesser technical difficulty than those with HLH.

Preoperative CA19.9 level predicts lymph node metastasis in resectable adenocarcinoma of the head of the pancreas: A further plea for biological resectability criteria.

INTRODUCTION: Lymph-nodal involvement (N+) represents an adverse prognostic factor after pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). Preoperative diagnostic and staging modalities lack sensitivity for identifying N+. This study aimed to investigate preoperative CA19.9 in predicting the N+ stage in resectable-PDAC (R-PDAC). METHODS: Patients included in a multi-institutional retrospective database of PDs performed for R-PDAC from January 2000 to June 2021 were analyzed. A preoperative laboratory value of CA19.9 >37 U/L was used in univariate and multivariate logistic regression analysis to determine a possible association with N+. Additionally, different cut-offs of CA19.9 related to the preoperative clinical T (cT) stage was assessed to evaluate the risk of N+. RESULTS: A total of 2034 PDs from thirteen centers were included in the study. CA19.9>37 U/L was significantly associated with higher N+ at univariate and multivariate analysis (P<0.001). CA19.9 levels >37 U/L were associated with N+ in 75.9%, 81.3%, and 85.7% of patients, respectively, in cT1, cT2, and cT3 tumors and with higher cut-off values for all cT stages. CONCLUSION: Lymph nodal involvement is strongly related to preoperative CA19.9 levels. Specially in patients staged as cT3 the CA 19.9 could represent a valid and easy tool to suspect nodal involvement. Due to these findings, R-PDAC patients with elevated CA19.9 values should be considered in a more biologically advanced stage.