A case report of carcinoma of the papilla of Vater associated with a hyperplasia-dysplasia-carcinoma sequence by pancreaticobiliary maljunction.

BACKGROUND: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia-dysplasia-carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer. CASE PRESENTATION: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia-dysplasia-carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor. CONCLUSIONS: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca.

Reconsidering resectable oncological conditions in pancreatic tail cancer: A multicenter retrospective study on prognostic factors in pancreatic tail cancer after resection (HOPS Pt-01).

BACKGROUND: Pancreatic tail cancer (Pt-PC) is generally considered resectable when metastasis is absent, but doubts persist in clinical practice due to the variability in local tumor extent. We conducted a multicenter retrospective study to comprehensively identify prognostic factors associated with Pt-PC after resection. METHODS: We enrolled 100 patients that underwent distal pancreatectomy. The optimal combination of factors influencing relapse-free survival (RFS) was determined using the maximum likelihood method (MLM) and corrected Akaike and Bayesian information criteria (AICc and BIC). Prognostic elements were then validated to predict oncological outcomes. RESULTS: Therapeutic interventions included neoadjuvant treatment in 16 patients and concomitant visceral resection (CVR) in 37 patients; 89 patients achieved R0. Median RFS and OS after surgery were 23.1 and 37.1 months, respectively. AICc/BIC were minimized in the model with ASA-PS (≥2), CA19-9 (≥112 U/mL at baseline, non-normalized postoperatively), need for CVR, 6 pathological items (tumor diameter ≥19.5 mm, histology G1, invasion of the anterior pancreatic border, splenic vein invasion, splenic artery invasion, lymph node metastasis), and completed adjuvant treatment (cAT) for RFS. Regarding the predictive value of these 11 factors, area under the curve was 0.842 for 5-year RFS. Multivariate analysis of these 11 factors showed that predictors of RFS include CVR (hazard ratio, 2.13; 95 % confidence interval, 1.08-4.19; p = 0.028) and cAT (0.38, 0.19-0.76; p = 0.006). CONCLUSIONS: The MLM identified certain Pt-PC cases warranting consideration beyond resectable during clinical management. Particular attention should be paid to conditions requiring CVR, even though immortal time bias remains unresolved with adjuvant treatment.

Synergistic antitumor effect of histone deacetylase class IIa inhibitor with lenvatinib in hepatocellular carcinoma.

BACKGROUND: Histone deacetylase (HDAC) class I and IIa are highly expressed in hepatocellular carcinoma (HCC) and associated with decreased survival. However, clinically used pan and class I inhibitors have serious adverse events. In this study, we assessed the antitumor effects and tolerability of class IIa HDAC inhibitor (HDACI) with lenvatinib, which is a standard therapy for HCC. METHODS AND RESULT: Combination therapy with class IIa HDACI and lenvatinib exerted synergistic antitumor effect in human HCC cell lines. In mouse models, this therapy showed significant antitumor effects, and few adverse events occurred. In immunoblotting, the expression of fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) was high in cell lines that showed a high antitumor effect. In addition, class IIa HDACI administration decreased the expression of FGFR4. In the small interfering RNA (siRNA) analysis, knockdown of HDAC9, which is an isoform of HDAC class IIa, reduced the expression of FGFR4 and induced apoptosis. Immunohistochemistry of human clinical specimens showed a positivity rate of 32% for FGFR4 and 84% for HDAC9 in HCC, and all FGFR4-positive patients were HDAC9 positive. CONCLUSION: Class IIa HDACI and lenvatinib combination therapy induces apoptosis by downregulating FGFR4 and blocking the FGFR signaling in FGFR4-positive HCC cell lines and has demonstrated synergistic antitumor effects and safety. This combination therapy overcomes the problems of conventional therapies and will be beneficial for FGFR4-positive HCC patients.

Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) Syndrome Precedes the Development of Hepatocellular Carcinoma.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by bilateral synovitis and marked pitting edema of the hands and/or feet. Despite the unknown etiology of RS3PE, several reports have described the putative association of this disease with malignant tumors. We herein report the findings of a 76-year-old man with RS3PE syndrome who developed hepatocellular carcinoma 3 years after achieving clinical remission of RS3PE using corticosteroid treatment; high vascular endothelial growth factor and tumor necrosis factor-alpha levels were considered to have contributed to carcinogenesis in this patient. The sequence of clinical events in this case strongly suggests that careful follow-up, even after clinical remission, is necessary for patients with RS3PE syndrome whose malignancy is not confirmed at diagnosis.

Genomic analysis of an aggressive case with metastatic intrahepatic mucinous cholangiocarcinoma.

Intrahepatic mucinous cholangiocarcinoma (IHMC) is rare and behaves notoriously; however, the details of the clinicopathological characteristics of IHMC remain unknown. A 70-year-old man was admitted for examination of the hepatic mass in the S1 segment. He underwent extended left hepatic lobectomy. Histopathological evaluation demonstrated mixed papillary carcinoma that comprised well to moderately differentiated tubular adenocarcinoma and signet-ring cell carcinoma with large amounts of mucus lakes. Tumor was relapsed 9 months after surgery. Although he received chemotherapy with the combination of gemcitabine and cisplatin, he had renal failure and discontinued the chemotherapy. He received palliative radiotherapy for metastasis in the cervical spine. Then, the patient treated with S-1, however, he died 16 months after the initial diagnosis. The autopsy findings showed multiple nodules in the lungs, pleura, kidneys, adrenal glands, stomach, pancreas, and lymph nodes. Histological examination revealed that all nodules were IHMC. Next-generation sequencing revealed that somatic mutations in ADGRB3, TAF1L and EPHA3 may affect carcinogenesis, and those in TAF1, EPHA3, PIK3C2B, FN1, ERBB3, BRIP1, SYNE1 and TGFBR2 may affect metastasis. Molecular carcinogenesis of IHMC may be distinct from that of ordinary cholangiocarcinoma. Further studies are needed to elucidate the genetic mutations and their functions in IHMC.

A Case of Unresectable Combined Hepatocellular-Cholangiocarcinoma Successfully Treated with Lenvatinib.

A 77-year-old man was referred to our hospital because of a hepatic tumor. Blood biochemistry showed elevated serum alfa-fetoprotein, protein induced by vitamin K absence-II, and carbohydrate antigen 19-9 levels. Gd-EOB-DTPA-enhanced magnetic resonance imaging revealed a 95-mm-sized tumor in liver S7. The tumor showed heterogeneous hyperintensity in the arterial phase, slightly washed out from the portal vein phase, and hypointensity in the hepatocellular phase. Post-enlargement segmental resection was performed, and the pathological diagnosis was combined hepatocellular cholangiocarcinoma. Seven months after surgery, multiple liver tumors were found, and biopsy revealed combined hepatocellular-cholangiocarcinoma. Hepatic arterial infusion chemotherapy with cisplatin was initiated. However, the patient developed a pulmonary abscess, which was treated with antibiotics. He then underwent treatment with lenvatinib, 11 months after surgery. At 8 weeks follow-up, a complete response (according to the modified Response Evaluation Criteria in Solid Tumors [RECIST]) and a partial response (RECIST version 1.1) was noted. To the best of our knowledge, thus far, only a single case of lenvatinib treatment of unresectable mixed liver cancer has been reported. In that case, lenvatinib was used as a third-line treatment. The present report is the first to describe lenvatinib as a first-line therapy for unresectable combined hepatocellular-cholangiocarcinoma, which resulted in a meaningful response. This case provides useful insights into the choice of appropriate drug treatment in this disease in the absence of randomized controlled trials of drug treatment.

Association between Hepatic Oxidative Stress Related Factors and Activation of Wnt/ß-Catenin Signaling in NAFLD-Induced Hepatocellular Carcinoma.

We investigated the association between iron overload, oxidative stress (8-oxo-7,8-dihydroguanine: 8-oxo-dG scores), Wnt/ß-catenin pathway activation (expression of glutamine synthetase: GS), and tumor hyperintensity in the Gd-EOB-DTPA-enhanced MRI hepatobiliary phase (relative enhancement ratio: RER). This was a retrospective analysis of 94 hepatocellular carcinoma (HCC) patients who underwent surgical resection. In HBV-, HCV-, and alcohol-associated HCC, serum ferritin levels in the high and low RER groups were equivalent. In contrast, ferritin levels were elevated in the 'high RER' group of patients with nonalcoholic fatty liver disease (NAFLD)-HCC. As predictors of GS positivity, high RER had a sensitivity of 57.2% and a specificity of 100%. High serum ferritin had a sensitivity of 85.7% and a specificity of 85.7%. All cases with serum ferritin ≥275.5 ng/mL and high RER were 8-oxo-dG- and iron staining-positive. Additionally, GS positivity was seen in all cases with "serum ferritin levels above the upper limits or iron staining-positive" and '8-oxo-dG high' cases. Therefore, combining serum ferritin levels with RER may increase the accuracy with which activated Wnt/ß-catenin signaling is predicted in NAFLD-HCC. We suggest that 8-oxo-dG accumulates following increased oxidative stress due to hepatic tissue iron deposition; this may activate Wnt/ß-catenin signaling and trigger carcinogenesis.

National survey of hepatobiliary and pancreatic surgery in hemophilia patients in Japan.

BACKGROUND: Approximately 8300 hemophiliacs are registered in Japan, but no comprehensive reports on hepatobiliary and pancreatic surgery (HBPS) have been conducted. This report investigates the current status of HPBS in hemophilia patients in Japan. METHODS: The subjects were hemophiliac patients seen between January 1 2007, and December 31 2017, at facilities participating in this study among the facilities for performing high-difficulty cases nationwide designated by the Japanese Society for HBPS. A retrospective examination of short-term outcomes in 49 cases was conducted to assess patient background, disease, surgical procedure, and complications. RESULTS: The types of hemophilia were A: 43 cases, B: four cases, and von Willebrand disease: two cases (hemophilia severity: mild 32, moderate seven, severe 10). The target malignant diseases for surgery were hepatocellular carcinoma (HCC) in 20 cases, intrahepatic cholangiocellular carcinoma (CCC) in four cases, combined HCC-CCC in two cases, hilar CCC in two cases, and pancreatic cancer in four cases. As for the surgical procedure, limited resection (subsegmentectomy and partial hepatectomy) was performed in 16 cases of HCC even with normal liver function tests. Pancreaticoduodenectomy and distal pacreatectomy were performed for pancreatic cancers as in the standard procedure. Postoperative complications were postoperative bleeding in two cases after hepatectomy and one after pancreatectomy in one case. When compared with Japanese National Clinical Data base, the complication rates after hepatectomy and pancreatectomy were not conspicuous in hemophilic patients. CONCLUSIONS: As long as they are performed in qualified centers, complication rate is not increased in hemophilic patients undergoing HBPS.

Nature of the liver volume depending on the gender and age assessing volumetry from a reconstruction of the computed tomography.

Although the liver is a regenerating organ, excessive loss of liver volume (LV) can cause fatal liver failure. It is unclear whether LV is correlated with age; however, it is known that liver function decreases with age. In addition, the gender-related role of LV remains unclear. This study aimed to investigate the changes in LV by age and gender. Between January and December 2018, 374 consecutive patients who underwent abdominal multidetector computed tomography (MDCT) for any abdominal examinations were enrolled. LV was evaluated using MDCT. The relationship between the LV and body mass index (BMI), body surface area (BSA), age, and gender was investigated. The modified LV (mLV) was calculated by a formula measured LV × 1.5/BSA. LV correlated to BSA more than to BMI in both the males (R: 0.559 vs. 0.416) and females (R: 0.479 vs. 0.300) in our study. Age was negatively correlated to LV and BSA, and correlated to LV more than to BSA in males (R: 0.546 vs. 0.393) and females (R: 0.506 vs. 0.385). In addition, the absolute slope between age and LV in the males was higher than that in the females (14.1 vs. 10.2, respectively). Furthermore, the absolute slope of age and mLV in the males was slightly higher than in the females (9.1 vs. 7.3, respectively). In conclusion, LV in the normal liver is correlated to age rather than the one in the diseased liver. Liver volume in the males decreased more with age than LV in the females.

Programmed cell death ligand 1 expression in a case of poorly differentiated lymphocyte-rich hepatocellular carcinoma.

Our pathological study of a case of poorly differentiated lymphocyte-rich hepatocellular carcinoma suggested that immune checkpoint inhibitor may be an effective therapy. The histological type is an important factor in determining treatment choices.

Laparoscopic low anterior resection for rectal cancer wherein the inferior mesenteric artery arose from the superior mesenteric artery: a case report.

BACKGROUND: Few cases have been reported of colorectal cancer with inferior mesenteric artery (IMA) branching abnormalities; therefore, the lymphatic flow in such cases remains unknown. We report the first case of locally advanced rectal cancer in which the IMA arose from the superior mesenteric artery (SMA) in which we achieved to visualize the lymphatic flow. CASE PRESENTATION: A 65-year-old woman complaining of bloody stools was investigated in our hospital and suspected with rectal cancer. Colonoscopy and abdominal enhanced computed tomography (CT) revealed a circumscribed, localized ulcerative tumor in the rectum. 3-Dimensional contrast-enhanced computed tomography (3D-CT) showed that the IMA arose from the SMA. The patient was diagnosed with rectal cancer (cT3N0M0, cStage IIa) and laparoscopic low anterior resection was performed. The sigmoid colon was resected using the medial approach. Only the plexus of the colic branch of the lumbar splanchnic nerve was observed at the site where the root of the IMA usually exists and showed interruption of the indocyanine green (ICG) fluorescence-illuminated lymphatics. The root of the IMA was ligated, and Japanese D3 lymphadenectomy was performed, preserving the accessory middle colic artery. All fluorescent lymph nodes were resected. The pathological diagnosis was pT4aN1aM0 stage IIIb. The patient's postoperative course was uneventful. Adjuvant chemotherapy was administered, and the patient was recurrence-free at 1.5 years after surgery. CONCLUSIONS: We were able to perform safe and appropriate surgery oncologically, despite abnormal vascular anatomy, due to preoperative identification using 3D-CT and intraoperative navigation using ICG administration.

Indocyanine green fluorescence imaging ensures perfusion of the remnant stomach during laparoscopic splenectomy in a patient after distal gastrectomy: A case report.

BACKGROUND: After distal gastrectomy, ischemic necrosis of the remnant stomach is a rare but serious complication. For distal pancreatectomy or splenectomy, ensuring adequate blood supply to the remnant stomach is important for patients with a history of distal gastrectomy. We report a case of successful splenectomy with indocyanine green (ICG) used to evaluate the blood supply to the remnant stomach in a patient after distal gastrectomy. CASE PRESENTATION: A 65-year-old woman who underwent distal gastrectomy for gastric cancer a year earlier had a splenic tumor that was increasing in size. We planned laparoscopic splenectomy because there was a possibility of a malignant splenic tumor. Intraoperative ICG fluorescence imaging confirmed perfusion of the remnant stomach. The patient was discharged on postoperative day 8 after an uncomplicated postoperative course. CONCLUSION: ICG fluorescence imaging is useful for evaluating blood flow to the remnant stomach during laparoscopic splenectomy in patients after distal gastrectomy.

Perioperative Predictors of Early Recurrence for Resectable and Borderline-Resectable Pancreatic Cancer.

We aimed to identify the perioperative predictors of the early recurrence (ER) of resectable and borderline-resectable pancreatic ductal adenocarcinomas (PDACs). After surgery for a PDAC, most patients develop a recurrence. Predictive factors may therefore guide therapeutic decision-making. Patients (n = 234) who underwent a pancreatectomy for a PDAC between 2006 and 2019 were included. The postrecurrence survival (PRS) was estimated using Kaplan-Meier curves. Predictive factors for an ER were assessed using logistic regression analyses; 93 patients (39.7%) were recurrence-free at the last follow-up. Patients with an ER (n = 85, 36.3%), defined as a recurrence within the first 12 months after surgery, had 1- and 2-year PRS rates of 38.7% and 9.5%, respectively, compared with 66.9% and 37.2% for those with a late recurrence (n = 56, 23.9%; both p < 0.001). The most common site of an ER was the liver (55.3%) with a significantly shorter median overall survival time than that with either a local or a lung recurrence (14.5 months; p < 0.001). Preoperative and postoperative risk factors for an ER included a tumor size >3.0 cm (odds ratio (OR): 3.11, 95% confidence interval (CI): 1.35-7.14) and preoperative carbohydrate antigen 19-9 (CA19-9) levels >52 U/mL (OR: 3.25, 95% CI: 1.67-6.30) and a pathological tumor size >3.0 cm (OR: 2.00, 95% CI: 1.03-3.90) and postoperative carbohydrate antigen 19-9 levels >37 U/mL (OR: 2.11, 95% CI: 1.02-4.36), respectively. Preoperatively (>52 U/mL) and postoperatively (>37 U/mL) elevated CA19-9 and a tumor size >3.0 cm were independent predictors for an ER after a pancreatectomy for a PDAC.

A case of hypervascular tumors in the liver and pancreas: synchronous hepatocellular carcinoma and pancreatic metastasis from renal cell carcinoma 36 years after nephrectomy.

It is sometimes difficult to distinguish between multiple cancers and metastases using only diagnostic imaging, particularly when multiple hypervascular tumors are found in multiple organs. We present a case in which the preoperative histological evaluation was essential to determine the management of a hypervascular pancreatic tumor and liver tumor.

Effect of Rikkunshito, a Traditional Japanese Herbal Medicine, on Delayed Gastric Emptying and Oral Dietary Intake After Pancreaticoduodenectomy: A Prospective, Randomized, Single-Center, Open-Labeled Study.

INTRODUCTION: Delayed gastric emptying (DGE) remains an important problem after pancreaticoduodenectomy (PD). There is a lack of effective treatments for early recovery of oral dietary intake. Rikkunshito (RKT), a Japanese herbal medicine, has been gaining attention as a facilitator of gastric emptying. We evaluated the effects of RKT on DGE after PD. METHODS: In this prospective, randomized, open-labeled study, patients were randomly allocated before PD in a 1:1 ratio to the RKT group or the control group that received no additional treatment. The RKT group received 2.5 g of RKT three times daily (7.5 g/day) from postoperative day (POD) 1 to POD 21. The primary endpoint was the incidence of DGE. Secondary endpoints were short-term postoperative outcomes including oral dietary intake volume and perioperative changes in levels of the hormones ghrelin and leptin. Patients were observed until hospital discharge. RESULTS: Twenty-six patients in each group (n = 52) completed the protocol treatment and were included in the analysis set. There were no statistically significant differences in basic characteristics and operative factors. The overall incidence of DGE was not statistically different between the RKT and control groups (30.8% vs 30.8%, p>0.9999). There were no statistically significant differences in the amount of postoperative oral dietary intake represented by total dietary intake (TDI) up to POD 14 and POD 21, complications, and length of hospital stay. No adverse events related to this study were observed. In the RKT group, total ghrelin and acyl-ghrelin were significantly upregulated and leptin was significantly downregulated earlier than in the control group. CONCLUSION: RKT treatment from POD 1 to 21 did not reduce the incidence of DGE and had no clinically beneficial effect on short-term postoperative outcomes irrespective of changes in hormone levels.

Arteriovenous malformation in the pancreatic head initially mimicking a hypervascular mass treated with duodenum-preserving pancreatic head resection: a case report.

BACKGROUND: The mainstay treatment for arteriovenous malformation in the pancreatic head (Ph-AVM) is standard pancreatectomy, especially pancreaticoduodenectomy (PD), or interventional endovascular treatment. We report the first case of Ph-AVM treated with duodenum-preserving pancreatic head resection (DPPHR) performed to preserve the periampullary organs. CASE PRESENTATION: A 59-year-old man presenting with back pain underwent contrast-enhanced computed tomography followed by angiography of the anterior superior pancreaticoduodenal artery. He was diagnosed with Ph-AVM and indicated for DPPHR with preservation of the periampullary organs; Ph-AVM's benign nature seldom requires lymph node dissection. During the operation, the right colon was mobilized and the omental bursa was released to expose the periampullary structures. The pancreas was transected just above the superior mesenteric vein. The inferior pancreaticoduodenal artery and papillary arteries branching from the posterior superior pancreaticoduodenal artery were carefully preserved to maintain the blood flow to the lower bile duct and papilla of Vater. The remnant pancreas was reconstructed with pancreaticogastrostomy using the modified Blumgart method. Pathological examination of the resected specimen revealed an irregular course of the arteries and veins concomitant with marked dilation throughout the pancreatic head. The patient was pathologically diagnosed with Ph-AVM. He developed hematemesis caused by a rupture of the pseudoaneurysm on postoperative day 20 and underwent coil embolization. A bilio-enteric fistula and stenosis of the common bile duct were found and treated by placement of an endoscopic biliary stent. At the 8-month follow-up, the Ph-AVM had not recurred. CONCLUSIONS: Compared to PD, DPPHR confers the clinical benefit of preserving the periampullary organs, although further studies are needed to confirm this. Therefore, the choice of this procedure should be based on the surgical morbidities and long-term outcome of the patient.

Clinical usefulness of saphenous vein graft in major arterial reconstruction during extended pancreatectomy.

PURPOSE: Extended pancreatectomy for locally advanced pancreatobiliary malignancy often involves combined major arterial resection (AR) and reconstruction (ARc). By limiting candidate inflow for ARc after combined resection of the celiac arterial system over a long distance, we evaluated whether great saphenous vein graft (GSVG) is an alternative conduit for obtaining non-anatomical arterial inflow. METHODS: ARc with GSVG conduit was undertaken prior to resection. GSVG was harvested and anastomosed end-to-side with the reconstructing artery and then mostly passed via the retroperitoneal para-inferior vena cava route. Side-to-end anastomosis of GSVG inflow was established with the right common iliac artery or abdominal aorta. RESULTS: Among 468 consecutive pancreatobiliary surgeries, ARc with GSVG was undertaken in seven cases. Primary cancers were in the pancreas in six patients and distal bile duct in one. Radical surgery was performed with pancreaticoduodenectomy in six patients and total pancreatectomy in one. Hepatic artery (HA) was concomitantly resected and reconstructed by GSVG in six patients or by the jejunal artery in one patient. Median operative time and intraoperative blood loss were 763 min and 350 ml, respectively. Serum level of AST, ALT, and LDH in patients with HA reconstruction by GSVG peaked by the second postoperative day and promptly normalized. Postoperative morbidity (CD ≥ III) was encountered in one patient. No surgical mortality was observed. Postoperative serum liver enzymes promptly decreased in ARc patients with GSVG to HA. CONCLUSION: Arterial reconstruction with GSVG prior to resection was performed securely and might help to reduce postoperative liver dysfunction.

Conversion surgery for initially unresectable biliary malignancies: a multicenter retrospective cohort study.

PURPOSE: Few studies have focused on conversion surgery for biliary malignancy; thus, it is not clear if this treatment modality can extend the survival of patients with unresectable biliary malignancy. We conducted a multicenter retrospective cohort study to evaluate the surgical outcomes of conversion surgery in this setting and analyze long-term survival. METHODS: We collected clinical data retrospectively on patients who underwent conversion surgery for biliary malignancy. RESULTS: Twenty-four patients met our inclusion criteria. Preoperative chemotherapy regimens or chemoradiation therapy regimens were administered based on the institutional criteria, and surgical procedures were chosen based on tumor location. Morbidity occurred in 16 patients (66.7%), and 1 patient died of liver failure after surgery. The overall 5-year survival rate following initial therapy was 43.2%, and the median survival time was 57.4 months. The corresponding values following surgery were 38.2% and 34.3 months, respectively. The 5-year survival rate of the 24 patients who received both chemotherapy and surgery was significantly better than that of 110 patients treated with chemotherapy only (p < 0.001). CONCLUSION: Conversion surgery for initially unresectable biliary malignancies may be feasible and achieve long-term survival for selected patients.

Clinical usefulness of conversion surgery for unresectable pancreatic cancer diagnosed on multidetector computed tomography imaging: Results from a multicenter observational cohort study by the Hokkaido Pancreatic Cancer Study Group (HOPS UR-01).

BACKGROUND AND AIM: Effective multidisciplinary approaches for unresectable pancreatic cancer (UR-PC) that include modern chemotherapeutic regimens and subsequent conversion surgery (CS) are being developed. The aim of this study was to evaluate outcomes of patients clinically diagnosed with UR-PC, focusing on the efficacy of CS. METHODS: Patients ineligible for two multicenter phase II studies conducted by the Hokkaido Pancreatic Cancer Study Group (HOPS) were recruited. Sequential treatment regimens, conversion to radical surgery, and overall survival (OS) were analyzed by multidetector computed tomography (MDCT)-based UR factors. Univariate and multivariate analyses were performed to identify predictors of OS. RESULTS: Sixty-six of 247 intended recruits for HOPS studies from October 2013 to April 2016 were included. Unresectability was due to locally advanced (LA) disease and metastasis (M) in 42 and 24 patients, respectively. Induction therapy began with chemotherapy (CT) and chemoradiotherapy (CRT) in 44 and 17 patients, respectively, of whom 23 received modern CT regimens. Radical surgery was completed in 12 (LA, 10; M, two) with a median treatment interval of 10.3 months (range, 2-32). Eleven patients (91.6%) achieved pathological R0 resection. Median OS was significantly longer in patients who underwent CS than those who did not (44.1 vs 14.5 months, P < 0.0001). CS was an independent predictor of OS (hazard ratio, 0.078; 95% confident interval, 0.017-0.348; P = 0.001). CONCLUSION: Conversion surgery after a favorable response to sequential treatment might prolong survival in patients with UR-PC. Precise diagnosis on MDCT followed by sequential multimodal anticancer treatment is essential.

Central pancreatectomy in portal annular pancreas for metastatic renal cell carcinoma: a case report.

BACKGROUND: Portal annular pancreas (PAP) is a rare congenital anatomical abnormality of the pancreas in which the portal vein is encircled by aberrant parenchyma, and special attention is needed for pancreatic resections. This is the first report of central pancreatectomy (CP) in a PAP for metastatic renal cell carcinoma (RCC). CASE PRESENTATION: A 76-year-old man who had a history of left nephrectomy for renal cancer not otherwise specified 36 years earlier and radical cystectomy for bladder cancer 4 years earlier was incidentally found to have a pancreatic tumor and a liver tumor. The pancreatic tumor was diagnosed as metastasis of clear cell RCC, and the liver tumor was diagnosed as moderately differentiated hepatocellular carcinoma (HCC) on preoperative histological evaluation. Preoperative computed tomography imaging showed a type 3A PAP, in which the main pancreatic duct (MPD) ran ventral to the portal vein (anteportal type), and the aberrant parenchyma was located cranial to the confluence of the portal vein and splenic vein (suprasplenic type). After adhesiotomy and partial liver resection, CP was performed. With intraoperative ultrasound guidance, the aberrant parenchyma of the PAP could be preserved, avoiding additional resection. Thus, two pancreatic transections were performed, creating a single-cut margin that contained the MPD in the distal pancreas. Oncologically safe margins were confirmed by intraoperative pathological diagnosis. The distal pancreas was reconstructed by pancreatojejunostomy in the routine procedures. The pathological diagnosis of the surgical specimens was identical to the preoperative diagnosis. A postoperative pancreatic fistula (POPF) developed from the proximal stump of the head of the pancreas, necessitating no specific treatment other than drainage. The patient showed no signs or symptoms of recurrent RCC or abnormal pancreatic function for 2 years after the operation, although a histologically proven new HCC lesion developed distant from the initial site 8 months after the operation. CONCLUSIONS: Precise preoperative evaluation of the tumor features and PAP allowed adequate surgical strategies to be planned. Intraoperative ultrasound was useful to minimize parenchymal resections of the PAP. CP is still a challenging procedure in terms of the development of POPF.