内田 雄一郎

BACKGROUND: Although minimally invasive distal pancreatectomy (MIDP) is considered a standard approach it still presents a non-negligible rate of conversion to open that is mainly related to some difficulty factors, as obesity. The aim of this study is to analyze the preoperative factors associated with conversion in obese patients with MIDP. METHODS: In this multicenter study, all obese patients who underwent MIDP at 18 international expert centers were included. The preoperative factors associated with conversion to open surgery were analyzed. RESULTS: Out of 436 patients, 91 (20.9%) underwent conversion to open, presenting higher blood loss, longer operative time and similar rate of major complications. Twenty (22%) patients received emergent conversion. At univariate analysis, the type of approach, radiological invasion of adjacent organs, preoperative enlarged lymphnodes and ASA ≥ III were significantly associated with conversion to open. At multivariate analysis, robotic approach showed a significantly lower conversion rate (14.6 % vs 27.3%, OR = 2.380, p = 0.001). ASA ≥ III (OR = 2.391, p = 0.002) and preoperative enlarged lymphnodes (OR = 3.836, p = 0.003) were also independently associated with conversion. CONCLUSION: Conversion rate is significantly lower in patients undergoing robotic approach. Radiological enlarged lymphnodes and ASA ≥ III are also associated with conversion to open. Conversion is associated with poorer perioperative outcomes, especially in case of intraoperative hemorrhage.

BACKGROUND: The optimal approach for the safe implementation and education of robotic pancreaticoduodenectomy (RPD) remains unclear. Prolonged operation time may cause surgeon fatigue and result in perioperative complications. To solve this issue, our department adopted task division by the console surgeon turnover between resection and reconstruction in 2022. METHODS: This study retrospectively investigated consecutive patients who underwent RPD from November 2009 (initial introduction of RPD) to December 2023. The analysis excluded patients who underwent concomitant resection of other organs. The cases performed by a single console surgeon (single approach) were compared with those performed by two or more console surgeons (multiple approach). RESULTS: This study analyzed 85 consecutive RPD cases, including 51 with the single approach and 34 with the multiple approach. The operation time was significantly shorter (832 vs. 618 min, p < 0.001), and the postoperative major complication was less frequent (45% vs. 12%, p = 0.003) in the multiple approach group, although less experienced surgeons performed the multiple approach (number of RPD experiences: 19 cases vs. 5 cases, p < 0.001). The console surgeon turnover between the resection and reconstruction resulted in a safe pancreatojejunostomy performed by the less experienced surgeon (number of pancreatic reconstruction experiences: 6.5 vs. 14 cases, p = 0.010). Surgeons who started RPD with a multiple approach observed a reduction in surgical time and a lower incidence of complications earlier than those who started with a single approach. CONCLUSION: Task division during the early introduction phase of RPD using the multiple approach demonstrated potential contributions to improved surgical outcomes and enhanced educational benefits.

BACKGROUNDS: Pancreatojejunostomy is a technically demanding procedure during robotic pancreaticoduodenectomy (RPD). Modified Blumgart anastomosis (mBA) is a common method for the pancreatojejunostomy; however, the technical details for robotic mBA are not well established. During RPD, we performed a mBA for the pancreatojejunostomy using thread manipulation with gauze and an additional assist port. METHODS: Patients who underwent robotic pancreatoduodenectomy at Fujita Health University from November 2009 to May 2023 were retrospectively investigated, and technical details for the robotic-modified Blumgart anastomosis were demonstrated. RESULTS: Among 78 patients who underwent RPD during the study period, 33 underwent robotic mBA. Postoperative pancreatic fistula (POPF) occurred in six patients (18%). None of the patients suffered POPF Grade C according to the international study group of pancreatic surgery definition. The anastomotic time for mBA was 80 min (54-125 min). CONCLUSION: Robotic mBA resulted in reasonable outcomes. We propose that mBA could be used as one of the standard methods for robotic pancreatojejunosotomy.

Robotic distal pancreatectomy (RDP) has emerged as a minimally invasive approach to left-sided pancreatic tumors. This study aimed to evaluate the efficacy of the robot-assisted approach (RAA) using a laparoscopic articulating vessel-sealing device (LAVSD) during RDP by comparing it with the pure-robotic approach (PRA). Among 62 patients who underwent RDP between April 2020 and December 2023 at Fujita Health University, 22 underwent RAA (the RAA group). In RAA, console surgeons mainly prepared the surgical fields, and assistant surgeons actively dissected the adipose and connective tissues using LAVSD. The surgical outcomes of these patients were compared with those of 40 consecutive patients who underwent RDP with PRA. In total, 28 males and 34 females with a median age of 71 years were analyzed. The console surgeon's prior experience of performing RDP was similar between the groups (RAA; median, 6 [range, 0-36], PRA; median, 5.5 [range, 0-34] cases). The operation time was significantly shorter in the TST group (median, 300.5 [range, 202-557] vs. 363.5 [range, 230-556] min, p = 0.015). Major complications (Clavien-Dindo ≥ grade 3a) occurred less frequently in the RAA group (4.6% vs. 25.0%, p = 0.028). Although the median postoperative hospital stay was slightly shorter in the RAA group (median, 12 [range, 8-38] vs. 14.5 [8-44] days, p = 0.095), no statistically significant difference was observed. Compared with PRA, RAA using LAVSD is found to be safe and feasible in introducing RDP for operators with little experience.

BACKGROUND: Robotic pancreaticoduodenectomy (RPD) is technically demanding, and 20-50 cases are required to surpass the learning curve. This study aimed to show our experience of 76 cases from the introduction of RPD and report the changes in surgical results owing to the accumulation of cases and optimization of surgical techniques. METHODS: A total of 76 patients who underwent RPD between November 2009 and May 2023 at the Fujita Health University Hospital were divided into three groups: competency (n = 23, Nov 2009-Mar 2020), proficiency (n = 31, Apr 2020-Jun 2022), and mastery (n = 22, Jul 2022-May 2023) phases. In the mastery phase, for the education of new surgeons and maintenance of surgical quality, optimization of the procedure, including hanging maneuver with or without stapling transection of the retropancreatic tissue was implemented. The surgical outcomes were compared between the groups. RESULTS: The mean operation time decreased over time despite of the participation of newly started operators in mastery phase [competency: 921.5 min (IQR 775-996 min) vs. proficiency: 802.8 min (IQR 715-887 min) vs. mastery: 609.2 min (IQR 514-699 min), p < 0.001]. Additionally, Clavien-Dindo ≥ grade IIIa complications decreased from 52.2% in competency phase to 35.5% and 9.1% in proficiency and mastery phases, respectively (p = 0.005). CONCLUSION: Operation time and major complications decreased along the learning curve from the introduction of RPD. In addition, optimization of the procedure, including hanging maneuver of the retropancreatic tissue seemed to be effective in reducing operation time and educating new RPD surgeons.

Pancreatic tumor enucleation is a procedure that can preserve pancreatic function and is sometimes performed using a minimally invasive approach. Recently, a single-port robotic platform called da Vinci SP has been developed. However, the technical details of pancreatic tumor enucleation using da Vinci SP have not been reported to date. We report a male patient in his 70s who underwent robotic SP pancreatic tumor enucleation for a pancreatic neuroendocrine tumor. The dissection between the tumor and pancreatic parenchyma was performed using the double bipolar technique. The operative time was 139 min, and the estimated blood loss was 4 mL. The patient had an uneventful recovery and was discharged on the sixth day after the surgery. Robotic SP pancreatic tumor enucleation appears to be a feasible procedure with lower invasiveness and better cosmesis.

BACKGROUND: Although robotic distal pancreatectomy (RDP) has a lower conversion rate to open surgery and causes less blood loss than laparoscopic distal pancreatectomy (LDP), clear evidence on the impact of the surgical approach on morbidity is lacking. Prior studies have shown a higher rate of complications among obese patients undergoing pancreatectomy. The primary aim of this study is to compare short-term outcomes of RDP vs. LDP in patients with a BMI ≥ 30. METHODS: In this multicenter study, all obese patients who underwent RDP or LDP for any indication between 2012 and 2022 at 18 international expert centers were included. The baseline characteristics underwent inverse probability treatment weighting to minimize allocation bias. RESULTS: Of 446 patients, 219 (50.2%) patients underwent RDP. The median age was 60 years, the median BMI was 33 (31-36), and the preoperative diagnosis was ductal adenocarcinoma in 21% of cases. The conversion rate was 19.9%, the overall complication rate was 57.8%, and the 90-day mortality rate was 0.7% (3 patients). RDP was associated with a lower complication rate (OR 0.68, 95% CI 0.52-0.89; p = 0.005), less blood loss (150 vs. 200 ml; p < 0.001), fewer blood transfusion requirements (OR 0.28, 95% CI 0.15-0.50; p < 0.001) and a lower Comprehensive Complications Index (8.7 vs. 8.9, p < 0.001) than LPD. RPD had a lower conversion rate (OR 0.27, 95% CI 0.19-0.39; p < 0.001) and achieved better spleen preservation rate (OR 1.96, 95% CI 1.13-3.39; p = 0.016) than LPD. CONCLUSIONS: In obese patients, RDP is associated with a lower conversion rate, fewer complications and better short-term outcomes than LPD.

BACKGROUND ＆ AIMS: Optimizing treatments balancing prognosis and therapeutic invasiveness is important in the management of pancreatic cancer (PC) owing to global ageing. This study aimed to verify the different utility of biomarkers by patients' age. MATERIALS ＆ METHODS: This is a single-center, retrospective cohort analysis involving 160 patients who undertook pancreaticoduodenectomy (PD) for PC. After comparing clinicopathological factors and survival after PD between aged (≥70 y/o) and young (＜70 y/o) patients, we compared neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), controlling nutrition (CONUT) score, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 as well as clinicopathological factors between long and short survivors in each group. We also performed Kaplan-Meyer analysis between patients stratified by biomarkers. RESULTS: Overall survival (OS) was significantly worse in aged patients (p = 0.002). In aged patients, CEA was significantly higher in short survivors. In young patients, CONUT score and CA19-9 were higher in short survivors. Kaplan-Meyer analysis showed that NLR and CEA stratified OS in aged patients, whereas CONUT score and CA19-9 could stratify OS in young patients. CONCLUSION: Our current results suggest that these biomarkers had different impact on survivals according to the patients' age.

Robotic surgery has technical advantages including high optical magnification and articulation of forceps. However, the surgical field tends to be narrow due to the high magnification, and the forceps have no tactile sensation. A case of severe intraoperative bleeding from the splenic artery during robotic distal pancreatectomy is presented, with a video. A man in his 80s with a cystic tumor located at the pancreatic tail underwent robotic distal pancreatectomy. During mobilization of the pancreatic tail by an inferior approach, the root of the splenic artery was injured by the joints of the robotic instruments located outside the surgical field and the bleeding became uncontrollable under the robotic operation. It is important to always be aware of what the forceps are in contact with outside the surgical field. While dissecting the left subdiaphragmatic area in robotic distal pancreatectomy, the root area of splenic artery tends to be outside the surgical field. More attention should be paid to the positional relationship between the forceps trajectory and the major blood vessels by checking the surgical field from a distant view on a regular basis.

Surgical techniques and outcomes of minimally invasive anatomic liver resection (AR) using the extrahepatic Glissonian approach for hepatocellular carcinoma (HCC) are undefined. In 327 HCC cases undergoing 185 open (OAR) and 142 minimally invasive (MIAR; 102 laparoscopic and 40 robotic) ARs, perioperative and long-term outcomes were compared between the approaches, using propensity score matching. After matching (91:91), compared to OAR, MIAR was significantly associated with longer operative time (643 vs. 579 min, p = 0.028); less blood loss (274 vs. 955 g, p < 0.0001); a lower transfusion rate (17.6% vs. 47.3%, p < 0.0001); lower rates of major 90-day morbidity (4.4% vs. 20.9%, p = 0.0008), bile leak or collection (1.1% vs. 11.0%, p = 0.005), and 90-day mortality (0% vs. 4.4%, p = 0.043); and shorter hospital stay (15 vs. 29 days, p < 0.0001). On the other hand, laparoscopic and robotic AR cohorts after matching (31:31) had comparable perioperative outcomes. Overall and recurrence-free survivals after AR for newly developed HCC were comparable between OAR and MIAR, with potentially improved survivals in MIAR. The survivals were comparable between laparoscopic and robotic AR. MIAR was technically standardized using the extrahepatic Glissonian approach. MIAR was safe, feasible, and oncologically acceptable and would be the first choice of AR in selected HCC patients.

The diagnosis of bile duct tumors can be difficult at times. A transpapillary bile duct biopsy findings with endoscopic retrograde cholangiopancreatography sometimes contradict diagnostic imaging findings. In bile duct tumors, inflammatory polyps in the extrahepatic bile duct are relatively rare with extrahepatic cholangitis. The disease's clinical relevance, including its natural history and prognosis, is not always clear. We show here a rare case of an inflammatory polyp in the common bile duct. A 69-year-old woman with abdominal pain was diagnosed with cholangitis. The findings of contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography suggested that she had extrahepatic cholangiocarcinoma. The examination and therapy of cholangitis were performed by endoscopic retrograde cholangiopancreatography. The cholangiography revealed a suspected tumor in the hilar bile duct with some common bile duct stones. Then, after endoscopic sphincterotomy to remove tiny common bile duct stones, further detailed examinations were performed at the same time using an oral cholangioscope revealed a papillary raised lesion with a somewhat white surface in the bile duct; a biopsy was conducted on the same spot, and epithelial cells with mild atypia appeared in the shape of a papilla. Since the malignant tumor or the intraductal papillary neoplasm of the bile duct could not be ruled out, extrahepatic bile duct resection was conducted with the patient's informed consent. Bile duct inflammatory polyp was the histopathological diagnosis.

BACKGROUND/PURPOSE: Surgical outcomes and utility of robotic liver resection (RLR) are undefined. METHODS: We retrospectively studied perioperative and long-term outcomes of the single-center 120 RLRs including non-anatomic (NAR, n = 58) and anatomic (AR, n = 62) resections. To evaluate the feasibility and safety of RLR, perioperative outcomes of RLR (n = 103) were compared to those of open (OLR, n = 495) or laparoscopic (LLR, n = 451) resection in liver-only resections without reconstruction, using 1:1 propensity score matching (PSM). The changing trends from the earlier to the later RLR cases were assessed. Long-term outcomes were compared between RLR and LLR. RESULTS: Various types of RLR with different surgical difficulties were performed, with mostly comparable postoperative morbidity between AR and NAR, or among AR subtypes. In segmentectomy and sectionectomy cases, perioperative outcomes significantly improved in the later period. In comparison between PSM-selected OLR and RLR cases (87:87), RLR had significantly longer operative time, less blood loss, and shorter hospital stay. PSM-selected LLR and RLR cases (91:91) showed comparable perioperative outcomes. Overall and recurrence-free survivals after RLR for newly diagnosed hepatocellular carcinoma and colorectal metastasis were comparable to those after LLR. CONCLUSIONS: RLR is applicable to various types of liver resection with acceptable perioperative and long-term outcomes in select patients.

BACKGROUND: Conventional open distal pancreatectomy with en bloc celiac axis resection (DP-CAR) using the ventral approach is technically challenging, highly invasive, and not easy to ensure ample dorsal surgical margins. Hence, we describe a novel minimally invasive strategy for DP-CAR using the retroperitoneal-first laparoscopic approach (Retlap), i.e., Retlap DP-CAR, for locally advanced pancreatic body cancer (LAPC), and assess its utility. METHODS: Retlap DP-CAR was performed in 10 patients with LAPC that was categorized as either unresectable (UR-LA, n = 4) or borderline (BR-A, n = 6). Neoadjuvant chemotherapy was applied on 8 patients and upfront surgery on 2. Retlap was used to create a working space in the retroperitoneal cavity between the pancreatic body and the left kidney and confirm technical resectability, such as securing the celiac axis and preserving the superior mesenteric artery in an early operative stage. Retlap DP-CAR was laparoscopic in 8 patients and robotic in 2. Surgical procedures are directly manipulated from the dorsal side of the pancreas and tumor, facilitating confirmation of technical resectability and obtaining ample dorsal margins in a no-touch isolation approach. Once technical resectability was confirmed, the procedure was converted to the ventral approach for completing DP-CAR. RESULTS: Median operating time and blood loss during Retlap were 271 min and 10 mL, respectively, while median resection time and intraoperative blood loss were 582 min and 412 mL, respectively. Tumor-free resection margins were obtained in all cases. The major morbidity rate (C-D > IIIa) was 10%. No mortality was recorded within 90 days. Median overall survival was 53.8 months [95% confidence interval 32.7-75.0]. CONCLUSIONS: Retlap DP-CAR is a novel minimally invasive procedure for resecting LAPC located close to the celiac axis. It is both safe and feasible, enables determination of technical resectability, achieves dorsal surgical margins, and can improve outcomes and QOL in patients with LAPC.

PURPOSE: Anatomic isolated liver segmentectomy 8 (ILSeg8) for malignancies remains technically challenging. The feasibility, safety, and oncologic validity of laparoscopic ILSeg8 are undefined, and thus were evaluated in comparison with the open approach. METHODS: This study enrolled 35 open and 29 laparoscopic ILSeg8 cases of hepatocellular carcinoma (n = 47), metastatic liver tumors (n = 16), and intrahepatic cholangiocarcinoma (n = 1) at our institution. The surgical techniques were based on the pre-hepatectomy extrahepatic Glissonian pedicle control, followed by cranial-to-caudal parenchymal dissection from the hepatic vein root side. The short- and long-term outcomes after ILSeg8 were retrospectively evaluated and compared between the open and laparoscopic approaches using 1:1 propensity score matching (PSM). RESULTS: Both before and after PSM, the laparoscopic ILSeg8 group had significantly less blood loss, lower postoperative serum bilirubin level, and a shorter postoperative hospital stay than the open group. The overall survival rates were comparable between the laparoscopic and open groups before (P = 0.017) and after (P = 0.043) PSM, with the similar recurrence-free survival rates between the groups. In a multivariable analysis of the cohort before PSM (n = 64), the laparoscopic approach was identified to be an independent factor for favorable overall survival (hazard ratio = 0.20, P = 0.039). CONCLUSION: Laparoscopic ILSeg8 using the extrahepatic Glissonian approach and hepatic vein root at first parenchymal dissection was feasible, safe, and oncologically acceptable. In ILSeg8 for malignancy, the laparoscopic approach potentially confers short-term advantages over the open approach with comparable long-term outcomes in select patients.

BACKGROUND: Borderline resectable pancreatic cancer (BRPC) is a category of pancreatic cancer that is anatomically widely spread, and curative resection is uncommon with upfront surgery. Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that delivers precise radiation to a tumor while minimizing the dose to surrounding normal tissues. Here, we conducted a phase 2 study to estimate the curability and efficacy of neoadjuvant chemoradiotherapy using IMRT (NACIMRT) for patients with BRPC with arterial abutment (BRPC-A). METHODS: A total of 49 BRPC-A patients were enrolled in this study and were treated at our hospital according to the study protocol between June 2013 and March 2021. The primary endpoint was microscopically margin-negative resection (R0) rates and we subsequently analyzed safety, histological effect of the treatment as well as survivals among patients with NACIMRT. RESULTS: Twenty-nine patients (59.2%) received pancreatectomy after NACIMRT. The R0 rate in resection patients was 93.1% and that in the whole cohort was 55.1%. No mortality was encountered. Local therapeutic effects as assessed by Evans classification showed good therapeutic effect (Grade 1, 3.4%; Grade 2a, 31.0%; Grade 2b, 48.3%; Grade 3, 3.4%; Grade 4, 3.4%). Median disease-free survival was 15.5 months. Median overall survival in the whole cohort was 35.1 months. The only independent prognostic pre-NACIMRT factor identified was serum carbohydrate antigen 19-9 (CA19-9) > 400 U/ml before NACIMRT. CONCLUSIONS: NACIMRT showed preferable outcome without significant operative morbidity for BRPC-A patients. NACIMRT contributes to good local tumor control, but a high initial serum CA19-9 implies poor prognosis even after neoadjuvant treatment. TRIAL REGISTRATION: UMIN-CTR Clinical Trial: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011776 Registration number: UMIN000010113. Date of first registration: 01/03/2013.

BACKGROUND: /Objectives: Although the presence of lymph node metastasis (LNM) defines malignant potential, preoperative prediction of LNM has not been established for non-functional pancreatic neuroendocrine neoplasm (NF-PNEN). We sought to develop a prediction system using only preoperatively available factors that would stratify the risk of LNM for NF-PNEN. METHODS: We retrospectively reviewed patients who underwent R0/1 resection of NF-PNEN at Kyoto University (2007-2019) and the University of California, San Francisco (2010-2019). Risk stratification of LNM was developed using preoperative factors by the logistic regression analysis. Long-term outcomes were compared across the risk groups. RESULTS: A total of 131 patients were included in this study. Lymph nodes were pathologically examined in 116 patients, 23 (20%) of whom had LNM. Radiological tumor size [1.5-3.5 cm (odds ratio: 13.5, 95% confidence interval: 1.77-398) and >3.5 cm (72.4, 9.06-2257) against ≤1.5 cm], <50% cystic component (8.46 × 10^6, 1.68 × 10^106-), and dilatation of main pancreatic duct ≥5 mm (31.2, 3.94-702) were independently associated with LNM. When patients were classified as the low-risk (43 patients), intermediate-risk (44 patients), and high-risk groups (29 patients), proportions of LNM differed significantly across the groups (0%, 14%, and 59%, respectively). Recurrence-free survival (RFS) of the low- and intermediate-risk groups were significantly better than that of the high-risk group (5-year RFS rates of 92.2%, 85.4%, and 47.1%, respectively). CONCLUSIONS: The prediction system using preoperative radiological factors stratifies the risk of LNM for NF-PNEN. This stratification helps to predict malignant potential and determine the surgical procedure and necessity of regional lymphadenectomy.

BACKGROUND: Minimally invasive pancreaticoduodenectomy (MIPD), including laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD), is technically demanding because of pancreaticojejunostomy (PJ). Postoperative pancreatic fistula (POPF) is the most serious complication of MIPD and open pancreaticoduodenectomy (OPD). Contrary to expectations, conventional PJ in MIPD did not improve POPF rate and length of hospital stay. High POPF rates are attributed to technical issues encountered during MIPD, which include motion restriction and insufficient water tightness. Therefore, we developed wrapping double-mattress anastomosis, the Kiguchi method, which is a novel PJ technique that can improve MIPD. Herein, we describe the Kiguchi method for PJ in MIPD and compare the outcomes between this technique and conventional PJ in OPD. METHODS: The current retrospective study included 83 patients in whom the complete obstruction of the main pancreatic duct by pancreatic tumors was absent on preoperative imaging. This research was performed from September 2016 to August 2020 at Fujita Health University Hospital. All patients were evaluated as having a soft pancreatic texture, which is the most important factor associated with POPF development. Briefly, 50 patients underwent OPD with conventional PJ (OPD group). Meanwhile, 33 patients, including 15 and 18 who had LPD and RPD, respectively, underwent MIPD using the Kiguchi method (MIPD group). After a 1:1 propensity score matching, 30 patients in the OPD group were matched to 30 patients in the MIPD group. RESULTS: The patients' preoperative data did not differ. The grade B/C POPF rate was significantly lower in the MIPD group than in the OPD group (6.7% vs 40.0%, p = 0.002). The MIPD group had a significantly shorter median length of hospital stay than the OPD group (24 vs 30 days, p = 0.004). CONCLUSION: The novel Kiguchi method in MIPD significantly reduced the POPF rate in patients without complete obstruction of the main pancreatic duct.

BACKGROUND: Although duodenal neuroendocrine neoplasms (DuNENs) usually have indolent phenotypes, some DuNENs exhibit aggressive clinical manifestations. Tumor size > 1 cm, lymph node metastasis, and high grade have been associated with poor prognosis. However, preoperative risk evaluation is often difficult, because Ki-67 index on biopsy is frequently underestimated due to the intratumor heterogeneity. Here, we present a case of a subcentimeter DuNEN with a low Ki-67 index on endoscopic biopsy, who developed lymph node metastasis and high-grade liver metastasis. CASE PRESENTATION: The patient was a 52-year-old female who presented an epigastric pain. Esophagogastroduodenoscopy revealed a duodenal submucosal lesion with a size of 8 mm. The endoscopic biopsy showed DuNEN with a Ki-67 index of 3.3% (G2 categorized by the World Health Organization 2019 classification). We performed an open partial duodenectomy with adjacent lymph node dissection. Pathological examination of the resected specimens revealed a Ki-67 index of 13.5% (G2) in the "hot spot" and lymph node metastasis. A hepatic low-density area detected on preoperative contrast-enhanced computed tomography appeared to be a liver metastasis on postoperative gadoxetic acid-enhanced magnetic resonance imaging. Subsequently, we performed a laparoscopic partial hepatectomy. Pathological examination of the liver specimen showed a metastatic neuroendocrine tumor with a Ki-67 index of 27.5% (NET-G3). The patient has been alive for 14 months since the hepatectomy. CONCLUSIONS: This case shows the possibility of high malignant potential of DuNEN even if the primary lesion is < 1 cm and has a low Ki-67 index on biopsy.

BACKGROUND: Acute obstruction of the hepatic vein (HV) or the portal vein (PV), particularly when it occurs during liver surgery, is potentially fatal unless repaired swiftly. As surgical interventions for this problem are technically demanding and potentially unsuccessful, other treatment options are needed. CASE PRESENTATION: We report two cases of acute, surgically uncorrectable HV or PV obstruction during liver resection or living donor liver transplantation (LDLT), which was successfully treated with urgent intraoperative placement of endovascular stents using interventional radiology (IVR). In Case 1, a patient with colonic liver metastases underwent a non-anatomic partial hepatectomy of the segments 4 and 8 with middle hepatic vein (MHV) resection. Additionally, the patient underwent an extended right posterior sectionectomy with right hepatic vein (RHV) resection for tumors involving RHV. Reconstruction of the MHV was needed to avoid HV congestion of the anterior section of the liver. The MHV was firstly reconstructed by an end-to-end anastomosis between the MHV and RHV resected stumps. However, the reconstruction failed to retain the HV outflow and the anterior section became congested. Serial trials of surgical revisions including re-anastomosis, vein graft interposition and vein graft patch-plasty on the anastomotic wall failed to recover the HV outflow. In Case 2, a pediatric patient with biliary atresia underwent an LDLT and developed an intractable PV obstruction during surgery. Re-anastomosis with vein graft interposition failed to restore the PV flow and elongated warm ischemic time became critical. In both cases, the misalignment in HV or PV reconstruction was likely to have caused flow obstruction, and various types of surgical interventions failed to recover the venous flow. In both cases, an urgent IVR-directed placement of self-expandable metallic stents (SEMS) restored the HV or PV perfusion quickly and effectively, and saved the patients from developing critical conditions. Furthermore, in Cases 1 and 2, the SEMS placed were patent for a sufficient period of time (32 and 44 months, respectively). CONCLUSIONS: The IVR-directed, urgent, intraoperative endovascular stenting is a safe and efficient treatment tool that serves to resolve the potentially fatal acute HV or PV obstruction that occurs in the middle of liver surgery.

BACKGROUND: /Objectives: This study aimed to elucidate the efficacy of CT findings and perioperative characteristics to predict post-pancreatectomy hemorrhage (PPH): a critical complication after pancreaticoduodenectomy. METHODS: The records of 590 consecutive patients who underwent pancreaticoduodenectomy at three institutes between 2012 and 2018 were included. The presence of a vascular wall abnormality or ascites with high density (vascular abnormality) on postoperative day (POD) 5-10 contrast-enhanced CT (early CT), perioperative characteristics, and any PPH or pseudoaneurysm formation (PPH events) were analyzed through a multivariate analysis. RESULTS: PPH events occurred in 48 out of 590 patients (8%). The vascular abnormality on early CT and the C-reactive protein (CRP) value on POD 3 were independent risk factors for PPH events after POD5 (vascular abnormality: odds ratio 6.42, p = 0.001; CRP on POD 3: odds ratio 1.17, p = 0.016). The sensitivity of vascular abnormality for PPH events was 24% (7/29), and the positive predictive value was 30% (7/23). The combination of vascular abnormality and a high CRP value (≥15.5 mg/dL) on postoperative day 3 had a higher positive predictive value of 64% (7/11) than the vascular abnormality alone. None of the seven PPH events that occurred more than one month after surgery were foreseen via early CT. CONCLUSION: The combination of vascular abnormality and high CRP value was associated with increasing risk of PPH events after pancreaticoduodenectomy, but the low sensitivity of early CT must be noted as an important shortcoming. The normal findings on early CT could not eliminate the risk of late PPH.

BACKGROUND AND OBJECTIVES: A postoperative pancreatic fistula (POPF) is a critical complication after surgery for pancreatic cancer. Whether a POPF affects the long-term prognosis of pancreatic cancer cases remains controversial. This study aimed to clarify the effect of a POPF on the long-term prognosis of pancreatic cancer patients, especially after neoadjuvant chemoradiotherapy (NACRT). METHODS: Patients who underwent curative pancreatectomy for pancreatic cancer between January 2012 and June 2019 at Kyoto University Hospital were retrospectively investigated. A fistula ≥ Grade B was considered a POPF. RESULTS: During the study period, 148 patients underwent upfront surgery (Upfront group), and 52 patients underwent surgery after NACRT (NACRT group). A POPF developed in 16% of patients in the Upfront group and 13% in the NACRT group (p = 0.824). In the Upfront group, development of a POPF did not have a significant effect on recurrence-free survival (p = 0.766) or overall survival (p = 0.863). However, in the NACRT group, development of a POPF significantly decreased recurrence-free survival (HR 5.856, p = 0.002) and overall survival (HR 7.097, p = 0.020) on multivariate analysis. CONCLUSIONS: The development of a POPF decreases the survival of pancreatic cancer patients treated by surgery after NACRT.

BACKGROUND: Although 18 F-FDG-PET/CT is a widely used diagnostic tool for several malignancies, its efficacy in diagnosing pancreatic neuroendocrine tumors is reported to be controversial because of the short-term follow-up. METHODS: We retrospectively compared demographics and pathological features between 18 F-FDG-positive and -negative diseases. Additionally, we evaluated whether the avidity of 18 F-FDG-PET/CT affected earlier recurrence after curative treatment of non-functioning tumors. The median duration of observation was 65.6 months. RESULTS: Seventy-two patients were enrolled. 18 F-FDG-positive diseases were pathologically advanced and significantly associated with metastatic behavior. In a multivariate analysis, metastatic behavior and WHO tumor grade was independently associated with 18 F-FDG accumulation. Only 25% of functional tumors (4/16) and 8% of insulinomas (1/12) were 18 F-FDG-positive. In a Kaplan-Meier analysis in patients with non-functioning tumors (n = 56), 18 F-FDG-positivity was significantly correlated with poorer recurrence-free survival (RFS) but had no correlation with overall survival. In univariate analysis of factors associated with shorter RFS, male gender, prevalence of nodal metastasis, WHO tumor grade ≥G2, or 18 F-FDG-positive disease were significantly higher in patients with shorter RFS, whereas only 18 F-FDG-positivity was associated with shorter RFS in multivariate analyses. CONCLUSIONS: The avidity of 18 F-FDG-PET/CT was associated with metastatic behavior of pancreatic neuroendocrine tumors and recurrence after treatment of non-functioning tumors.

Although pancreatic neuroendocrine neoplasms (PanNENs) are generally indolent, patients with distant metastasis have a dismal prognosis. Recently, the autophagy inhibitor chloroquine (CQ) has been shown to suppress the tumour growth of PanNENs, but the detailed mechanisms have not been elucidated. Furthermore, these results were obtained from poorly differentiated cell lines rather than well-differentiated cell lines, which is the most prevalent type in this tumour. To explore the mechanism and efficacy of CQ on PanNENs, we applied CQ to cell lines and evaluated the resulting apoptosis and endoplasmic reticulum (ER) stress. CQ treatment induced ER stress, and an unfolded protein response was activated through the PERK-eIF2α-ATF4 pathway, resulting in the expression of the pro-apoptotic protein C/EBP homologous protein (CHOP), which reflects ER-stress-mediated apoptotic cell death. Furthermore, hydroxychloroquine (HCQ) was effective in Men1 heterozygous-deficient (Men1+/ΔN3-8) mice, a mouse PanNEN model that is considered to correspond to human low-grade PanNEN. HCQ administration decreased tumour size in Men1+/ΔN3-8 mice. In the HCQ group, histological analyses revealed that proliferative activity was unchanged, but apoptosis was accelerated, accompanied by CHOP expression. These results suggest that autophagy inhibition by CQ/HCQ could be used for the treatment of PanNEN, including the well-differentiated type.

Background: In the treatment of metastatic pancreatic neuroendocrine tumors (PanNETs), surgical resection is the first choice if curative resection is expected. However, most patients develop recurrence after resection of liver metastasis. Because one of the benefits of resection is to gain a tumor-free period for the patients, it is important to identify which patients achieve longer recurrence-free survival (RFS) by resection. In this study, the clinicopathological factors associated with RFS after resection of metastatic PanNETs in the liver were evaluated to identify the patient group that is suitable for resection.Methods: Consecutively diagnosed patients with PanNET liver metastasis with resection at our hospital from January 2000 to July 2019 were evaluated. A total of 26 metastatic PanNET patients with primary liver resections were evaluated. The median follow-up time was 48.3 months.Results: There were 18 NET recurrences of the total 26 resections, with a median RFS of 17.9 months. Independent risk factors for short RFS were a high Ki67 index (p = .009) and the number of resected tumors (p = .045). When the cut-off value for the Ki67 index was 5.0% and that for the number of resected tumors was 6, Ki67 > 5.0% tumors had shorter RFS (4.9 months vs. 38.2 months p = .006), and patients with tumors > = 7 tumors had shorter RFS (4.7 months vs. 27.5 months p = .001).Conclusions: These findings indicate that good candidates for resection of metastatic tumors of PanNETs could be patients with low Ki67 tumors and a small number of metastatic tumors.

BACKGROUND: Recent management after pancreatoduodenectomy recommends either omission of prophylactic drainage or early removal. This potentially makes the diagnosis of postoperative pancreatic fistula (POPF) difficult because the diagnosis is based on the amylase value of drain effluent. The aim of this study was to determine if severe POPF could be predicted independent of drainage information. METHODS: Records of consecutive patients who underwent pancreatoduodenectomy between 2012 and 2018 were included for further analysis. The presence of a peripancreatic collection (PC) on routine postoperative (day7) computed tomography (early CT) and perioperative characteristics were analyzed. RESULTS: PC appeared in 82/211 patients (39%) and was associated with clinically relevant POPF (p < 0.001). The C-reactive protein (CRP) on postoperative day5 was a good predictor of severe POPF (needing interventional therapy or Grade C) (area under the receiver operating characteristics curve, 0.802; 95% confidence interval, 0.702-0.875). Presence of a PC and a high CRP value were independent risk factors for severe POPF following multivariate analysis. The combination of CRP<5.0 mg/dL on postoperative day 5 and the absence of a PC had 98% negative predictive value. CONCLUSION: The combination of CRP measurement and PC evaluation by early CT was useful in predicting severe POPF after pancreatoduodenectomy.

BACKGROUND: Preoperative simulation of liver resection to visualize the intraoperative cutting process, including liver deformation, may help surgeons to more accurately implement hepatectomy. We developed a novel simulation software called Resection Process Map (RPM). The present study was performed to evaluate the feasibility and efficacy of RPM as a tool for preoperative simulation and surgical education for liver surgery. MATERIALS AND METHODS: Twenty-four patients who underwent anatomical hepatic resection at our institute from February 2017 to May 2018 were enrolled in this study. The time needed to prepare RPM for each patient was recorded. The imaging similarity between the image provided by RPM and the intraoperative photograph was evaluated with the Dice similarity coefficient and locational displacement of the vessels of interest. The surgeons completed questionnaires. The educational effect was assessed by a survey administered to medical students who attended clinical clerkship at our department from October 2017 to December 2018. RESULTS: The time required to prepare the dataset for RPM was 199 ± 20 s after completion of operative planning in SYNAPSE VINCENT. The Dice similarity coefficient for surface similarity was 0.85 ± 0.06, where 1.00 indicates perfect concordance. The mean positional displacement of the vessels of interest was 8.7 ± 6.7 mm. Medical students' application of RPM significantly improved their survey score (use vs. non-use of RPM, 6.5 vs, 4.6, respectively; p < 0.001). CONCLUSION: RPM allows for preoperative simulation of hepatectomy and might be helpful for many surgeons. RPM is also useful for education of medical students.

BACKGROUND: We evaluated the clinicopathological factors associated with lymph node metastasis in patients with non-functioning pancreatic neuroendocrine neoplasms (PanNENs), focusing on the risk factors and range of lymph node metastasis for tumors ≤ 2 cm in diameter. METHODS: The subjects of this study were patients with PanNENs consecutively diagnosed at our hospital between January, 2000 and June, 2018. We analyzed 69 patients who underwent R0 resection of a non-functioning sporadic PanNEN with no distant metastasis, as well as 43 patients with tumors ≤ 20 mm in radiological diameter. RESULTS: Nineteen patients (27.5%), including 7 (16.3%) with a small PanNEN, had lymph node metastasis. A large radiological diameter, a high Ki67 index, and cyst formation correlated significantly with positive lymph node metastasis. In patients with tumors ≤ 20 mm in diameter, a high Ki67 index correlated significantly with lymph node metastasis. When we set the cut-off Ki67 index as 3.3%, 2 of 43 patients had lymph node metastasis. Tumors in the uncinate process readily metastasized to the region around the superior mesenteric artery. CONCLUSIONS: These findings suggest that a high Ki67 index indicates a risk of lymph node metastasis for tumors ≤ 20 mm in diameter and that lymphadenectomy should be performed in the region spatially adjacent to the primary tumor.

BACKGROUND: Peripancreatic collections occur frequently after distal pancreatectomy. However, the sequelae of peripancreatic collections vary from case to case, and their clinical impact is uncertain. In this study, the correlations between CT findings of peripancreatic collections and complications after distal pancreatectomy were investigated. METHODS: Ninety-six consecutive patients who had undergone distal pancreatectomy between 2010 and 2015 were retrospectively investigated. The extent and heterogeneity of peripancreatic collections and background clinicopathological characteristics were analyzed. The extent of peripancreatic collections was calculated based on three-dimensional computed tomography images, and the degree of heterogeneity of peripancreatic collections was assessed based on the standard deviation of their density on computed tomography. RESULTS: Of 85 patients who underwent postoperative computed tomography imaging, a peripancreatic collection was detected in 77 (91%). Patients with either a large extent or a high degree of heterogeneity of peripancreatic collection had a significantly higher rate of clinically relevant pancreatic fistula than those without (odds ratio 5.95, 95% confidence interval 2.12-19.72, p = 0.001; odds ratio 8.0, 95% confidence interval 2.87-24.19, p = 0.0001, respectively). CONCLUSIONS: A large and heterogeneous peripancreatic collection was significantly associated with postoperative complications, especially clinically relevant postoperative pancreatic fistula. A small and homogenous peripancreatic collection could be safely observed.

BACKGROUND: The primary site of a neuroendocrine neoplasms (NEN) around the head of the pancreas is sometimes difficult to assess before resection, and the characteristics of the primary site around this region have not been elucidated for recurrence after curative resection. In this study, the clinicopathologic characteristics of pancreatic NEN (PanNEN) and duodenal NEN (DuNEN) were evaluated, and the risk factors as well as the recurrence types after resection were investigated. METHODS: Consecutively diagnosed NEN patients at the authors' hospital from January 2000 to July 2016 were evaluated in this study. For 117 PanNEN patients and 31 non-ampullary DuNEN patients, R0 resection was achieved. The median follow-up period was 8.1 years. RESULTS: In this study, 27 PanNEN patients (23.1%) had recurrences, with a median disease-free survival (DFS) of 133 months, whereas 11 DuNEN patients (35.5%) had recurrences, with a median DFS of 156 months. The PanNEN patients tended to have primary recurrence in the liver (85.2%), followed by lymph nodes (11.1%). The independent risk factors for short DFS were lymph node metastasis at resection (p = 0.001) and microvascular invasion (p = 0.048). In contrast, the DuNEN patients were likely to have lymph node metastasis (81.8%). The independent risk factors for short DFS were lymph node metastasis at resection (p = 0.003) and large diameter (p = 0.013). CONCLUSIONS: Most initial recurrences of PanNEN occurred in the liver, whereas those of DuNEN appeared in lymph nodes, suggesting that proper diagnosis of the primary site and appropriate imaging methods for surveillance after resection are necessary.

BACKGROUND: Although pancreatic neuroendocrine tumors generally have a far better prognosis relative to pancreatic cancer, the varied manifestations lead to treatment-related challenges. Everolimus therapy is generally recommended for patients with advanced pancreatic neuroendocrine tumors; however, its efficacy in a neoadjuvant setting remains unclear. Here we present a case of a giant pancreatic neuroendocrine tumor with a portal tumor thrombus that became resectable after everolimus therapy. CASE PRESENTATION: A 62-year-old woman was admitted to our hospital for surgical resection of a giant pancreatic neuroendocrine tumor in the left upper abdomen. Unfortunately, she was ineligible for surgery because the tumor had extended near the hepatic hilus in the portal vein, and she was administered everolimus (10 mg/day). After 2 years of this therapy, the extent of portal vein involvement had decreased, despite the lack of significant changes in the tumor size, and the hepatic hilus became free of disease. She was subsequently referred to us for resection via distal pancreatectomy with portal vein reconstruction because the tumor had begun to grow slowly. Pathological review identified a grade 2 neuroendocrine tumor with no lymph node metastasis. The patient's postoperative course was uneventful, and she has remained recurrence-free for 27 months, despite a lack of additional treatment. CONCLUSIONS: Our experience suggests that everolimus could be useful for neoadjuvant therapy in cases of locally advanced pancreatic neuroendocrine tumor.

BACKGROUND/AIM: Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that allows accurate irradiation with reduced damage to surrounding tissues. Here, we analyzed borderline-resectable pancreatic cancer (BRPC) with arterial abutment (BR-A) patients with IMRT as neoadjuvant therapy and performed comparisons with patients with conventional RT to clarify the advantages of IMRT as a neoadjuvant therapy. PATIENTS AND METHODS: Thirty BR-A patients treated at our hospital between January 2012 and December 2015 were divided into two groups: 12 patients underwent conventional 3D-RT before resection (RT group); and 18 patients underwent IMRT before resection (IMRT group). We analyzed safety, tumor resection rate, histological classification of the tumor and overall survival. RESULTS: The R0 rate was 84% for the IMRT group and 83% for the RT group. Local therapeutic effects as assessed by Evans classification showed a higher local control rate in the IMRT group (Grade: 1, 0%; 2a, 25%; 2b, 41.6%; 3, 17%; 4, 8%) than in the RT group (Grade: 1, 17%; 2a, 50%; 2b, 17%; 3, 17%; 4, 0%). The cumulative dose of S1 treatment as adjuvant therapy was much smaller in the RT group (18.3%) compared to that in the IMRT group (57.1%, p=0.047), and with better subsequent overall survival rate (MST 32 months vs. 13.8 months, p=0.0273). CONCLUSION: The IMRT group showed a better control rate than the RT group. The neoadjuvant IMRT has advantages of higher completion rate of adjuvant chemotherapy with better nutritional status and better subsequent overall survival rate (OS).

BACKGROUND Lymph node metastasis of hepatocellular carcinoma is rare, and lymph nodes located on hepatic hilar and hepatoduodenal ligaments are primary targets. Metastasis to a mesocolic lymph node has not been reported previously. CASE REPORT A 65-year-old woman with liver cirrhosis underwent primary resection of hepatocellular carcinoma. Two and a half years later, tumor marker levels increased remarkably and imaging revealed a mesocolic mass. The tumor measured 27 mm in diameter and showed characteristic findings consistent with hepatocellular carcinoma in dynamic computed tomographic images, although the tumor was negative in fluorine-18-fluorodeoxyglucose positron emission tomographic images. A preoperative diagnosis of solitary metastasis to a mesocolic lymph node was made, and we elected to perform surgical resection, although therapeutic strategies for rare solitary extrahepatic metastasis are controversial. The tumor was located in the mesocolon nearly at the wall of the descending colon. Curative resection was performed and histopathological analysis confirmed metastatic hepatocellular carcinoma to a mesocolic lymph node. Tumor marker levels normalized immediately postoperatively. To date, the patient remains free from recurrence without adjuvant therapy. CONCLUSIONS This is the first known case of solitary hepatocellular carcinoma metastasis to a distant mesocolic lymph node, successfully treated. Diagnosing solitary hepatocellular carcinoma metastases to distant lymph nodes can be difficult. Although the ideal therapeutic approach has not be defined, surgical resection of solitary metastatic lymph nodes may be beneficial in carefully selected cases.

Background. Hepatectomy, an important treatment modality for liver malignancies, has high perioperative morbidity and mortality rates. Safe, comprehensive criteria for selecting patients for hepatectomy are needed. Since June 2011, we have used a cut-off value of ≧ 0.05 for future liver remnant plasma clearance rate of indocyanine green as a criterion for hepatectomy. The aim of this study was to verify the validity of this criterion. Methods. From June 2011 to December 2015, 212 hepatectomies were performed in Tenri Yorozu Hospital. Of these 212 patients, 107 who underwent preoperative computed tomography imaging volumetry, indocyanine green clearance test, and hepatectomy (excluding partial resection or enucleation) were retrospectively analyzed. Results. There was no postoperative mortality. Posthepatectomy liver failure occurred in 59 patients (55.1%) (International Study Group of Liver Surgery Grade A: 43 cases (40.2%), Grade B: 16 cases (15.0%), and Grade C: no cases). Operative morbidity greater than Clavien-Dindo Grade 3 occurred in 23 patients (21.5%). A low future liver remnant plasma clearance rate of indocyanine green was a good predictor for Grade B cases (area under curve = 0.804; 95% confidence interval, 0.712-0.895). Conclusion. Liver remnant plasma clearance rate of indocyanine green is a valid criterion for hepatectomy.

A 72-year-old woman was admitted to our hospital because of muscle weakness and was diagnosed as having polymyositis. Whole-body evaluation revealed advanced transverse colon cancer, and we therefore considered it likely that the patient had paraneoplastic myositis. We performed a curative surgical resection for colon cancer, after which her serum creatine phosphokinase(CPK)level greatly decreased. Steroid therapy was administered postoperatively. However, her CPK levels remained persistently high, even after steroid pulse therapy, and we considered that this was due to steroid-resistance myositis. We administered chemotherapy for colon cancer using 5-fluorouracil plus Leucovorin(5-FU/LV), after which the CPK levels gradually decreased. There have been few previous reports of polymyositis associated with colon cancer and a standard treatment for paraneoplastic myositis has not been established. Most clinicians believe that treatment of the primary tumor may contribute to an improvement of myositis, and in our case, tumor resection and chemotherapy were effective.

A 63-year-old woman was admitted because of epigastric pain and obstructive jaundice. Endoscopic retrograde cholangiopancreatography and intraductal ultrasonography revealed a 25-mm papillary nodule in the middle to inferior portion of the common bile duct (CBD). Pancreaticobiliary maljunction (PBM) was also identified. Contrast-enhanced computed tomography also showed an enhanced nodule in the CBD, and we suspected intraductal papillary neoplasm of the bile duct. We performed pylorus-preserving pancreatoduodenectomy. Postoperative pathological examination revealed an inflammatory polyp in the middle CBD. Inflammatory polyp in the bile duct is rare and there are no previous reports accompanied by PBM. PBM is a major risk factor for biliary tract cancer. Preoperative diagnosis of a benign disorder was difficult in this case.