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Microbiota have been reported to influence the development of various gastrointestinal neoplasms through the mechanism of sustained inflammation; however, few data are available regarding their influence on intraductal papillary mucinous neoplasms. The aim of this study was to assess the association between specific microbiota and the clinicopathologic characteristics of intraductal papillary mucinous neoplasms of the pancreas.DNA was extracted from formalin-fixed, paraffin-embedded samples of 30 patients who underwent pancreatectomy for intraductal papillary mucinous neoplasm, and polymerase chain reaction was used to create sequence libraries using the primer set for the V3 and V4 region of 16S recombinant DNA. Filtered sequence reads were then processed into operational taxonomic units with a 97% identity threshold and the relative abundance of bacteria compared between the 2 groups using operational taxonomic units.There was a trend toward fewer Firmicutes and more Proteobacteria and Fusobacteria in the relative abundance of main duct operational taxonomic units than in branch duct operational taxonomic units. The relative abundances of Bacteroidetes (P.01) and Fusobacteria (P = .04) were significantly higher in invasive intraductal papillary mucinous neoplasms than in noninvasive intraductal papillary mucinous neoplasms. The relative abundance of the intestinal type was significantly lower in Firmicutes than the relative abundance of the nonintestinal type (P = .04). Notably, main duct operational taxonomic units with the intestinal subtype were affected by increased proportions of Proteobacteria and Fusobacteria, and Fusobacteria were abundant in the intestinal type of invasive main duct operational taxonomic units.Intratumoral microbiota may be involved in the progression of operational taxonomic units.

Lymphatic metastasis is a major route of metastasis in distal cholangiocarcinoma (DCC). The present study aimed to elucidate the pattern of lymph node (LN) metastasis and the effectiveness of LN dissection and postoperative adjuvant chemotherapy in patients with DCC.Patients who underwent surgical resection with curative intent for DCC were enrolled. The nomenclature of the LN stations was defined according to the Japanese Society of Hepato-Biliary-Pancreatic Surgery guidelines. Effectiveness of LN dissection of each station was calculated using frequency of LN metastasis to the station and 5-year survival rate of patients with LN metastasis to that station.Of the 105 patients included in the study, 46 (43.8%) had LN metastasis, and 43 (41.0%) underwent postoperative adjuvant therapy. LN metastasis, serum carbohydrate antigen (CA) 19-9 level 37 U/mL, and positive bile duct margin were independent risk factors for shorter overall survival (OS). The most common metastatic LN station at surgery was No. 13 (32.7%), followed by No. 12 (19.2%), No. 17 (9.6%), and No. 8 (6.6%). There was no effectiveness of LN dissection of the station No. 8, 14, and 16. Adjuvant chemotherapy was significantly associated with longer OS in patients with LN metastasis but not in those with positive ductal margins or serum CA 19-9 level 37 U/mL.Postoperative adjuvant chemotherapy was associated with a better prognosis in patients with DCC and LN metastasis. However, a more effective therapeutic strategy is required to improve the prognosis of patients with other negative prognostic factors.

Background Creating a good surgical visual field is one of the most important factors for performing a successful surgery. Here, we introduce a useful technique for creating a good liver parenchymal visual transection plane during laparoscopic partial hepatectomy and compare the perioperative outcomes of our current technique with those of conventional techniques. Methods We reviewed the data of patients who underwent laparoscopic partial hepatectomy between July 2016 and December 2020. The current technique for creating transection planes was first applied in our department in April 2019. The patients were divided into conventional (forceps) and current (silicone ring) technique groups, depending on the surgical technique. Results Twenty-eight and 12 patients underwent laparoscopic partial hepatectomy using the conventional and current techniques, respectively, when the difficulty level-as determined by IWATE criteria-was low. Although the tumor size was significantly larger (median: 22.5 vs. 15 mm, P=0.04) in the current technique group, the estimated intraoperative blood loss was significantly lower (median: 50 vs. 100 mL, P=0.01), and the median surgical margin was significantly longer (median: 7 vs. 3 mm, P=0.02). There were no significant between-group differences in surgical time (median: 344 vs. 240 min, P=0.14), postoperative hospital stay duration (median: 11 vs. 9.5 d, P=0.051), and the incidence of complications (P=0.63). Conclusion We believe that the technique involving the use of a silicone ring can result in better surgical outcomes as it provides a good visual hepatic transection plane during laparoscopic partial hepatectomy.

BACKGROUND Carcinoma of the ampulla of Vater is an uncommon ampullo-pancreatobiliary neoplasm, and the most common histological type is adenocarcinoma with a tubular growth pattern. Invasive micropapillary carcinoma (IMPC) is an aggressive variant of adenocarcinoma in several organs that is associated with lymph node metastasis and poor prognosis. IMPC was first described as a histological subtype of breast cancer; however, IMPC of the ampulla of Vater is extremely rare, with only three articles reported in the English literature. CASE SUMMARY We have reported a case of IMPC of the ampulla of Vater in an 80-year-old man. Microscopically, the surface area of the carcinoma was composed of tubulopapillary structures mimicking intra-ampullary papillary-tubular neoplasm, and the deep invasive front area exhibited a pattern of IMPC. The carcinoma showed lymphatic invasion and extensive lymph node metastasis. The immunohistochemical study revealed mixed intestinal and gastric/pan-creatobiliary phenotypes. CONCLUSION This rare subtype tumor in the ampulla of Vater showed a histologically mixed phenotype and exhibited aggressive behavior.

Neoadjuvant therapy (NAT) is used to treat not only advanced pancreatic cancer but also resectable lesions. The present study investigated the effectiveness of postoperative adjuvant chemotherapy for patients with pancreatic cancer who underwent surgical resection after NAT. Patients who underwent macroscopically curative resection after NAT for pancreatic cancer were enrolled. Adjuvant chemotherapy was defined as at least 1 cycle of planned chemotherapy within 3 months after the date of surgery and included S-1, gemcitabine, or both. We retrospectively examined the effect of adjuvant chemotherapy on overall survival (OS) and recurrence-free survival (RFS) as a function of patients’ clinicopathological factors. Ninety-seven patients were included in the study, of which 68 (70.1%) underwent adjuvant chemotherapy. Administration of adjuvant chemotherapy was significantly associated with prolonged OS and RFS in patients whose elevated levels of carbohydrate antigen 19-9 or duke pancreatic monoclonal antigen type-2 did not normalize after NAT. In patients with pathological lymph node metastasis, the administration of adjuvant chemotherapy was significantly associated with longer OS but did not improve PFS. Postoperative adjuvant chemotherapy was associated with prolonged postoperative survival in patients with pancreatic cancer who did not sufficiently respond to NAT as judged by tumor marker expression.

Background Cholangiolocellular carcinoma (CoCC) is an extremely rare disease comprising less than 1% of all primary malignant liver tumors. No effective treatment other than resection has been established. Herein, we report a case of locally advanced CoCC diagnosed as unresectable, which was successfully treated with curative resection after downsizing chemotherapy. Case presentation A 59-year-old Japanese woman with chronic hepatitis B was diagnosed with locally advanced intrahepatic cholangiocellular carcinoma. As it was difficult to perform R0 resection in the local hospital, chemotherapy combined with gemcitabine plus cisplatin was administered every 3 weeks. After a total of 10 courses of chemotherapy over 10 months the tumor was shown to be reduced in size by computed tomography imaging, and she was referred to our department for surgical resection. The effect of chemotherapy was classified as a “partial response” in the response evaluation criteria of solid tumors. After adding one course of chemotherapy, an extended left hepatectomy with resection of the caudate lobe was performed. R0 resection was achieved. Based on the pathological findings, the final diagnosis of CoCC was determined and eight courses of S-1 adjuvant chemotherapy were administered. At 14 months after the operation, the patient was alive without tumor recurrence. Conclusions Downsizing chemotherapy with gemcitabine and cisplatin may be an effective treatment strategy in locally advanced CoCC. Further evidence is required to establish an optimal strategy for the treatment of locally advanced CoCC.

A 55-year-old man presented with vomiting and upper abdominal pain. Two months later, computed tomography revealed jejunal wall thickening and contrast enhancement. Double-balloon endoscopy revealed severe jejunal stenosis and mucosal prolapse. The patient was diagnosed with stenotic ischemic small bowel inflammation and underwent partial small bowel resection. Clinicians should consider intraperitoneal band formation in the differential diagnosis of patients without a history of abdominal surgery or trauma. Surgical resection should be considered to prevent strangulation ileus.

The development and application of cancer immunotherapy to pancreatic cancer has not progressed because its efficacy has not been proven in clinical trials. In this study, we aimed to explore potential targets of immune checkpoint inhibitor therapy for pancreatic cancer treatment.We collected resected specimens from 40 patients with pancreatic cancer who underwent resection at our Institution without any preoperative treatment. We evaluated the expression of molecules in the programmed death receptor-1 (PD-1), T cell immunoglobulin mucin-3 (Tim-3)/Galectin-9, and CD155/T cell immunoreceptor with Ig and ITIM domains (TIGIT) pathways using immunohistochemical staining. The correlation between the expression pattern of these molecules and patient prognosis were assessed using Kaplan-Meier analysis.An increased number of CD8Modifications in the immune environment to increase T cell infiltration into tumors could result in the PD-1 pathway becoming a potential target to treat pancreatic cancer using immune checkpoint inhibition.

Although distant metastasis from pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, some single center studies reported that lung metastasis has a favorable prognosis. The aim of this study is to evaluate the prognostic value of site-specific metastasis after pancreatectomy for PDAC, with a focus on lung metastasis.Data from 117 cases of lung metastasis after pancreatectomy were collected retrospectively from 23 institutions in Japan. To compare the sites of metastasis we also collected the data of 134 patients with liver only metastasis, 67 patients with peritoneal only metastasis and 121 patients with locoregional recurrence alone.In patients with lung only metastasis, the median time from recurrence to death (RTD) was 23.1 months, which was better in comparison to other sites of recurrence. In lung metastasis group, the patients who underwent pulmonary resection had better long-term outcomes in comparison to those who did not. (RTD: 29.2 vs 15.2, P .001). In the multivariate analysis, solitary metastasis (HR 5.03; 95% CI 1.195-21.144, P = .022) and postoperative chemotherapy (HR 14.089; 95% CI 1.729-114.77, P = .023) were identified as significant prognostic factors after lung resection.Surgical resection is a favorable option for selected patients with a solitary lung metastasis and for whom adjuvant chemotherapy can be administrated.

Highlights • Retroperitoneal schwannomas in the abdominal cavity are rare and pose difficulty in preoperative diagnosis and management. • Imaging modalities are usually not sufficient to conclude a diagnosis. • EUS-FNA is useful to confirm preoperative diagnosis. • In EUS-FNA, diagnosis can be accurate if the tumor size is small and tumor is devoid of intratumoral degenerations., Introduction Schwannomas are tumors that originate from the Schwann cells present in the nerve sheath of peripheral nerves. They are commonly seen in cephalocervical areas. Schwannomas in the abdominal cavity are rare. Here, we discuss a case of retroperitoneal schwannoma lying dorsal to pancreas with critical relations to surrounding vessels. Presentation of case A 74 years old asymptomatic male was found with elevated amylase level on his routine blood examination. MR imaging revealed retroperitoneal mass of size 21*18*24 mm. EUS-FNA confirmed retroperitoneal schwannoma. The patient had co-morbid renal disease and was on hemodialysis. During the latest follow up, the tumor was 41*37*41 mm in size located dorsal to the confluence of right renal vein and inferior vena cava. The tumor was in contact with inferior vena cava, horizontal part of duodenum, right renal artery, right kidney, and adrenal gland. The patient underwent laparotomy and the tumor was extract with intact capsule. There were no post-operative complications. Discussion Pre-operative diagnosis in retroperitoneal schwannomas is challenging because imaging features are usually non-specific, and biopsy is the only diagnostic technique. EUS-FNA, which has low diagnostic accuracy, is useful in pre-operative diagnosis of small tumors devoid of intra-tumoral degeneration. Conclusion Retroperitoneal schwannoma is a rare entity. Preoperative diagnosis and curative resection are technically difficult. Care should be given during preoperative investigations and surgical resection of the tumor. EUS-FNA can be a useful diagnostic tool.

The diagnostic value of 18F-fluorodeoxyglucose (FDG) uptake in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas remains unclear. This study aimed to assess the role of FDG uptake in the diagnosis of different degrees of dysplasia of IPMNs. We retrospectively analyzed the following three points in 84 patients with IPMNs: (1) risk factors to predict high-grade dysplasia (HGD) and invasive carcinoma (INV), (2) the relationship between FDG uptake and glucose transporter 1 (GLUT-1) expression, and (3) the relationship between FDG uptake and the presence of mural nodules. The histopathological diagnosis was low-grade dysplasia (LGD) in 43 patients, HGD in 16, and INV in 25. The maximum standardized uptake value (SUV-max) was significantly higher in INV than in LGD/HGD (p &lt, 0.0001, p = 0.0136). The sensitivity and specificity to discriminate INV from LGD/HGD were 80.0% and 86.2%, respectively, using the receiver operator characteristic curve, when the optimal cutoff score of SUV-max was set at 4.03. Those values were not different between HGD and LGD. More than half of HGD patients had low GLUT-1 expression. Taken together, FDG-PET/CT is useful in distinguishing between non-invasive and invasive IPMN. Our results offer critical information that may determine surgical treatment strategies.

Simple Summary Even today, there are no effective targeted therapies for intrahepatic cholangiocarcinoma (ICC) patients. Clarifying the molecular pathogenesis of ICC will contribute to the development of treatment strategies for this disease. In this study, we searched for the role of the miR-29-3p-family and its association with oncogenic pathway. Interestingly, aberrant expression of ITGA6 and ITGB1 was directly regulated by the miR-29-3p-family which are involved in multiple oncogenic pathways in ICC, and enhanced malignant transformation of ICC cells. Furthermore, SP1 which is a transcriptional activator of ITGA6/ITGB1, is regulated by the miR-29-3p-family. These molecules may be novel therapeutic targets for ICC. Abstract The aggressive nature of intrahepatic cholangiocarcinoma (ICC) renders it a particularly lethal solid tumor. Searching for therapeutic targets for ICC is an essential challenge in the development of an effective treatment strategy. Our previous studies showed that the miR-29-3p-family members (miR-29a-3p, miR-29b-3p and miR-29c-3p) are key tumor-suppressive microRNAs that control many oncogenic genes/pathways in several cancers. In this study, we searched for therapeutic targets for ICC using the miR-29-3p-family as a starting point. Our functional studies of cell proliferation, migration and invasion confirmed that the miR-29-3p-family act as tumor-suppressors in ICC cells. Moreover, in silico analysis revealed that “focal adhesion”, “ECM-receptor”, “endocytosis”, “PI3K-Akt signaling” and “Hippo signaling” were involved in oncogenic pathways in ICC cells. Our analysis focused on the genes for integrin-α6 (ITGA6) and integrin-β1 (ITGB1), which are involved in multiple pathways. Overexpression of ITGA6 and ITGB1 enhanced malignant transformation of ICC cells. Both ITGA6 and ITGB1 were directly regulated by the miR-29-3p-family in ICC cells. Interestingly, expression of ITGA6/ITGB1 was positively controlled by the transcription factor SP1, and SP1 was negatively controlled by the miR-29-3p-family. Downregulation of the miR-29-3p-family enhanced SP1-mediated ITGA6/ITGB1 expression in ICC cells. MicroRNA-based exploration is an attractive strategy for identifying therapeutic targets for ICC.

Background: Unresectable pancreatic ductal adenocarcinoma (UR-PDAC) has a poor prognosis. Conversion surgery is considered a promising strategy for improving the prognosis of UR-PDAC. This study aimed to investigate the clinical benefits of conversion surgery in patients with UR-PDAC. Methods: We retrospectively evaluated patients with PDAC who were referred to our department for possible surgical resection between January 2006 and December 2019. Conversion surgery was performed only in patients with UR-PDAC who could expect R0 resection. We analyzed the prognostic factors for overall survival among patients who underwent conversion surgery. Results: Overall, 638 patients with advanced pancreatic cancer were enrolled in this study. According to resectability, resectable cancer (R) was present in 180 patients, borderline resectable cancer (BR) was present in 60 patients, unresectable locally advanced cancer (UR-LA) was present in 252 patients, and unresectable cancer with distant metastasis (UR-M) was present in 146 patients. Conversion surgery was performed in 20 of the 398 UR cases (5.1%). The median period between the initial therapy and conversion surgery was 15.5 months. According to the Response Evaluation Criteria in Solid Tumors (RECIST) evaluation, the treatment response was CR in one patient, PR in 13, SD in five, and PD in one. Downstaging was pathologically determined in all cases. According to the Evans grading system, grade I was observed in four patients (20%), grade IIb was observed in seven (35%), III was observed in seven (35%), and IV was observed in two (10%). We compared the overall survival period from initial treatment among patients undergoing conversion surgery, the median overall survival durations in the conversion surgery, R, BR, UR-LA, and UR-M groups were 73.7, 32.7, 22.7, 15.7, and 8.8 months, respectively. Multivariate analysis revealed that the presence or absence of chemoradiotherapy (CRT) and the RECIST partial response (PR)/complete response (CR) for the main tumor were statistically significant prognostic factors for overall survival among patients undergoing conversion surgery (p = 0.004 and 0.03, respectively). Conclusion: In UR-PDAC, it is important to perform multidisciplinary treatment, including CRT with conversion surgery.

Background The clamp crushing method and the use of the Cavitron ultrasonic surgical aspirator (CUSA) are widely accepted techniques for hepatic parenchymal transection. The actuator-driven pulsed water jet (ADPJ) with high tissue selectivity is a new technology that was shown as a safe transection tool in preclinical models, although not much is known about its safety criteria in patients. Therefore, its strongest advantage, the best indications for its use, and its performance in comparison with other transection methods remain to be clarified. In this report, we present several representative cases to help answer these questions. Methods We started using the ADPJ in December 2017, only in cases where the tumor was very close to major vessels or attached to them, along a considerable length, to preserve vessels and prevent postoperative liver failure. All the cases underwent highly demanding procedures. We avoided using this device in cases such as liver cirrhosis, where the hepatic parenchyma was very hard. Results Six cases fulfilled our limited indications for using ADPJ. The median age and number of tumors were 55 years (10 to 69 y) and 2.5 years (1 to 4 y), respectively. The mean tumor size was 7.8 cm (2.8 to 21 cm), the minimum distance between the tumor and major vessels to be preserved was 0 mm (0 to 4 mm), and the contact length of the tumor and major vessels was 26 mm (19 to 40 mm). Regarding the surgical outcome, the median operation time and blood loss were 559 minutes (508 to 919 min) and 620 mL (230 to 860 mL), respectively. We achieved a negative surgical margin (R0 resection) in all cases. Conclusions Using ADPJ, we could perform R0 hepatectomy in all cases, which preoperatively were considered to have a high chance of being margin positive. We consider the best indication for using ADPJ is when the tumor and vessels to be preserved are attached or very close over a long distance.

A 78-year-old woman underwent left total mastectomy for breast cancer at 65 years of age.Thirteen years after the primary surgery, CT showed a single 46mm tumor located in liver segment 4.The tumor was difficult to distinguish between cholangiocellular carcinoma and liver metastasis of the breast cancer.We did not perform biopsy, considering dissemination, and performed left hemihepatectomy and left caudate lobectomy.Pathological findings revealed liver metastasis of breast cancer.Hepatic resection is a useful option in cases of single liver metastasis from breast cancer that are difficult to distinguish from cholangiocellular carcinoma.

To investigate the differences in nutritional status 1 year after pancreaticogastrostomy (PG) using vertical suturing (VS) vs. twin square horizontal mattress (HMS) suturing in patients undergoing pancreaticoduodenectomy (PD). The subjects of this study were 134 patients who underwent PD, followed by PG, which was closed by VS in 52 and by HMS in 82. We evaluated the peri- and postoperative factors, nutritional parameters, diameter of the remnant main pancreatic duct, and glucose intolerance 1 year postoperatively. Forty-five (87%) patients from the VS group and 75 (91%) patients from the HMS group survived for more than 1 year. The incidences of intraabdominal abscess and pancreatic fistula were significantly lower in the HMS group than in the VS group (19.2% vs. 6.6% and19.2% vs. 2.6%, respectively). There were no significant changes in the total protein, serum albumin, and HbA1c levels 1 year postoperatively. The postoperative expansion ratio of the main pancreatic duct diameter was significantly smaller in the HMS group than in the VS group. The strongest risk factor for body weight loss 1 year postoperatively was a non-soft pancreas texture. HMS was superior to VS for preventing early postoperative complications and did not affect pancreatic function.

A metabolic shift to glycolysis is reportedly involved in radioresistance. We examined whether pretreatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), which can detect enhanced glucose uptake, was able to predict the therapeutic response to chemoradiotherapy (CRT) in patients with pancreatic cancer (PC). Of 125 PC patients (75 unresectable and 50 borderline resectable), 37 and 26 underwent induction chemotherapy before CRT and surgical resection after CRT, respectively. FDG-PET was performed at three different institutions. Of the 88 patients who underwent upfront CRT, 31 (35%), 34 (39%), and 23 (26%) showed a partial response (PR), stable disease, and progressive disease, respectively. The tumor PR rate was an independent factor associated with longer overall survival (OS) on multivariate analysis. We evaluated the optimal cut-off of maximum standardized uptake values (SUVmax) at initial diagnosis to detect the tumor PR rate at the three institutions separately. The SUVmax was independently associated with tumor response rate on multivariate analysis. In the low SUVmax group, induction chemotherapy had no significant impact on OS. In contrast, induction chemotherapy was significantly associated with longer OS in the high SUVmax group. FDG-PET SUVmax was significantly associated with the therapeutic response to CRT in PC patients. Moreover, induction chemotherapy may improve the prognosis of patients with a high SUVmax tumor.

MicroRNAs (miRNAs) are unique in that a single miRNA molecule regulates a vast number of RNA transcripts. Thus, aberrantly expressed miRNAs disrupt tightly controlled RNA networks in cancer cells. Our functional screening showed that expression of miR-124-3p was downregulated in pancreatic ductal adenocarcinoma (PDAC) tissues. Here, we aimed to investigate the anti-tumor roles of miR-124-3p in PDAC cells and to identify miR-124-3p-mediated oncogenic signaling in this disease. Ectopic expression of miR-124-3p inhibited cancer cell migration and invasion in PDAC cells. Moreover, restoration of miR-124-3p suppressed oncogenic signaling, as demonstrated by reduced phosphorylation of focal adhesion kinase, AKT, and extracellular signal-regulated kinase, in PDAC cells. Our in silico database analyses and luciferase reporter assays showed that two cell-surface matrix receptors, integrin α3 (ITGA3) and integrin β1 (ITGB1), were directly regulated by miR-124-3p in PDAC cells. Overexpression of ITGA3 and ITGB1 was confirmed in PDAC clinical specimens. Interestingly, a large number of cohort analyses from TCGA database showed that high expressions of ITGA3 and ITGB1 were significantly associated with poor prognosis of patients with PDAC. Knockdown of ITGA3 and ITGB1 by siRNAs markedly suppressed the migration and invasion abilities of PDAC cells. Moreover, downstream oncogenic signaling was inhibited by ectopic expression of miR-124-3p or knockdown of the two integrins. The discovery of anti-tumor miRNAs and miRNA-mediated oncogenic signaling may provide novel therapeutic targets for the treatment of PDAC.

Background/aim High mobility group box-1 (HMGB1) induces the release of proinflammatory cytokines and chemokines as a late-acting mediator of inflammation. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer. However, little is known about the relationship between HCC and HMGB1 and its receptor RAGE (receptor for advanced glycation end products). This study analyzes the clinicopathological relevance of HMGB1 expression level and the effect of HMGB1 expression on the characteristics of HCC. Materials and methods Samples from 75 HCC patients including 13 with positive hepatitis B surface antigen and 36 with hepatitis C antibody were studied. The expression of HMGB1 in paired cancer and non-cancerous tissues from patients with HCC was assessed using reverse-transcription polymerase chain reaction (RT-PCR) and western blotting. Quantitative RT-PCR data were analyzed in association with the clinicopathological factors of patients with HCC. Results The expression of HMGB1 mRNA in HCC was high in well-differentiated tumors, but declined as tumors dedifferentiated to moderately and poorly differentiated HCC. The levels of HMGB1 mRNA showed a negative correlation with the presence of portal invasion (p=0.005) and the rise of serum PIVKA-II (p=0.034). There was no clear correlation between HMGB1 expression and proliferation activity of HCC using Ki-67 staining. Conclusion In HCC, HMGB1 expression level correlated inversely with tumor differentiation. The RAGE-HMGB1 interaction may play a greater role in the early stages of HCC tumorigenesis than during cancer development.

BACKGROUND The aim of this study was to confirm whether intraoperative fluorescence vascular imaging using indocyanine green (FVI-ICG) is useful for evaluating splenic perfusion after spleen-preserving distal pancreatectomy (SPDP) performed with the Warshaw technique (SPDP-W). METHODS We evaluated the blood perfusion of the spleen with an intraoperative FVI-ICG system after SPDP-W. All of the patients underwent dynamic computed tomography (CT) scans at one post-operative week and one post-operative month to evaluate the post-operative blood perfusion of the spleen. Then, the post-operative perfusion status of the spleen according to CT and the intraoperative fluorescence status of the spleen were compared. RESULTS Five patients were enrolled in this study. None of the patients required secondary splenectomies. We detected a tendency towards a close relationship between the intraoperative fluorescence level of the spleen according to FVI-ICG performed after SPDP-W and post-operative splenic perfusion as evaluated by CT. Improved splenic perfusion was seen at one post-operative month in all cases, including a case in which poor splenic perfusion was initially detected. CONCLUSION We detected a close relationship between the fluorescence level of the spleen on intraoperative FVI-ICG and the post-operative perfusion status of the spleen among patients who underwent SPDP-W. Intraoperative FVI-ICG could help surgeons to safely preserve the spleen after SPDP-W.

Highlights • Severe acute pancreatitis with necrotizing colonic perforation is refractory and the mortality is high. • Step-up approach for severe acute pancreatitis with infectious walled-off necrosis has been increasingly used. • We performed percutaneous drainage, ileostomy, and video-assisted retroperitoneal debridement (VARD) as a step-up approach. • VARD enable sufficient washing of the abscess and radical debridement of the necrotic tissues under direct view., Introduction Colorectal complications including penetration and perforation in acute pancreatitis often become severe and fatal. Effective drainage is pivotal for successful treatment. We present a case of large retroperitoneal abscess with colonic necrotizing perforation due to severe acute pancreatitis treated with video-assisted retroperitoneal debridement (VARD) in a step-up approach. Presentation of case A 31-year-old man was admitted to a general hospital with a diagnosis of severe acute pancreatitis. Ten days after onset, he was referred to our hospital for more intensive treatment. On day 16, he experienced melena and shock, and embolization of the three straight arteries of the descending colon was performed. On day 30, percutaneous drainage was performed for large retroperitoneal abscess. On day 36, ileostomy was performed because the drained pus from the retroperitoneal abscess became feces-like. On day 58, VARD was performed to treat the refractory retroperitoneal abscesses causing high systemic inflammation due to insufficient drainage. On day 85, fluoroscopic examination showed disappearance of the abscess cavity. He was transferred to the previous hospital on day 89. Discussion Colonic perforation due to severe acute pancreatitis often causes sepsis and fatal condition of patients, and drainage of the retroperitoneal abscesses via laparotomy is thought to be highly invasive and risky. VARD enables radical necrosectomy and drainage less invasively. Conclusions VARD enabled less invasive treatment for patients with large retroperitoneal abscess due to colonic necrotizing perforation in severe pancreatitis.

// Keiichi Yonemori 1 , Naohiko Seki 2 , Tetsuya Idichi 1 , Hiroshi Kurahara 1 , Yusaku Osako 1 , Keiichi Koshizuka 2 , Takayuki Arai 2 , Atsushi Okato 2 , Yoshiaki Kita 1 , Takaaki Arigami 1 , Yuko Mataki 1 , Yuko Kijima 1 , Kosei Maemura 1 and Shoji Natsugoe 1 1 Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Sakuragaoka, Kagoshima 890-8520, Japan 2 Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan Correspondence to: Naohiko Seki, email: naoseki@faculty.chiba-u.jp Keywords: pancreatic ductal adenocarcinoma, microRNA, expression signature, miR-216b-3p , FOXQ1 Received: February 07, 2017 Accepted: June 26, 2017 Published: July 26, 2017 ABSTRACT We analysed the RNA sequence-based microRNA (miRNA) signature of pancreatic ductal adenocarcinoma (PDAC). Aberrantly expressed miRNAs were successfully identified in this signature. Using the PDAC signature, we focused on 4 clustered miRNAs, miR-216a-5p , miR-216a-3p , miR-216b-5p and miR-216b-3p on human chromosome 2p16.1. All members of the miR-216 cluster were significantly reduced in PDAC specimens. Ectopic expression of these miRNAs suppressed cancer cell aggressiveness, suggesting miR-216 cluster as anti-tumour miRNAs in PDAC cells. The impact of miR-216b-3p (passenger strand of pre- miR-216b ) on cancer cells is still ambiguous. Forkhead box Q1 ( FOXQ1 ) was directly regulated by miR-216b-3p and overexpression of FOXQ1 was confirmed in clinical specimens. High expression of FOXQ1 predicted a shorter survival of patients with PDAC by Kaplan–Meier analysis. Loss-of-function assays showed that cancer cell migration and invasion activities were significantly reduced by si FOXQ1 transfectants. We investigated pathways downstream from FOXQ1 by using genome-wide gene expression analysis. Identification of the miR-216-3p/FOXQ1 -mediated network in PDAC should enhance understanding of PDAC aggressiveness at the molecular level.

Background Among gastrointestinal cancers, the prognosis of pancreatic cancer is one of the poorest, with a large number of patients being diagnosed with unresectable tumors at the first visit to a doctor. The aims of the present study were to investigate the circulating tumor cells (CTC) in peripheral blood in order to assess their clinical significance in patients with pancreatic cancer. Methods Sixty-five patients with advanced pancreatic cancer were enrolled. Borderline resectable pancreatic tumor patients were 9, and Unresectable patients were 56. The CellSearch system was used to isolate and enumerate CTCs. Results CTCs were identified in 21 out of 65 patients (32.3%) with only unresectable tumors. The overall survival rate was significantly lower in unresectable patients with than in those without CTCs ( P = 0.0051). CTC positivity was significantly higher in patients with than in those without liver metastasis. A multivariate analysis identified the presence or absence of CTCs as an independent prognostic factor. Follow-up blood specimens were obtained from 40 patients treated with chemotherapy or chemoradiotherapy. The incidences of CTC positivity at three months after beginning of treatments in patients with progressive disease and stable disease or a partial response were 45.4% and 24.1%, respectively. The overall survival rate was significantly lower in patients with than in those without CTCs even after treatments ( P = 0.045). Conclusion CTC numbers represents a useful tool for predicting prognoses and therapeutic responses to chemotherapy among patients with advanced pancreatic cancer.

Laparoscopic surgical training using a box trainer facilitates mastery of laparoscopic surgery. Few studies have investigated whether visualizing the surgical field in the box trainer improves performance of laparoscopic surgical procedures during laparoscopic training. An original box trainer equipped with a transparent top made of mesh covered with a latticed structure was developed and used for evaluation of novices during laparoscopic training. Three tasks (levels 1 to 3) involving organ handling while setting the surgical field were arranged to evaluate the efficacy of training. Forty‐five students were divided into three groups: group A, students without practical training; group B, students trained using the covered box trainer; and group C, students trained using the transparent box trainer. Completion time of each task before and after training was compared. Training significantly reduced the operating time, with a significant difference between the level 1 task and the levels 2 (P

// Tetsuya Idichi 1 , Naohiko Seki 2 , Hiroshi Kurahara 1 , Keiichi Yonemori 1 , Yusaku Osako 1 , Takayuki Arai 2 , Atsushi Okato 2 , Yoshiaki Kita 1 , Takaaki Arigami 1 , Yuko Mataki 1 , Yuko Kijima 1 , Kosei Maemura 1 and Shoji Natsugoe 1 1 Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan 2 Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan Correspondence to: Naohiko Seki, email: naoseki@faculty.chiba-u.jp Keywords: microRNA, miR-217 , pancreatic ductal adenocarcinoma, ANLN , tumor-suppressor Received: January 11, 2017 Accepted: May 08, 2017 Published: May 29, 2017 ABSTRACT Analysis of our microRNA (miRNA) expression signature of pancreatic ductal adenocarcinoma (PDAC) revealed that microRNA-217 ( miR-217 ) was significantly reduced in cancer tissues. The aim of this study was to investigate the antitumor roles of miR-217 in PDAC cells and to identify miR-217 -mediated molecular pathways involved in PDAC aggressiveness. The expression levels of miR-217 were significantly reduced in PDAC clinical specimens. Ectopic expression of miR-217 significantly suppressed cancer cell migration and invasion. Transcription of actin-binding protein Anillin (coded by ANLN ) was detected by our in silico and gene expression analyses. Moreover, luciferase reporter assays showed that ANLN was a direct target of miR-217 in PDAC cells. Overexpression of ANLN was detected in PDAC clinical specimens by real-time PCR methods and immunohistochemistry. Interestingly, Kaplan–Meier survival curves showed that high expression of ANLN predicted shorter survival in patients with PDAC by TCGA database analysis. Silencing ANLN expression markedly inhibited cancer cell migration and invasion capabilities of PDAC cell lines. We further investigated ANLN -mediated downstream pathways in PDAC cells. “Focal adhesion” and “Regulation of actin binding protein” were identified as ANLN -modulated downstream pathways in PDAC cells. Identification of antitumor miR-217 / ANLN -mediated PDAC pathways will provide new insights into the potential mechanisms underlying the aggressive course of PDAC.

// Takaaki Arigami 1, 2, * , Yoshikazu Uenosono 2, * , Shigehiro Yanagita 1 , Keishi Okubo 1 , Takashi Kijima 1 , Daisuke Matsushita 1 , Masahiko Amatatsu 1 , Takahiko Hagihara 1 , Naoto Haraguchi 1 , Yuko Mataki 1 , Katsuhiko Ehi 1 , Sumiya Ishigami 1 and Shoji Natsugoe 1, 2 1 Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan 2 Molecular Frontier Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan * These authors have contributed equally to this work Correspondence to: Takaaki Arigami, email: arigami@m.kufm.kagoshima-u.ac.jp Keywords: sentinel node navigation surgery, basin dissection, sentinel node mapping, outcomes, early gastric cancer Received: January 21, 2017 Accepted: April 11, 2017 Published: May 03, 2017 ABSTRACT Sentinel node navigation surgery (SNNS) has been recognized as a minimally invasive tool for individualized lymphadenectomy in patients with early gastric cancer (EGC). The aim of this study was to compare clinicopathological factors, adverse events, and clinical outcomes between sentinel node mapping (SNM) and SN dissection (SND) groups and assess the clinical utility of SNNS in patients with EGC. The clinical data of 157 patients with EGC, diagnosed as clinical T1N0M0 with tumors ≤ 40 mm, undergoing SNNS between March 2004 and April 2016 were retrospectively reviewed. Twenty-seven patients were excluded from the analysis. In the remaining 130 patients, 59 and 71 patients underwent standard lymphadenectomy for SNM and SND, respectively. The sentinel node detection rate in the SNM and SND groups was 98.3% (58/59) and 100% (71/71), respectively. Two (3.5%), 15 (25.9%), and 41 (70.7%) patients having sentinel nodes underwent total gastrectomy, proximal gastrectomy (PG), and distal gastrectomy (DG), respectively, in the SNM group. One (1.4%), 5 (7.0%), 10 (14.1%), 39 (54.9%), and 16 (22.5%) patients underwent PG, DG, segmental gastrectomy, local resection, and endoscopic submucosal dissection, respectively, in the SND group. There was no significant difference in postoperative complications between the SNM and SND groups ( P = 0.781). Survival did not differ between the both groups ( P = 0.856). The present results suggest that personalized surgery with SND provides technical safety and curability related with a favorable survival outcome in patients with EGC.

Background:Stratification of pancreatic cancer patients based on early recurrence and prognosis is essential for selecting optimal therapeutic strategies. The aim of this study was to investigate whether serum carbohydrate antigen (CA) 19-9 levels can be better used to predict early recurrence and prognosis.Methods:Patients whose CA 19-9 levels obtained in association with total bilirubin >2.0 mg/dL and whose CA 19-9 levels Results:Larger tumor size, higher serum CA 19-9 level, higher C-reactive protein (CRP) level, more advanced T status, and lymph node metastasis were significantly associated with recurrence within 1 year after surgery (early recurrence). The rate of early recurrence in patients with CA 19-9 levels >100 U/mL (76.9%) was significantly higher than that of patients with CA 19-9 levels ≤100 U/mL (27.9%). We performed combination analysis of 2 additional risk factors, CRP level (cutoff: 1.0 mg/dL) and tumor size (cutoff: 3.0 cm), with serum CA 19-9 level (cutoff: 100 U/mL). Patients were divided into 3 groups according to their number of risk factors. Rates of early recurrence in patients with 0, 1, and 2 or 3 risk factors were 22.0%, 45.2%, and 91.7%, respectively. Moreover, overall survival was significantly different in each group.Conclusion:Serum CA 19-9 level, in addition to CRP level and tumor size, improve patient stratification in early recurrence as well as prognosis.

This study describes our experience with a new method of identifying and cannulating the main pancreatic duct (MPD) using only an ultrasonically activated scalpel that overcomes the disadvantages of previously used methods. The main difference between our new method and that of previous methods is the greater ability to identify the MPD (success rate was greater than 81.3%). This technique is easy to learn, even for inexperienced surgeons, and is a reliable way of identifying the MPD.

Background /Objectives: The lung is a major metastatic site of pancreatic cancer (PC). We aimed to assess the features and prognosis of patients with PC according to the recurrence pattern and the effect of resection of recurrent lung lesion. Methods We enrolled 168 PC patients who had undergone macroscopically curative resection. All resected lung tumors were evaluated immunohistochemically for expressions of thyroid transcription factor-1 (TTF-1) and napsin A. Results The most common site of first recurrence was the liver and local site, followed by the lung, peritoneum, and lymph node. Lung recurrence was observed significantly later than was liver recurrence. The median survival time (MST) after recurrence in patients with first recurrence in the lung was significantly longer than MST in patients with first recurrence in the liver (15.2 months vs 5.2 months, p = 0.039). Seven patients with lung recurrence underwent resection of the recurrent lesion. Surgical resection of single metastasis limited to the lung showed favorable overall survival after recurrence (MST = 36.5 months). Patients with single metastasis limited to the lung showed significantly lower value of FDG-PET SUVmax of the primary pancreatic tumor. Conclusions Patients with first recurrence in the lung showed better prognosis than did patients with first recurrence in the liver. Single metastasis limited to the lung could benefit from surgical resection and was significantly associated with lower FDG-PET SUVmax of the primary pancreatic tumor.

Highlights • There is anomaly that bile ducts and portal veins of the Spiegel lobe do not run together. • Incidence of bile leakage after hepatic surgery was reported to be 2.6–15.6%. • A number of treatment strategies for excluded bile leakage have been reported. • Surgical treatment for excluded bile leakage is a quick and reliable procedure., Inroduction The treatments of excluded bile duct leakage after hepatectomy are not easy and various strategies have been reported, such as surgery, ethanol or fibrin glue injection, and portal vein embolization. Presentation of case A 72-year-old man with a surgical history of laparoscopic ileocecal resection for diverticular bleeding was diagnosed as having hepatocellular carcinoma. Right hemihepatectomy was performed, and computed tomography examination on postoperative day 9 showed abdominal fluid collection in the right subphrenic space. Percutaneous intra-abdominal fluid drainage was performed and it was diagnosed as bile leakage. After that it was diagnosed as excluded bile leakage from the Spiegel lobe by drip infusion cholangiographic-computed tomography and endoscopic retrograde cholangiography. To improve this clinical condition, we performed the Spiegel lobe excision on postoperative day 48. The postoperative course was uneventful and the patient was discharged. Discussion According to the postoperative examination, it appeared that the bile duct from the Spiegel lobe joined to the right main bile duct or the bile duct of the right posterior section. This bile duct anomaly was not detected preoperatively on imaging examination. It is most likely that the bile duct from the Spiegel lobe was cut when the hepatoduodenal ligament in the hepatic hilum was peeled. To prevent excluded bile leakage, the hepatoduodenal ligament should be carefully peeled and ligated instead of using energy devices. Conclusion We consider that surgical treatment for postoperative excluded bile leakage is both a quick and reliable procedure in patients with acceptable liver function and anatomical subject.

Background Gemcitabine and S-1 are drugs commonly used for treating locally advanced pancreatic cancer (LAPC). However, the safety and efficacy of combination of these agents for induction chemotherapy (IC) followed by chemoradiotherapy are not well-defined. Patients and methods Fifteen patients with LAPC (IC-CRT group) were treated with gemcitabine and S-1 IC, followed by S-1 chemoradiotherapy. The clinical outcomes were compared to a cohort of 38 patients who received chemoradiotherapy alone (CRT group). Results Disease control rates in the CRT and IC-CRT groups were 84% and 93%, respectively (p=0.024). The median time of disease progression was 10.8 and 15.4 months in the CRT and IC-CRT group, respectively (p=0.043). The median overall survival time was longer in the IC-CRT group compared to CRT (23.4 vs. 17.3 months), but this increase was not statistically significant. Conclusion Gemcitabine and S-1 combination chemotherapy, followed by CRT, is a promising IC regimen for treating LAPC.