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Lymph node metastasis (LNM) is one of the most adverse prognostic factors in extrahepatic cholangiocarcinoma (EHCC) cases. As next-generation sequencing technology has become more widely available, the genomic profile of biliary tract carcinoma has been clarified. However, whether LNMs have additional genomic alterations in patients with EHCC has not been investigated. Here, we aimed to compare the genomic alterations between primary tumors and matched LNMs in patients with EHCC.Sixteen patients with node-positive EHCCs were included. Genomic DNA was extracted from tissue samples of primary tumors and matched LNMs. Targeted amplicon sequencing of 160 cancer-related genes was performed.Among the 32 tumor samples from 16 patients, 91 genomic mutations were identified. Genomic mutations were noted in 31 genes, including TP53, MAP3K1, SMAD4, APC, and ARID1A. TP53 mutations were most frequently observed (12/32; 37.5%). Genomic mutation profiles were highly concordant between primary tumors and matched LNMs (13/16; 81.3%), and an additional genomic mutation of CDK12 was observed in only one patient.Genomic mutations were highly concordant between primary tumors and matched LNMs, suggesting that genotyping of archived primary tumor samples may help predict genomic mutations of metastatic tumors in patients with EHCC.

Background: Surgery for perihilar cholangiocarcinoma (PHCC) remains a challenging procedure with high morbidity and mortality. The Academic Medical Center (Amsterdam UMC) and Memorial Sloan Kettering Cancer Center proposed a postoperative mortality risk score (POMRS) and post-hepatectomy liver failure score (PHLFS) to predict patient outcomes. This study aimed to validate the POMRS and PHLFS for PHCC patients at Hokkaido University. Methods: Medical records of 260 consecutive PHCC patients who had undergone major hepatectomy with extrahepatic bile duct resection without pancreaticoduodenectomy at Hokkaido University between March 2001 and November 2018 were evaluated to validate the PHLFS and POMRS. Results: The observed risks for PHLF were 13.7%, 24.5%, and 39.8% for the low-risk, intermediate risk, and high-risk groups, respectively, in the study cohort. A receiver-operator characteristic (ROC) analysis revealed that the PHLFS had moderate predictive value, with an analysis under the curve (AUC) value of 0.62. Mortality rates based on the POMRS were 1.7%, 5%, and 5.1% for the low-risk, intermediate-risk, and high-risk groups, respectively. The ROC analysis demonstrated an AUC value of 0.58. Conclusions: This external validation study showed that for PHLFS the threshold for discrimination in an Eastern cohort was reached (AUC >0.6), but it would require optimization of the model before use in clinical practice is acceptable. The POMRS were not applicable in the eastern cohort. Further external validation is recommended.

The antibodies and dilutions for Immunohistochemical staining

Supplemental Figure 5 shows (A) treatment schedule of subcutaneous model, (B) therapeutic result of PK-9 subcutaneous tumor model mice (n= 5). 3 groups (PBS: non-treatment group, 11R-7_14 AAA: negative control peptide group, 11R-DB: treatment group). In the 11R-DB group, tumor growth was suppressed significantly (11R-DB vs 11R-7â,‹14AAA and PBS: *p

Supplemental Figure 2 shows, (A) analysis of expression of C16orf74 in PDAC and other cancer cell lines by qRT-PCR and (B) analysis of expression of endogenous C16orf74 protein in PDAC and NHDF by Western blot.

Supplemental Figure 4 shows the quantitative graph of AKt phosphorylation and mTOR phosphorylation. (A) AKt phosphorylation in PK-1, PK-9, PANC-1 and MIAPaCa-2 cells. (B) mTOR phosphorylation in PK-1, PK-9, PANC-1 and MIAPaCa-2 cells.

Supplemental Figure 1 shows, (A) analysis of expression of C16orf74 in C16orf74 stable and MOCK cell lines by qRT-PCR, (B) expression of C16orf74 in C16orf74 stable and MOCK by Western blotting, (C) expression of C16orf74 in C16orf74 stable clonal cell lines by Immunofluorescence. C16orf74 localizes under the cell membrane, and (D) expression of endogenous C16orf74 protein in PK-9 cells shown by Immunofluorescence. Endogenous C16orf74 localizes under the cell membrane.

Supplemental Figure 3 shows matrigel invasion assay of C16orf74 stable cell lines (Clone C16-A. C16-B. C16-C) with 11R-DB administration and no administration. In the administered group, the invasion was significantly suppressed. * P

The antibodies and dilutions for Immunofluorescence

The primary antibodies and dilutions for Western blot analysis

RT-PCR primers for construction of the expression vectors

Simple Summary Extrahepatic cholangiocarcinoma (EHCC) is an aggressive tumor. The five-year survival rate for patients who undergo surgical resection is only 20-40% due to recurrences. Therefore, elucidating the molecular mechanisms underlying invasion and metastasis in EHCC is crucial for developing adjuvant therapy. The epithelial-mesenchymal transition (EMT) contributes to the metastatic cascade in various tumors. C-C chemokine receptor 7 (CCR7) interacts with its ligand, chemokine (C-C motif) ligand 19 (CCL19), to promote EMT. The association between CCR7 expression and clinicopathological features and EMT status was examined via the immunohistochemical staining of tumor sections from 181 patients with perihilar cholangiocarcinoma. This association was then investigated in two EHCC cell lines. CCR7 mediates cell invasion and migration in EHCC by inducing EMT, which was abrogated by a CCR7 antagonist. CCR7 may be a potential target for adjuvant therapy in EHCC. The epithelial-mesenchymal transition (EMT) contributes to the metastatic cascade in various tumors. C-C chemokine receptor 7 (CCR7) interacts with its ligand, chemokine (C-C motif) ligand 19 (CCL19), to promote EMT. However, the association between EMT and CCR7 in extrahepatic cholangiocarcinoma (EHCC) remains unknown. This study aimed to elucidate the prognostic impact of CCR7 expression and its association with clinicopathological features and EMT in EHCC. The association between CCR7 expression and clinicopathological features and EMT status was examined via the immunohistochemical staining of tumor sections from 181 patients with perihilar cholangiocarcinoma. This association was then investigated in TFK-1 and EGI-1 EHCC cell lines. High-grade CCR7 expression was significantly associated with a large number of tumor buds, low E-cadherin expression, and poor overall survival. TFK-1 showed CCR7 expression, and Western blotting revealed E-cadherin downregulation and vimentin upregulation in response to CCL19 treatment. The wound healing and Transwell invasion assays revealed that the activation of CCR7 by CCL19 enhanced the migration and invasion of TFK-1 cells, which were abrogated by a CCR7 antagonist. These results suggest that a high CCR7 expression is associated with an adverse postoperative prognosis via EMT induction and that CCR7 may be a potential target for adjuvant therapy in EHCC.

Pancreatic ductal adenocarcinoma (PDA) is a fatal cancer for which even unfavorable clinicopathological factors occasionally fail to preclude long-term survival. We sought to establish a scoring system that utilizes measurable pre-intervention factors for predicting survival following surgical resection.We retrospectively analyzed 34 patients who died from short-term recurrences and 32 long-term survivors among 310 consecutively resected patients with PDA. A logistic regression model was used to define factors related to clinical parameters, molecular profiles of 18 pancreatic cancer-associated genes, and aberrant expression of major tumor suppressors.Carbohydrate antigen 19-9 (CA19-9) had the best ability to classify patients with short-term recurrence and long-term survivors [odds ratio 21.04, 95% confidence interval (CI) 4.612-96.019], followed by SMAD4 and TP53 mutation scoring (odds ratio 41.322, 95% CI 3.156-541.035). Missense TP53 mutations were strongly associated with the nuclear expression of p53, whereas truncating mutations were associated with the absence of nuclear p53. The former subset was associated with a worse prognosis. The combination of aberrant SMAD4 and mutation types of TP53 exhibited a better resolution for distinguishing patients with short-term recurrences from long-term survivors (compared with the assessment of the number of mutated KRAS, CDKN2A, TP53, and SMAD4 genes). Calibration of mutation scores combined with CA19-9 in a logistic regression model setting demonstrated a practical effect in classifying long survivors and patients with early recurrence (c-statistic = 0.876).Genetic information, i.e., TP53 mutation types and SMAD4 abnormalities, combined with CA19-9, will be a valuable tool for improving surgical strategies for pancreatic cancer.

Purpose This study evaluated the short-term outcomes and prognosis after laparoscopic total gastrectomy (LTG) in elderly patients aged >= 80 years in a multicenter retrospective cohort study using propensity score matching. Methods We retrospectively enrolled 440 patients who underwent curative LTG for gastric cancer at six institutions between January 2004 and December 2018. Patients were categorized into an elderly patient group (EG; age >= 80 years) and non-elderly patient group (non-EG; age < 80 years). Patients were matched using the following propensity score covariates: sex, body mass index, American Society of Anesthesiologists physical status, extent of lymph node dissection, and Japanese Classification of Gastric Carcinoma stage. Short-term outcomes and prognoses were compared. Results We identified 37 propensity score-matched pairs. The median operative time was significantly shorter, and postoperative stay was longer in the EG. In terms of postoperative outcomes, the rates of all complications were comparable. The median follow-up period of the EG and non-EG was 11.5 (1-106.4) months and 35.7 (1-110.0) months, respectively; there were significant differences in 5-year overall survival between the two groups (EG, 58.5% vs. non-EG, 91.5%; P = 0.031). However, there were no significant differences in 5-year disease-specific survival (EG, 62.1% vs. non-EG, 91.5%; P = 0.068) or 5-year disease-free survival (EG, 52.9% vs. non-EG, 60.8%; P = 0.132). Conclusions LTG seems to be safe and feasible in elderly patients. LTG had a limited effect on morbidity, disease recurrence, and survival in elderly patients. Therefore, age should not prevent elderly patients from benefitting from LTG.

Biliary cancer has a poor prognosis due to a lack of specific biomarkers and difficulty in diagnosis. The present study aimed to identify serum tumor markers for the diagnosis of biliary cancer via serological identification of antigens by recombinant cDNA expression cloning. Wingless‑type MMTV integration site family, member 7 (WNT7B) was identified as a target antigen, suggesting the presence of serum antibodies against this antigen. Deletion mutants were then prepared to evaluate the response to serum antibodies. When serum antibody levels against WNT7B deletion mutants (WNT7B

Purpose Delirium is associated with longer hospital stays and increased medical costs and mortality. This study explored the risk factors for postoperative delirium in gastroenterological surgery and investigated the association between qualitative changes in risk factors and the incidence of postoperative delirium. Methods A total of 418 patients > 18 years old who underwent gastroenterological surgery at our department between April 2018 and September 2019 were included. Risk factors were identified by comparing patients with and without postoperative delirium. Continuous variables were evaluated graphically using cubic spline curves. A logistic regression analysis was performed to assess independent risk factors. Results The incidence of postoperative delirium was 6.9%. The cubic spline curve showed that the incidence of postoperative delirium began to increase at 50 years old and increased sharply at 70 years old. A multiple logistic regression analysis of patients > 50 years old identified 5 risk factors: age >= 70 years, preoperative serum albumin 50 years old undergoing gastroenterological surgery.

Pancreatic neuroendocrine microadenoma (NEMA) is a nonfunctioning neuroendocrine tumor of less than 5 mm. Most studies of NEMA were based on autopsies, and few reports have revealed the clinical frequency of NEMA. We investigated the clinicopathological features of NEMA.The pathological results of the pancreatic resection specimens of patients, older than 18 years, who underwent pancreatic resection at Hokkaido University Hospital between April 2008 and December 2020 were retrospectively reviewed. The NEMAs were re-examined in detail and examined by immunohistochemical staining.Among 850 patients enrolled in this study, 24 NEMAs were identified in 12 patients (1.4%). Of the 12 patients, 2 patients had multiple endocrine neoplasia type 1, and the others had no hereditary disease, including 2 patients with multiple NEMAs. A difference in the number of NEMA was observed between patients with multiple endocrine neoplasia type 1 and sporadic NEMA. Intratumoral Ki-67 heterogeneity was correlated with the Ki-67 index. One grade 2 NEMA (Ki-67 index, 4.6%) was detected, but ATRX and DAXX labeling showed intact nuclear protein expression.Multiple sporadic NEMAs and grade 2 NEMAs were observed, suggesting that NEMA may have malignant potential. Thus, NEMAs should be carefully monitored for lymph node metastasis and postoperative recurrence.

Background The aim of this study was to evaluate the long-term nutritional state of patients with gastric cancer who underwent laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DTR) using oblique jejunogastrostomy method (OJG). Methods Medical records of 38 patients who underwent LPG-DTR using OJG (21 patients) or laparoscopic total gastrectomy with Roux-en-Y reconstruction (LTG-RY) (17 patients) between October 2011 and March 2018 were retrospectively reviewed. In these patients, clinicopathologic variables were analyzed using propensity score matching for age, sex, body mass index, American Society of Anesthesiologists physical state, clinical stage, and lymph node dissection. Operative outcomes and postoperative nutritional status were compared between the 2 groups. Results A total of 16 patients were matched to analyze the LPG-DTR and LTG-RY groups. The serum hemoglobin, total protein, and albumin levels at 12 months postoperatively (P=0.008, 0.034, and 0.049) and serum hemoglobin level at 24 months (P=0.025) in the LPG-DTR group was significantly superior to those in the LTG-RY group. Conclusions The postoperative nutritional status as long-term outcomes of patients who underwent LPG-DTR using OJG was significantly superior to those who underwent LTG-RY. The results hereby presented suggest that LPG-DTR using OJG for gastric cancer produces better postoperative nutritional status.

The pathological tumor classification of distal cholangiocarcinoma in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th edition is based on invasive depth, whereas that of perihilar cholangiocarcinoma (PHCC) continues to be layer-based. We aimed to clarify whether invasive depth measurement based on invasive tumor thickness (ITT) could help determine postoperative prognosis in patients with PHCC. We enrolled 184 patients with PHCC who underwent hepatectomy plus extrahepatic bile duct resection or hepatopancreatoduodenectomy with curative intent. ITT was measured using simple definitions according to the sectioning direction or gross tumor pattern. The median ITT was 5.8 mm (range 0.7–15.5). Using the recursive partitioning technique, ITT was classified into grades A (ITT

Background Lymph node (LN) metastasis in pancreatic body-tail cancer is a poor prognostic factor and the optimal LN dissection area for distal pancreatectomy (DP) remains unclear. Lymphatic flow from the tumors is thought to depend on the tumor sites. We examined LN metastasis frequency based on tumor site and recurrent patterns post-DP. Methods With a retrospective, single institutional study, we examined 100 patients who underwent DP as an upfront surgery for pancreatic cancer over 17 years. Tumor sites were classified as tumor confined to pancreatic body (and neck) (Pb(n) ); and pancreatic tail (Pt). We compared metastatic LN and recurrence patterns based on tumor site. The median overall survival (OS) and disease-free survival (DFS) were analyzed. Results LN metastasis occurred in 59/100 (59.0%), with 23 and 25 tumors located in the Pb(n) , and Pt, respectively. Those with the tumor in Pt had metastases to #10, #11d/p, and #18 LN mainly. However , the patients with the Pb(n) tumor had metastases to #8a/p, #11p, and #14p/d LN. There was no metastasis to #10 and #11d LN . The OS and DFS were 34 and 15 months, respectively. No significant difference was found in the OS, DFS, and recurrence patterns based on tumor sites. Conclusion Differences in metastatic LN sites were observed in pancreatic body-tail cancer when tumors were confined to the left or right of the left aortic edge. Although it is necessary to validate this finding with a large-scale study, organ-preserving DP might be a treatment option for selected patients depending on the tumor sites.

Objectives Neoadjuvant chemotherapy (NAC) has improved overall survival in patients with pancreatic ductal adenocarcinoma (PDAC), but its effects on immune gene signatures are unknown. Here, we examined the immune transcriptome after NAC for PDAC. Methods Resected tumor specimens were obtained from 140 patients with PDAC who received surgery first (n = 93) or NAC (n = 47). Six patients were randomly selected from each group, and RNA was extracted from tumor tissues. We compared 770 immune-related genes among the 2 groups using nCounterPanCancer Immune Profiling (NanoString Technologies, Seattle, Wash). Gene clusters were classified into 14 immune function groups based on gene ontology argolism by nSolver 4.0 software (NanoString Technologies), and corresponding immune cell function scores were compared. Results Eleven genes (LY86, SH2D1A, CD247, TIGIT, CR2, CD83, LAMP3, CXCR4, DUSP4, SELL, and IL2RA) were significantly downregulated in the NAC group. Gene expression analysis showed that the functions of regulatory T cells, B cells, and natural killer CD56 dim cells were significantly decreased in the NAC group. Conclusions Neoadjuvant chemotherapy may suppress regulatory T cells and B-cell function in the PDAC microenvironment. The 11 identified genes could be useful for predicting the efficacy of NAC and could be therapeutic targets for PDAC.

Highlights • It is unclear how Epstein–Barr virus causes cancer. • EBVaGC should be considered when multiple gastric cancer is recognized. • Robotic surgery has high-resolution three-dimensional images. • Using forceps with multi-joint functions was effective for this case., Introduction Epstein–Barr virus-associated gastric cancer (EBVaGC) sometimes appears as multiple gastric cancer lesions. Here, we report a case of robot-assisted laparoscopic total gastrectomy (RTG) for a relatively rare disease with four synchronized lesions in EBVaGC and discuss the usefulness of robotic gastrectomy. Presentation of case A 60-year-old woman was diagnosed with multiple gastric cancer because she had five lesions in the stomach and biopsy showed the presence of adenocarcinoma in four of the five lesions. We performed robot-assisted laparoscopic total gastrectomy on the patient. The histopathological diagnosis was multiple gastric cancer T1bN0M0 pStage IA. The four lesions were positive for the Epstein–Barr virus encoding region in in-situ hybridization and were considered to be EBVaGC. The patient had no sign of recurrence without postoperative therapy for 24 months. Disscussion EBVaGC was found in about 10% of all gastric cancer cases worldwide. EBVaGC sometimes appears as multiple gastric cancer, suggesting that EBV infection is closely related to the early stages of tumor formation. Total gastrectomy may be necessary for multiple gastric cancer such as EBVaGC, and robotic surgery is useful in total gastrectomy in terms of high-resolution three-dimensional images and using forceps with multi-joint functions. Conclusions We performed RTG on a patient with four synchronous lesions of EBVaGC, which is relatively rare. Robot-assisted laparoscopic total gastrectomy is known to be a safe procedure, and we effectively performed total gastrectomy for multiple EBVaGC.

Over the past 30 years, the therapeutic outcome for pancreatic ductal adenocarcinoma (PDAC) has remained stagnant due to the lack of effective treatments. We performed a genome-wide analysis to identify novel therapeutic targets for PDAC. Our analysis showed that Homo sapiens chromosome 16 open reading frame 74 (C16orf74) was upregulated in most patients with PDAC and associated with poor prognosis. Previously, we demonstrated that C16orf74 interacts with the catalytic subunit alpha of protein phosphatase 3 and plays an important role in PDAC invasion. However, the pathophysiologic function of C16orf74 is still unclear. In this study, through the analysis of C16orf74 interaction, we demonstrate a new strategy to inhibit the growth and invasion of PDAC. C16orf74 exists in the homodimer form under the cell membrane and binds integrin αVβ3 and is also involved in invasion by activating Rho family (Rac1) and MMP2. Considering that this dimeric form was found to be involved in the function of C16orf74, we designed an 11R-DB (dimer block) cell-permeable dominant-negative peptide that inhibits the dimer form of C16orf74. 11R-DB suppressed invasion and proliferation of PDAC cell lines by inhibiting phosphorylation of Akt and mTOR and also by inactivation of MMP2. 11R-DB also showed antitumor effects in an orthotopic xenograft model and peritoneal metastasis model. Thus, this study demonstrates that dimerized C16orf74, present in the cell membrane, is involved in pancreatic cancer invasion and proliferation. In addition, the C16orf74 dimer block cell-permeable peptide (11R-DB) has a potent therapeutic effect on PDAC in vitro and in vivo.

Purpose: This study aimed to evaluate the relationship between the body mass index (BMI) and the short-term outcomes of laparoscopic total gastrectomy (LTG). Subjects and Methods: Data of patients who underwent LTG for gastric cancer at six institutions between 2004 and 2018 were retrospectively collected. The patients were classified into three groups: low BMI (= 18.5 and = 25 kg/m2). In these patients, clinicopathological variables were analysed using propensity score matching for age, sex, the American Society of Anaesthesiologists physical state, clinical stage, surgical method, D2 lymph node dissection, combined resection of other organs, anastomosis method and jejunal pouch reconstruction. The surgical results and post-operative outcomes were compared among the three groups. Results: A total of 82 patients were matched in the analysis of the low BMI and normal BMI groups. There were no differences in operative time (P = 0.693), blood loss (P = 0.150), post-operative complication (P = 0.762) and post-operative hospital stay (P = 0.448). In the analysis of the normal BMI and high BMI groups, 208 patients were matched. There were also no differences in blood loss (P = 0.377), post-operative complication (P = 0.249) and post-operative hospital stay (P = 0.676). However, the operative time was significantly longer in the high BMI group (P = 0.023). Conclusions: Despite the association with a longer operative time in the high BMI group, BMI had no significant effect on the surgical outcomes of LTG. LTG could be performed safely regardless of BMI.

Bacteremia occurring after extensive hepatic resection and biliary reconstruction (Hx + Bx) for biliary cancer is a critical infectious complication. This study evaluated postoperative bacteremia and examined the potential usefulness of surveillance cultures.We retrospectively reviewed 179 patients who underwent Hx + Bx for biliary cancer from January 2008 to December 2018 in our department.Bacteremia occurred in 41 (23.0%) patients. Patients with bacteremia had a longer operation time and more frequent intraoperative transfusion and more frequently developed organ/space surgical site infection (SSI) than those without bacteremia. The most frequently isolated bacterial species from blood cultures were Enterococcus faecium (29.3%), Enterobacter cloacae (24.4%), and Enterococcus faecalis (22.0%). The SIRS duration of bacteremia associated with organ/space SSI was significantly longer than that of other infectious complications (median 96 h vs. 48 h; p = 0.043). Bacteremia associated with organ/space SSI occurred most often by postoperative day (POD) 30. The concordance rate of bacterial species between blood and surveillance cultures within POD 30 was 67-82%.Bacteremia associated with organ/space SSI required treatment for a long time and typically occurred by POD 30. Postoperative surveillance cultures obtained during this period may be useful for selecting initial antibiotic therapy because of their high concordance rate with blood cultures.

Pancreatic neuroendocrine neoplasms (PNENs) are rare, but their incidence has increased in recent years. Curative surgery is recommended in several global guidelines for resectable PNENs. Lymph node recurrence after R0 resection for PNENs is infrequent, and global guidelines recommend surgical resection for recurrence, if resectable. However, data on the prognosis after surgical resection for nodal recurrence of PNENs are limited. We herein report two cases in which long-term survival was achieved after repetitive lymphadenectomy for nodal recurrence of PNENs. In both cases, the pathological findings for primary PNEN showed well-differentiated neuroendocrine neoplasms and R0 resection was successfully performed. The Ki-67 index increased with each resection in both cases. Both patients showed long-term survival (10 and 14 years, respectively). Repetitive lymphadenectomy for nodal recurrence of PNENs may improve patient prognosis.

Simple Summary Distal pancreatectomy has become the standard surgery for patients with pancreatic body-tail cancers. The optimal area for dissection remains controversial, and there is an emphasis on preserving as much tissue as possible while eradicating the cancer. This multicenter, retrospective study evaluated the frequency and patterns of lymph node metastasis based on tumor site among 235 patients with pancreatic body-tail cancers to determine the optimal lymph node dissection area for distal pancreatectomy. Patients with pancreatic body cancer tumors showed no metastasis to the splenic hilum lymph node. Spleen-preserving pancreatectomy might be feasible for Pb cancer. Distal pancreatectomy (DP) with lymphadenectomy is the standard surgery for pancreatic body-tail cancer. However, the optimal lymph node (LN) dissection area for DP remains controversial. Thus, we evaluated the frequency and patterns of LN metastasis based on the tumor site. In this multicenter retrospective study, we examined 235 patients who underwent DP for pancreatic cancer. Tumor sites were classified as confined to the pancreatic body (Pb) or pancreatic tail (Pt). The efficacy index (EI) was calculated by multiplying the frequency of metastasis to each LN station by the five-year survival rate of patients with metastasis to that station. LN metastasis occurred in 132/235 (56.2%) of the patients. Patients with Pb tumors showed no metastasis to the splenic hilum LN. Distal splenic artery LNs and anterosuperior/posterior common hepatic artery LNs did not benefit from dissection for Pb and Pt tumors, respectively. In multivariate analysis, splenic artery LN metastasis was identified as an independent predictor of poor overall survival in patients with pancreatic body-tail cancer. In conclusion, differences in metastatic LN sites were evident in pancreatic body-tail cancers confined to the Pb or Pt. Spleen-preserving pancreatectomy might be feasible for Pb cancer.

Introduction A gastrointestinal stromal tumor (GIST) often arises in the stomach and small intestine, while esophageal GIST is rare. The first-choice treatment is surgical resection, but there is no standard technique. Herein, we describe our experience in the treatment of esophageal GIST and discuss the usefulness of robotic esophagectomy. Presentation of case The patient was a 60-year-old woman, who was diagnosed with a 30 mm GIST in the middle thoracic esophagus. We underwent robot-assisted thoracoscopic esophagectomy in the prone position. The duration of the thoracoscopic part was 69 min and the total operation time was 319 min. Total blood loss was 135 ml. The patient's postoperative course was uneventful after surgery and the patient was discharged home in good condition on the 18th postoperative day. Discussion The prognosis of esophageal GIST was less favorable compared with gastric GIST, and due to the anatomical peculiarities of the esophagus, which surgical procedure should be performed is still under debate. Robotic surgery has several technological advantages as it provides a three-dimensional view, ten times magnification, tremor control, and ambidexterity. Therefore, Robotic-assisted minimally invasive esophagectomy (RAMIE) allows achieving for safe R0 resection of esophageal GIST. Conclusion RAMIE may be useful for esophageal GIST because it facilitates safe and minimally invasive surgery in a limited space of the thoracic cavity., Highlights • There is no standard technique due to the anatomical peculiarities of the esophagus. • We think McKeown's procedure in the prone position has some advantages from others. • Robot surgery has a three-dimensional view, tremor control, and ambidexterity. • RAMIE would be useful techniques in a limited space of the thoracic cavity.

This retrospective study aimed to clarify whether the postoperative prognosis differs between right and left hepatectomy for Bismuth type I/II perihilar cholangiocarcinoma. Preoperative images of 195 patients with perihilar cholangiocarcinoma were reexamined. Patients with Bismuth type I/II perihilar cholangiocarcinoma without a difference in extraductal tumor invasion between the right and left sides of the hepatic portal region were classified into those undergoing left (L group) or right (R group) hepatectomy. Twenty-three patients (11.8%) were classified into the L group and 33 (16.9%) into the R group. All eight patients with pTis/1 belonged to the L group. The L group had significantly less liver failure than the R group (p = 0.001). One patient (4.3%) in the L group and four patients (12.1%) in the R group died from postoperative complications. Among 48 patients with pT2, the L group tended to have better overall survival (median, 12.2 vs. 5.6 years; p = 0.072), but not recurrence-free survival (median, 9.1 vs. 3.6 years; p = 0.477), in comparison to the R group. Postoperative survival after left hepatectomy for Bismuth type I/II perihilar cholangiocarcinoma is expected to be as long as that after right hepatectomy.

Boerhaave's syndrome is a rare life-threatening disease that requires prompt intervention. Thoracotomy has traditionally been considered the gold standard approach for treatment, but other minimally invasive approaches have recently been reported. Our institute reported the efficacy of minimally invasive abdominal and left thoracic approach in the treatment of patients with esophagogastric junction cancer and introduced it for the treatment of two patients with Boerhaave's syndrome. We intraoperatively sutured the rupture sites and irrigated the pleural cavity using thoracoscopy. Then, after confirming the absence of intraabdominal contamination, we performed jejunostomy or gastrostomy using laparoscopy. Patients' vital signs remained stable intraoperatively, and their postoperative periods were uneventful with no leakage or stricture. The minimally invasive abdominal and left thoracic approach for Boerhaave's syndrome is convenient and useful as it provides excellent visualization of the thoracic and abdominal cavities with the possibility of quickly switching between views.

Background There is no international consensus concerning the role of surgical treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC), but favorable prognoses can be expected for highly selected patients. Methods A comprehensive literature search of the PubMed and Cochrane databases was conducted using combinations of keywords to 4 July 2018. Eligible studies were those reporting on patients with histologically confirmed mPDAC undergoing surgery with curative intent. We excluded case reports with fewer than five patients, insufficient descriptions of survival data, and palliative or cytoreductive surgery as well as studies that assessed para-aortic lymph node metastasis or peritoneal washing cytology. Results Thirteen studies were deemed eligible, and six studies were identified from their references. The studies involved 428 patients who underwent surgical resection for liver metastases (n = 343), lung metastases (n = 57), and peritoneal dissemination (n = 28). Median overall survival (OS) in patients with synchronous liver metastases who underwent conversion surgery following favorable response to initial chemotherapy was 27 or 34 months, and peritoneum metastases was 28 months. Median OS after the initial treatment was varied from 51 to 121 months in metachronous lung metastasis and from 24 to 40 months in metachronous liver metastasis, respectively. Conclusion Encouraging OS was indicated in patients with synchronous mPDAC of liver and peritoneum who underwent conversion surgery. Metastasectomy for metachronous lung and liver oligometastases could be considered a practical treatment option.

The pT classification of the 8th American Joint Committee on Cancer (AJCC) for distal cholangiocarcinoma (DCC) is classified according to depth of invasion (DOI), which is the distance from the basal lamina to the most deeply advanced tumor cells. The Nagoya group proposed a new T classification for DCC based on invasive tumor thickness (ITT), which is the maximal vertical distance of the invasive cancer component (the ITT grade). In this study, we aimed to validate the ITT grade for the next pT classification of DCC in 110 patients. ITT could be measured in all patients, but DOI could only be measured in 62 (56%) patients. According to ITT grade, patients were classified into grades A to D, as follows: grade A, ITT1 mm (n=9); grade B, ITT 1 mm or more but5 mm (n=35); grade C, ITT 5 mm or more but10 mm (n=40); and grade D, ITT 10 mm or greater (n=26). The median overall survival times in patients with ITT grades A, B, C, and D were 12.8, 5.7, 3.7, and 2.0 years, respectively. ITT grade could discriminate postoperative survivals between grades. On multivariate analysis, ITT grade, regional lymph node metastasis, and distant metastasis were selected as independent prognostic factors. In summary, our results showed that ITT grade was a suitable alternative to DOI for pT classification in the next edition of the AJCC for DCC.

Background: Upfront surgery is recommended in patients with potentially resectable pancreatic ductal adenocarcinoma (R-PDAC) by National Comprehensive Center Network (NCCN) guidelines. However, even among R-PDACs, there is a subset that demonstrates extremely poor prognosis. The purpose of this study was to identify preoperative prognostic factors for upfront surgical resection of R-PDACs. Methods: The records of 278 consecutive patients with PDAC who underwent curative resection between 2001 and 2015 in a single institution were retrospectively reviewed. Preoperative factors to predict prognosis in patients with R-PDAC according to the NCCN guidelines were analyzed. Results: Of the 278 patients who underwent resection, 153 R-PDACs received upfront surgery with a median survival time (MST) of 26.4months. Tumor location (pancreatic head) (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.14-3.40; P=0.015), preoperative cancer antigen 19-9 (CA19-9) >100U/mL (OR 1.92, 1.31-2.80; P=0.0009), and tumor size >20mm (OR 1.50, 1.02-2.19; P=0.038) were identified as preoperative independent predictive risk factors for poor prognosis in patients with R-PDACs. In the patients with R-PDAC, 5-year survival was 60.7%, 21.5%, and 0% in patients with 0, 1 or 2, and 3 risk factors, respectively. There were significant differences in overall survival between the three groups (P