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Liver cancer, including hepatocellular carcinoma (HCC), is the fifth most common cause of cancer deaths in Japan. The main treatment options for HCC are surgical resection, liver transplantation, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and systemic chemotherapy. Here, recent medical treatments for HCC, including surgery, percutaneous ablation, transcatheter arterial chemoembolization/transcatheter arterial embolization, and drug therapy, are reviewed with a focus on Japan.

Background We modified and administered capecitabine + epirubicin + cyclophosphamide combination therapy (CEX) as neoadjuvant chemotherapy (NAC) for HER-2-negative breast cancer and retrospectively analyzed its effectiveness and tolerability at our center. Methods The inclusion criteria were presence of breast cancer negative for HER-2 and positive lymph node metastasis, or negative lymph node metastasis when tumor diameter was 20 mm or greater without distant metastasis. Additional inclusion criteria were a performance status of 0 or 1, an EF >60%, and an age of 75 years or less. Clinical outcomes were evaluated after 4 courses of epirubicin 80 mg/m2, cyclophosphamide 500 mg/m2 (administered every 3 weeks), and capecitabine 1,500 mg/m2 (administered for 2 weeks and withdrawn for 1 week). Results A clinical benefit was noted in all 18 patients who received CEX as neoadjuvant chemotherapy during the period from 2009 through 2013. The clinical response rate was 83.3% (15/18), and the clinical complete response rate was 50%. Aesthetic outcomes of breast-conserving surgery were positive in all patients. Among patients with satisfactory outcomes, 33.3% had a pathologic complete response (triple-negative: 6, luminal: 0) and 68.8% were n0 (triple-negative: 8, luminal: 3). All patients with a pathologic complete response are presently alive, free of recurrence, and currently undergoing follow-up. Adverse events were classified as grade 2 or lower in all patients. Conclusions CEX therapy administered as neoadjuvant chemotherapy could be useful for individualized treatment. In particular, this regimen was effective for triple-negative breast cancer.

Introduction The common metastatic sites of renal cell cancer (RCC) are the lung, bone, liver, brain, adrenal glands, and contralateral kidney. Metastasis to the gallbladder is rare, and cystic duct metastasis from RCC has been reported in only one metachronous case. This is the first report of a case of synchronous cystic duct metastasis from RCC. Case report A 72-year-old woman presenting with hematuria had a history of Cushing disease approximately 10 years previously. Enhanced computed tomography of the abdomen showed a mass measuring 5.8 × 3.0 cm in the left kidney, which was strongly enhanced in the early phase and washed out in the late phase. A mass measuring 2 cm in diameter was seen in the left adrenal gland, and a 1.0-cm mass was noted in the right adrenal gland. Multiple tiny masses were detected in the cystic duct. Left renal cell carcinoma, cystic duct metastasis, and bilateral adrenal gland metastases were diagnosed. Because the metastatic tumor was close to the common bile duct, we performed left nephrectomy, bilateral adrenalectomy, cholecystectomy, resection of the extrahepatic bile duct, and hepaticojejunostomy. Pathological findings showed that the renal tumor was clear cell carcinoma, as were the bilateral adrenal tumors and cystic duct tumor. The patient died 30 months after the operation.

Simple hepatic cysts are typically saccular, thin-walled masses with fluid-filled epithelial lined cavities that arise from aberrant bile duct cells during embryonic development. With the development of diagnostic modalities such as ultrasonography, computed tomography and magnetic resonance imaging, simple hepatic cysts are seen with relative frequency in daily clinical examination. US is the most useful and noninvasive tool for the diagnosis of simple hepatic cysts, and can generally differentiate simple hepatic cysts from abscesses, hemangiomas and malignancies. Cysts with irregular walls, septations, calcifications or daughter cysts on US should be evaluated with enhanced CT or MRI to differentiate simple hepatic cysts from cystic neoplasms or hydatid cysts.Growth and compression of hepatic cysts cause abdominal discomfort, pain, distension and dietary symptoms such as nausea, vomiting, a feeling of fullness and early satiety. Complications of simple hepatic cysts include infection, spontaneous hemorrhage, rupture, and external compression of biliary tree or major vessels.Asymptomatic simple hepatic cysts should be observed. Treatment for symptomatic simple hepatic cysts includes percutaneous aspiration, aspiration followed by sclerotherapy, and surgery. The American College of Gastroenterology clinical guidelines recommend laparoscopic fenestration based on its high success rate and low invasiveness. Percutaneous procedures for treatment of simple hepatic cysts are particularly effective for the immediate palliation of patient symptoms; however, they are not generally recommended because of the high rate of recurrence.Management of simple hepatic cysts requires correct differentiation from neoplasms and infections, and the selection of a reliable treatment.

Background Pancreatic body and tail cancer easily invades retroperitoneal tissue, including the transverse mesocolon. It is difficult to ensure a dissected peripancreatic margin with standard distal pancreatectomy for advanced pancreatic body and tail cancer. Thus, we developed a novel surgical procedure to ensure dissection of the peripancreatic margin. This involved performing dissection deeper than the fusion fascia of Toldt and further extensive en bloc resection of the root of the transverse mesocolon. We performed distal pancreatectomy with transverse mesocolon resection (DP-TCR) using a mesenteric approach and achieved good outcomes. Methods There are two main considerations for surgical procedures using a mesenteric approach: 1) dissection deeper than the fusion fascia of Toldt (securing the vertical margin) and 2) modular resection of the pancreatic body and tail, with the root of the transverse mesocolon and adjacent organs in a horizontal direction (ensuring the caudal margin). Results From 2017 to 2019, we performed DP-TCR using a mesenteric approach for six patients with advanced pancreatic body and tail cancer. Histopathological radical surgery was possible in all patients who underwent DP-TCR. No Clavien-Dindo grade IIIa or worse perioperative complications were observed in any patient. Conclusions We believe that DP-TCR is useful as a radical surgery for advanced pancreatic body and tail cancer with extrapancreatic invasion.

Portal vein thrombosis (PVT) following hepatectomy is potentially life-threatening. We aimed to evaluate the incidence of PVT after hepatectomy for hepatocellular carcinoma and identify coagulation and fibrinolytic factors that could predict early-stage postoperative PVT. A retrospective analysis was conducted on 65 hepatocellular carcinoma patients who underwent radical hepatectomy. The risk factors for postoperative PVT were identified based on univariate and multivariate analyses, and the levels of coagulation and fibrinolytic factors were measured during the perioperative period. The incidence of PVT after hepatectomy was 20.0%. The patients were divided into two groups: those with PVT (n=13; PVT group) and those without PVT (n=52; no-PVT group). The frequency of the use of the Pringle maneuver during surgery was higher in the PVT group than in the no-PVT group, and the postoperative/preoperative ratios of thrombin-antithrombin III complex (TAT) and of D-dimer were significantly higher in the PVT group. A high incidence of PVT was found in hepatocellular carcinoma patients after hepatectomy. The frequency of the Pringle maneuver is a potential risk factor for postoperative PVT, and the postoperative/preoperative TAT and D-dimer ratios may be used as early predictors of PVT after hepatectomy for hepatocellular carcinoma.

The Pringle maneuver is often used in liver surgery to minimize bleeding during liver transection. Many authors have demonstrated that intermittent use of the Pringle maneuver is safe and effective when performed appropriately. However, some studies have reported that the Pringle maneuver is a significant risk factor for portal vein thrombosis. In this study, we evaluated the effectiveness of portal vein flow after the Pringle maneuver and the impact that massaging the hepatoduodenal ligament after the Pringle maneuver has on portal vein flow. Patients treated with the Pringle maneuver for hepatectomies performed to treat hepatic disease at our hospital between August 2014 and March 2019 were included in the study (N = 101). We divided these patients into two groups, a massage group and nonmassage group. We measured portal vein blood flow with ultrasonography before and after clamping of the hepatoduodenal ligament. We also evaluated laboratory data after the hepatectomy. Portal vein flow was significantly lower after the Pringle maneuver than before clamping of the hepatoduodenal ligament. The portal vein flow after the Pringle maneuver was improved following massage of the hepatoduodenal ligament. After hepatectomy, serum prothrombin time was significantly higher and serum C-reactive protein was significantly lower in the massage group than in the nonmassage group. Massaging the hepatoduodenal ligament after the Pringle maneuver is recommended in order to quickly recover portal vein flow during hepatectomy and to improve coagulability.

Keratinized mucosa is of fundamental importance to maintain healthy gingival tissue, and understanding the mechanisms of oral mucosa keratinization is crucial to successfully manage healthy gingiva. Previous studies have shown a strong involvement of the basement membrane in the proliferation and differentiation of epithelial cells. Therefore, first, to identify the keratinized mucosa-specific basement membrane components, immunohistochemical analysis for the six alpha chains of type IV collagen was performed in 8-week-old mice. No difference in the expression pattern of type IV collagen α1(IV) and α2(IV) chains was observed in the keratinized and non-keratinized mucosa. Interestingly, however, type IV collagen α5(IV) and α6(IV) chains specifically were strongly detected in the keratinized mucosa. To analyze the functional roles of the type IV collagen isoform α6(IV) in oral mucosa keratinization, we analyzed Col4a6-knockout mice. Epithelial developmental delay and low levels of KRT10 were observed in new-born Col4a6-knockout mice. Additionally, in vitro experiments with loss-of function analysis using human gingival epithelial cells confirmed the important role of α6(IV) chain in epithelial keratinization. These findings indicate that α112:α556 (IV) network, which is the only network that includes the α6(IV) chain, is one regulator of KRT10 expression in keratinization of oral mucosal epithelium.

Before the first laparoscopic hepatectomy (LH) was described in 1991, open hepatectomy (OH) was the only choice for surgical treatment of liver tumors. LH indications were initially based solely on tumor location, size, and type. Use of LH has spread rapidly worldwide because it reduces incision size. This review systematically assesses the current status of LH. As compared with OH, LH is significantly less complicated, requires shorter hospital stays, and results in less blood loss. The long-term survival rates of LH and OH are comparable. Development of new techniques and instruments will improve the conversion rate and reduce complications. Furthermore, development of surgical navigation will improve LH safety and efficacy. Laparoscopic major hepatectomy for HCC remains a challenging procedure and should only be performed by experienced surgeons. In the near future, a training system for young surgeons will become mandatory for standardization of LH, and LH will likely become better standardized and have broader applications.

A 59-year-old woman who complained of melena and lightheadedness visited the outpatient clinic at our hospital.According to her blood test result, she had anemia, and her tumor marker levels were high.Enhanced computed tomography(CT) findings showed small intestinal cancer with multiple liver metastases.Partial resection of the small bowel for the small intestinal cancer was performed.Following the administration of fourth-line outpatient chemotherapy containing S-1 plus irinotecan( IRIS)and IRIS plus bevacizumab(IRIS plus Bev), S-1 plus oxaliplatin plus Bev(SOX plus Bev), and weekly paclitaxel (wPAC), she survived with good condition for 19 months after the surgery.

We report a case of metastatic pancreatic-head mucinous carcinoma (with multiple lymph node and bone metastases) and review the relevant literature. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was useful for diagnosis, and a satisfactory outcome was achieved after systemic chemotherapy with FOLFIRINOX followed by resection of the primary lesion as conversion surgery. The patient was a 55-year-old man. Hematological findings included elevated serum tumor marker levels: CEA 12.7 ng/mL, DUPAN-2 400 U/mL. Findings from several imaging modalities and EUS-FNA confirmed a clinicopathological diagnosis of metastatic pancreatic mucinous carcinoma with multiple bone and lymph node metastases. Five courses of modified FOIFIRINOX (m-FFX) were given as systemic chemotherapy, which had an antitumor effect. Subtotal stomach-preserving pancreaticoduodenectomy and extensive lymph-node dissection were thus performed. Histopathological analysis showed invasive ductal carcinoma, muc (pT3, pN1b, cM1). After surgery, the clinical course was notable for the absence of complications. Tegafur/gimeracil/oteracil (S-1) was started as maintenance adjuvant chemotherapy postoperatively, and no disease progression has been observed at 10 months after surgery.

Background Recently, some reports have revealed a relationship between post-hepatectomy prognosis in hepatocellular carcinoma (HCC) and hepatic fibrosis markers. We evaluated the relationship between these markers of hepatic fibrosis, clinicopathological findings, and prognosis. Methods Three hundred and sixty patients underwent hepatectomy for HCC in the Nippon Medical School Hospital between 1993 and 2013. We divided these patients into two groups: normal serum hyaluronic acid (HA) levels and abnormal levels. We also divided patients into groups with normal serum type IV collagen levels and abnormal levels. Results The overall survival rate and recurrence-free survival rate of the normal group were significantly higher than those of the abnormal group. In the normal hyaluronic acid group, serum albumin and prothrombin time were significantly higher than in the abnormal group, and age, hepatitis C virus antibody (HCV)-Ab positivity, Child-Pugh grade B, liver cirrhosis, indocyanine green retention rate at 15 min (ICGR15), type IV collagen level, and type IV collagen 7s level were significantly lower than those in the abnormal group. In the normal type IV collagen group, HCV-Ab positivity, liver cirrhosis, ICGR15, HA level, and type IV collagen 7s level were significantly lower than those in the abnormal group, and the serum albumin level was significantly higher than that in the abnormal group. Multivariate analysis independently revealed the significant effect of serum type IV collagen on the overall survival rate as well as the significant effect of serum HA on the recurrence-free survival rate in patients who underwent hepatectomy for HCC. Conclusions Preoperative examinations of serum hyaluronic acid levels and type IV collagen levels are imperative for hepatic resection for HCC because these markers are significantly associated with liver function and prognosis.

Portal vein thrombosis (PVT) is a rare complication of liver transplantation which can lead to graft failure and patient death. Treatment can be difficult, especially in cases of PVT from the intrahepatic portal vein to the proximal jejunal veins. A 55-year-old woman had undergone living-donor liver transplantation with splenectomy for end-stage liver cirrhosis due to hepatitis C with hepatocellular carcinoma. Ten months after transplantation, massive ascites and slight abdominal pain developed, and computed tomography revealed a PVT between the intrahepatic portal vein and the superior mesenteric vein. Repeated interventional radiology procedures were used in combination with thrombolysis, thrombectomy, and metallic stent replacement to obtain favorable portal flow to the graft. Five years after being treated, the patient is well, with favorable portal flow having been confirmed. In conclusion, repeated and assiduous interventional radiological treatment combined with thrombolytic therapy, thrombectomy, and metallic stent replacement could be important for severe PVT.

Growth factors are crucial regulators of cell differentiation towards tissue and organ development. Insulin and transforming growth factor-β (TGF-β) have been used as the major factors for chondrogenesis in vitro, by activating the AKT and Smad signaling pathways. Previous reports demonstrated that AKT and Smad3 have a direct interaction that results in the inhibition of TGF-β-mediated cellular responses. However, the result of this interaction between AKT and Smad3 during the chondrogenesis of human bone marrow-derived stem/progenitor cells (hBMSCs) is unknown. In this study, we performed functional analyses by inducing hBMSCs into chondrogenesis with insulin, TGF-β3 or in combination, and found that TGF-β3, when applied concomitantly with insulin, significantly decreases an insulin-induced increase in mRNA levels of the master regulator of chondrogenesis, SOX9, as well as the regulators of the 2 major chondrocyte markers, ACAN and COL2A1. Similarly, the insulin/TGF-β3-treated group presented a significant decrease in the deposition of cartilage matrix as detected by safranin O staining of histological sections of hBMSC micromass cultures when compared to the group stimulated with insulin alone. Intracellular analysis revealed that insulin-induced activation of AKT suppressed Smad3 activation in a dose-dependent manner. Accordingly, insulin/TGF-β3 significantly decreased the TGF-β3-induced increase in mRNA levels of the direct downstream factor of TGF-β/Smad3, CCN2/CGTF, compared to the group stimulated with TGF-β3 alone. On the other hand, insulin/TGF-β3 stimulation did not suppress insulin-induced expression of the downstream targets TSC2 and DDIT4/REDD1. In summary, insulin and TGF-β3 have antagonistic effects when applied concomitantly, with a minimal number of factors. The application of an insulin/TGF-β3 combination without further supplementation should be used with caution in the chondrogenic differentiation of hBMSCs.

As a strategy to diagnose early-stage pancreatic ductal adenocarcinoma (PDAC) is urgently needed, we aimed to clarify characteristics of early-stage PDAC.We retrospectively reviewed medical records of 299 consecutive patients who underwent R0 or R1 surgical resection for PDAC between 1994 and 2013 and compared clinical characteristics between patients with early-stage (stages 0-I by Japanese General Rules for Pancreatic Cancer) and advanced-stage (stages II-IV) disease. Diagnostic processes were also analyzed.Twenty-four patients (8%) had early-stage PDAC (stage 0: 11; stage I: 13). Univariate and multivariate analyses showed that presence or history of intraductal papillary mucinous neoplasm (P0.01), history of pancreatitis (P0.01), and presence or history of extrapancreatic malignancies (P = 0.01) independently predicted detection of early-stage PDAC. Cytological examination during endoscopic retrograde pancreatography cytology was ∼65% sensitive in preoperative diagnosis of early-stage PDAC, whereas other imaging modalities were only 29% to 38% sensitive; 9 of 24 early-stage PDACs were diagnosed by endoscopic retrograde pancreatography cytology alone.Endoscopic retrograde pancreatography cytology for patients with intraductal papillary mucinous neoplasm or pancreatitis may help diagnose early-stage PDAC. Surveillance of extrapancreatic malignancies might also provide opportunities to detect early-stage PDAC as a second malignancy.

The aims of this study were to investigate the GNAS mutational status in pancreatic intraductal papillary mucinous neoplasm (IPMN) with and without distinct pancreatic ductal adenocarcinoma (PDAC) and to evaluate the significance of GNAS analysis using duodenal fluid (DF) in patients with IPMN.The clinicopathologic features of 110 patients with IPMN including 16 with distinct PDAC were reviewed. The GNAS status in the IPMN tissue and 23 DF specimens was assessed by sensitive mutation scanning methods.The GNAS mutation rate in IPMN with distinct PDAC was significantly lower than that in IPMN without PDAC (4/16, 25%, vs 61/94, 65%; P = 0.0047). By multivariate analysis, GNAS wild-type and gastric type IPMNs were significantly associated with distinct PDAC. Of 45 GNAS wild-type IPMNs, 10 (43%) of 23 gastric type IPMNs had distinct PDAC, whereas only 2 (9%) of 22 non-gastric type IPMNs had distinct PDAC (P = 0.017). The GNAS status in DF was consistent with that in tissue in 21 (91%) of 23 patients.Distinct PDACs frequently develop in the pancreas with gastric type IPMN without GNAS mutations. Duodenal fluid DNA test would predict the GNAS status of IPMN, whereas the detection of the gastric subtype using noninvasive test remains to be determined.

Pancreatic ductal adenocarcinoma (PDAC) is associated with a high incidence of hepatic metastases, as well as occasional pulmonary metastases. To delineate the potential role of cancer stem cells (CSCs) in PDAC metastasis, human PDAC cells were injected into the spleen of mice. The characteristics and expression of markers associated with CSC and epithelial–mesenchymal transition (EMT) of metastatic cells that developed in the liver and lung were then compared with parental cells. The metastatic cells were polygonal, and larger than parental cells. Metastatic cells also exhibited decreased proliferation and increased adhesion to extracellular matrices, as well as enhanced migration and invasion in vitro and increased metastatic capacity in vivo . The CSC markers ALDH1A1, ABCG2, and nestin were expressed at high levels in metastatic cells and exhibited changes consistent with EMT (eg, decreased E-cadherin expression). Moreover, metastatic cells readily formed spheres in culture and exhibited an increased side population by flow analysis. Nestin and ABCG2 were also expressed at high levels in metastatic lesions from PDAC patients, and silencing nestin with shRNA in PDAC cells derived from lung metastases resulted in a marked decrease in the capacity of the cells to form spheres and to yield pulmonary or hepatic metastases. Thus, the metastatic potential of human PDAC cells correlates with CSCs and with EMT characteristics and is dependent on nestin expression.

We herein present a 71-year-old man who underwent pancreatoduodenectomy with the diagnosis of follicular pancreatitis. We could not completely deny malignancy by a preoperative imaging study. Endoscopic ultrasonography-guided fine needle aspiration biopsy demonstrated clusters of benign acinar cells and no proliferation of atypical lymphoid cells or rich plasma cells. Histologically, the prominent lymphoid follicle formation was seen in an ill-defined mass, 15 mm in size, in the pancreatic parenchyma. Duct-centered fibrotic rims were seen in the pancreatic ducts accompanied by mild fibrotic change between the follicles and obliterative phlebitis. No neoplastic epithelial cells were observed in the resected specimen, and infiltrating lymphocytes did not show any morphological atypia and monoclonal proliferation by immunohistochemical staining with B and T cell markers. In addition, we could exclude IgG4-related disease, because plasmacytic cells were rarely positive for IgG4. Although follicular pancreatitis is rare, this mass-forming inflammatory disease (pancreatitis) should be included in the preoperative differential diagnosis of pancreatic cancer.

Background Patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas may have concomitant distinct pancreatic ductal adenocarcinoma (PDAC). We evaluated the safety and usefulness of intraoperative irrigation cytology of the remnant pancreas (IICP) during pancreatectomy to detect remnant distinct PDAC in patients with IPMN. Methods The records of all 48 patients with IPMN who underwent IICP during partial pancreatectomy at our institution from April 2007 to March 2012 were reviewed retrospectively. After division of the pancreas, a 4-French tube was inserted into the main pancreatic duct of the remnant pancreas from the cut edge, and fluid for cytologic examination was obtained by saline irrigation through the tube. If the third IICP was positive, patients underwent additional pancreatic resection. Clinical and pathologic outcomes were evaluated. Results The third IICP was positive in 5 patients. Postoperative pathologic examination showed that these patients all had remnant distinct PDAC in the additionally resected specimen, which was not detectable on preoperative imaging examination or on intraoperative macroscopic examination, ultrasonography, or palpation. This PDAC was stage 0 in 4 patients and stage III in 1 patient. No procedure-related complications were observed. One patient developed peritoneal metastasis after 10 months, 1 developed liver metastasis after 20 months, and 1 developed PDAC in the remnant pancreas after 24 months. Conclusion IICP seems to be a safe and useful method for detection of early stage PDAC concomitant with IPMN that cannot be detected by preoperative imaging or intraoperative examination.

Background It is difficult to predict the malignant potential of pancreatic neuroendocrine tumors (PNETs) precisely. This study investigated the validity of a new grading system adopted by the World Health Organization 2010 classification to determine risk factors for recurrence of PNETs. Methods Data of 70 patients with PNETs who underwent curative resection were retrospectively examined by uni- and multivariate analyses. Histopathological findings were re-reviewed by experienced pathologists. NET G1 was defined as mitotic count

Epithelial splicing regulatory protein 1 (ESRP1) binds the FGFR-2 auxiliary cis-element ISE/ISS-3, located in the intron between exon IIIb and IIIc, and primarily promotes FGFR-2 IIIb expression. Here we assessed the role of ESRP1 in pancreatic ductal adenocarcinoma (PDAC). Immunohistochemical analysis was performed using anti-ESRP1, FGFR-2 IIIb and FGFR-2 IIIc antibodies in 123 PDAC cases. ESRP1-expression vector and small interference RNA (siRNA) targeting ESRP1 were transfected into human PDAC cells, and cell growth, migration and invasion were analyzed. In vivo heterotopic and orthotopic implantations using ESRP1 overexpression clones were performed and effects on pancreatic tumor volumes and hepatic and pulmonary metastases determined. ESRP1 immunoreactivity was strong in the nuclei of cancer cells in well-to-moderately differentiated PDACs, but weak in poorly-differentiated cancers. Well-to-moderately differentiated cancers also exhibited high FGFR-2 IIIb and low FGFR-2 IIIc expression, whereas this ratio was reversed in the poorly-differentiated cancers. Increased ESRP1 expression was associated with longer survival by comparison with low-ESRP1 expression, and PANC-1 cells engineered to express ESRP1 exhibited increased FGFR-2 IIIb expression and decreased migration and invasion in vitro, whereas ESRP1 siRNA-transfected KLM-1 cells exhibited increased FGFR-2 IIIc expression and increased cell growth, migration and invasion. In vivo, ESRP1-overexpressing clones formed significantly fewer liver metastases as compared with control clones. ESRP1 regulates the expression pattern of FGFR-2 isoforms, attenuates cell growth, migration, invasion, and metastasis, and is a favorable prognostic factor in PDAC. Therefore, devising mechanisms to up-regulate ESRP1 may exert a beneficial therapeutic effect in PDAC.

Cutaneous metastasis of an internal malignancy is uncommon and is estimated to occur in 0.7–9% of patients with internal cancer including autopsy cases. We would like to report a case of long survival of sigmoid colon adenocarcinoma diagnosed as an instance of facial cutaneous metastasis. A 68-year-old male was admitted to our hospital for a tumor mass on the left side of his cheek. In his past history, acute myocardial infarction had occurred 2 years earlier. He also had chronic renal failure and chronic obstructive pulmonary disease. Histologic findings from the biopsy sample of this facial lesion were moderately differentiated adenocarcinoma. Colonoscopy revealed a tumor 20 mm × 30 mm in diameter in the sigmoid colon. Histologic findings of the biopsy sample of this tumor also indicated moderately differentiated adenocarcinoma. The patient was diagnosed with sigmoid colon cancer with cutaneous metastasis to the face. We performed a sigmoidectomy with lymph node dissection and resection of the facial cutaneous metastasis. After being discharged, low dose chemotherapy was performed in consideration of the patient's renal function. Although long-term management of his general condition was provided, the patient died 37 months after surgery because of chronic heart failure.

Bleeding from gastric varices (GVs) is generally considered more severe than that from esophageal varices (EVs) but occurs less frequently. We review the risk factors for bleeding EVs and GVs. GVs were divided into 2 groups: cardiac varices (CVs, Lg-c) and fundal varices (FVs), i.e., varices involving the fundus alone (Lg-f) or varices involving both the cardia and fundus (Lg-cf). Elevated pressure in the portal vein is a risk factor for bleeding EVs. The portal pressure in patients with GVs and a gastrorenal shunt is lower than that in patients with EVs. The large size of varices is a risk factor for bleeding EVs. Red color signs are elevated red areas that are important for predicting the risk of variceal bleeding, and red wale markings, dilated venules oriented longitudinally on the mucosal surface, have been considered to be the sign with the highest risk. Red color signs are rare in FVs, possibly because of the pronounced thickness of the mucosal layer. Bleeding EVs are not associated with use of antiulcer drugs or nonsteroidal anti-inflammatory drugs (NSAIDs). Although, in patients with bleeding GVs, "occasional" use of an oral NSAID is an important step leading to variceal hemorrhage, especially from FVs, even if the mucosa is protected by antiulcer drugs. Constipation, vomiting, severe coughing, and excessive consumption of alcohol may precipitate rupture of EVs.

A liver tumor metastatic from a sigmoid colon carcinoma was diagnosed in a 70-year-old man. Because hepatectomy was not indicated, the patient was treated with a combination of oxaliplatin, levofolinate, and fluorouracil (5-FU) (modified FOLFOX 6 regimen). After 15 cycles of chemotherapy, this regimen was considered to have been ineffective; therefore, treatment was started with the topoisomerase inhibitor irinotecan and an intravenous infusion of 5-FU and levofolinate (FOLFIRI). After receiving irinotecan and levofolinate, the patient had chills, a severe cough, and dyspnea. We diagnosed pulmonary edema as a side effect due to oxaliplatin, and the chemotherapeutic regimen was changed from FOLFIRI to FOLFOX plus bevacizumab. After the third cycle of oxaliplatin and levofolinate, pulmonary edema recurred, and a preshock state developed again. We suspected that either oxaliplatin or irinotecan had caused the pulmonary edema and, therefore, administered levofolinate, 200 mg/m(2); 5-FU, 400 mg/m(2); and bevacizumab, 330 mg/m(2); intravenously on day 1, followed by 5-FU, 2,400 mg/m(2), as a continuous intravenous infusion at 46 hours without either of oxaliplatin, levofolanate, and bevacizumab. After being treated with levofolinate again, the patient suddenly complained of severe dyspnea; this symptom confirmed that levofolinate had caused the pulmonary edema. To our knowledge, severe pulmonary edema caused by levofolinate has not been reported previously. This adverse effect was clinically significant because it led to the patient's death.

We describe a cystic intraductal papillary neoplasm of bile duct (IPNB) of adenocarcinoma treated with surgical resection. An 82-year-old man was admitted to our hospital because of distension of the right upper quadrant of the abdomen. On admission, a huge nontender mass was palpated in the right upper abdomen. Initial laboratory tests revealed the following serum values: aspartate aminotransferase, 123 IU/L; alanine aminotransferase, 113 IU/L; alkaline phosphatase, 376 IU/L; bilirubin, 1.6 mg/dL; alpha-fetoprotein, 7.4 ng/mL; CA19-9, 39.8 U/mL; carcinoembryonic antigen, 4.1 ng/mL; and Duke pancreatic monoclonal antigen type 2, 200 U/mL. Abdominal ultrasonography revealed an anechoic mass with an elevated papillary lesion in the right paramedian section. Computed tomography showed a low-density hepatic lesion, measuring 12 × 10 cm, with thick, irregular walls. A T2-weighted magnetic resonance scan showed mural nodules with signal intensity higher than that of the liver. The cystic lesion was suspected to be a cystic IPNB, but we could not determine whether it was a carcinoma. We performed extensive right paramedian sectionectomy and cholecystectomy. The resected multilocular tumor was filled with a yellow fluid, and the cut surface showed multiple, yellowish papillary nodules lining the cystic wall. On histologic examination, the neoplastic biliary epithelium showed papillary growth in the dilated lumen. Papillary and micropapillary lesions exhibited cellular atypia: nuclear enlargement and hyperchromasia, mutilayering, and mitosis. Ovarian-like stroma was not detected. The tumor was diagnosed as an IPNB (carcinoma in situ lesion). These lesions had expanded into several intrabiliary ducts. No recurrence has been detected 2 year after operation.

We report the first documented case of pancreatic metastasis from a gastrointestinal stromal tumor of the stomach. A 42-year-old Japanese man presented with severe abdominal discomfort. Computed tomography of the abdomen showed a huge heterogeneous mass consisting of cystic and solid components in the left upper abdomen. (18)F-Fluorodeoxyglucose positron-emission tomography revealed high tracer uptake in the abdominal mass. After total gastrectomy with lymphnodectomy was performed, a hard mass was palpated in the pancreatic tail. The pancreatic tumor was also resected under the therapeutic strategy. Histological examinations of the resected gastric and pancreatic specimens revealed that both tumors consisted of uniform spindle cells with a fascicular growth pattern and were immunohistochemically positive for CD34 and CD117/KIT. Gene sequencing analysis of DNA from each tumor revealed an identical deletion of 21 nucleotides in exon 11 of the gene KIT. On the basis of these results, we concluded that the pancreatic tumor was a metastatic tumor from the gastrointestinal stromal tumor of the stomach.

Chronic pain and discomfort is a notable complication after inguinal hernia repair. This study assesses the incidence and degree of chronic pain and discomfort after primary inguinal hernia repair performed in our hospital and aims to clarify its relationship to the type of mesh placement.A retrospective analysis was conducted of 334 patients (378 lesions) who underwent primary inguinal hernia using the Lichtenstein (onlay mesh), Ultrapro Plug (UPP; onlay plus plug mesh), modified Kugel Patch (onlay and underlay mesh), or laparoscopic transabdominal preperitoneal (TAPP; underlay mesh) procedure. Postoperative pain was assessed using a numerical rating scale at postoperative 2-3 wk, 3 mo, and 6 mo. Postoperative discomfort was assessed 6 mo afterward.Questionnaire responses were received for 378 lesions (100%) after 2-3 wk, 229 (60.6%) after 3 mo, and 249 (65.9%) after 6 mo. The majority of chronic pain experienced was mild, and no patient suffered from severe pain. The level of pain tended to be less for the TAPP procedure than for other methods. Discomfort at rest was significantly less for TAPP versus Ultrapro Plug (P 0.01), and discomfort with movement was significantly less for TAPP versus modified Kugel (P 0.05).Onlay mesh appears to be a risk factor in chronic pain and discomfort. The lower level of chronic pain and discomfort with underlay mesh placement is considered to result from the reduced risk of nerve damage in this procedure than in the onlay mesh placement procedure.

Primary retroperitoneal teratoma in an adult is rare, as is the occurrence of a malignant tumor within a mature teratoma, known as "malignant transformation". A 24-year-old woman was admitted to our hospital for investigation of an abdominal mass. Computed tomography and magnetic resonance imaging revealed a multilocular mass in the right upper abdomen. The tumor consisted of fat, soft tissue, and bone, with a slightly enhanced solid component. The tumor was diagnosed preoperatively as a retroperitoneal mature teratoma with an immature component, and excised. Histologically, it was composed mainly of mature fat, soft tissue, and bone, accompanied by a solid component of prostate-like tissue. In addition, a latent carcinoid tumor was recognized in the middle of the tumor. The tumor was finally diagnosed as a primary carcinoid tumor within the retroperitoneal mature teratoma. The patient has been followed-up for 24 months since her operation without any evidence of recurrence. We report this case to highlight the possibility of malignant transformation in adult retroperitoneal teratoma, even when the preoperative diagnosis is benign mature teratoma.

Bleeding from esophageal varices (EVs) or gastric varices (GVs) is a catastrophic complication of chronic liver disease. In this paper, we review the management of bleeding EVs and GVs. DIAGNOSIS OF EVS AND GVS: The grading system for esophagogastric varices proposed by the Japan Society for Portal Hypertension classifies GVs into those involving the cardia (Lg-c), the fundus (Lg-f), and both the cardia and the fundus (Lg-cf). In this review, we divide GVs into 2 categories: Lg-c (cardiac varices: CVs) and Lg-cf or Lg-f (fundal varices: FVs). TREATMENT MODALITIES FOR EVS AND GVS: Treatment modalities for EVs and GVs include placement of a Sengstaken-Blakemore tube, pharmacologic therapy, surgery, interventional radiology, and endoscopic treatment. MANAGEMENT OF BLEEDING EVS AND GVS: In Japan, endoscopic treatment has recently become the therapy of choice for bleeding EVs or GVs. In other countries, especially the United States, vasoactive drugs and endoscopic treatment are routinely used to manage variceal hemorrhage. BLEEDING EVS: Endoscopic variceal ligation is useful for controlling bleeding from EVs. However, confirmation of ligation precisely at the site of bleeding is usually difficult in patients with massive variceal bleeding. The site of acute bleeding can generally be identified by means of water instillation and suction. Ligation is then performed at the bleeding point. If endoscopic hemostasis is unsuccessful, a Sengstaken-Blakemore tube is used as a temporary bridge to other treatments. Transportal obliteration is useful for blocking variceal blood flow. BLEEDING GVS: Endoscopic injection sclerotherapy with a tissue adhesive, such as N-butyl-cyanoacrylate or isobutyl-2-cyanoacrylate, is effective for acute bleeding from GVs. However, bleeding from the GV injection site and rebleeding from the rupture point have been reported in patients receiving endoscopic injection sclerotherapy. If endoscopic hemostasis is unsuccessful, a Sengstaken-Blakemore tube is used as a temporary bridge to other treatments. Balloon-occluded retrograde transvenous obliteration and transportal obliteration are useful for the treatment of uncontrolled bleeding from GVs. PREVENTION OF RECURRENT VARICEAL HEMORRHAGE: Given the high recurrence rate, survivors of an acute variceal hemorrhage should receive treatment to prevent recurrence. Complete eradication of EVs or GVs and maintenance of low portal venous pressure are essential for preventing recurrence of variceal hemorrhage.

Keratinocyte growth factor (KGF), also known as fibroblast growth factor-7, and KGF receptor (KGFR) play important roles in the growth of epithelial cells and are overexpressed in a variety of malignant epithelial tumors, including pancreatic ductal adenocarcinoma (PDAC). We previously reported that co-expression of KGF and KGFR in PDAC is associated with venous invasion, enhanced vascular endothelial growth factor A expression and poor prognosis. Matrix metalloproteinase-9 (MMP-9) is known to participate in the degradation of type IV collagen, which is a primary component of extracellular matrices in the vascular basement membrane. In the present study, we examined the expression and roles of KGF, KGFR and MMP-9 in human PDAC cell lines and tissues. Quantitative real-time polymerase chain reaction analysis demonstrated the expression of MMP-9 mRNA in all eight PDAC cell lines. KGF, KGFR and MMP-9 were, respectively, expressed in 27 (43%), 23 (37%) and 35 (56%) of 63 patients. Each expression of KGF, KGFR or MMP-9 correlated positively with venous invasion. Furthermore, expression of KGF or MMP-9 correlated positively with liver metastasis. KGF-positive cases exhibited shorter survival than KGF-negative cases, while KGFR and MMP-9 expression were unrelated to prognosis. Administration of recombinant human KGF increased MMP-9 expression in PDAC cells, while transient transfection with short hairpin RNAs targeting KGF transcripts reduced MMP-9 expression in PDAC cells. Moreover, recombinant human KGF significantly enhanced migration and invasion of PDAC cells. These findings suggest that KGF and KGFR promote venous invasion via MMP-9 in PDAC, and closely correlate with liver metastasis. The KGF/KGFR pathway may be a critical therapeutic target for PDAC metastasis.

A hypoxic microenvironment is a characteristic feature of pancreatic cancer, and induces the expressions of various genes involved in malignant behaviors. Insulin-induced gene 2 (Insig2) has recently been shown to be correlated with cellular invasion in colon cancer. However, there have been no reports regarding its expression in pancreatic cancer. In this study, we evaluated Insig2 mRNA expression and the biological function of Insig2 in pancreatic cancer. We measured Insig2 mRNA expression in cultured pancreatic cancer cell lines and invasive ductal carcinoma (IDC) cells, normal pancreatic epithelial cells, and pancreatic intraepithelial neoplasia cells obtained by laser-capture microdissection. We also investigated the effects of Insig2-targeting siRNAs on the cell proliferation and cell invasion of pancreatic cancer cell lines. All pancreatic cancer cell lines expressed Insig2 mRNA. The PANC-1 and MIA PaCa-2 pancreatic cancer cell lines showed >2-fold higher Insig2 mRNA expression levels under hypoxic conditions (1% O2) than under normoxic conditions (21% O2). Cell proliferation was significantly decreased in SUIT-2 cells and cell invasion was significantly decreased in SUIT-2, Capan-2, and CFPAC-1 cells after transfection of the Insig2-targeting siRNAs. In analyses of microdissected cells, cells from IDC tissues expressed significantly higher levels of Insig2 mRNA than normal pancreatic cells (P

Background To improve the prognosis of patients after resection of pancreatic cancer, the most appropriate and efficient treatment should be provided to specific subsets of patients. Our aim was to identify promising microRNAs as markers to predict responses to gemcitabine in patients with resected pancreatic cancer. Methods Two gemcitabine-resistant pancreatic cancer cell lines were established, and global microRNA expression analyses was performed by quantitative reverse transcription–polymerase chain reaction (qRT-PCR). Eleven miRNAs were selected as putative predictive markers and analyzed by means of macrodissected formalin-fixed, paraffin-embedded samples obtained from 90 patients with or without gemcitabine treatment after resection of pancreatic cancer. Results We identified 24 microRNAs whose expression was altered in gemcitabine-resistant cells. qRT-PCR analyses showed that patients with high miR-142-5p and miR-204 expression had significantly longer survival times than those with low miR-142-5p (P = 0.0077) and miR-204 (P = 0.0054) expression in the gemcitabine-treated group. This was not seen in the nontreated group. Multivariate analyses showed that miR-142-5p expression was an independent prognostic marker only in patients treated with gemcitabine (P = 0.034). Conclusions miR-142-5p is a promising predictive marker for gemcitabine response in patients with resected pancreatic cancer.

We report a case of xanthogranulomatous cholecystitis (XGC) that was diagnosed preoperatively by means of ultrasonography (US) with the contrast-enhancement agent Sonazoid after a false-positive result had been obtained with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET). A 69-year-old woman was admitted because of right upper quadrant pain. Blood tests revealed a serum CA19-9 level of 749.8 IU/L. Computed tomography (CT), US, and magnetic resonance imaging of the abdomen showed abnormal thickening of the gallbladder wall but no stones. The border between the gallbladder and the liver was unclear. FDG-PET revealed a lesion with increased uptake of tracer in the gallbladder wall. The thickness of the lesion was similar to that on CT. We suspected gallbladder carcinoma with hepatic invasion. To confirm the tentative diagnosis, we performed US with the contrast-enhancement agent Sonazoid. The gallbladder wall was homogeneously enhanced in the early vascular phase and remained enhanced for 90 seconds. Enhancement of the gallbladder wall was smooth and regular. The border between the gallbladder and liver was clear and smooth. On the basis of these examinations, we diagnosed chronic cholecystitis (XGC suspected), not gallbladder carcinoma. At surgery, the gallbladder wall was observed to be extremely thick because of severe inflammation, and cholecystectomy was performed. XGC was diagnosed on intraoperative pathological examination. Histopathological examination showed XGC, severe proliferative fibrosis with formation of multiple yellow-brown intramural nodules, and foamy histiocytes without malignant cells. In conclusion, the present case of XGC was diagnosed preoperatively with contrast-enhanced US after a false-positive result had been obtained with FDG-PET. Contrast-enhanced US can thus play important roles in diagnosing gallbladder disease and selecting treatment.

Hepatic angiomyolipoma is a rare hepatic mesenchymal tumor. We report a case of hepatic angiomyolipoma that was successfully resected along with a giant hemangioma. A 53-year-old Japanese woman was admitted to our hospital for further evaluation of a liver tumor in segment 4. The tumor was detected on positron emission tomography during a health check-up. Abdominal ultrasonography revealed a well-defined mass of mixed echogenicity, 1.5 cm in diameter, in segment 4, and a giant hemangioma of mixed echogenicity, 7 cm in diameter, in segment 7. On enhanced computed tomography, the tumor in segment 4 showed hyperattenuation in the early phase and hypoattenuation in the delayed phase. On magnetic resonance imaging, the tumor in segment 4 showed hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and hyperintensity on diffusion-weighted images. On angiography, the tumor in segment 4 appeared as a circumscribed hypervascular mass in the early phase and a slightly hypovascular mass in the delayed phase. The imaging findings suggested a primary hepatocellular carcinoma. The patient consented to resection of the tumor in segment 4 along with the giant hemangioma in segment 7. These tumors were resected with tumor-free surgical margins by partial resection of segments 4 and 7 of the liver. The cut surface of the resected specimen of segment 4 showed a yellowish tumor consisting of mature adipose tissue. The histopathological diagnoses of the resected specimens were angiomyolipoma in segment 4 and cavernous hemangioma in segment 7. The tumor in segment 4 consisted of mature lipocytes with angiomatous and small lymphocytic components, but no mitotic figures. The tumor showed immunoreactivity to smooth muscle antigen and homatropine methylbromide 45 and no immunoreactivity to AE/E3. The postoperative course was uneventful, and the patient remains well 1 year after the operation.

We describe a 35-year-old man with hepatocellular carcinoma (HCC) that recurred in the diaphragm after right hepatic lobectomy. The patient had undergone right hepatic lobectomy for HCC with chronic hepatitis B virus infection 1 year previously. On pathological examination, the tumor measured 15 × 14.4 × 11 cm and was moderately well differentiated. The surgical margins were negative. After 1 year, computed tomography of the abdomen revealed a mass extending from the right side of the diaphragm to the retroperitoneal space. The mass was enhanced in the early phase and washed out in the late phase. Extrahepatic recurrence of HCC in the diaphragm was diagnosed. We performed tumor resection with partial resection of the right side of the diaphragm and wedge resection of the right lower lobe of the lung. The diaphragm was reconstructed with a sheet of artificial pericardium. The histopathological diagnosis was recurrence of HCC in the diaphragm with invasion of the right lung. The postoperative course was uneventful, and the patient was discharged on postoperative day 8. He underwent chemotherapy with cisplatin and 5-fluorouracil. After 9 months, the patient died of unresectable recurrence of HCC in the brain. No recurrence was detected in the right subphrenic area.

Laparoscopic distal pancreatectomy (LDP) has been shown to be an effective surgical option for benign lesions in the body and tail of the pancreas. However, its advantages and disadvantages have not been well characterized. In this study, we compared the outcomes of LDP and open pancreatectomy performed in our clinic.Peri- and postoperative outcomes were retrospectively compared between patients with benign pancreatic disorders who underwent open distal pancreatectomy (ODP) (n = 35) and those who underwent LDP (n = 40). The peri- and postoperative factors analyzed included operative time, blood loss, hospital stay, postoperative recovery, biochemical findings, and complications.LDP was associated with significantly less operative blood loss (363 versus 606 mL; P = 0.001) and shorter hospital stay (22 versus 27 day; P = 0.009), but longer operative time (342 versus 250 min; P = 0.000), compared with ODP. There were no significant differences between the two groups in complication rates or postoperative recovery, except for the significantly shorter duration of postoperative pain-killer intake and earlier improvement of the biochemical analysis in LDP than in ODP.LDP appears to be a safe, desirable procedure for the management of benign pancreatic diseases, with outcomes similar to ODP.

We describe the spontaneous rupture of a simple hepatic cyst associated with a benign course. A 64-year-old woman was admitted for right upper quadrant pain. The patient denied a history of abdominal trauma. Abdominal computed tomography (CT) showed a huge solitary hepatic cyst (diameter, 10 cm) in the right lobe. Part of the cyst surface was irregular, and the interior was heterogeneous on ultrasonography. Fluid retention was detected under the liver capsule. Spontaneous rupture of a nonparasitic hepatic cyst was suspected. The patient was admitted to our hospital for further evaluation and treatment. Examination of the abdomen revealed right upper quadrant pain but no signs or symptoms of peritonitis. One week after admission, CT revealed that the volume of fluid retained under the liver capsule had decreased. Percutaneous puncture was performed with a needle and an 8-French pigtail catheter under ultrasonographic guidance. Serous, brown fluid was aspirated. After percutaneous aspiration, the patient's symptoms resolved. Minocycline hydrochloride was given daily by intravenous injection for 7 days. The catheter was then removed. There has been no evidence of recurrence after 1 year.

We describe a 43-year-old woman who underwent laparoscopic distal pancreatectomy preserving the spleen and splenic vessels for the treatment of insulinoma in the pancreatic body. The patient experienced cold sweats on fasting, received diagnosis of insulinoma, and was referred to our hospital for laparoscopic surgery. Blood biochemistry studies showed low fasting blood glucose of 42 mg/dL, serial immunoreactive insulin of 15.2 microU/mL, and a Fajans index (immunoreactive insulin/blood glucose) of 0.36 (normal

Laparoscopy-assisted distal gastrectomy (LADG) has been widely accepted for the treatment for early gastric cancer. Obesity is a rapidly growing epidemic, and the number of obese patients with gastric cancer is increasing, but the impact of visceral fat (VF) accumulation on laparoscopic gastric surgery remains unknown. The aim of the present study was to determine the impact of VF accumulation on LADG.The medical charts of 30 patients who underwent LADG for early gastric cancer in our hospital between November 2000 and November 2006 were analyzed retrospectively. The patients were divided into two groups on the basis of VF accumulation measured on cross-sectional computed tomography at the level of the umbilicus. Twelve patients had high VF accumulation (or =100 cm2) and 18 had low VF accumulation (100 cm2).Although subcutaneous fat accumulation was not correlated with operation time or operative blood loss, VF accumulation was strongly, and significantly, correlated with both operation time and operative blood loss. The high-VF-accumulation group had a significantly longer operation time and significantly more operative blood loss than the low-VF-accumulation group. There was no significant difference in the rate of postoperative complications or conversion to open laparotomy between the two groups. There were no operative deaths or requirements for blood transfusion in either group.VF accumulation was significantly correlated with operative difficulties during LADG. Although LADG was as safe for patients with high VF accumulation as for patients with low VF accumulation, a longer operative time and more operative blood loss were observed in patients with high VF accumulation. VF accumulation appears to be a possible risk factor in LADG and should be considered when making a decision about treating early gastric cancer with LADG.

The CCN family of proteins plays important roles in development and homeostasis of bone and cartilage. To understand the role of CCN4 in chondrogenesis, human bone marrow stromal cells (hBMSCs) were transduced with CCN4 adenovirus (adCCN4) or siRNA to CCN4 (siCCN4) in the presence or absence of transforming growth factor-β3 (TGF-β3). Overexpression of CCN4 enhanced TGF-β3-induced SMAD2/3 phosphorylation and chondrogenesis of hBMSCs in an in vitro assay using a micromass culture model. On the other hand, knockdown of CCN4 inhibited the TGF-β3-induced SMAD2/3 phosphorylation and synthesis of cartilage matrix in micromass cultures of hBMSCs. Immunoprecipitation-western blot analysis revealed that CCN4 bound to TGF-β3 and regulated the ability of TGF-β3 to bind to hBMSCs. In vivo analysis confirmed there was a significant decrease in the gene expression levels of chondrocyte markers in cartilage samples from Ccn4-knock out (KO) mice, compared to those from wild type (WT) control. In order to investigate the regenerative properties of the articular cartilage in Ccn4-KO mice, articular cartilage defects were surgically performed in the knee joints of young mice, and the results showed that the cartilage was partially repaired in WT mice, but not in Ccn4-KO mice. In conclusion, these results show, for the first time, that CCN4 has a positive influence on chondrogenic differentiation by modulating the effects of TGF-β3.

This retrospective study was conducted to find preoperatively assessable risk factors for postoperative pancreatic fistula (POPF) in patients undergoing laparoscopic distal pancreatectomy (LDP) using a slow compression method with a stapler, which we call pen-firing compression (PFC).Fifty-two patients underwent LDP, of whom 42 underwent PFC for pancreatic division using a stapler. The relationship between preoperatively assessable factors and the incidence of clinical POPF was statistically analyzed.Overall rate of POPF was 7.1% in 42 patients. Univariate analysis showed that greater BMI (p = 0.004) and thicker pancreatic stump (0.0022) were significant risk factors for POPF. BMI and stump thickness remained significant (P0.0001, P0.0001) by multivariate analysis. Cutoff points estimated by ROC curve were 27 kg/m2 for BMI and 27 mm for stump thickness.High BMI value and thick pancreatic stump are significant risk factors for POPF after LDP. Alternative treatment of the pancreatic stump may prevent POPF in high-risk patients.

We report a rare case of bleeding ileal varices successfully treated with emergency enterectomy. A 72-year old woman with hepatic cirrhosis due to hepatitis C was admitted to our hospital because of anemia and hematochezia. An endoscopic examination showed no evidence of bleeding in the upper and lower gastrointestinal tracts. Angiographic studies of portal hemodynamics revealed extravasation from the ileal varices and total occlusion of the portal vein due to portal thrombus. This made it difficult to remove the ileal varices using interventional radiology. Therefore, the patient underwent emergency enterectomy for the ileal varices. No further gastrointestinal bleeding occurred during the 1-year follow-up.

Although recent studies have confirmed the safety of total pancreatectomy (TP), appropriate selection of patients for TP has not been well documented. Because patients require lifelong medical treatment and self-management of pancreatic insufficiency after TP, indications for TP should be determined carefully according not only to disease factors but also to the social background of patients. We aimed to clarify long-term outcomes after TP, including the living conditions and quality of life (QoL), of surviving patients.Medical records of 44 consecutive patients who underwent TP between 1990 and 2013 were reviewed retrospectively; 25 survivors completed cross-sectional clinical surveys and responded to a questionnaire about QoL using Short Form 36v2.Prevalence of morbidity and mortality after TP was 32 and 5 %, respectively. Postoperative complications occurred more frequently in elderly patients than in young patients (48 vs. 14 %; P = 0.02); however, there was no significant difference in mortality, postoperative hospital stay, or survival. Twenty-four of 25 survivors (96 %) could manage pancreatogenic diabetes by themselves, and the median level of glycosylated hemoglobin was 7.4 %. Although one-third of patients after TP complained of diarrhea and the QoL scores of patients with diarrhea were lower than those of patients without diarrhea, QoL scores after TP were virtually comparable with those of the national population, even in elderly patients.TP can be performed safely, even in elderly patients. QoL after TP seems to be acceptable if patients are capable of self-management.

Routine endoscopic retrograde pancreatography (ERP) for pancreatic juice cytology (PJC) during management of intraductal papillary mucinous neoplasm (IPMN) is not recommended in the international consensus guidelines 2012. The aim of the present study was to investigate the roles of PJC in relation to the new stratification of clinical findings in the consensus guidelines 2012. Medical records of 70 consecutive patients who underwent preoperative PJC, subsequent pancreatectomy, and a pathological diagnosis of IPMN were reviewed. Diagnostic ability of PJC to detect malignant lesions was calculated by the stratification of clinical findings. Forty patients had malignant lesions, including 29 with malignant IPMN, 10 with concomitant pancreatic adenocarcinoma, and one with both. Accuracies of PJC in all 70 patients and in 59 patients with IPMN alone were 77 and 80 %, respectively. The sensitivity and accuracy of PJC in patients with “worrisome features” were 100 and 94 %, respectively. Eight of 11 patients with concomitant pancreatic adenocarcinoma had non-malignant IPMN without risk factors, and 3 significant lesions could be diagnosed only by ERP/PJC. In addition, the management plan based on imaging study changed from observation to resection in two patients who had the single “worrisome feature” of branch duct IPMN and positive PJC results. As a result, PJC altered the management plan in 5 patients. Pancreatic juice cytology potentially has important roles to determine the adequate treatment choice in patients with IPMNs with “worrisome features,” and to detect significant lesions that could not be detected by other imaging modalities.

The majority of patients with pancreatic cancer present with far advanced disease and jaundice. With the advancement of endoscopic interventional techniques, the role of surgical bypass has declined. However, surgical bypass is still considered to be appropriate in patients who are able to tolerate surgery. We performed hepaticocholecystojejunostomy consecutively as a palliative surgical biliary bypass for the purpose of long-term palliation. The aim of this study was to analyze the results of our palliative surgical biliary bypass, hepaticocholecystojejunostomy.Between January 2001 through December 2009, 69 patients received palliative surgical biliary bypass (bypass group) and 33 patients received endoscopic biliary stenting (stent group) for unresectable pancreatic cancers. Mortality, morbidity and survival between the two groups were compared.There was no in-hospital death in the bypass group, but 2 patients (6%) in the stent group died in the hospital (p = 0.04). The surgical morbidity rate was 15% in the bypass group, while 20 patients (61%) in the stent group developed complications, mainly due to stent blockage. There was no significant difference in overall survival between the two groups. Among patients who underwent systemic chemotherapy but did not present with jaundice at the time of diagnosis, those who underwent prophylactic surgical biliary bypass before chemotherapy showed better survival than those who underwent systemic chemotherapy preceding biliary bypass or biliary stenting after occurrence of jaundice (p = 0.01).Hepaticocholecystojejunostomy resulted in negligible mortality, low morbidity and effective long-term palliation. Prophylactic surgical biliary bypass with gastrointestinal bypass might be a good treatment option for non-jaundiced patients undergoing chemotherapy for unresectable pancreatic cancer.

A 70 -year-old female patient with a palpable mass in the left upper abdomen suffered from abdominal pain and fever. Abdominal computed tomography showed a jejunal tumor 11 cm in diameter with ascites, suggesting rupture of the tumor. Histological diagnosis via endoscopic ultrasound-guided fine needle aspiration indicated c-kit-positive gastrointestinal stromal tumor. Diagnostic laparoscopy demonstrated a large jejunal tumor possibly invading the stomach and pancreas. The patient then underwent tube jejunostomy. Thereafter, preoperative induction chemotherapy with imatinib mesylate(400mg/ body/day)via jejunostomy was administered for 6 months, resulting in 20%reduction of the tumor diameter and disappearance of any indication of stomach and pancreas invasion. The patient then underwent radical partial resection of the jejunum without combined resection of either the stomach or pancreas. Postoperative adjuvant chemotherapy with imatinib mesylate (400mg/body/day)was also indicated. No sign of recurrence has been detected to date after 1 year of follow-up.

Background: Because T2 carcinoma of the gallbladder that invades perimuscular connective tissue without extension beyond serosa or into the liver has a hope for longterm survival, we attempted to clarify significant prognostic factors with respect to tumor- and surgery-related variables. Study Design: Of 65 patients with gallbladder carcinoma who had undergone surgical resection from 1983 to 1999, 28 had T2 carcinoma histologically proved. The significance of variables for survival was examined by the Kaplan-Meier method and log-rank test followed by multivariate analyses using Cox's proportional hazard model. Results: There were 17 patients with stage II carcinoma (T2 N0 M0), 6 with stage III (T2 N1 M0), and 5 with stage IVB. Lymph node metastasis was present in 11 patients (39%) and it reached to the peripancreatic head region (N2) in 5 of them. Lymphatic, venous, and perineural invasions were found in 68%, 57%, and 43%, respectively. With respect to tumor factors, the absence of perineural invasion (Odds ratio [OR] 16.77, 95% confidence interval [CI] 2.17–129.94, p=0.0069), absence of lymph node metastasis (OR 15.00, 95% CI 2.08–108.33, p=0.0073), and stage II (II versus III and IVB, OR 15.00, 95% CI 2.08–108.33, p=0.0073) were significant factors related to good postoperative survival in the multivariate analysis. Surgical procedure (radical resection versus cholecystectomy, OR 4.31, 95% CI 1.34–13.82, p=0.0142) and surgical margin (OR 7.41, 95% CI 2.19–25.13, p=0.0013) were significant factors in the univariate analysis. Cancer-free surgical margins provided a significantly better survival (5-year survival rate, 62%); none with cancer-positive surgical margins survived for more than 27 months. In the multivariate analysis, surgical procedure was significant (OR 25.49, 95% CI 1.62–400.72, p=0.021). Radical surgery, including extended cholecystectomy (resection of the gallbladder together with the gallbladder bed of the liver) and anatomic resection of liver segment 5 and of the lower part of segment 4, gave a significantly better 5-year survival rate than cholecystectomy (59% versus 17%). The 5-year survival rate after radical resection in patients with stage II was 75%; that in patients with stage III and IVB was 33%. Conclusions: Results suggest that radical surgery is the treatment of choice for patients with T2 carcinoma of the gallbladder. The presence of lymph node metastasis, perineural invasion, or both suggests the necessity of additional treatment after radical surgery.

Aberrant expression of several microRNAs (miRs) has been reported in various neoplasms including intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. MicroRNA-196a (miR-196a) is up-regulated in Barrett esophagus (characterized by intestinal metaplasia) and in colorectal cancer; this relationship between intestinal characteristics and miR-196a might also be applicable to intestinal-type IPMNs. The aim of this study was to evaluate whether intestinal-type IPMNs can be discriminated from non-intestinal-type IPMNs by the expression level of miR-196a in tissue and pancreatic juice samples.Thirty-seven formalin-fixed paraffin-embedded tissue samples (including 3 of normal pancreatic ducts) and 36 pancreatic juice samples were obtained. The expression level of miR-196a measured by quantitative reverse transcription-polymerase chain reaction assays was compared between intestinal-type and non-intestinal-type IPMNs.MicroRNA-196a expression in intestinal-type IPMN tissue samples (n = 18) was significantly higher than that of non-intestinal-type IPMNs (n = 16) (P0.001). Similarly, miR-196a expression in pancreatic juice samples of intestinal-type IPMNs (n = 6) was significantly higher than that of non-intestinal-type IPMNs (n = 30) (P = 0.008), and the sensitivity and specificity for prediction of intestinal-type IPMNs using pancreatic juice samples were both 83%.Elevated expression of miR-196a in pancreatic juice samples is predictive of intestinal-type IPMNs.