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Abstract Aim Pancreatic reconstruction after pancreaticoduodenectomy (PD) that leaves a small remnant pancreas is often difficult. Pancreatic fistula is a major complication after PD, and fistulas are rare in patients with hard pancreas. However, the clinical impact of non‐reconstructed small remnant after PD with hard pancreas is unknown. Methods We included all patients who underwent PD for pancreatic tumor without pancreatic reconstruction in two institutions supervised by one surgeon between January 2004 and March 2021. Their short‐ or long‐term outcome after surgery was retrospectively analyzed. Results PD was performed in 774 patients, of whom 16 patients were without reconstruction (2.1%) with negative margins at the pancreatic stump. Pancreatic transection was performed above or to the left of the superior mesenteric artery, with a median remnant pancreas length of 3.7 cm (range, 1.3–10.0). A major complication (≥ Clavien–Dindo Grade IIIa) occurred in one patient (6%). Fistula of grade B occurred in one patient (6%). After a median follow‐up of 44 months (95%CI, 10.6–77.3), insulin administration was unnecessary in 11 patients. Conclusion The preservation of a small pancreatic remnant without reconstruction after PD can be performed safely and may enable the keeping of pancreatic endocrine function for some selected patients with hard pancreas.

Abstract Resection is the only potential curative treatment for perihilar cholangiocarcinoma (PHC); however, complete resection is often technically challenging due to the anatomical location. Various innovative approaches and procedures were invented to circumvent this limitation but the rates of postoperative morbidity (20%–78%) and mortality (2%–15%) are still high. In patients diagnosed with resectable PHC, deliberate and coordinated preoperative workup and optimization of the patient and future liver remnant are crucial. Biliary drainage is recommended to relieve obstructive jaundice and optimize the clinical condition before liver resection. Biliary drainage for PHC can be performed either by endoscopic biliary drainage or percutaneous transhepatic biliary drainage. To date there is no consensus about which method is preferred. The volumetric assessment of the future remnant liver volume and optimization mainly using portal vein embolization is the gold standard in the management of the risk to develop post hepatectomy liver failure. The improvement of systemic chemotherapy has contributed to prolong the survival not only in patients with unresectable PHC but also in patients undergoing curative surgery. In this article, we review the literature and discuss the current surgical treatment of PHC.

Abstract Objectives Hepaticojejunostomy anastomotic stricture (HJAS) is a serious adverse event of pancreaticoduodenectomy. Preoperative biliary drainage with a self‐expandable metal stent (SEMS) is often performed before pancreaticoduodenectomy. The purpose of this study is to evaluate the risk factors and impact of preoperative SEMS placement on developing benign HJAS after pancreaticoduodenectomy. Methods We retrospectively analyzed consecutive patients who underwent pancreatoduodenectomy at our institution between July 2014 and June 2020. Risk factors for benign HJAS were identified using univariate and multivariate logistic regression analysis. We also compared outcomes of preoperative biliary drainage using SEMS and non‐SEMS. Results Of the 626 included patients, benign HJAS occurred in 36 patients (5.8%). The median follow‐up time was 36.7 months (interquartile range, 25.4–57.4 months). Multivariate logistic regression analysis revealed that lack of preoperative biliary drainage, preoperative bile duct diameter

Abstract Aim The National Clinical Database (NCD) of Japan is a nationwide data entry system for surgery, and it marked its 10th anniversary in 2020. The aim was to present the 2020 annual report of gastroenterological surgery of the NCD. Methods The data of the surgical procedures stipulated by the training curriculum for board‐certified surgeons of the Japanese Society of Gastroenterological Surgery in the NCD from 2011 to 2020 were summarized. Results In total, 5 622 845 cases, including 593 088 cases in 2020, were extracted from the NCD. The total number of gastroenterological surgeries increased gradually in these 10 years, except for the year 2020 due to the COVID‐19 pandemic. The annual number of surgeries of each organ, except the pancreas and liver, decreased by 0.4%–13.1% in 2020 compared to 2019. The surgical patients were consistently aging, with more than 20% of all gastroenterological surgeries in 2020 involving patients aged 80 years or older. The participation of board‐certified surgeons increased for each organ (75.9%–95.7% in 2020). The rates of endoscopic surgery also increased constantly. Although the incidences of postoperative complications of each organ increased by 0.7%–7.9% in these 10 years, postoperative mortality rates decreased by 0.2%–1.5%. Conclusions We present here the short‐term outcomes of each gastroenterological operative procedure in 2020. This review of the 10‐years of NCD data of gastroenterological surgery revealed a consistent increase of the number of surgeries (except for in 2020), especially endoscopic procedures, and aging of the Japanese population. The good safety of Japanese gastroenterological surgeries was also indicated.

BackgroundRobotic pancreatoduodenectomy (RPD) is a newly introduced procedure, which is still evolving and lacks standardization. An objective assessment is essential to investigate the feasibility of RPD. The current study aimed to assess our initial ten cases of RPD based on IDEAL (Idea, Development, Exploration, Assessment, and Long-term study) guidelines.MethodsThis was a prospective phase 2a study following the IDEAL framework. Ten consecutive cases of RPD performed by two surgeons with expertise in open procedures at a single center were assigned to the study. With objective evaluation, each case was classified into four grades according to the achievements of the procedures. Errors observed in the previous case were used to inform the procedure in the next case. The surgical outcomes of the ten cases were reviewed.ResultsThe median total operation time was 634 min (interquartile range [IQR], 594-668) with a median resection time of 363 min (IQR, 323-428) and reconstruction time of 123 min (IQR, 107-131). The achievement of the whole procedure was graded as A, "successful", in two patients. In two patients, reconstruction was performed with a mini-laparotomy due to extensive pneumoperitoneum, probably caused by insertion of a liver retractor from the xyphoid. Major postoperative complications occurred in two patients. One patient, in whom the jejunal limb was elevated through the Treitz ligament, had a bowel obstruction and needed to undergo re-laparotomy.ConclusionsRPD is feasible when performed by surgeons experienced in open procedures. Specific considerations are needed to safely introduce RPD.

Abstract Pancreas‐preserving duodenectomy is indicated for select patients with a duodenal tumor in the second portion. In this procedure, identification and closure of the accessory pancreatic duct is important to prevent postoperative pancreatic fistula. A 63‐y‐old man was diagnosed with duodenal mucosal carcinoma in the second portion, with invasion of the major ampullary. We performed pancreas‐preserving duodenectomy. Intraoperatively, indocyanine green‐fluorescent imaging identified the accessory pancreatic duct clearly and it was successfully closed. Postoperative pancreatic fistula did not occur. Indocyanine green‐fluorescent imaging is effective in identifying the accessory pancreatic duct in pancreas‐preserving duodenectomy.

Abstract Background Infectious complications are the main causes of morbidity after pancreaticoduodenectomy (PD). Early enteral nutrition (EN) is a reasonable form of nutritional support that aims to mitigate the occurrence and severity of infectious complications by maintaining gut immunity. However, it remains unclear whether EN is beneficial for patients who underwent PD and are under enhanced recovery after surgery (ERAS) protocol. Methods A multicenter (six hospitals), open-label, randomized controlled trial will be started in July 2022. A total of 320 patients undergoing open PD will be randomly assigned to an EN group or a peripheral parental nutrition (PPN) group in a 1:1 ratio. The stratification factors will be the hospital, age (≥ 70 or not), and preoperative diagnosis (pancreatic cancer or not). In the EN group, enteral nutrition will start on postoperative day (POD) 1 at 200–300 ml/day via the percutaneous tube placed operatively. The volume of the diet will be increased to 400–600 ml/day on POD 2 and depend on the surgeon’s decision from POD 3. In the PPN group, PPN will be delivered after surgery. In both groups, oral feeding will start on POD 3. Each treatment will be finished when patients’ oral food intake reaches 60% of the nutritional requirement (25–30 kcal/day). The primary endpoint will be the occurrence of postoperative infectious complications within 90 days of surgery. The secondary endpoints will be all complications, including major ones such as Clavien–Dindo grade 3 or more and clinically relevant postoperative pancreatic fistula. Data will be analyzed per the intention to treat. Discussion This will be the first, large, and well-designed RCT that aims to determine whether EN is beneficial for patients who underwent PD under the ERAS protocol. According to the results of this study, either EN or PPN would be adopted as the standard nutritional support for patients undergoing PD. Trial registration jRCT1030210691. Registered on March 23, 2022.

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.

Abstract Pancreatic mucinous cystic neoplasm (MCN) has two histological components: tumor epithelia and ovarian-like stroma (OLS). To examine the progression and changes in pancreatic MCNs, we analyzed the distribution, amount, immunohistochemical phenotype, presence of theca cells of OLS, and tumor epithelium in 45 surgically resected MCN cases, comparing them with tumor sizes. The OLS data of female MCN cases were also compared between those who were ≤ 51 years old and those > 51 years old to see the effect of menopause on MCN histology. Non-mucinous type epithelium was present in all low-grade MCNs, but its ratio decreased with tumor size (p 51 years than those ≤ 51 years old, however it did not reach statistical significance. This is the first study to show the intralobular distribution of OLS.

An 80-year-old woman underwent pancreatoduodenectomy. Post-operation, she experienced a fever, and a culture of blood revealed metallo-beta-lactamase-producing Raoultella ornithinolytica. For treatments with aminoglycoside antimicrobial agents, a therapeutic drug monitoring-based dosing design can lower the risk of adverse events and enable appropriate treatment. Key Clinical Message. When aminoglycoside antimicrobial agents are administered for MBL-producing bacteremia, prescription suggestions based on TDM by antimicrobial stewardship team can reduce the occurrence of adverse events and enable appropriate treatment.

Abstract Background Fibrolamellar hepatocellular carcinoma (FL-HCC) is a liver tumor that occurs almost exclusively in young adults without underlying liver disease. In spite of its distinct clinical characteristics and specific imaging findings, preoperative diagnosis is often difficult due to the extremely low incidence of the tumor. Although FL-HCC shows particular morphological features on H&E-stained tissue sections, differential diagnosis from ordinary HCC, especially the scirrhous variant of HCC, and intrahepatic cholangiocarcinoma needs additional immunohistochemical (IHC) analyses and/or molecular genetic testing. Case presentation A 21-year-old male patient was referred to our hospital for further evaluation of a large liver mass. Abdominal ultrasound examination, contrast-enhanced computed tomography, and magnetic resonance imaging revealed a well-defined hypervascular lobulated liver mass, 11 × 11 cm in diameter, with a central scar and calcification, in segments 5/8. Under the diagnosis of FL-HCC, we carried out extended anterior sectorectomy, including a part of segment 4. On microscopic examination, the tumor was composed of proliferating polygonal cells with abundant eosinophilic granular cytoplasm containing nuclei with vesicular chromatin and enlarged nucleoli, in an abundant stroma. Collagen fibers arranged in a parallel lamellar pattern were seen in the tumor stroma. These findings, together with the results of subsequent IHC analyses using HAS, CK7, and CD 67, we made the diagnosis of FL-HCC, which was further confirmed by detection of the DNAJB1-PRKACA fusion gene in the tumor cells by RT-PCR. Conclusion FL-HCC shows distinct imaging appearances. Although it also has characteristic morphological features, combined use of IHC and/or molecular genetic studies are necessary for the final diagnosis.

Abstract Background We aimed to present the 2019 annual report of the gastroenterological section of the National Clinical Database (NCD). Methods We reviewed 609,589 cases recorded in 2019 and 5,029,764 cases registered from 2011 to 2019 for the 115 selected gastroenterological surgical procedures. Results The main features of gastroenterological surgery in Japan were similar to those described in the 2018 annual report, namely, that 1) operative numbers gradually increased in all procedures, except gastrectomy and hepatectomy, which decreased in these years; 2) in all eight major gastroenterological surgeries, the age distribution tended toward older patients; 3) the morbidity of esophagectomy, hepatectomy, and pancreaticoduodenectomy increased, but mortality was minimized in all procedures; 4) all eight major gastroenterological procedures have increasingly been performed under laparoscopy; and 5) board‐certified surgeons were increasingly involved. These trends in recent years were more prominent in 2019. Conclusions Thanks to the continuous cooperation and dedication of the surgeons, medical staff, and surgical clinical reviewers who registered the clinical data into the NCD, it is possible to understand the comprehensive landscape of surgery in Japan and to disclose new evidence in this field. The Japanese Society of Gastroenterological Surgery will continue to promote the value of this database and encourage the use of feedback and clinical studies using the NCD, now and in the future. Generating further approaches to surgical quality improvement are important directions for future research.

We added a comment to the the article by Kim et al.. We first described how the hazard function and commonly used survival function act complementary, although these two functions are mathematically equivalent. Then, we pointed out two notable findings of the present article: 1) a recurrence by metastasis is presumed to occurred constantly at an annualized incidence of 4%-10% until 6 postoperative years; and 2) the annualized recurrence rates between the 5th and 10th postoperative years were between 3%-10% in cirrhotic patients and this figure was comparable to or even lower than the reported annual incidence of HCC in cirrhotic patients (up to 8%). We also pointed out three issues to be paid attention for: 1) the authors amalgamated patients with HBV- and HCV-related HCC together when calculating the hazard function, although the background liver of HCV-related HCC is hypothesized to have a higher carcinogenetic activity than that of HBV-related HCC, at least during the era before the advent of direct-acting antivirals; 2) the authors would have obtained interesting results had they evaluated the risk factors for late-phase recurrence exclusively in patients with HBV infection, including HBV-specific covariates into the analysis; and 3) many investigators may confuse a pathogenic factor with its surrogate marker when interpreting the significance of fibrosis in studies investigating risk factors leading to HCC development.

Abstract Background Percutaneous transhepatic gallbladder drainage (PTGBD) is indicated for patients with acute cholecystitis (AC) who are not indicated for urgent surgery, but external tubes reduce quality of life (QOL) while waiting for elective surgery. The objective of the present study was to investigate the feasibility of laparoscopic cholecystectomy after endoscopic trans-papillary gallbladder stenting (ETGBS) comparing with after PTGBD. Methods Intraoperative and postoperative outcomes of patients with ETGBS and PTGBD were retrospectively compared. Results Eighteen ETGBS and ten PTGBD patients were compared. Differences in the duration of ETGBS and PTGBD [median 209 min (range 107–357) and median 161 min (range 130–273), respectively, P = 0.10], median blood loss [ETGBS 2 (range 2–180 ml) and PTGBD 24 (range 2–100 ml), P = 0.89], switch to laparotomy (ETGBS 11% and PTGBD 20%, P = 0.52), and median postoperative hospital stay [ETGBS 8 (range 4–24 days) and ETGBS 8 (range 4–16 days), P = 0.99]. Thickening of the cystic duct that occurred in 60% of the ETGBS patients and none of the PTGBD patients (P = 0.005) interfered with closure of the duct by clipping. No obstruction occurred in ETGBS patients. Conclusion ETGBS did not make laparoscopic cholecystectomy less feasible than after PTGBD. This is a pilot study, and further investigations are needed to validate the results of the present study.

Abstract Background Expansion of the indication for liver resection and new regimens for systemic chemotherapy have improved postoperative outcomes for synchronous colorectal liver metastases (CRLM). However, such cases can still have a high recurrence rate, even after curative resection. Therefore, there is a need for postoperative adjuvant chemotherapy (POAC) after liver resection in patients with CRLM. There are few studies of the efficacy of POAC with an oxaliplatin-based regimen after simultaneous resection for colorectal cancer and CRLM with curative intent. The goal of the study was to compare POAC with oxaliplatin-based and fluoropyrimidine regimens using propensity score (PS) matching analysis. Methods The subjects were 94 patients who received POAC after simultaneous resection for colorectal cancer and synchronous CRLM, and were enrolled retrospectively. The patients were placed in a L-OHP (+) group (POAC with an oxaliplatin-based regimen, n = 47) and a L-OHP (−) group (POAC with a fluoropyrimidine regimen, n = 47). Recurrence-free (RFS), cancer-specific (CSS), unresectable recurrence-free (URRFS), remnant liver recurrence-free (RLRFS), and extrahepatic recurrence-free (EHRFS) survival were analyzed. Results Before PS matching, the L-OHP (+) and (−) groups had no significant differences in RFS, CSS, URRFS, RLRFS, and EHRFS. Univariate analysis indicated significant differences in age, preoperative serum CEA (≤ 30.0 ng/mL/ > 30.0 ng/mL), differentiation of primary tumor (differentiated/undifferentiated), T classification (T1–3/T4), number of hepatic lesions and maximum diameter of the hepatic lesion between the L-OHP (+) and (−) groups. After PS matching using these confounders, RFS was significantly better among patients in the L-OHP (+) group compared with the L-OHP (−) group (HR 0.40, 95% CI 0.17–0.96, p = 0.04). In addition, there was a trend towards better RLRFS among patients in the L-OHP (+) group compared with the L-OHP (−) group (HR 0.42, 95% CI 0.17–1.02, p = 0.055). However, there were no significant differences in CSS, URRFS and EHRFS between the L-OHP (+) and (−) groups. Conclusions PS matching analysis demonstrated the efficacy of POAC with an oxaliplatin-based regimen in RFS and RLRFS.

Abstract Background Pancreaticoduodenectomy after esophageal resection is technically difficult, because blood flow of the gastric conduit should be preserved. Celiac axis stenosis (CAS) is also a problem for pancreaticoduodenectomy, because arterial blood supply for the liver comes mainly through the collateral route from the superior mesenteric artery (SMA) via the gastroduodenal artery (GDA). Herein, we report the case of a patient with pancreatic head cancer who underwent a pancreaticoduodenectomy after esophagectomy with concomitant CAS. Case presentation A 76-year-old man with pancreatic head cancer was referred to our department. He had a history of esophagectomy with retrosternal gastric conduit reconstruction for esophageal cancer. Computed tomography showed severe CAS and a dilated collateral route between the SMA and the splenic artery (SPA). We prepared several surgical options depending on the intraoperative findings, and performed radical pancreaticoduodenectomy with concomitant resection of the distal gastric conduit. The right gastroepiploic artery (RGEA) of the remnant gastric conduit was fed from the left middle colic artery (MCA) with microvascular anastomosis. Despite CAS, when the GDA was dissected and clamped, good blood flow was confirmed, and the proper hepatic artery did not require reconstruction. The patient was discharged on postoperative day 90. Conclusions We successfully performed radical pancreaticoduodenectomy after esophagectomy with concomitant CAS, having prepared multiple surgical options depending upon the intraoperative findings.

Abstract Background Primary neuroendocrine tumor (NET) originating from the extrahepatic bile duct is rare, although liver metastasis from gastroenteropancreatic NET is frequently observed. We herein report a case who successfully underwent repeat hepatectomy for liver metastases from bile duct NET grade 2 (G2). Case presentation A 75-year-old man presented with jaundice and was suspected of perihilar cholangiocarcinoma by computed tomography (CT) and magnetic resonance imaging (MRI). He underwent extended left hepatectomy, extrahepatic bile duct resection, and hepaticojejunostomy. Pathological findings showed a NET G2 of the biliary tract arising from the common bile duct. Two years and 11 months after surgery, a liver metastasis was detected and hepatectomy was performed. During the surgery, another liver metastasis was detected, and limited liver resection for the two lesions was performed. Pathological findings showed four liver metastases of NET G2. Five years and 4 months after the first surgery (2 years and 5 months after the second hepatectomy), four liver metastases were detected. Thereafter, he received somatostatin analogues for 1 year. Although the size of tumors increased slightly, the number did not change. He underwent limited liver resections and was diagnosed with 7 liver metastases of NET G2. Finally, another hepatectomy (fourth hepatectomy) was performed and long-term survival without recurrence was obtained for as long as 8 years after the first surgery. Conclusions Repeat hepatectomy is a good option to obtain long-term survival for liver metastases from bile duct NET G2 in select patients.

Abstract Background Limited data describe the therapeutic practice and outcomes of colorectal liver metastases (CRLMs) in elderly patients. We aimed to evaluate the impact of age on multidisciplinary treatment for CRLMs. Methods We reviewed treatment and outcomes for patients in different age groups who underwent initial hepatectomy for CRLMs from 2004 through 2012. Results We studied 462 patients who were divided into three groups by age: ≤ 64 years (n = 265), 65–74 years (n = 151), and ≥ 75 years (n = 46). The rate of major hepatectomy and incidence of postoperative complications did not differ between groups. Adjuvant chemotherapy was used less in the ≥ 75-year group (19.6%) than that in the ≤ 64 (54.3%) or 65–74 age group (43.5%). Repeat hepatectomy for liver recurrence was performed less in the ≥ 75-year group (35%) than in the ≤ 64 (57%) or 65–74 (66%) age group. The 5-year disease-specific survival (DSS) rate of 44.2% in the ≥ 75-year group was lower than in the ≤ 64 (59.0%) or 65–74 (64.7%) age group. Multivariate analysis revealed age ≥ 75 years was an independent predictor of poor DSS. Conclusions Liver resection for CRLMs can be performed safely in elderly patients. However, repeat resection for recurrence are performed less frequently in the elderly, which may lead to the poorer disease-specific prognosis.

Objective:. We hypothesized that preoperatively planned portal vein resection (PVR), which prevents from approaching tumors, improves survival in patients with resectable pancreatic head cancer adjacent to the portal vein (PhC-PV). Summary:. The decision to perform PVR is difficult in patients with resectable PhC-PV. Methods:. This is a retrospective, bi-institutional study of patients undergoing pancreatoduodenectomy (PD) for resectable PhC-PV from 2009 to 2018. We compared clinical data of patients who underwent PD with preoperatively planned PVR (planned PVR group) and those who underwent conventional PD (cPD) in which decision to perform PVR was made intraoperatively (cPD group). Results:. Among the study population of 176 patients, 53 patients (30.1%) underwent PD with planned PVR. The remaining 123 patients (69.9%) underwent cPD. Tumor characteristics were similar between the 2 groups. Operation time and major complication rates did not differ between the 2 groups. The local recurrence rate of patients in the planned PVR group (28.3%) was lower than that of the cPD group (44.7%; P = 0.041). Median overall survival (OS) was longer in the planned PVR group than in the cPD group (32 vs 27 months; P = 0.011). Multivariate analysis revealed that having undergone planned PVR was an independent factor for favorable OS (hazard ratio = 1.65; 95% confidence interval = 1.08–2.61; P = 0.021). Conclusions:. The preoperative decision to perform PVR improves survival by enhancing local control of resectable PhC-PV.

Abstract Background There are no optimal indication criteria for neoadjuvant chemotherapy (NAC) in patients with resectable colorectal liver metastases (CLM). The aim of this study was to prospectively assess the survival benefit of selective NAC administration in this patient population based on tumor characteristics. Methods Borderline resectable CLM (BR-CLM) were defined as four or more liver metastases, CLM larger than 5 cm, or CLM with concomitant resectable extrahepatic metastases. From 2010 to 2015, NAC was administered to BR-CLM patients. Upfront surgery without NAC was performed to patients having clearly resectable CLM (less than 3 lesions, smaller than 5 cm, and no extrahepatic metastases: CR-US group). Survival outcomes of the two groups were assessed. Results The BR-NAC group comprised 73 patients and the CR-US group 172. All patients in the BR-NAC group underwent subsequent resection, as none showed disease progression or chemotherapy-associated liver damage. The 3- and 5-year overall survival rates of the CR-US group were 83.0% and 74.0%, while patients in the BR-NAC group had comparable 3-year and 5-year overall survivals (80.5% and 66.6%, P = 0.397). Conclusion Defining BR-CLM based on tumor characteristics optimizes patient selection for NAC. Favorable overall survival can be achieved by upfront surgery in patients with clearly resectable CLM and by NAC in patients with BR-CLM.

Non-alcoholic fatty liver disease (NAFLD) is a progressive disorder that can develop into liver fibrosis and hepatocellular carcinoma. Natural killer (NK) cells have been shown to protect against liver fibrosis and tumorigenesis, suggesting that they may also play a role in the pathogenesis of NAFLD. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of inhibitory and activating receptors expressed by many cell types, including NK cells. Here, we investigated the phenotypic profiles of peripheral blood and intrahepatic NK cells, including expression of Siglecs and immune checkpoint molecules, and their association with NK cell function in patients with NAFLD. Immune cells in the peripheral blood of 42 patients with biopsy-proven NAFLD and 13 healthy volunteers (HVs) were identified by mass cytometry. The function of various NK cell subpopulations was assessed by flow cytometric detection of intracellular IFN-γ and CD107a/LAMP-1, a degranulation marker, after in vitro stimulation. We found that peripheral blood from NAFLD patients, regardless of fibrosis stage, contained significantly fewer total CD56+ NK cell and CD56dim NK cell populations compared with HVs, and the CD56dim cells from NAFLD patients were functionally impaired. Among the Siglecs examined, NK cells predominantly expressed Siglec-7 and Siglec-9, and both the expression levels of Siglec-7 and Siglec-9 on NK cells and the frequencies of Siglec-7+CD56dim NK cells were reduced in NAFLD patients. Notably, Siglec-7 levels on CD56dim NK cells were inversely correlated with PD-1, CD57, and ILT2 levels and positively correlated with NKp30 and NKp46 levels. Further subtyping of NK cells identified a highly dysfunctional Siglec-7−CD57+PD-1+CD56dim NK cell subset that was increased in patients with NAFLD, even those with mild liver fibrosis. Intrahepatic NK cells from NAFLD patients expressed elevated levels of NKG2D and CD69, suggesting a more activated phenotype than normal liver NK cells. These data identify a close association between NK cell function and expression of Siglec-7, CD57, and PD-1 that could potentially be therapeutically targeted in NAFLD.

BackgroundTechnical proficiency of the operating surgeons is one of the most important factors in the safe performance of pancreaticoduodenectomy. The objective of the present study was to investigate whether surgical simulation of pancreatico-jejunostomy (PJ) using an inanimate biotissue model could improve the technical proficiency of hepato-biliary pancreatic (HBP) surgical fellows.MethodsThe biotissue drill consisted of sewing biotissues to simulate PJ. The drill was repeated a total of five times by each of the participant surgical fellows. The improvement of the surgical fellows' technical proficiency was evaluated by the supervisor surgeons using the Objective Structured Assessment of Technical Skills (OSATS) scale.ResultsEight HBP surgical fellows completed all the 5 drills. Both the OSATS 25 score and OSATS summary score, assessed by the two supervisor surgeons, improved steadily with repeated execution of the PJ drill. The average OSATS score, as assessed by both the supervisor surgeons, improved significantly from the first to the final drill, with a P value of 0.003 and 0.014 for the assessment by the two surgeons, respectively. On the other hand, no chronological alteration was observed in time of procedure (P = 0.788).ConclusionRepeated execution of a biotissue PJ drill improved the HBP surgical fellows' technical proficiency, as evaluated by OSATS. The present study lends support to the evidence that simulation training can contribute to shortening of the time required to negotiate the learning curve for the technique of PJ in the actual operating room.

Abstract Background The prognostic biomarker for patients undergoing curative liver metastasectomy for colorectal cancer (CRC) is lacking. The purpose was to investigate the prognostic role of a lack of CDX2 expression, which has been proposed as a potential biomarker for high-risk relapse in early-stage CRC, in patients undergoing curative liver metastasectomy. Methods A total of 396 consecutive patients with CRC liver metastasis who underwent potentially curative liver metastasectomy at a single center in Japan between 2005 and 2015 were included. For the immunohistochemical analysis of nuclear CDX2 expression, we adopted the tissue microarray approach using the resected metastatic liver CRCs. Patient subgroups were compared with respect to disease-free survival (DFS) and overall survival (OS) by applying the Kaplan-Meier curve, log-rank tests, and multivariate analyses based on the Cox proportional hazards method. OS is defined as the period from the date of curative liver resection for metastatic CRC until death. DFS is defined as the length of time from curative liver resection to either the first recurrence or death. In patients without recurrence, the latest imaging inspection date was used as the censored date. Results Thirty-six of the 396 CRCs (9.1%) reduced CDX2 expression. The reduced expression of CDX2 was associated with poor differentiation (P = 0.02). DFS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median DFS: 245 days versus 420 days; hazard ratio for disease recurrence: 1.64; 95% confidence interval: 1.08–2.38; P = 0.02). OS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median OS: 1024 days versus 3145 days; hazard ratio: 2.41; 95% confidence interval: 1.52–3.85; P

Abstract Background Postoperative pancreatic fistula (PF) is the main cause of operative mortality in patients who undergo pancreatoduodenectomy. Various pancreatoenteric anastomosis techniques have been reported to minimize the postoperative PF rate. However, the optimal method remains unknown. This study was performed to clarify the impact of pancreatojejunostomy on clinically relevant PF (CR-PF) between Blumgart anastomosis and Kakita anastomosis in patients with a soft pancreas. Methods In total, 620 consecutive patients underwent pancreatoduodenectomy at our institute from January 2010 to December 2016, and 282 patients with a soft pancreas were analyzed (Blumgart anastomosis, n = 110; Kakita anastomosis, n = 176). Short-term outcomes were assessed, and univariate and multivariate analyses of several clinicopathological variables were performed to analyze factors affecting the incidence of CR-PF. Results The CR-PF rate was 42.7% (122/286). The CR-PF rate was not significantly different between the Blumgart and Kakita groups (42.7% and 42.6%, respectively; p = 0.985). The morbidity rate (Clavien–Dindo grade ≥ IIIa) was 24.5% (70/286), and the operation-related mortality rate was 0.7% (2/286). In the multivariate analysis, male sex (p = 0.0245) and a body mass index of ≥22 kg/m2 (p

Pathological assessments of the treatment effect are critical for predicting patient outcomes after surgery. This study included 82 localized pancreatic cancer, 40 of whom were treated with neoadjuvant therapy (NAT) using four courses of gemcitabine plus nab-paclitaxel (GnP) followed by pancreatectomy (GnP group). The remaining 42 patients were treated with upfront pancreatectomy (UP) followed by adjuvant chemotherapy (UP group). We reviewed clinicopathological data of these patients to assess differences between the GnP and UP groups and further evaluate the prognostic impact of residual tumors after GnP treatment. Adjuvant treatment (S1, GnP or gemcitabine) was administered for 36 patients in the GnP group and 33 patients in the UP group. Compared to the UP group, the GnP group showed lower serum CA19-9 levels, microscopic tumor volume, and tumor-stroma ratio and decreased number of lymph node metastasis and vascular invasion. Higher incidence of encapsulating fibrosis was observed in the GnP group than in the UP group. Relative to the UP group (69%), a higher R0 rate was observed in the GnP group (85%). As for prognosis, encapsulating fibrosis was correlated with the overall survival of patients in the GnP group. However, overall survival did not show any correlation with other clinicopathological factors, including tumor reduction ratio (determined by computed tomography) and tumor regression grade (determined following criteria of Evans' grading system or those of the College of American Pathologists). In conclusion, the present study revealed that GnP-induced encapsulating fibrosis could predict patients' outcome. Nevertheless, large cohort studies are warranted to further evaluate the prognostic value of fibrosis, possibly with the help of imaging and biomarkers.

An amendment to this paper has been published and can be accessed via the original article.

The high recurrence rate after surgery for colorectal cancer liver metastasis (CLM) remains a crucial problem. The aim of this trial was to evaluate the efficacy of adjuvant therapy with uracil-tegafur and leucovorin (UFT/LV).In the multicenter, open-label, phase III trial, patients undergoing curative resection of CLM were randomly assigned in a 1:1 ratio to either the UFT/LV group or surgery alone group. The UFT/LV group orally received 5 cycles of adjuvant UFT/LV (UFT 300mg/m2 and LV 75mg/day for 28 days followed by a 7-day rest per cycle). The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included overall survival (OS).Between February 2004 and December 2010, 180 patients (90 in each group) were enrolled into the study. Of these, 3 patients (2 in the UFT/LV group and 1 in the surgery alone group) were excluded from the efficacy analysis. Median follow-up was 4.76 (range, 0.15-9.84) years. The RFS rate at 3 years was higher in the UFT/LV group (38.6%, n = 88) than in the surgery alone group (32.3%, n = 89). The median RFS in the UFT/LV and surgery alone groups were 1.45 years and 0.70 years, respectively. UFT/LV significantly prolonged the RFS compared with surgery alone with the hazard ratio of 0.56 (95% confidence interval, 0.38-0.83; P = 0.003). The hazard ratio for death of the UFT/LV group against the surgery alone group was not significant (0.80; 95% confidence interval, 0.48-1.35; P = 0.409).Adjuvant therapy with UFT/LV effectively prolongs RFS after hepatic resection for CLM and can be recommended as an alternative choice.UMIN Clinical Trials Registry C000000013.