Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus.

BACKGROUND: Pancreatic cancer is an aggressive, immunologically "cold" tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702). METHODS: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps). RESULTS: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection. CONCLUSION: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer.

Oncolytic virus-mediated reducing of myeloid-derived suppressor cells enhances the efficacy of PD-L1 blockade in gemcitabine-resistant pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is often refractory to treatment with gemcitabine (GEM) and immune checkpoint inhibitors including anti-programmed cell death ligand 1 (PD-L1) antibody. However, the precise relationship between GEM-resistant PDAC and development of an immunosuppressive tumor microenvironment (TME) remains unclear. In this study, we investigated the immunosuppressive TME in parental and GEM-resistant PDAC tumors and assessed the therapeutic potential of combination therapy with the telomerase-specific replication-competent oncolytic adenovirus OBP-702, which induces tumor suppressor p53 protein and PD-L1 blockade against GEM-resistant PDAC tumors. Mouse PDAC cells (PAN02) and human PDAC cells (MIA PaCa-2, BxPC-3) were used to establish GEM-resistant PDAC lines. PD-L1 expression and the immunosuppressive TME were analyzed using parental and GEM-resistant PDAC cells. A cytokine array was used to investigate the underlying mechanism of immunosuppressive TME induction by GEM-resistant PAN02 cells. The GEM-resistant PAN02 tumor model was used to evaluate the antitumor effect of combination therapy with OBP-702 and PD-L1 blockade. GEM-resistant PDAC cells exhibited higher PD-L1 expression and produced higher granulocyte-macrophage colony-stimulating factor (GM-CSF) levels compared with parental cells, inducing an immunosuppressive TME and the accumulation of myeloid-derived suppressor cells (MDSCs). OBP-702 significantly inhibited GEM-resistant PAN02 tumor growth by suppressing GM-CSF-mediated MDSC accumulation. Moreover, combination treatment with OBP-702 significantly enhanced the antitumor efficacy of PD-L1 blockade against GEM-resistant PAN02 tumors. The present results suggest that combination therapy involving OBP-702 and PD-L1 blockade is a promising antitumor strategy for treating GEM-resistant PDAC with GM-CSF-induced immunosuppressive TME formation.

Innovative suture technique for robotic hepaticojejunostomy: double-layer interrupted sutures.

PURPOSE: Biliary reconstruction remains a technically demanding and complicated procedure in minimally invasive hepatopancreatobiliary surgeries. No optimal hepaticojejunostomy (HJ) technique has been demonstrated to be superior for preventing biliary complications. This study aimed to investigate the feasibility of our unique technique of posterior double-layer interrupted sutures in robotic HJ. METHODS: We performed a retrospective analysis of a prospectively collected database. Forty-two patients who underwent robotic pancreatoduodenectomy using this technique between September 2020 and November 2022 at our center were reviewed. In the posterior double-layer interrupted technique, sutures were placed to bite the bile duct, posterior seromuscular layer of the jejunum, and full thickness of the jejunum. RESULTS: The median operative time was 410 (interquartile range [IQR], 388-478) min, and the median HJ time was 30 (IQR, 28-39) min. The median bile duct diameter was 7 (IQR, 6-10) mm. Of the 42 patients, one patient (2.4%) had grade B bile leakage. During the median follow-up of 12.6 months, one patient (2.4%) with bile leakage developed anastomotic stenosis. Perioperative mortality was not observed. A surgical video showing the posterior double-layer interrupted sutures in the robotic HJ is included. CONCLUSIONS: Posterior double-layer interrupted sutures in robotic HJ provided a simple and feasible method for biliary reconstruction with a low risk of biliary complications.

Regulatory T cells induce a suppressive immune milieu and promote lymph node metastasis in intrahepatic cholangiocarcinoma.

BACKGROUND: Emerging evidence indicates that immunogenicity plays an important role in intrahepatic cholangiocarcinoma (ICC). Herein, we systematically evaluated the clinical relevance of immunogenicity in ICC. METHODS: Highly immunogenic ICCs identified in the public dataset and the Cancer Immunome Atlas (TCIA) were assessed to determine the prognostic impact of immunogenicity in ICC and key components after curative resection. We also investigated the clinical relevance of the immune milieu in ICC. RESULTS: Using the Gene Expression Omnibus dataset 89749 and TCIA, we identified CD8+/forkhead box P3 (FoxP3)+ tumour-infiltrating lymphocytes (TILs), T-cell immunoglobulin and mucin domain 3 (TIM-3) and human leukocyte antigen-A (HLA-A) in highly immunogenic ICCs. Immunohistochemical analysis of the in-house cohort showed that intratumoral FoxP3+ TILs correlated with CD8+ TILs (P = 0.045, Fisher's exact test) and that high FoxP3+/CD8+ ratio (FCR) was an important marker for poor survival (P < 0.001, log-rank test). Furthermore, the FCR was higher in tumour-free lymph nodes in ICCs with lymph node metastases than in those without lymph node metastases (P = 0.003, Mann-Whitney U test). CONCLUSIONS: FCR should be considered an important biomarker that represents the immune environment of ICC based on its potentially important role in tumour progression, especially lymph node metastasis.

Optimal surveillance of intraductal papillary mucinous neoplasms of the pancreas focusing on remnant pancreas recurrence after surgical resection.

BACKGROUND: The international consensus guidelines for intraductal papillary mucinous neoplasm of the pancreas (IPMN) presented clinical features as indications for surgery. Whereas surveillance for recurrence, including de novo lesions, is essential, optimal surveillance protocols have not been established. AIM AND METHODS: This study aimed to assess the clinical features of recurrence at the remnant pancreas (Rem-Panc) and extra-pancreas (Ex-Panc) after surgery for IPMN. Ninety-one patients of IPMN that underwent detailed preoperative assessment and pancreatectomy were retrospectively analyzed, focusing especially on the type of recurrence. RESULTS: The IPMNs were finally diagnosed as low-grade dysplasia (LDA, n = 42), high-grade dysplasia (HAD, n = 19), and invasive carcinoma (IPMC, n = 30). Recurrence was observed in 26 patients (29%), of which recurrence was seen at Rem-Panc in 19 patients (21%) and Ex-Panc in 7 patients (8%). The frequency of Rem-Panc recurrence was 10% in LDA, 21% in HDA, and 37% in IPMC. On the other hand, Ex-Panc recurrence was observed only in IPMC (23%). Ex-Panc recurrence showed shorter median recurrence-free survival (RFS) and overall survival (OS) than Rem-Panc recurrence (median RFS 8 months vs. 35 months, p < 0.001; median OS 25 months vs. 72 months, p < 0.001). Regarding treatment for Rem-Panc recurrence, repeat pancreatectomy resulted in better OS than no repeat pancreatectomy (MST 36 months vs. 15.5 months, p = 0.033). On multivariate analysis, main duct stenosis or disruption as a preoperative feature (hazard ratio [HR] 10.6, p = 0.002) and positive surgical margin (HR 4.4, p = 0.018) were identified as risk factors for Rem-Panc recurrence. CONCLUSIONS: The risk factors for Rem-Panc and Ex-Panc recurrence differ. Therefore, optimal surveillance on these features is desirable to ensure that repeat pancreatectomy for Rem-Panc recurrence can be an appropriate surgical intervention.

Feasibility of local therapy for recurrent pancreatic cancer.

BACKGROUND: Despite advances in perioperative management, recurrence after curative pancreatectomy is a critical issue in the treatment of pancreatic ductal adenocarcinoma (PDAC). The significance of local therapy for recurrent PDAC remains unclear. METHODS: We reviewed the medical records of patients with PDAC who underwent curative resection at our institution between January 2009 and December 2019. We examined the patterns of relapse and assessed the clinical outcomes of patients with recurrence who underwent local therapy, including surgical resection, radiotherapy, and radiofrequency ablation. RESULTS: A total of 246 patients with PDAC who underwent R0 or R1 resection were included in this study. The 3-year overall survival (OS) rate was 39.8%, and the 1-year recurrence-free survival rate was 51.2% for the entire population. Recurrence was observed in 172/246 (69.9%) patients, including multiple site recurrences in 50, liver metastasis in 41, locoregional recurrence in 34, and peritoneal dissemination in 27. Of the 172 patients, treatment was administered in 137 (79.7%), and 16 received local therapy, including surgical resection (n = 13), radiotherapy (n = 5), and RFA (n = 1). PS-matched analysis revealed that patients with recurrence who were treated with chemotherapy combined with local therapy showed better post-recurrence survival rates than those treated with chemotherapy alone (P = 0.016). Detailed clinical courses of these patients are presented in the main manuscript. CONCLUSIONS: Our results suggest that a multimodal approach may improve the clinical outcomes of patients with recurrent PDAC.

Robotic Spleen-Preserving Distal Pancreatectomy with Preservation of Splenic Vessels Using the Gastrohepatic Ligament Approach: The Superior Window Approach in the Kimura Technique.

Minimally invasive spleen-preserving distal pancreatectomy (SPDP) is technically challenging, and only a few reports have described surgical approaches for minimally invasive SPDP. This report demonstrates our novel gastrohepatic ligament approach in robotic SPDP with preservation of the splenic vessels (the superior window approach in the Kimura technique). Our gastrohepatic ligament approach for robotic SPDP included four steps. First, the gastrohepatic ligament was divided extensively, and the pancreas was confirmed (step 1). In this step, we did not lift the stomach, nor did we divide the gastrocolic ligament. Next, the superior and inferior borders of the pancreas were dissected, and the tunneling of the pancreas on the superior mesenteric vein was performed (step 2). Following the division of the pancreas (step 3), the pancreatic body and tail were dissected from the medial to the lateral side with preservation of the splenic vessels (step 4). Using this approach, the pancreas can be directly accessed via the gastrohepatic ligament route and dissected without division of the gastrocolic ligament or retraction of the stomach. The present approach for robotic SPDP preserves splenic vessels, facilitating easy access to the pancreas with minimal dissection, and may be optional in selected patients, including those with low body mass index.

Surgical technique of suprapancreatic D2 lymphadenectomy focusing on the posterior hepatic plexus for advanced gastric cancer.

PURPOSE: Although D2 lymphadenectomy is currently considered a standard procedure for advanced gastric cancer (GC) worldwide, there is room for discussion about the appropriate range of suprapancreatic D2 lymphadenectomy. Focusing on the posterior hepatic plexus (PHP), which is not well recognized, we developed a surgical technique of suprapancreatic D2 lymphadenectomy, which we have called PHP-D2, and its short-term and long-term efficacies were evaluated in comparison with non-PHP-D2. METHODS: GC patients who underwent distal gastrectomy with D2 lymphadenectomy between July 2006 and May 2013 were enrolled, from which patients who had peritoneal metastasis and/or were peritoneal cytology-positive during surgery were excluded. Their medical records were retrospectively reviewed. RESULTS: Ninety-two patients (non-PHP-D2: 48, PHP-D2: 44) were enrolled. Shorter operation time (330 min vs 275 min, p < 0.0001) and less blood loss (290 mL vs 125 mL, p < 0.0001) were observed in PHP-D2, and no pancreatic fistulas were observed in PHP-D2. More lymph nodes of #11p (1 vs 1.5, p = 0.0328) and #12a lymph nodes (0 vs 1, p = 0.0034) were retrieved in PHP-D2, with no significant differences in #8a and #9 lymph nodes. Lymphatic recurrence was significantly less in PHP-D2 (p = 0.0166), and univariate and multivariate analyses showed that non-PHP-D2 was a significant risk factor for lymphatic recurrence (p = 0.0158), although there were no significant differences between non-PHP-D2 and PHP-D2 in 5-year overall survival and 5-year relapse-free survival. CONCLUSION: PHP-D2 was a safe and feasible procedure that had the potential to reduce lymphatic recurrence, and it can be a standard procedure of D2 lymphadenectomy for advanced GC.

Technique of vessel-skeletonized parenchyma-sparing hepatectomy for the oncological treatment of bilobar colorectal liver metastases.

BACKGROUND: To aid in the oncological management of multiple bilobar colorectal liver metastases (CRLMs), we describe a new surgical procedure, VEssel-Skeletonized PArenchyma-sparing Hepatectomy (VESPAH). STUDY DESIGN: Of 152 patients with CRLMs treated with hepatectomy, 33 patients had multiple bilobar liver metastases (≥8 liver metastases); their surgical procedures and clinical outcomes were retrospectively summarized and compared between those who underwent VESPAH and those who underwent major hepatectomy (Major Hx). RESULTS: Of the 33 patients, 20 patients were resected by VESPAH (the VESPAH group) and 13 patients by major hepatectomy (Major Hx group). The median number of CRLMs was 13 (range, 8-53) in the VESPAH group and 10 (range, 8-41) in the Major Hx group (P=0.511). No operative mortality nor severe morbidity was observed in either group. The VESPAH group showed earlier recovery of remnant liver function after surgery than the Major Hx group; the incidence of grade B/C post hepatectomy liver failure was 5% in the VESPAH group and 38% in the Major Hx group, P=0.048). Intrahepatic tumor recurrence was confirmed in 14 (70%) and 7 (54%) patients in the VESPAH and Major Hx groups, respectively (P=0.416). There was no significant difference in median overall survival (OS) after hepatectomy between the two groups; the median OS was 47 months in the VESPAH group and 33 months in the Major Hx group (P=0.481). The VESPAH group showed the higher induction rate of adjuvant chemotherapy within 2 months after surgery (P=0.002) and total number of repeat hepatectomy for intrahepatic recurrence (P=0.060) than the Major Hx group. CONCLUSIONS: VESPAH enables us to clear surgical navigation by hepatic vessel skeletonization and may enhance patient tolerability of not only adjuvant chemotherapy but also repeat hepatectomies during the patients' lifetimes.

Neonatal hemochromatosis with εγδß-thalassemia: a case report and analysis of serum iron regulators.

BACKGROUND: Neonatal hemochromatosis causes acute liver failure during the neonatal period, mostly due to gestational alloimmune liver disease (GALD). Thalassemia causes hemolytic anemia and ineffective erythropoiesis due to mutations in the globin gene. Although neonatal hemochromatosis and thalassemia have completely different causes, the coexistence of these diseases can synergistically exacerbate iron overload. We report that a newborn with εγδß-thalassemia developed neonatal hemochromatosis, which did not respond to iron chelators and rapidly worsened, requiring living-donor liver transplantation. CASE PRESENTATION: A 1-day-old Japanese boy with hemolytic anemia and targeted red blood cells was diagnosed with εγδß-thalassemia by genetic testing, and required frequent red blood cell transfusions. At 2 months after birth, exacerbation of jaundice, grayish-white stool, and high serum ferritin levels were observed, and liver biopsy showed iron deposition in hepatocytes and Kupffer cells. Magnetic resonance imaging scans showed findings suggestive of iron deposits in the liver, spleen, pancreas, and bone marrow. The total amount of red blood cell transfusions administered did not meet the criteria for post-transfusion iron overload. Administration of an iron-chelating agent was initiated, but iron overload rapidly progressed to liver failure without improvement in jaundice and liver damage. He underwent living-donor liver transplantation from his mother, after which iron overload disappeared, and no recurrence of iron overload was observed. Immunohistochemical staining for C5b-9 in the liver was positive. Serum hepcidin levels were low and serum growth differentiation factor-15 levels were high prior to living-donor liver transplantation. CONCLUSIONS: We reported that an infant with εγδß-thalassemia developed NH due to GALD, and that coexistence of ineffective erythropoiesis in addition to erythrocyte transfusions may have exacerbated iron overload. Low serum hepcidin levels, in this case, might have been caused by decreased hepcidin production arising from fetal liver damage due to neonatal hemochromatosis and increased hepcidin-inhibiting hematopoietic mediators due to the ineffective hematopoiesis observed in thalassemia.

Extracellular vesicles shed from gastric cancer mediate protumor macrophage differentiation.

BACKGROUND: Peritoneal dissemination often develops in gastric cancer. Tumor-associated macrophages (TAMs) are present in the peritoneal cavity of gastric cancer patients with peritoneal dissemination, facilitating tumor progression. However, the mechanism by which macrophages differentiate into tumor-associated macrophages in the peritoneal cavity is not well understood. In this study, the interplay between gastric cancer-derived extracellular vesicles (EVs) and macrophages was investigated. METHODS: The association between macrophages and EVs in peritoneal ascitic fluid of gastric cancer patients, or from gastric cancer cell lines was examined, and their roles in differentiation of macrophages and potentiation of the malignancy of gastric cancer were further explored. RESULTS: Immunofluorescent assays of the ascitic fluid showed that M2 macrophages were predominant along with the cancer cells in the peritoneal cavity. EVs purified from gastric cancer cells, as well as malignant ascitic fluid, differentiated peripheral blood mononuclear cell-derived macrophages into the M2-like phenotype, which was demonstrated by their morphology and expression of CD163/206. The macrophages differentiated by gastric cancer-derived EVs promoted the migration ability of gastric cancer cells, and the EVs carried STAT3 protein. CONCLUSION: EVs derived from gastric cancer play a role by affecting macrophage phenotypes, suggesting that this may be a part of the underlying mechanism that forms the intraperitoneal cancer microenvironment.

Surgical training model and safe implementation of robotic pancreatoduodenectomy in Japan: a technical note.

BACKGROUND: Growing evidence for the advantages of robotic pancreatoduodenectomy (RPD) has been demonstrated internationally. However, there has been no structured training program for RPD in Japan. Herein, we present the surgical training model of RPD and a standardized protocol for surgical technique. METHODS: The surgical training model and surgical technique were standardized in order to implement RPD safely, based on the Dutch training system collaborated with the University of Pittsburgh Medical Center. RESULTS: The surgical training model included various trainings such as basic robotic training, simulation training, biotissue training, and a surgical video review. Furthermore, a standardized protocol on the surgical technique was established to understand the tips, tricks, and pitfalls of RPD. CONCLUSIONS: Safe implementation of RPD can be achieved through the completion of a structured training program and learning surgical technique. A nationwide structured training system should be developed to implement the program safely in Japan.

Multiple Hepatolithiasis Following Hepaticojejunostomy Successfully Treated with Left Hemihepatectomy and Double Hepaticojejunostomy Reconstruction.

Surgical intervention for hepatolithiasis following hepaticojejunostomy (HJ) has rarely been reported. Herein, we present a case of post-HJ multiple hepatolithiasis treated with left hemihepatectomy with double HJ reconstruction. A 72-year-old woman who had undergone HJ for iatrogenic bile duct injury developed repeated cholangitis due to complicated hepatolithiasis accompanied by an atrophied left hepatic lobe and HJ stricture. Since endoscopic intervention was unsuccessful, the patient underwent left hemihepatectomy with HJ re-anastomoses of the common hepatic duct and left hepatic duct (double HJ technique). The double HJ technique with hepatectomy can be a useful option for treating complicated hepatolithiasis following HJ.

Left Hemihepatectomy for Hepatocellular Carcinoma Following Esophagectomy with Retrosternal Gastric Tube Reconstruction for Esophageal Cancer.

Approximately 4% of patients with esophageal cancer develop a second primary malignancy in the upper gastrointestinal trunk. However, hepatectomy following esophagectomy for esophageal cancer has rarely been reported. We report the case of a 70-year-old man who underwent an esophagectomy for esophageal cancer with retrosternal gastric tube reconstruction. Nine years later, he developed hepatocellular carcinoma with tumor thrombus involving the left portal vein, and was successfully treated with left hemihepatectomy. Special attention should be paid to avoiding incidental injury of the gastric tube as well as the right gastroepiploic artery during the hepatectomy.

Usefulness of Middle Colic Artery Transposition Technique for Hepatic Arterial Reconstruction in Conversion Surgery for an Initially Unresectable, Locally Advanced Pancreatic Cancer.

The outcomes of pancreatectomy with resection and reconstruction of the involved arteries for locally advanced pancreatic cancer following chemotherapy have improved in recent years. In pancreatic head cancers in which there is contact with the common and proper hepatic arteries, margin-negative resection requires pancreati-coduodenectomy, with the resection of these arteries and the restoration of hepatic arterial flow. Here, we describe a middle colic artery transposition technique in hepatic arterial reconstruction during pancreatoduo-denectomy for an initially unresectable locally advanced pancreatic cancer. This technique was effective and may provide a new option for hepatic artery reconstruction in such cases.

[A Case of Type 4 Gastric Cancer with Peritoneal Dissemination Successfully Treated with Conversion Surgery after Intensive S-1 plus Oxaliplatin Chemotherapy].

S-1 plus oxaliplatin(SOX)chemotherapy is now widely used for the treatment of unresectable gastric cancer but there are few case reports about conversion surgery following SOX. Hereby, we report a case of type 4 gastric cancer with peritoneal dissemination successfully treated with conversion surgery after intensive SOX chemotherapy. A 69-year-old female was diagnosed of type 4 gastric cancer by upper endoscopy(por1, HER2 negative)and peritoneal disseminations were identified on left diaphragm and mesentery under direct vision. After 11 courses of SOX chemotherapy, CT revealed that primary tumor markedly decreased in size. Therefore, staging laparoscopy was performed and peritoneal disseminated lesions disappeared. Peritoneal cytology also turned negative. Subsequently, total gastrectomy and splenectomy were performed. Histology revealed that tumor was categorized as por2, ypT2N3M0, ypStage ⅢA, and Grade 2 in histological evaluation criteria. SOX was continued as an adjuvant chemotherapy for another 6 months and the patients remain healthy without recurrence. Unresectable gastric cancer with peritoneal dissemination can be successfully treated with conversion surgery following SOX chemotherapy and staging laparoscopy was useful to evaluate peritoneal dissemination. When conversion surgery is indicated for gastric cancer with peritoneal dissemination, downstaging should be confirmed by staging laparoscopy.

The efficacy of pancreatic juice cytology with liquid-based cytology for evaluating malignancy in patients with intraductal papillary mucinous neoplasm.

BACKGROUND: Pancreatic juice cytology (PJC) is a tool for diagnosing malignant intraductal papillary mucinous neoplasm (IPMN); however, the accuracy is insufficient using the conventional method. Liquid-based cytology (LBC) improves the cell recovery rate, and almost all cells can be evaluated. We evaluated the efficacy of PJC with LBC for malignant IPMN. METHODS: We retrospectively analyzed 90 patients with suspected malignant IPMN who underwent PJC before pancreatectomy. PJC with smear and LBC methods was conducted in 52 patients (between June 2003 to December 2011) and 38 patients (between January 2012 to December 2018). Based on the imaging studies, all of the patients were classified according to the international consensus guidelines for IPMN revised in 2017. RESULTS: Of the 90 patients, 43 (48%) had malignant IPMN (high-grade dysplasia or invasive carcinoma), and the remaining patients had non-malignant IPMN (intermediate- or low-grade dysplasia). LBC increased the accuracy of PJC for the diagnosis of malignant IPMN (smear method: 56% [29/52] vs. LBC method: 76% [29/38]; P = 0.044). In a multivariate analysis, LBC was a significant factor influencing the accurate diagnosis of PJC (odds ratio: 3.52; P = 0.021). Furthermore, LBC increased the accuracy of PJC for malignant IPMN in patients with worrisome features (smear method: 66% [19/29] vs. LBC method: 93% [14/15]; P = 0.043). CONCLUSIONS: LBC increases the accuracy of PJC for diagnosing malignant IPMN compared with the conventional smear method.

Systematic review on immunonutrition in partial pancreatoduodenectomy.

BACKGROUND: The effect of immunonutrition (IM) on postoperative outcomes has been investigated in gastrointestinal cancer surgery; however, strong evidence regarding IM in partial pancreatoduodenectomy (PD) is lacking. This study evaluated the effect of IM on short-term outcomes in patients undergoing PD. METHODS: A systematic literature review of randomized controlled trials was conducted to identify the studies investigating the IM effect on outcomes in PD. Random-effects meta-analyses were conducted to calculate the pooled risk ratio (RR). Studies were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Five studies were included in the meta-analysis. IM was associated with a lower incidence of overall complications (RR 0.74; 95% confidence interval (CI) 0.58, 0.94; P = 0.01; I2 = 0%) and infectious complications (RR 0.60; 95% CI 0.42, 0.84; P = 0.003; I2 = 0%). However, no significant association was noted in the incidence of major complications (RR 0.68; 95% CI 0.41, 1.12; P = 0.13), mortality (RR 0.79; 95% CI 0.16, 3.99; P = 0.78), postoperative pancreatic fistula (RR 0.92, 95% CI 0.59, 1.46; P = 0.74), and delayed gastric emptying (RR 1.09; 95% CI 0.55, 2.15; P = 0.81). CONCLUSIONS: IM administration in PD can prevent the incidence of overall and infectious complications postoperatively (GRADE recommendation: moderate). However, IM has no impact on major complications, mortality, and PD-specific complications (GRADE recommendation: low).

Hemobilia after bile duct resection: perforation of pseudoaneurysm into intra-pancreatic remnant bile duct: a case report.

BACKGROUND: Hemobilia occurs mainly due to iatrogenic factors such as impairment of the right hepatic or cystic artery, and/or common bile duct in hepatobiliary-pancreatic surgery. However, little or no cases with hemobilia from the intra-pancreatic remnant bile duct after bile duct resection (BDR) has been reported. Here, we report a case of massive hemobilia due to the perforation of psuedoaneurysm of the gastroduodenal artery (GDA) to the intra-pancreatic remnant bile duct after hepatectomy with BDR. CASE PRESENTATION: A 68-year-old male underwent extended right hepatectomy with BDR for gallbladder carcinoma. He presented with upper gastrointestinal bleeding 2 months after the initial surgery. Upper endoscopy identified a blood clot from the ampulla of Vater and simultaneous endoscopic balloon tamponade contributed to temporary hemostasis. Abdominal CT and angiography revealed a perforation of the psuedoaneurysm of the GDA to the intra-pancreatic remnant bile duct resulting in massive hemobilia. Subsequent selective embolization of the pseudoaneurysm with micro-coils could achieve complete hemostasis. He survived without any recurrence of cancer and bleeding. CONCLUSION: Hemobilia could occur in a patient with BDR due to perforation of the pseudoaneurysm derived from the GDA to the intra-pancreatic remnant bile duct. Endoscopic balloon tamponade was useful for a temporal hemostasis and a subsequent radiologic interventional approach.

Efficacy and safety of scheduled early endoscopic ultrasonography-guided ethanol reinjection for patients with pancreatic neuroendocrine tumors: Prospective pilot study.

Endoscopic ultrasonography (EUS)-guided ethanol injection was recently proposed for treatment of patients with small pancreatic neuroendocrine tumors (p-NET); however, tips on how to carry out safe and effective procedures are unclear. We launched a pilot study for scheduled early EUS-guided ethanol reinjection for small p-NET. Major eligibility criteria were presence of pathologically diagnosed grade (G) 1 or G2, tumor size ≤2 cm and being a poor or rejected candidate for surgery. For the treatment, we used a 25-gauge needle and pure ethanol. Contrast-enhanced computed tomography (CE-CT) was carried out on postoperative day 3, and if enhanced areas of the tumor were still apparent, an additional session was scheduled during the same hospitalization period. Primary endpoint was complete ablation rate at 1 month after treatment, and secondary endpoint was procedure-related adverse events. A total of five patients were treated. Median size of the tumor was 10 (range: 7-14) mm. Of the five patients, three underwent an additional session. Median volume of ethanol injection per session was 0.8 (range: 0.3-1.0) mL, and the total was 1.0 (0.9-1.8) mL. Complete ablation was achieved in four of the five tumors (80%) with no adverse events. During 1 year of follow up, none of the patients reported any procedure-related adverse events, and no recurrence of tumor. Scheduled early EUS-guided ethanol reinjection appears to be safe and effective for treating small p-NET (UMIN number: 000018834).