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Pancreaticobiliary maljunction (PBM) is a congenital malformation. The reflux of pancreatic juice into the biliary tract caused by PBM plays a significant role in the development of biliary tract cancers (BTCs), such as gallbladder cancer and cholangiocarcinoma. Previous studies have demonstrated a high incidence of BTC in patients with PBM. However, there are only a few reports of patients who developed BTC after a diagnosis of PBM. We report the cases of two patients who developed gallbladder cancer after being diagnosed with PBM. They had refused treatment and were being managed with follow-up observation alone after the diagnosis of PBM and developed gallbladder cancer after several years of observation. Thus, surgical treatment should be recommended for all patients with PBM in order to prevent the development of BTC. Moreover, long-term, close, regular follow-up is necessary to facilitate the early diagnosis of subsequent BTC in patients with untreated PBM.

AIM We investigated effects of direct-acting antiviral (DAA)-induced sustained virological response (SVR) after liver resection in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) for postoperative recurrence and survival. METHODS Surgical outcomes in 18 patients with postoperative DAA-induced SVR (HCC-DAA group) were compared with those in 23 patients with preoperative DAA-induced SVR (DAA-HCC group) and those in 10 patients who did not receive DAA therapy (control group). Patients who received DAA therapy >1 year after surgery and those with recurrence

Aim This study aimed to evaluate the indications of laparoscopic repeat liver resection (LRLR) for recurrent hepatocellular carcinoma from the viewpoint of its difficulty. Methods One hundred and one patients who underwent LRLR and 59 patients who underwent open repeat liver resection (ORLR) were included. The difficulty was classified according to the preoperative predictive factors for difficult LRLR, including an open approach during previous liver resection, history of two or more previous liver resections, history of previous major liver resection, tumor near the resected site of the previous liver resection, and intermediate or high difficulty with the difficulty scoring system. We compared the surgical outcomes between the LRLR and ORLR groups based on the difficulty class (low‐ or intermediate difficiulty class, 0 to 3 predictive factors; high difficiulty class, 4 or 5 factors). Results In the low‐ or intermediate difficiulty class, intraoperative blood loss and the proportion of patients with postoperative complications were significantly lower in LRLR than in ORLR, and the duration of the postoperative hospital stay was significantly shorter in LRLR than in ORLR. In the high difficiulty class, total operative time and operative time before starting hepatic parenchymal resection were significantly longer in LRLR than in ORLR, and there were no significant differences in other surgical outcomes between the two groups. Conclusion LRLR is recommended for patients in the low or intermediate difficulty class. However, LRLR does not have an advantage with longer operative time for patients in the high difficulty class compared with ORLR., Laparoscopic repeat liver resection (LRLR) is recommended for patients in our suggested low or intermediate difficulty class. On the other hands, LRLR does not have an advantage with longer operative time for patients in the high difficulty class, compared with open repeat liver resection.

Despite the recently increasing number of elderly patients undergoing liver resection, the impact of advancing age on postoperative infections (PIs) incidence and risk remains unclear. This study aimed to investigate the impact of advancing age on PIs incidence and status. This retrospective study included 744 patients undergoing liver resection without biliary reconstruction or combined resection of other organs. Multivariable analysis with a restricted cubic spline was used to evaluate the impact of advancing age on PIs and to determine its association with PIs risk in patients undergoing open and laparoscopic liver resection (OLR and LLR, respectively). Multivariable analysis demonstrated that advancing age was significantly associated with increased PIs risk (P = 0.017). The spline curve showed that the odds ratio for PIs sharply increased starting approximately at 65 years of age. Unadjusted restricted cubic splines assessing the subcategories of PIs demonstrated that advancing age was associated with increased risks of organ/space surgical site infection and sepsis (P = 0,064 and 0.048, respectively). Multivariable analysis revealed that LLR was associated with the lower PIs risk compared with OLR (P = 0.025), whereas the lower PIs risk with LLR was not significantly obscured by advancing age (P = 0.29). Advancing age was associated with increased risk of PIs, including organ/space surgical site infections and sepsis, after liver resection especially in patients aged ≥ 65 years.

Purpose Locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) involving the celiac artery (CeA), the common hepatic artery and the gastroduodenal artery (GDA) is considered unresectable. We developed the novel procedure of pancreaticoduodenectomy with celiac artery resection (PD-CAR) for such LA-PDACs. Methods From 2015 to 2018, we performed curative pancreatectomy with major arterial resection for 13 LA-PDACs as a clinical study (UMIN000029501). Of those, four patients with pancreatic neck cancer involving the CeA and GDA were candidates for PD-CAR. Prior to surgery, blood flow alterations were performed to unify the blood flow to the liver, stomach, and pancreas, resulting in feeding from the cancer-free artery. During PD-CAR, arterial reconstruction of the unified artery was performed as needed. Based on the records of PD-CAR cases, we retrospectively analyzed the validity of the operation. Results R0 resection was achieved in all patients. Arterial reconstruction was performed in three patients. In another patient, the hepatic arterial flow was maintained by preserving of the left gastric artery. The mean operative time was 669 min and the mean blood loss was 1003 g. Although Clavien-Dindo classification III-IV postoperative morbidities occurred in three patients, no reoperations nor mortalities occurred. Although two patients died of cancer recurrence, one patient survived for 26 months without recurrence (died of cerebral infarction), and another is alive at 76 months without recurrence. Conclusion PD-CAR, which enabled R0 resection and preservation of the residual stomach, pancreas, and spleen, provided acceptable postoperative outcomes.

Few studies compared the oncological and biological characteristics between ampullary carcinoma (AC) and cancer of the second portion of the duodenum (DC-II), although both tumors arise from anatomically close locations.To elucidate differences in clinicopathological characteristics, especially the patterns of lymph node metastasis (LNM), between AC and DC-II.This was a retrospective cohort study of 80 patients with AC and 27 patients with DC-II who underwent pancreaticoduodenectomy between January 1998 and December 2018 in two institutions. Clinicopathological factors, LNM patterns, and prognosis were compared between the two groups.The patients with AC and DC-II did not exhibit significant differences in 5-year overall survival (66.0% and 67.1%, respectively) and 5-year relapse-free survival (63.5% and 62.2%, respectively). Compared to the patients with DC-II, the rate of preoperative biliary drainage was higher (Although there were no significant differences in the prognosis and recurrence rates between the two groups, metastases to N-He and N-Py were more frequent in patients with DC-II than in those with AC.

We aimed to develop the deep learning (DL) predictive model for postoperative early recurrence (within 2 years) of hepatocellular carcinoma (HCC) based on contrast-enhanced computed tomography (CECT) imaging. This study included 543 patients who underwent initial hepatectomy for HCC and were randomly classified into training, validation, and test datasets at a ratio of 8:1:1. Several clinical variables and arterial CECT images were used to create predictive models for early recurrence. Artificial intelligence models were implemented using convolutional neural networks and multilayer perceptron as a classifier. Furthermore, the Youden index was used to discriminate between high- and low-risk groups. The importance values of each explanatory variable for early recurrence were calculated using permutation importance. The DL predictive model for postoperative early recurrence was developed with the area under the curve values of 0.71 (test datasets) and 0.73 (validation datasets). Postoperative early recurrence incidences in the high- and low-risk groups were 73% and 30%, respectively (p = 0.0057). Permutation importance demonstrated that among the explanatory variables, the variable with the highest importance value was CECT imaging analysis. We developed a DL model to predict postoperative early HCC recurrence. DL-based analysis is effective for determining the treatment strategies in patients with HCC.

Introduction Pancreatic acinar cell carcinoma (ACC) is a relatively rare neoplasm. Furthermore, tumor rupture is extremely rare. Only 1 case of ruptured pancreatic ACC has been reported, and the long-term outcome of the case is unknown. Here, we present a case of spontaneously ruptured ACC with long-term survival after successful resection. Case Presentation A 67-year-old man was brought to our hospital by ambulance, presenting with progressive left abdominal pain. Laboratory data showed an increased inflammatory response, and contrast-enhanced computed tomography showed a mass in the pancreas tail with nonuniform enhancement in the early phase. Fluid collection was detected around the spleen to the left kidney. Spontaneous rupture of a pancreatic tumor was strongly suspected. After improvement of his general condition, the patient underwent resection of the pancreas and adjacent organs. The resected tumor was surrounded by organs and adipose tissue, so obvious exposure was not observed in the surgical margins. Pathologically, neither exposure of tumor cells at the surgical margins nor lymph node involvement was detected. The patient has survived 80 months since initial diagnosis without any evidence of recurrence. Conclusion Although ruptured pancreatic ACC has the potential for dissemination, surgical resection including adjacent organs remains an option for curative treatment.

Background Cholangiocarcinoma and secondary biliary cirrhosis can develop after liver resection for hepatolithiasis and are causes of hepatolithiasis-related death. We determined potential risk factors for hepatolithiasis-related death and subsequent cholangiocarcinoma, including precancerous lesions such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct, in patients undergoing liver resection for hepatolithiasis. Methods The study cohort included 62 patients who underwent liver resection for hepatolithiasis without concomitant cholangiocarcinoma and had surgical specimens available for pathological examination. Univariate and multivariate analyses were conducted to examine risk factors associated with subsequent cholangiocarcinoma after hepatolithiasis and hepatolithiasis-related death. In 28 patients with BilIN lesions, the specimens were immunohistochemically stained for γ-H2AX and S100P. Results In the study cohort, the causes of death were subsequent cholangiocarcinoma, biliary cirrhosis, and other diseases in 5, 3, and 7 patients, respectively. Liver atrophy, precancerous lesions, postoperative repeated cholangitis, and jaundice for ≥1 week during the follow-up period were risk factors for hepatolithiasis-related death. Multivariate analysis showed that liver atrophy and precancerous lesions were independent risk factors for hepatolithiasis-related death. Liver atrophy or precancerous lesions were also risk factors for subsequent cholangiocarcinoma by univariate analysis. The positive expression of γ-H2AX and S100P was observed in 18 and 14 of the 28 BilIN lesions, respectively. Conclusions Liver atrophy and precancerous lesions with malignant transformation were risk factors not only for subsequent cholangiocarcinoma but also hepatolithiasis-related death after liver resection for hepatolithiasis, indicating that long-term follow-up is necessary even after liver resection in patients harboring these risk factors. .

This study is aimed to compare the occurrence of postoperative infections between patients with hepatocellular carcinoma (HCC) undergoing laparoscopic liver resection (LLR) and those undergoing open liver resection (OLR).This study included 446 patients who underwent initial curative liver resection for HCC 5 cm or less in size without macroscopic vascular invasion. To adjust for confounding factors between the LLR and OLR groups, propensity score matching and inverse probability weighting (IPW) analysis were performed. The incidence rates of postoperative infection, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI), were compared between the two groups.An imbalance in several confounding variables, including period of surgery, extent of liver resection, difficult location, proximity to a major vessel, tumor size ≥ 3 cm, and multiple tumors, was observed between the two groups in the original cohort. After matching and weighting, the imbalance between the two groups significantly decreased. Compared with OLR, LLR was associated with a lower volume of intraoperative blood loss (140 vs. 350 mL, P 0.001 in the matched cohort; 120 vs. 320 mL, P 0.001 in the weighted cohort) and reduced risk of postoperative infection (2.0% vs. 12%, P = 0.015 in the matched cohort; 2.9% vs. 14%, P = 0.005 in the weighted cohort). Of the types of postoperative infections, organ/space SSI and RI were less frequently observed in the LLR group than in the OLR group in the matched cohort (1.0% vs. 6.0%, P = 0.091 for organ/space SSI; 0% vs. 6.0%, P 0.001 for RI) and in the weighted cohort (1.2% vs. 7.8%, P 0.001 for organ/space SSI; 0.3% vs. 5.1%, P = 0.009 for RI).Compared with OLR, LLR for HCC might reduce postoperative infections, including organ/space SSI and RI.

We aimed to investigate the difference in engraftment rates depending on the transplant site for a patient-derived xenograft (PDX) of pancreatic ductal adenocarcinoma (PDAC) and the effects of the microenvironment on engraftment.Frozen cancer tissues from PDAC tumors were used, and tumor fragments were directly implanted into the subcutaneous, orthotopic pancreas, peritoneum, and liver of X-linked severe combined immunodeficiency (XSCID) rats. We assessed the success of engraftment in each organ. Additionally, to evaluate the effect of the microenvironment in each organ, we performed immunohistochemical analysis.Subcutaneous transplantation was successful in 8 of 10 PDAC cases (16 of 30 rats). This was a higher rate than for other organ transplants. The vascular endothelial cells in the stroma were replaced with those from rats instead of humans. Vascular endothelial growth factor-A (VEGF-A) and cluster of differentiation-31 (CD31) was significantly more strongly expressed in the subcutaneous transplantation model (VEGF-A: p0.001, CD31: p=0.0036).The engraftment rate was significantly higher for the subcutaneous PDX model than for the orthotopic pancreatic, peritoneal, and liver PDX models. Blood vessels of the PDX stroma had been replaced by rat-derived vessels instead of the original human vessels, suggesting that angiogenesis in the PDX microenvironment may be a major factor in engraftment.

The incidence of postoperative adhesions is directly correlated with the difficulty level of repeat hepatectomies. However, the incidence, location, and severity of postoperative adhesions in relation to hepatectomy-related operative procedures are yet unclear.First hepatectomy-induced hard dense adhesions were evaluated from the surgical records and/or videos of 168 patients who underwent second hepatectomies.The incidence of postoperative hard dense adhesions around the liver was significantly associated with locations, such as the hepatic cut surface, dissected areas around the liver, and peri-incision peritoneum, and hepatectomy-related operative procedures, such as Pringle maneuver and cholecystectomy. The incidence of hard dense adhesions after dissection was higher around the right liver than in the left infraphrenic space. Further, the incidence of hard dense adhesions around the hepatoduodenal ligament or Morison pouch was greater than 30% even in patients who did not undergo Pringle maneuver, cholecystectomy, or hepatorenal ligament dissection. Although the incidence of hard dense adhesions of the peritoneum around the incision was higher after open hepatectomy than after laparoscopic hepatectomy, adhesion barrier use reduced the incidence of such adhesions in patients after open hepatectomy.Hepatectomy-related operative procedures such as peri-hepatic dissection, Pringle maneuver and cholecystectomy are directly associated with postoperative hard dense adhesions. However, the incidence of postoperative hard dense adhesions around the hepatoduodenal ligament and Morison pouch was high even when the above-mentioned operative procedures were not performed. These findings may help inform clinical decisions regarding the indications and sites for adhesion barrier use during hepatectomies.

The effectiveness and extent of regional lymph node dissection in primary duodenal cancer (DC) remains unclear. This study aimed to analyze the prognostic factors and lymph node metastasis (LNM) patterns in DC. Fifty-three patients who underwent surgical resection for DC between January 1998 and December 2018 at two institutions were retrospectively analyzed. Univariate and multivariate analyses were performed on the prognostic factors of resected DC. Moreover, the relationships between depth of tumor invasion and incidence of LNM and between tumor location and LNM stations were analyzed. The five-year survival rate of the study population was 68.9%. Multivariate survival analysis demonstrated that histologic grade G2–G4, presence of LNM, pT3–4, and elevated preoperative CA19-9 were the independent poor prognostic factors. No patient with pTis–T2 had LNM. On the other hand, LNM was found in 70% of patients with pT3–4. Among 36 patients who underwent pancreaticoduodenectomy (PD), LNM around the pancreatic head was observed, regardless of the duodenal cancer site, including the duodenal bulb and the third to the fourth portion. Histologic grade G2–G4, presence of LNM, pT3–T4, and elevated preoperative CA19-9 were the independent poor prognostic factors in patients with resected DC. Our results suggested that lymph node dissection could be omitted for DC Tis–T1a. Moreover, based on the high frequency of LNM in T3–4 cases, PD with lymph node dissection in the pancreatic head region was considered necessary for T3–4 DC at any site.

Introduction This study aimed to investigate the predictive factors and classifications for difficulty of laparoscopic repeated liver resection (LRLR) in patients with recurrent hepatocellular carcinoma. Methods Sixty patients who underwent LRLR were included. Potential predictive factors for difficult LRLR included the approach of the previous liver resection (laparoscopic or open), the number of previous liver resections, a history of cholecystectomy in previous liver resection, the operative procedure of previous liver resection, whether the tumor was near the resected site of the previous liver resection, non-surgical treatments before the present surgery, and the difficulty scoring system for laparoscopic liver resection. The relationship between these factors and perioperative outcomes were evaluated to investigate the predictive factor for difficult LRLR. Results Univariate and multivariate analyses demonstrated that an open approach during previous liver resection, two or more previous liver resections, a history of previous liver resection with not less than sectionectomy, tumor near the resected site of the previous liver resection, and intermediate or high difficulty in the difficulty scoring system were independent risk factors for prolonged operative time and/or severe adhesion of LRLR. Three difficulty classifications were then suggested based on the number of these five predictive factors. The difficulty classification reflected operative time, intraoperative blood loss, and incidence of postoperative complication. Conclusion The difficulty of LRLR may be predicted by three difficulty classifications using five preoperative predictive factors.

Introduction We investigated the indications for laparoscopic liver resection (LLR) of mass-forming intrahepatic cholangiocarcinoma (MF-ICC), including the need for lymph node dissection for improved postoperative prognosis. Methods This study involved 36 patients who underwent surgery for solitary peripheral MF-ICC. Fifteen patients underwent LLR, and 21 underwent open liver resection (OLR). Surgical outcomes and prognostic factors were investigated to determine the indications for LLR. Results No significant differences were observed in perioperative outcomes between patients who underwent LLR and OLR. A significantly worse disease-free survival (DFS) rate was observed in patients who preoperatively had a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) levels. A significantly worse overall survival (OS) rate was observed in patients with a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19-9 levels. Therefore, a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19-9 and CEA levels were determined to be preoperative prognostic factors. DFS and OS rates were significantly better in patients without these factors. Moreover, in six patients without these factors who underwent LLR, neither lymph node metastasis nor postoperative recurrence was observed. Conclusion A tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19-9 and CEA levels are preoperative prognostic factors for peripheral MF-ICC. LLR is indicated for patients without these factors.

A 82-year-old female had received radiofrequency ablation for hepatocellular carcinoma(HCC)in segment 2 30 months before surgery. One month before surgery, enhanced CT showed enhanced lesion about 20 mm in diameter in the abdominal wall along the needle-tract. There was no other recurrent lesion including liver. We diagnosed the lesion as needle-tract implantation and she underwent surgical resection of the abdominal rectus muscle and sheath including needle-tract. The pathological findings revealed well differentiated HCC. After the surgery, she underwent transcatheter arterial embolization for the recurrent HCC in segment 3 and segment 4. Twenty one months after the surgery, she has been alive without recurrence. Our case demonstrated that surgical resection of the needle-tract implantation of the HCC is one of the useful therapeutic options for the selected patients.

A 66-year-old female with upper abdominal pain was diagnosed the pancreatic tail cancer infiltrating into the stomach and transverse colon by computed tomography(CT). Umbilical metastasis(so called Sister Mary Joseph's nodule)and peritoneal metastases in pouch of Douglas were detected by FDG-PET. The patient was diagnosed as unresectable pancreatic cancer with distant metastases. Thus, she received FOLFIRINOX therapy. After 9 courses of FOLFIRINOX therapy and 15 courses of FOLFIRI therapy, the pancreatic tumor shrunk on CT. In addition, umbilical metastasis and peritoneal metastases disappeared on FDG-PET. Therefore, conversion surgery was scheduled. Fourteen months after the initial treatment, we performed distal pancreatectomy with left adrenalectomy partial gastrectomy, transverse colectomy, and umbilical resection. The patient was discharged 15 days after the operation without serious complications. Histopathological findings revealed the presence of adenocarcinoma infiltrating into the preperitoneal adipose tissue in the umbilicus. Histological therapeutic effect was Grade Ⅰb according to the 7th Edition of the General Rules for the Study of Pancreatic Cancer. Seven months after the operation, local recurrence was showed. The patient is still alive 2 years and 5 months since the initial treatment.

A 46-year-old man presented with right lower quadrant pain. Enhanced CT revealed a 30 mm sized irregular shaped mass originating from the appendix and invading the abdominal wall. We performed the laparoscopic appendectomy. Finally, the pathologic finding revealed a local advanced appendiceal carcinoma. From the intraoperative findings, the residual tumor was existed around the right external iliac vessels and abdominal wall. The patient was treated with chemotherapy for 13 months. Although the residual tumor encased the right external iliac vessels, the abdominal wall, and psoas major muscle, there were no signs of distant metastasis. We performed ileocecal resection with D3 lymph node dissection. The right external iliac vessels, abdominal wall, and psoas major muscle were resected simultaneously, and reconstructed by femoral- femoral bypass. As a result, R0 resection was achieved pathologically.

Although it has recently been reported that immune checkpoint inhibitors (ICIs) constitute effective treatment for solid tumors, the success rate in patients with intrahepatic cholangiocarcinoma is limited. We administered pembrolizumab to a patient as treatment for liver and lymph node metastases of intrahepatic cholangiocarcinoma. The patient had abundant infiltration of programmed death ligand 1-positive macrophages, cytotoxic T cells (CD8-positive lymphocytes), and programmed death 1-positive lymphocytes as well as a high combined positive score of 33.1, high-frequency microsatellite instability, and mismatch repair deficiency. These characteristics are predictive biomarkers of the efficacy of ICIs. After pembrolizumab was administered four times (triweekly administration), the carbohydrate antigen 19-9 serum level fell within the normal range, and computed tomography revealed that the size of the metastatic liver tumors and enlarged hilar lymph node had markedly decreased. However, the patient developed pruritus and exanthema on the trunk and limbs after 14 administrations and was diagnosed with bullous pemphigoid. We discontinued pembrolizumab therapy and started treatment for bullous pemphigoid. Nine months after discontinuation of pembrolizumab therapy, the patient remains alive without tumor relapse. This patient had durable response even after discontinuation of pembrolizumab therapy for multiple metastases of intrahepatic cholangiocarcinoma.

A 76-year-old man was referred to our hospital for advanced hepatocellular carcinoma(HCC)with chronic hepatitis type B. Although he underwent right anterior sectionectomy and S3 segmentectomy, multiple recurrences were found in the hepatic remnant after 2 months. Transcatheter arterial chemoembolization(TACE)and transcatheter arterial infusion (TAI)were performed separately. One and a half month after the last TAI, AFP and PIVKA-Ⅱ levels markedly elevated, and multiple early enhancing nodules with portal vein tumor thrombosis were detected on CT. A half dose of sorafenib(400mg/ day)was administered to the patient who was refractory to TACE. Sorafenib was discontinued after 4 weeks because the patient developed general fatigue and anorexia(Grade 3). Furthermore, these adverse events became worse, and ascites appeared. He was hospitalized in the palliative care unit for best supportive care for 3 weeks and also received outpatient treatment for more than 14 months. Fifteen months after discontinuing sorafenib administration, his condition improved dramatically, and CT revealed that the multiple HCC had reduced in size. Moreover, the portal vein tumor thrombosis disappeared. As his performance status and liver function were well preserved, he underwent partial hepatectomy for residual HCC. The patient remains alive without recurrence at 18 months, despite no administration of sorafenib.This case demonstrates that sorafenib administration combined with surgical treatment could possibly cure advanced HCC refractory to TACE.

A 67-year-old woman was diagnosed with borderline resectable pancreatic cancer and obstructive jaundice. A covered self-expandable metallic stent(SEMS)was placed endoscopically. Neoadjuvant chemotherapy with gemcitabine plus nabpaclitaxel was provided. Forty-seven days after the SEMS placement, she presented with hematemesis. Computed tomography revealed migration of SEMS into the small bowel. No pseudoaneurysms were detected. Upper digestive endoscopy demonstrated hemobilia without obvious causes of bleeding in the stomach or duodenum. As hemorrhage recurrence was confirmed in the bile duct, we performed pancreaticoduodenectomy. Thus, bile duct hemorrhage can occur in patients with pancreatic cancer after SEMS placement.

The patient was an 81-year-old woman. She had undergone extended cholecystectomy with lymph node dissection for primary gallbladder cancer. The pathological diagnosis was moderately differentiated tubular adenocarcinoma(pT2, N0, M0, pStage Ⅱ). Eleven months after the initial surgery, dynamic CT revealed a solitary low-enhanced tumor in S5 ofthe liver. As the tumor was detected with abnormal FDG uptake by PET-CT, we diagnosed the patient with a metastatic liver tumor from gallbladder cancer. Although chemotherapy was considered, conservative treatment was selected as the patient did not want to undergo chemotherapy. Therefore, laparoscopic partial liver resection was performed 15 months after the initial surgery with the consideration that no other distant metastasis was found, and tumor markers were within normal ranges. The postoperative course was uneventful, and the patient was discharged 13 days after liver resection without any morbidities. The resected tumor was pathologically diagnosed as a metastatic liver tumor from gallbladder cancer. She has achieved 18 months recurrence free survival after the liver resection without adjuvant chemotherapy. Although liver resection for a metastatic liver tumor from gallbladder cancer is not a standardized treatment, it may be a therapeutic option in cases of limited metastasis.

This paper presents a visualization method of intestine (the small and large intestine) regions and their stenosed parts caused by ileus from CT volumes. Since it is difficult for non-expert clinicians to find stenosed parts, the intestine and its stenosed parts should be visualized intuitively. Furthermore, the intestine regions of ileus cases are quite hard to be segmented. The proposed method segments intestine regions by 3D FCN (3D U-Net). Intestine regions are quite difficult to be segmented in ileus cases since the inside the intestine is filled with liquids. These liquids have similar intensities with intestinal wall on 3D CT volumes. We segment the intestine regions by using 3D U-Net trained by a weak annotation approach. Weak-annotation makes possible to train the 3D U-Net with small manually-traced label images of the intestine. This avoids us to prepare many annotation labels of the intestine that has long and winding shape. Each intestine segment is volume-rendered and colored based on the distance from its endpoint in volume rendering. Stenosed parts (disjoint points of an intestine segment) can be easily identified on such visualization. In the experiments, we showed that stenosed parts were intuitively visualized as endpoints of segmented regions, which are colored by red or blue.

A 74-year-old woman presented with epigastric pain. Imaging revealed a tumor measuring 80 mm, with internal necrosis, originating from the gallbladder and invading the liver. We performed extended anterior segmentectomy of the liver and lymph node resection following a preoperative diagnosis of gallbladder cancer. Histologically, the tumor was diagnosed as an undifferentiated carcinoma of the gallbladder. Although curative resection was performed, the patient developed recurrence with liver metastasis and peritoneal dissemination after 6 postoperative weeks and died after 10 postoperative weeks.

Introduction: The anterior approach to the inferior vena cava (IVC) by the liver hanging maneuver is effective in resecting large retrohepatic tumors without mobilizing the right lobe. Case presentation: A 50-year-old man was referred to our hospital with a diagnosis of pheochromocytoma. He had severe congestive heart failure and cardiac ejection fraction was 15%. Abdominal magnetic resonance imaging (MRI) and ultrasonography (US) showed an adrenal mass about 80 mm in diameter. The tumor-infiltrated posterior segment of the right hepatic lobe and tumor were widely attached to the IVC. After treatment of congestive heart failure with conservative therapy, surgery was planned. Right adrenectomy and right hepatectomy were performed, the latter using the liver hanging maneuver to avoid mobilizing the right lobe, and we were able to minimize blood pressure fluctuations and perform the operation safely. The histopathologic diagnosis was malignant pheochromocytoma. Conclusions: We performed right hepatectomy without mobilizing the right lobe by the liver hanging maneuver and minimized stimulation of the tumor. We could perform the operation safely using the liver hanging maneuver, which seems effective in such cases.

Synchronous double cancers in the biliary system are rare. Double cancer of the common bile duct (CBD) and the ampulla of Vater without pancreaticobiliary maljunction (PBM) is extremely rare. To our knowledge, only 7 cases have been reported previously. Here we report a case of synchronous double cancer of the CBD and the ampulla of Vater without PBM. A 63-year-old man was referred to our hospital with epigastric pain and jaundice. Computed tomography (CT) showed dilatation of both intrahepatic and intrapancreatic bile ducts, and slightly enhanced tumor in the middle part of the CBD and the ampulla of Vater. Endoscopic retrograde cholangiopancreatography (ERCP) showed a tuberous filling defect in the middle part of the CBD and an exposed tumor of the ampulla of Vater. Under a diagnosis of synchronous double cancer of the middle bile duct and the ampulla of Vater, pancreaticoduodenectomy was performed. Histopathologically, the ampulla of Vater tumor was well-differentiated tubular adenocarcinoma while the middle bile duct tumor was moderately-differentiated tubular adenocarcinoma. Normal mucosa was interposed between both tumors. These findings suggest that they were 2 primary tumors. Double cancer of the CBD and the ampulla of Vater without PBM is extremely rare. We report a case of synchronous double cancer of the CBD and the ampulla of Vater without PBM.

Background We researched the origin and progression of anaplastic pancreatic cancer (APC) from the viewpoints of cell lineage, epithelial-mesenchymal transition (EMT) and cancer stem like cells (CSC). Methods Using specimens from patients with APC and differentiated pancreatic ductal adenocarcinoma (PDAC), expression of sex-determining region Y box 9 (SOX9), E-cadherin, vimentin, ZEB-1, Snail, N-cadherin, CD24 and CD44 was estimated using immunohistochemistry. Results Almost all cases were positive for SOX9 expression. APC cases were negative, but many PDAC cases were positive for the expression of E-cadherin. A much higher number of APC cases than PDAC cases were positive for the expression of other EMT related proteins and for the expression of CSC related proteins. The ductal cancerous component of APC accounted for an average of 12% of the cancerous lesion and the expression of each marker in this component was similar to that of PDAC cases. Conclusions APC had pancreatic duct cell like features and might gain dedifferentiate components through EMT and the acquisition of CSC properties. This article is protected by copyright. All rights reserved.

There are many reports about limited surgery for intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. However, there is no consensus on limited surgery for IPMNs. The primary objective of this study was to define the clinical indications for limited surgery for IPMNs. The data of 98 patients who underwent curative resections for IPMN were retrospectively analyzed. IPMNs were classified into four different pathological grades: low-grade dysplasia (LGD), intermediate-grade dysplasia (IGD), high-grade dysplasia (HGD), and invasive carcinoma (Inv-IPMN). Inv-IPMNs were divided into T1a, T1b, and T1c or over T1c (≥T1c). Based on preoperative radiological findings, IPMNs were stratified into the three groups using the 2012 International Consensus Guidelines: worrisome features, high-risk stigmata (HRS), and others. There were no positive lymph node cases and no recurrent cases of LGDs, IGDs, and HGDs. On the other hand, positive lymph node cases in T1a, T1b, and ≥T1c were seen in 37.5, 20, and 22.2% of cases, respectively. The recurrence rates of T1a, T1b, and ≥T1c were 50, 40, and 55.6%, respectively. Of the HRS cases, 30 (73.2%) were malignant and 25 (61%) were Inv-IPMN. HRS showed sensitivity of 92.6%, specificity of 77.5%, and accuracy of 81.6% to identify Inv-IPMN by preoperative imaging. Limited surgery such as parenchyma-sparing pancreatectomy should be avoided for all cases of Inv-IPMNs, because every Inv-IPMN including T1a has the potential for lymph node metastasis and recurrence. HRS had high preoperative diagnostic ability for predicting Inv-IPMN. For cases that meet HRS criteria, pancreatectomy with lymphadenectomy is needed, and limited surgery should be withheld.

Background Anaplastic pancreatic cancer (APC) cell lines have been scarcely established. Methods The morphology, gene expressions, karyotyping and epithelial-mesenchymal transition markers of newly established APC cell lines OCUP-A1 and OCUP-A2 were analyzed. Their abilities of proliferation under normoxia and hypoxia, migration and invasion were compared to 4 commercially available pancreatic ductal adenocarcinoma (PDA) cell lines. Their induction of angiogenesis, stem-like cell population and subcutaneous tumor growth in nude mice were estimated, comparing 2 PDA cell lines examined here. Results OCUP-A1 and OCUP-A2 cells continuously grew with spindle and polygonal shapes, respectively. Gene analysis revealed 9 gene mutations including KRAS and TP53. Karyotyping clarified numerical structural abnormalities in both cells. Loss of E-cadherin and expression of vimentin in both cell lines were observed. The doubling time of both cell lines was approximately 20 h. Proliferation, migration and invasion abilities were not notable compared to other PDA cell lines. However stem-like cell population of both cell lines was superior to a part of PDA cell lines. Moreover OCUP-A1 showed stronger hypoxia tolerance and induction of angiogenesis than other PDA cell lines. The tumorigenicity in vivo of OCUP-A2 was stronger than conventional PDA cell lines. Conclusions The OCUP-A1 and OCUP-A2 cell lines of rare malignancies might be useful for investigating the biology of pancreatic cancer.

Synchronous associations of Cushing's syndrome (CS) and primary aldosteronism (PA) with multiple adrenocortical adenomas secreting each hormone independently have rarely been reported. Herein, we describe a unique case of PA associated with CS with detailed clinical and pathological investigations. Bilateral adrenal masses with clinical symptoms of CS and PA were found in a 43-year-old woman. Venous sampling demonstrated excess secretion of cortisol, and aldosterone from right, and left tumor, respectively. A bilateral laparoscopic partial adrenalectomy was undergone. The right adrenal tumor (3 cm) was yellow in color with abundant lipofuscin granules, and was composed of both eosinophilic compact cells and clear cells. In situ hybridization showed that both mRNAs for HSD3B2 and CYP17A1 were strongly expressed in the tumor, suggesting cortisol synthesis. Left adrenal tumor (2.4 cm) was golden-yellow in color, and composed of clear cells only. Expression of HSD3B2 and CYP11B mRNAs were observed in the tumor compatible with the aldosterone synthesis. Furthermore, minute nodules were found at the surface of normal-appearing cortex on both sides of the adrenal glands, and the expression of HSD3B2 and CYP11B mRNAs was clearly demonstrated within the nodules, indicating aldosterone synthesis. We diagnosed that the present case had 1) cortisol-producing right adrenocortical adenoma, 2) aldosterone producing left adrenocortical adenoma, and 3) cortical minute nodules with aldosterone production in both adrenal glands compatible with idiopathic adrenal hyperplasia. We reviewed the cases reported, and discussed the significance of the minute nodules in the adrenal cortex, often found in association with the adrenocortical adenoma.

Study Background: In the International Consensus Guidelines 2012 for intraductal papillary mucinous neoplasm (IPMN), 'high-risk stigmata' (HRS) were described as indications for resection. The purpose of this study was to evaluate the prognostic meaning of HRS in the 2012 guidelines. Method: Clinical and pathological data from 98 patients who underwent pancreatic resection for IPMN at our institution between 1994 and 2014 were retrospectively analyzed. Results: The 98 resected IPMNs were categorized as demonstrating no criteria (NC) (n=18), worrisome features (WF) (n=39), or HRS (n=46) according to the guidelines. By multivariate analysis, positive lymph node metastasis and HRS were significantly identified as independent prognostic factors. Five-year disease-specific survival rates for NC and WF were both 100%, whereas that for HRS was significantly poorer at 49.5% (p

In this study, we investigated the efficacy and toxicity of fluorouracil(FU)+Leucovorin(LV)with oxaliplatin (FOLFOX)and irinotecan(FOLFIRI)for patients with advanced or metastatic colorectal cancer.Eleven patients with advanced or metastatic colorectal cancer underwent chemotherapy, such as FOLFOX4, mFOLFOX6, and FOLFIRI. Four and 7 patients underwent FOLFOX4 and mFOLFOX6 as a first-line therapy, respectively. Five patients underwent FOLFIRI as a second-line therapy.The response rate(RR)for FOLFOX4 and mFOLFOX6 as a firstline therapy was 0%(0 of 4 patients)and 71%(5 of 7 patients), respectively. The RR for FOLFIRI as a second-line therapy was 40%(2 of 5 patients). The survival time of the eight patients experiencing CR, PR or SD in the firstline FOLFOX4/mFOLFOX6 or the second-line FOLFIRI is 7 to 27 months. That of the three patients not showing CR, PR or SD is 4 to 8 months. The former is significantly longer than the latter(p=0.0023). Toxicities were paresthesia, neutropenia, thrombocytopenia and general fatigue in FOLFOX4, paresthesia, neutropenia, thrombocytopenia, diarrhea and anaphylaxis in mFOLFOX6, while those were neutropenia, thrombocytopenia, stomatitis and general fatigue in the second-line FOLFIRI.For advanced or metastatic colorectal cancer, FOLFOX4/mFOLFOX6 followed by FOLFIRI may be effective and comparatively safe treatments.

A 70-year-old woman with pulmonary carcinomatous lymphangitis and paraaortic lymph node metastases due to gastric cancer, was treated by combination chemotherapy of S-1 and irinotecan (CPT-11). After one course of the chemotherapy, pulmonary carcinomatous lymphangitis and paraaortic lymph node metastases were remarkably improved. Diet intake was improving and cancer pain remarkably declined. Because the origin of gastric cancer was not improved, total gastrectomy, distal pancreatectomy and splenectomy were performed. After surgery, relapse of pulmonary carcinomatous lymphangitis caused death of the patient. The combination chemotherapy of S-1 and CPT-11 was effective for pulmonary carcinomatous lymphangitis and paraaortic lymph nodes metastases due to gastric cancer. However, careful consideration is required since surgery is performed on a patient who had suffered pulmonary carcinomatous lymphangitis.

Introduction: Anaplastic pancreatic cancer (APC) is a rare subtype of pancreatic ductal adenocarcinoma (PDA). The prognosis of APC is poorer than that of ordinary PDA. There is no established therapeutic strategy as well as PDA. In this study, we compared the expression of molecular markers in intratumoral different lesions which are undifferentiated lesion (UL) and ductal lesion (DL) to reveal progression pattern of APC and hold important clue for the therapy of APC. Materials & Methods: Formalin fixed paraffin embedded blocks were made from the primary APC tissues obtained from 6 patients. Each block was manipulated for staining with Hematoxylin and Eosin (H&E) and immunohistochemistry (IHC) for SOX9, E-cadherin, vimentin, ZEB-1, Snail, N-cadherin, CD24 and CD44. Using H&E slice, each sample was divided from cancerous lesion and non-cancerous lesion. Furthermore, cancerous lesion were divided from DL and UL. And then, for each marker, the intensity of staining of UL was compared with that of DL. The intensity was scored from 0 to 3. The relation between DL and UL was estimated based on the intensity score of each sample. Results: The proportion of DL to all cancerous lesion was 0.5% to 32%. The score of SOX9 was all 3 except one case in both lesions. Although the expression of E-cadherin was almost negative in UL, DL showed various scores. About vimentin, the intensity in UL was largely 2 and 3. In contrast, that of DL was very weak or none. The score of ZEB1 was 0 or 1 in DL and 1 or 3 in UL. Although Snail showed various scores in both regions, the score was mostly higher in UL than in DL. The score of N-cadherin expression was comparatively high in UL. CD24 and CD44 were not almost expressed in DL. In UL, the expression of these markers were various intensity. Disscusion: In the current study, it was suggested that APC might be derived from PDA by showing the expression of SOX9. Previous studies were reported from the view of KRAS mutation and cytokeratin expression about the origin of APC. However, recent studies were reported that these markers were often expressed even in other pancreatic neoplasm. Furthermore the expression of SOX9 is only identified in PDA among pancreatic neoplasms. Also, it was suggested that UL might change from DL through EMT by confirming the difference of the expression pattern of markers relating EMT in DL and UL. Because the expression of CD24 and CD44 varied in each case, it is unclear whether the stemness concerned with the progression to APC in our study. We also need to estimate the other stem cell markers including CD133, Oct3/4 or Nanog. Conclusion: It was suggested that EMT might induce the progression from PDA to APC. Citation Format: Kotaro Miura, Kenjiro Kimura, Ryosuke Amano, Sadaaki Yamazoe, Go Ohira, Kohei Nishio, Masatsune Shibutani, Katsunobu Sakurai, Hisashi Nagahara, Takahiro Toyokawa, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Hiroshi Otani, Masakazu Yashiro, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa. Epithelial mesenchymal transition may contribute to anaplastic change of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5276. doi:10.1158/1538-7445.AM2015-5276