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Glycolysis is highly enhanced in pancreatic ductal adenocarcinoma (PDAC) cells; thus, glucose restrictions are imposed on nontumor cells in the PDAC tumor microenvironment (TME). However, little is known about how such glucose competition alters metabolism and confers phenotypic changes in stromal cells in the TME. Here, we report that cancer-associated fibroblasts (CAFs) with restricted glucose availability utilize lactate from glycolysis-enhanced cancer cells as a fuel and exert immunosuppressive activity in the PDAC TME. The expression of lactate dehydrogenase A (LDHA), which regulates lactate production, was a poor prognostic factor for patients with PDAC, and LDHA depletion suppressed tumor growth in a CAF-rich murine PDAC model. Coculture of CAFs with PDAC cells revealed that most of the glucose was taken up by the tumor cells and that CAFs consumed lactate via monocarboxylate transporter 1 to enhance proliferation through the TCA cycle. Moreover, lactate-stimulated CAFs upregulated IL-6 expression and suppressed cytotoxic immune cell activity synergistically with lactate. Finally, the LDHA inhibitor FX11 reduced tumor growth and improved antitumor immunity in CAF-rich PDAC tumors. Our study provides insight regarding the crosstalk among tumor cells, CAFs, and immune cells mediated by lactate and offers therapeutic strategies for targeting LDHA enzymatic activity in PDAC cells.

Abstract Background The albumin‐bilirubin (ALBI) grade was developed to predict the prognosis of patients with hepatocellular carcinoma (HCC), which can stratify the prognosis even in HCC patients with Child‐Pugh A. We evaluated the prognostic efficacy of the ALBI grade and Child‐Pugh classification in HCC patients with Child‐Pugh A stratified by the presence or absence of advanced fibrosis or a preoperative biomarker for advanced fibrosis. Methods We retrospectively analyzed 490 consecutive HCC patients with Child‐Pugh A who underwent initial hepatectomies. The accuracy of prognostic prediction using both models was compared by the presence or absence of advanced fibrosis (F3‐4) and its predictor, the preoperative platelet count (PLT). Results The prognostic accuracy of the ALBI grade was better in patients without advanced fibrosis (F3‐4; likelihood ratio: 4.39, corrected Akaike information criterion [AICc]: 453.0, P = .074), but Child‐Pugh score was better in the advanced fibrosis group (likelihood ratio: 10.67, AICc: 915.2, P = .0014). In the high PLT group (≥140 × 103/μL), the prognostic accuracy using the ALBI grade was better in overall survival (OS) and relapse‐free survival (RFS), but in the low PLT group, the Child‐Pugh score was the more accurate model in OS and RFS. Conclusions Depending on the degree of fibrosis or preoperative PLT, the ALBI grade and Child‐Pugh score may provide more accurate prognoses after initial hepatectomy in HCC patients with Child‐Pugh A.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma and cancer-associated fibroblasts (CAFs) provide a favorable tumor microenvironment. Smad4 is known as tumor suppressor in several types of cancers including PDAC, and loss of Smad4 triggers accelerated cell invasiveness and metastatic potential. The thrombospondin-1 (TSP-1) can act as a major activator of latent transforming growth factor-β (TGF-β) in vivo. However, the roles of TSP-1 and the mediator of Smad4 loss and TGF-β signal activation during PDAC progression have not yet been addressed. The aim is to elucidate the biological role of TSP-1 in PDAC progression. Methods and results: High substrate stiffness stimulated TSP-1 expression in CAFs, and TSP-1 knockdown inhibited cell proliferation with suppressed profibrogenic and activated stroma-related gene expressions in CAFs. Paracrine TSP-1 treatment for PDAC cells promoted cell proliferation and epithelial mesenchymal transition (EMT) with activated TGF-β signals such as phosphorylated Akt and Smad2/3 expressions. Surprisingly, knockdown of DPC4 (Smad4 gene) induced TSP-1 overexpression with TGF-β signal activation in PDAC cells. Interestingly, TSP-1 overexpression also induced downregulation of Smad4 expression and enhanced cell proliferation in vitro and in vivo. Treatment with LSKL peptide, which antagonizes TSP-1-mediated latent TGF-β activation, attenuated cell proliferation, migration and chemoresistance with enhanced apoptosis in PDAC cells. Conclusions: TSP-1 derived from CAFs stimulates loss of Smad4 expression in cancer cells and accelerates malignant behavior by TGF-β signal activation in PDAC. TSP-1 could be a novel therapeutic target, not only for CAFs in stiff stroma, but also for cancer cells in the PDAC microenvironment.

Abstract Two‐stage hepatectomy (TSH) is one of the specific surgical techniques that can expand the pool of resectable patients with initially unresectable colorectal liver metastases (CRLM). The indication of TSH for CRLM is only bilateral, multinodular disease, which cannot be resected by a single hepatectomy. TSH is nowadays considered an effective treatment for selected patients, with acceptable morbidity/mortality rates and promising long‐term outcomes. However, not all eligible patients can benefit from the TSH strategy. One of the most important issues is dropout from the strategy (failure to complete both of the two sequential procedures), because the survival of such patients is drastically worse compared with patients who can complete both stages. Another important issue is the early recurrence rate and subsequent poor survival even after completion of TSH. Thus, the selection of appropriate patients who can really benefit from the TSH strategy is crucial. This review discusses the optimal patient selection for TSH, which should be helpful for the development of treatment strategies for patients with extensive CRLM.

Abstract Background Myeloid sarcoma (MS) is a rare disease, mostly found in conjunction with acute myelogenous leukemia or other diseases, and primary nonleukemic MS of the spleen is particularly rare. Case presentation We report a 57-year-old male who presented with a spleen mass that was found incidentally, and was enlarged. As a result of various examinations, he was diagnosed with primary MS of the spleen with suspected involvement of the transverse colon, left kidney, pancreatic tail, and left diaphragm. He underwent a total splenectomy, partial pancreatectomy, partial colectomy, left nephrectomy, and left diaphragm partial resection. Histological examination revealed splenic primary MS. Bone marrow biopsy and immunophenotypic flow cytometry revealed no evidence of myeloid leukemia. He underwent umbilical cord blood transplantation, and he is currently living without a sign of recurrence at 10 months after surgery. Conclusions We experienced a very rare case of primary spleen MS that was discovered without a hematologic malignancy. Two cases of surgically resected primary splenic MS have been reported, including the present case.

Abstract Portal vein embolization (PVE) for hepatocellular carcinoma (HCC) was first introduced in 1986 and has been continuously developed throughout the years. Basically, PVE has been applied to expand the indication of liver resection for HCC patients of insufficient future liver remnant. Importantly, PVE can result in tumor progression in both embolized and non‐embolized livers; however, long‐term survival after liver resection following PVE is at least not inferior compared with liver resection alone despite the smaller future liver remnant volume. Five‐year disease‐free survival and 5‐year overall survival were 17% to 49% and 12% to 53% in non‐PVE patients, and 21% to 78% and 44% to 72% in PVE patients, respectively. At present, it has proven that PVE has multiple oncological advantages for both surgical and nonsurgical treatments. PVE can also enhance the anticancer effects of transarterial chemoembolization and can avoid intraportal tumor cell dissemination. Additional interventional transarterial chemoembolization and hepatic vein embolization as well as surgical two‐stage hepatectomy and associated liver partition and portal vein ligation for staged hepatectomy can enhance the oncological benefit of PVE monotherapy. Taken together, PVE is an important treatment which we recommend for listing in the guidelines for HCC treatment strategies.

Abstract Background Radiofrequency ablation (RFA) is widely used as a minimally invasive treatment for hepatocellular carcinoma (HCC). RFA has a low risk of complications, especially compared with liver resection. Nevertheless, various complications have been reported after RFA for HCC; however, diaphragmatic hernia (DH) is extremely rare. Case presentation A 78-year-old man underwent thoracoscopic RFA for HCC located at the medial segment adjacent to the diaphragm approximately 7 years before being transported to the emergency department due complaints of nausea and abdominal pain. Computed tomography revealed a prolapsed small intestine through a defect in the right diaphragm, and emergency surgery was performed. The cause of diaphragmatic hernia was the scar of RFA. We confirmed that the small intestine had prolapsed into the right diaphragm, and we resected the necrotic small intestine and repaired the right diaphragm. Herein, we report a case of ileal strangulation due to diaphragmatic hernia after thoracoscopic RFA. Conclusions Care should be taken when performing thoracoscopic RFA, especially for tumors located on the liver surface adjacent to the diaphragm. Patients should be carefully followed up for possible DH, even after a long postoperative interval.

Abstract Background Hepatic inflammatory pseudotumor (IPT) is a rare, benign, tumor-like lesion. Because there are no characteristic laboratory markers or radiological features, hepatic IPT is often misdiagnosed as a malignant neoplasm such as hepatocellular carcinoma (HCC). Case presentation A 68-year-old man with liver dysfunction due to chronic hepatitis C virus infection and alcoholic liver disease presented with hepatic tumors in segments III and VIII. The levels of serum alpha-fetoprotein (AFP) and its Lens culinaris agglutinin-reactive fraction, AFP lectin 3 (AFP-L3), were elevated to 822.8 ng/ml and 75.2%, respectively. The tumor showed contrast enhancement on contrast-enhanced computed tomography and various accumulation on positron emission tomography. Based on these biological and imaging features, HCC was suspected, and we performed laparoscopic partial hepatectomy for these two tumors. Pathological diagnosis revealed that both tumors were hepatic IPTs with no malignant characteristics. After hepatectomy, the serum AFP and AFP-L3 levels decreased to the normal range. Conclusion We report a very rare case of hepatic IPT with elevated serum AFP and AFP-L3, mimicking HCC. Clinicians should include this rare neoplasm in the differential diagnoses of hepatic tumors even when the serum markers for HCC are elevated.

Abstract Background An accurate diagnosis of the primary cancer or metastatic tumor is quite important because misdiagnosis may lead to the selection of incorrect adjuvant therapy and worse long-term outcomes after surgery. Here, we present a rare case with an unusual metastatic pattern mimicking a hilar cholangiocarcinoma originated from colon cancer Case presentation A 69-year-old man was referred to our hospital because of an upper bile duct stenosis. He had the past history of the sigmoidectomy for the primary colon cancer and the partial hepatectomy with radiofrequency ablation (RFA) for synchronous liver metastases 4 years ago. After 2 years from the initial operation, he had experienced the local recurrence of post-RFA lesion and had undergone a partial hepatectomy. According to the radiological findings of the bile duct stenosis, we diagnosed a hilar cholangiocarcinoma (Bismuth type II), and then he underwent the extended right hepatectomy with extrahepatic bile duct resection. Histological findings including the immune-histochemical examinations (CK7−, CK20+, CDX2+ and SATB2+) uncovered the metastatic tumor into extrahepatic bile duct originated from the primary colon cancer. Conclusion We experienced an extremely rare case with a colon cancer metastasis mimicking a hilar cholangiocarcinoma. In this case with a past history of colon cancer, an immunohistochemical staining led us to distinguish the primary hilar cholangiocarcinoma and the mimicking tumor.

Abstract. Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive malignancies, and the majority of patients with PDAC present with metastatic disease, mainly in the liver, at the time of diagnosis. Surgical resection is the only treatment that can offer prolonged survival and possible cure. However, the indications for surgery for patients with PDAC metastases remain extremely limited to highly selected patients with localized disease, and metastatic disease is generally regarded as a contraindication to surgery. Recently, however, the advent of more effective chemotherapy has changed the treatment strategy for metastatic PDAC. In fact, cases in which resection of synchronous or metachronous PDAC liver metastases lead to prolonged survival in highly selected patients have been reported. In this review, we provide current data regarding survival outcomes after surgery, and discuss the role of surgical resection and selection criteria for patients with PDAC liver metastases in the modern era.

Abstract Background Advancements in chemotherapy for metastatic colorectal cancer (mCRC) have improved long-term outcomes, and median survival currently exceeds 30 months. The recommended treatment for mCRC is multidisciplinary, including a combination of surgical resection and chemotherapy. In this study, we report the case of a patient who has survived for more than 5 years after an initial diagnosis of mCRC while undergoing first-line chemotherapy and six repeat metastasectomies. Case presentation A 55-year-old man was diagnosed at our hospital with sigmoid colon cancer and hepatic metastasis. We performed laparoscopic sigmoidectomy and hepatic segmentectomy (segment 5 [S5] and S8). After resecting the primary tumor and liver metastasis, other metastases were found. Together with perioperative chemotherapy (CAPOX + bevacizumab), we performed repeated metastasectomies for liver metastasis (S4 and S7), pulmonary S1 metastasis, aortic lymph node metastasis, and right adrenal metastasis. With six metastasectomies, the patient has survived for more than 5.5 years. Conclusions Multidisciplinary treatment extends survival and improves the quality of life in patients with mCRC. Planned surveillance after metastasectomy may also be necessary to promote the early detection of recurrence in these patients.

Abstract Background An outbreak of cholangiocarcinoma in Japan has led to widespread concern among workers in printing plants. In March 2013, the Japanese Ministry of Health, Labour and Welfare, confirmed a causal relationship between cholangiocarcinoma and long-term exposure to dichloromethane (DCM) and 1,2-dichloropropane (DCP), which were widely used in printing plants. We herein report a rare case of successful radical resection of multiple cholangiocarcinomas in the intrahepatic and extrahepatic bile ducts caused by past exposure to DCM. Case presentation A 54-year-old man developed brown urine 22 years after his last exposure to DCP and DCM. He had an 11-year history of working at a printing plant from the age of 21 to 31 years and dealt with organic solvents during his employment. Enhanced computed tomography revealed a thickened distal bile duct wall with upstream biliary dilatation and multiple intrahepatic cholangiocarcinomas located in liver segments III, VI, and VIII. Biopsy of the distal bile duct wall revealed adenocarcinoma, and a diagnosis of distal cholangiocarcinoma was made. Tumor marker levels were within the reference range (carcinoembryonic antigen, 3.3 ng/mL; carbohydrate antigen 19-9, 25.4 U/mL; SPAN-1, 13 U/mL; and DUPAN-2, 33 U/mL). The multiple intrahepatic and extrahepatic bile duct cancers were treated by subtotal stomach-preserving pancreatoduodenectomy and partial hepatectomy of segments III, VI, and VIII. Pathological examination of the surgical specimens revealed multiple cholangiocarcinomas with well-differentiated adenocarcinoma in the biliary tree. The patient was still alive without recurrence 17 months after the operation. Conclusions We experienced a rare case of multiple cholangiocarcinomas in the intrahepatic and extrahepatic bile ducts that developed 22 years after the patient’s last exposure to DCP and DCM. Long-term and careful follow-up is required for workers with an occupational history of exposure to organic solvents because of the risk of development of cholangiocarcinoma.

Abstract Background Schwannomas originate from Schwann cells, which are constituents of peripheral nerve sheaths, and can occur anywhere in the body at any age. Most occur in soft tissues such as subcutaneous tissues and muscles, occurrence in the abdominal cavity being relatively rare. In particular, schwannomas of the gallbladder are extremely rare. We herein report a rare case of a schwannoma that coexisted with systemic sarcoidosis and presented as a steroid-resistant mass in the gallbladder wall. Case presentation A 40-year-old woman was found to have thickening of the gallbladder wall during a routine medical examination and was referred to our hospital, where she was found to have granular shadows in the lungs; mediastinal, cervical, intraperitoneal, and inguinal lymphadenopathy; parotid gland enlargement; and an erythematous skin rash. She was diagnosed as having systemic sarcoidosis by transbronchial lung biopsy and bronchoalveolar lavage. All her systemic mass lesions except for the one in the gallbladder resolved or became smaller with steroid treatment. The steroid-resistant gallbladder lesion showed enhancement on contrast-enhanced computed tomography and was shown by endoscopic ultrasonography to be a 30-mm-diameter gallbladder wall lesion. We performed laparoscopic cholecystectomy, which resulted in diagnosis of the steroid-resistant tumor as a schwannoma. Five months after surgery, the patient’s prednisolone dosage had been gradually reduced to 5 mg/day and she was doing well with no evidence of recurrence. Conclusion Resection of a steroid-resistant tumor resulted in diagnosis of schwannoma, enabling reduction in the patient’s steroid dosage for sarcoidosis.

Abstract Background Hepatic artery anomalies are often observed, and the variations are wide-ranging. We herein report a case of pancreatic cancer involving the common hepatic artery (CHA) that was successfully treated with pancreaticoduodenectomy (PD) without arterial reconstruction, thanks to anastomosis between the root of CHA and proper hepatic artery (PHA), which is a very rare anastomotic site. Case presentation A 78-year-old woman was referred to our department for the examination of a tumor in the pancreatic head. Contrast-enhanced computed tomography (CT) revealed a low-density tumor of 40 mm in diameter located in the pancreatic head. The involvement of the common hepatic artery (CHA), the root of the gastroduodenal artery (GDA), and portal vein was noted. Although such cases would usually require PD with arterial reconstruction of the CHA, it was thought that the hepatic arterial flow would be preserved by the anastomotic site between the root of the CHA and the PHA, even if the CHA was dissected without arterial reconstruction. PD with dissection of the CHA and PHA was safely completed without arterial reconstruction, and sufficient hepatic arterial flow was preserved through the anastomotic site between the CHA and PHA. Conclusion We presented an extremely rare case of an anastomosis between the CHA and PHA in a patient with pancreatic cancer involving the CHA. Thanks to this anastomosis, surgical resection was successfully performed with sufficient hepatic arterial flow without arterial reconstruction.

Abstract Although surgical resection is the only treatment of choice that can offer prolonged survival and a chance of cure in patients with colorectal liver metastases (CRLM), nearly 80% of patients are deemed to be unresectable at the time of diagnosis. Considerable efforts have been made to overcome this initial unresectability, including expanding the indication of surgery, the advent of conversion chemotherapy, and development and modification of specific surgical techniques, regulated under multidisciplinary approaches. In terms of specific surgical techniques, portal vein ligation/embolization can increase the volume of future liver remnant and thereby reduce the risk of hepatic insufficiency and death after major hepatectomy. For multiple bilobar CRLM that were traditionally considered unresectable even with preoperative chemotherapy and portal vein embolization, two‐stage hepatectomy was introduced and has been adopted worldwide with acceptable short‐ and long‐term outcomes. Recently, ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) was reported as a novel variant of two‐stage hepatectomy. Although issues regarding safety remain unresolved, rapid future liver remnant hypertrophy and subsequent shorter intervals between the two stages lead to a higher feasibility rate, reaching 98%. In addition, adding radiofrequency ablation and vascular resection and reconstruction techniques can allow expansion of the pool of patients with CRLM who are candidates for liver resection and thus a cure. In this review, we discuss specific techniques that may expand the criteria for resectability in patients with initially unresectable CRLM.

Abstract Background Carcinosarcoma is a rare tumor that includes both carcinoma and sarcoma components. It develops commonly in the female reproductive tract, most often in the uterus. However, as there are a small number of similar cases in the English literature, we would like to present a rare case of a carcinosarcoma in Vater’s papilla. Case presentation A 76-year-old female patient was preoperatively diagnosed with a papillary adenocarcinoma in Vater’s papilla by endoscopic biopsy. The patient underwent subtotal stomach-preserving pancreaticoduodenectomy, and postoperative pathological examination diagnosed the carcinosarcoma. The patient received adjuvant chemotherapy with gemcitabine, but multiple liver metastases were found 3 months after the operation. Though chemotherapy with gemcitabine and cisplatin was introduced, she died owing to tumor progression 7 months after the operation. Conclusion Because carcinosarcoma of Vater’s papilla is a rare disease, a suitable treatment strategy has been unclear. We also present a review of the English literature regarding carcinosarcoma of Vater’s papilla.

BackgroundThe ribcage and diaphragm are mechanical barriers for laparoscopic access during hepatectomy. Here, we introduce the varied application of intercostal trans-diaphragmatic ports during laparoscopic hepatectomy, and describe the management of intercostal ports with key technical points.MethodsFrom January 2013 to December 2017, 180 patients underwent laparoscopic hepatectomy. In 32 of these patients (17.8%), intercostal ports (31 right and one left) were applied, and we analyzed the feasibility and safety of intercostal ports during laparoscopic hepatectomy.ResultsThe main tumor location was segment VII and VIII (78%). The major type of laparoscopic hepatectomy was partial hepatectomy (91%). In the majority of cases (66%) the number and size of intercostal trocars was a single 5-mm port. The median operative time and blood loss were 232 min and 50 mL, respectively. A chest drain was placed via the hole of the intercostal port on the chest wall in two cases (6.3%). The median duration of the post-operative hospital stay was 6 days. There was no conversion, and a pure laparoscopic hepatectomy was achieved in all cases. There was no mortality. As for complications due to the application of intercostal ports, an asymptomatic pneumothorax was detected in only one case, and it was cured by conservative treatment.ConclusionsThe ribcage and diaphragm could be overcome as barriers to laparoscopic access by the placement of intercostal ports with minimal access during laparoscopic hepatectomy. The use of an intercostal port and proper management allows for a feasible approach and safe resection during laparoscopic hepatectomy.

Abstract Background Several reported complications associated with radiofrequency ablation for liver tumors are due to thermal damage of neighboring organs. We herein report a first case of esophageal perforation due to thermal injury of laparoscopic radiofrequency ablation (RFA). Case presentation A 75-year-old woman was treated repeatedly with RFA (percutaneous and laparoscopic) and transcatheter arterial chemoembolization for hepatocellular carcinoma. One week after laparoscopic RFA for recurrent HCC located in segment 2 of the liver, dysphagia and thoracic pain occurred. Upper gastrointestinal endoscopy revealed a perforated esophageal ulcer at the esophago-gastric junction. Inflammation was localized because of severe intra-abdominal adhesion due to repeat surgery, so we decided to treat the patient conservatively. The perforation of the esophagus gradually scarred, and exacerbation did not occur after restarting oral intake. Conclusions When patients with a history of abdominal surgery or intra-abdominal inflammation undergo thermal ablation therapy, caution is required, as there is a possibility of thermal injury of unexpected organs.

Abstract Background Macroscopic diffuse-type hepatocellular carcinoma with concomitant major portal vein tumor thrombus (PVTT) and peritoneal dissemination indicates poor prognosis. Additionally, triple-positive tumor marker status is a predictor of poor outcome even after hepatectomy. Sorafenib is recommended in such patients, but it has limited therapeutic effectiveness. Case presentation A 54-year-old man was diagnosed with a liver abscess that was treated by puncture and drainage at a regional hospital. However, the diagnosis was subsequently changed to hepatocellular carcinoma with macroscopic portal vein tumor thrombus, based on the results obtained for the triple-positive tumor markers (alpha-fetoprotein, 45,928 ng/ml; protein induced by vitamin K absence or antagonist-II, 125,350 mAU/ml; and alpha-fetoprotein-L3, 38.3%). As the patient’s liver functional reserve was not adequate for curative resection, chemoembolization was performed with a hepatic arterial infusion of cisplatin (50 mg) and 5-FU (1000 mg), followed by mild embolization with cisplatin (50 mg) suspended in lipiodol (5 ml) and starch microspheres (300 mg) containing mitomycin C (4 mg). As the thrombus had progressed to the bifurcation of the right and left portal veins, the right vein was surgically ligated. Three peritoneal nodules could be identified and were removed. Three additional rounds of hepatic arterial chemotherapy/chemoembolization were performed after the initial surgery. At the 2-year evaluation, all tumor markers were observed to have normalized and diagnostic imaging showed complete remission. Conclusions Complete remission of hepatocellular carcinoma with macroscopic portal vein tumor thrombus and peritoneal dissemination was obtained with a treatment regimen that involved four rounds of hepatic arterial infusion chemotherapy and transient chemoembolization, portal vein ligation, and the removal of peritoneal dissemination. This regimen can be recommended for patients with advanced hemiliver lesions who cannot undergo curative resection.

Abstract Background A hepatic sclerosed hemangioma (HSH) is a very rare benign liver tumor. The correct preoperative diagnosis of HSH is very difficult because its features of imaging are similar to those of intrahepatic cholangiocarcinoma or colorectal liver metastasis. Case presentation We experienced five patients who were diagnosed histologically with HSH. The preoperative diagnoses were HSH in two patients, cavernous hemangioma in one, intrahepatic cholangiocarcinoma in one, and colorectal liver metastasis in one. All patients were treated with hepatectomy (one laparoscopic and four laparotomies), and the diagnosis was completed by histological investigation of the resected specimen. In particular, we investigated the apparent diffusion coefficient (ADC) mean value using diffusion-weighted sequences of magnetic resonance imaging (DW-MRI). The average of the ADC mean (ADCmean) value of HSH was 1.94 × 10−3 mm2/s (range 1.73–2.10 × 10−3 mm2/s), which was higher than the value of common malignant liver tumors. Interestingly, the ADCmean values were almost the same between the degenerate (1.90 ± 0.17 × 10−3 mm2/s) and the non-degenerate areas (1.95 ± 0.26 × 10−3 mm2/s) in HSH. Conclusions The ADCmean value seemed to be quite useful to preoperatively distinguish HSH from other malignant liver tumors.

The combined impact of an increasing demand for liver transplantation and a growing incidence of nonalcoholic liver disease has provided the impetus for the development of innovative strategies to preserve steatotic livers. A natural oxygen carrier, HEMO2life®, which contains M101 that is extracted from a marine invertebrate, has been used for static cold storage (SCS) and has shown superior results in organ preservation. A total of 36 livers were procured from obese Zucker rats and randomly divided into three groups, i.e., control, SCS-24H and SCS-24H + M101 (M101 at 1 g/L), mimicking the gold standard of organ preservation. Ex situ machine perfusion for 2 h was used to evaluate the quality of the livers. Perfusates were sampled for functional assessment, biochemical analysis and subsequent biopsies were performed for assessment of ischemia-reperfusion markers. Transaminases, GDH and lactate levels at the end of reperfusion were significantly lower in the group preserved with M101 (p < 0.05). Protection from reactive oxygen species (low MDA and higher production of NO2-NO3) and less inflammation (HMGB1) were also observed in this group (p < 0.05). Bcl-1 and caspase-3 were higher in the SCS-24H group (p < 0.05) and presented more histological damage than those preserved with HEMO2life®. These data demonstrate, for the first time, that the addition of HEMO2life® to the preservation solution significantly protects steatotic livers during SCS by decreasing reperfusion injury and improving graft function.

Abstract Background Although hilar cholangiocarcinoma (HCCA) has a very poor prognosis, there are cases in which long-term survival is rarely obtained by multidisciplinary treatment. Case presentation A 61-year-old man diagnosed with HCCA was referred to our hospital. We performed an extended left hemi-hepatectomy and caudate lobectomy with extrahepatic bile duct resection. The tumor stage was T2aN0M0, stage II, based on the TNM classification, seventh edition. R0 resection was successfully performed. Adjuvant chemotherapy was not administered. After 38 months, computed tomography revealed peritoneal dissemination. The patient received chemotherapy with tegafur-gimeracil-oteracil-potassium (S-1) and gemcitabine. The peritoneal dissemination was successfully controlled for more than 50 months. During the treatment, levels of CEA and CA19-9 kept rising slowly, which was followed by bowel obstruction due to peritoneal dissemination of HCCA. The patient underwent resection of transverse colon with tumor nodules, and the tumor was pathologically diagnosed as metastasis of HCCA. Tumor markers decreased to normal levels, and the patient has been free from tumor relapse for 6 months. Conclusions We here report a rare case of HCCA patient with recurrent peritoneal dissemination 3 years after R0 surgery which was sensitive to chemotherapy. The patient successfully received resection of peritoneal dissemination 50 months after the induction of chemotherapy and survived for 10 years.

Abstract Postpancreaticoduodenectomy (PD) bleeding, which is reported to occur in 5–7%, is a major complication that often causes life‐threatening secondary events. A transarterial catheter technique with coil embolization is a widespread procedure that could potentially cause massive hepatic infarction and subsequent sepsis with hepatic abscess, which can be a fatal complication. Here, we introduce a new transarterial technique that uses a hemostat with a stent graft, which successfully rescued a patient had suffered post‐PD bleeding.

BackgroundColorectal cancer (CRC) represents a major cause for cancer death and every third patient develops liver metastases (CRLM). Several factors including number and size of metastases and primary tumour lymph-node status have been linked to survival. The primary tumour location along the colo-rectum continuum (sidedness) was analysed in first-line chemotherapy trials, where right-sided CRCs showed decreased survival. This association has not yet been clearly established in patients undergoing resection for CRLM.MethodsClinicopathological differences in CRLM resections according to sidedness in two Austrian centres (2003-2016) are described and survival is compared through Kaplan-Meier and multivariable analysis. A risk-score is presented with time-dependent receiver operating curve analysis and international validation in two major hepatobiliary centres. Furthermore, a systematic meta-analysis of studies on primary tumour location and survival after CRLM resection was performed.Results259 patients underwent hepatectomy. Right-sided CRC patients (n = 59) more often had positive primary tumour lymph-nodes (76.3%/61.3%;p = 0.043) and RAS-mutations (60%/34.9%;p = 0.036). The median overall and disease-free survival was 33.5 and 9.1 months in right-sided versus 55.5 (p = 0.051) and 12.1 months (p = 0.078) in left-sided patients. In multivariable analysis nodal-status (HR 1.52), right-sidedness (HR 1.53), extrahepatic disease (HR 1.71) and bilobar hepatic involvement (HR 1.41) were significantly associated with overall survival. Sidedness was not independently associated with disease-free survival (HR 1.33; p = 0.099). A clinical risk score including right-sidedness, nodal-positivity and extrahepatic involvement significantly predicted overall (p = 0.005) and disease-free survival (p = 0.027), which was confirmed by international validation in 527 patients (p = 0.001 and p = 0.011). Meta-analysis including 10 studies (n = 4312) showed a significant association of right-sidedness with overall survival after resection (HR 1.55;pConclusionsPatients with liver metastases from right-sided CRC experience worse survival after hepatic resection. Sidedness is a simple yet effective factor to predict outcome.

AIM:The clinical impact of pathological classification based on architectural pattern in hepatocellular carcinoma (HCC) remains elusive in spite of its well-known and common feature. METHODS:The prognostic impact of pathological classification was examined with prospective database. Three hundred and eighty HCC patients who underwent curative hepatectomy as an initial treatment in Kumamoto University were enrolled as a test cohort. The outcome was confirmed with a validation cohort in Kyushu University. RESULTS:Macrotrabecular (macro-T) subtype (n = 38) and compact subtype (n = 43) showed similar biological and prognostic features. Both showed higher AFP level and worse overall survival than microrabecular (micro-T) subtype (n = 266). Multivariate analysis for overall survival revealed that DCP ≥ 40, multiple tumor and macro-T/compact subtype were associated with poor overall survival (risk ratio = 2.2, 1.6 and 1.6; p = 0.002, 0.020, and 0.047, respectively). Of note, 32% of macro-T/compact subtype showed early recurrence within 1 year, which showed substantially low (5%) 5 year overall survival, whereas 16% of micro-T/PG subtype did. Twenty-one percent of macro-T/compact subtype showed multiple intrahepatic metastases (≥ 4) or distant metastases, which resulted in non-curative treatment, whereas 5% of micro-T/PG subtype did. In validation cohort, macro-T/compact subtype was an independent predictor of worse overall survival. CONCLUSION:Macro-T/compact subtype is biologically discriminated from micro-T and PG subtypes due to its aggressive features and poor prognosis after curative treatment. Additional treatment with curative hepatectomy on Macro-T/compact subtype should be discussed because of high possibility of systemic residual cancer cell.

β-catenin signaling is a major oncogenic pathway in hepatocellular carcinoma (HCC). Since β-catenin phosphorylation by glycogen synthase kinase 3β (GSK3β) and casein kinase 1ε (CK1ε) results in its degradation, mutations affecting these phosphorylation sites cause β-catenin stabilization. However, the relevance of missense mutations in non-phosphorylation sites in exon 3 remains unclear. The current study explores significance of such mutations in addition to addressing the clinical and biological implications of β-catenin activation in human HCC.Gene alteration in exon3 of CTNNB1, gene expression of β-catenin targets such as glutamate synthetase (GS), axin2, lect2 and regucalcin (RGN), and protein expression of β-catenin were examined in 125 human HCC tissues.Sixteen patients (12.8%) showed conventional missense mutations affecting codons 33, 37, 41, and 45. Fifteen additional patients (12.0%) had other missense mutations in codon 32, 34, and 35. Induction of exon3 mutation caused described β-catenin target gene upregulation in HCC cell line. Interestingly, conventional and non-phosphorylation site mutations were equally associated with upregulation of β-catenin target genes. Nuclear localization of β-catenin was associated with poor overall survival (p = 0.0461). Of these patients with nuclear β-catenin localization, loss of described β-catenin target gene upregulation showed significant poorer overall survival than others (p = 0.0001).This study suggests that both conventional and other missense mutations in exon 3 of CTNNB1 lead to β-catenin activation in human HCC. Additionally, the mechanism of nuclear β-catenin localization without upregulation of described β-catenin target genes might be of clinical importance depending on distinct mechanism.

For unresectable colorectal liver metastases (CRLM), hepatic resection with or without chemotherapy is the only curative treatment that sufficiently achieves long-term survival. However, occasional severe allergic responses to anticancer drugs necessitate treatment discontinuation. A 45-year-old woman presented with metachronous unresectable colorectal liver metastases. Chemotherapy with oxaliplatin plus 5-FU and leucovorin (FOLFOX) was initiated, but severe allergic dermatitis developed after the second cycle. Although she reported no prior history of adverse reactions to tegafur-uracil, a drug lymphocyte stimulation test showed an allergic response to 5-FU. We subsequently replaced with Irinotecan plus S-1 (IRIS) chemotherapy which was well tolerated and resulted in a partial response after 3 cycles. As a result, right trisectionectomy was successfully performed and no recurrence was detected in the following 3 years. A severe allergic reaction to intravenous 5-FU-containing drug regimens can be successfully alleviated by switching to S-1-containing regimens such as IRIS or S-1 plus oxaliplatin (SOX).