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Objective We evaluated the effect of postgraduate surgical education on inguinal hernia repair for resident surgeons. Methods A total of 93 adult patients underwent open mesh repairs for inguinal hernias. These patients were randomly assigned to junior or senior resident surgeon groups for inguinal hernia repairs. The surgical training program for inguinal hernia repair was subdivided into 3 consecutive steps: sections A, B, and C. The sections were defined as follows: (A) the starting point of the surgery to hanging the spermatic cord, (B) dissection of the hernia sac, and (C) placement of the hernia mesh. The time to complete each procedure was recorded. We then evaluated the learning curve of the junior resident surgeons for open mesh repair of inguinal hernia. Results The mean operative time of the junior resident group was significantly longer than that of the senior resident group. Particularly, the mean times of the junior residents for sections B and C were significantly longer than those of the senior resident group. However, the volume of intraoperative blood loss and the short-term outcomes were not significantly different between the groups. For section C of the procedure, the learning curve seemed shorter for junior resident surgeons who had completed the training program for inguinal hernia repair than that for junior resident surgeons who were just beginning this program. Conclusion This study demonstrates that a junior resident surgeon's initial experience with hernia repair is associated with an identifiable learning curve when participating in a suitable training program.

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.

AIM To investigate the prevalence, clinicopathological characteristics and surgical outcomes of occult hepatitis B virus (HBV) infection (OBI) in patients with non-B, non-C (NBNC) hepatocellular carcinoma (HCC). METHODS This study retrospectively examined the cases of 78 NBNC patients with curative resection for HCC for whom DNA could be extracted from formalin-fixed paraffin-embedded tissue. OBI was determined by the HBV-DNA amplification of at least two different sets of primers by TaqMan real-time polymerase chain reaction. Possibly carcinogenetic factors such as alcohol abuse, diabetes mellitus, obesity and non-alcoholic steatohepatitis (NASH) were examined. Surgical outcomes were evaluated according to disease-free survival (DFS), overall survival (OS) and disease-specific survival (DSS). RESULTS OBI was found in 27/78 patients (34.6%) with NBNC HCC. The OBI patients were significantly younger than the non-OBI cases at the time of surgery (average age 63.0 vs 68.1, P = 0.0334) and the OBI cases overlapped with other etiologies significantly more frequently compared to the non-OBI cases (P = 0.0057). OBI had no impact on the DFS, OS or DSS. Only tumor-related factors affected these surgical outcomes. CONCLUSION Our findings indicate that OBI had no impact on surgical outcomes. The surgical outcomes of NBNC HCC depend on early tumor detection; this reconfirms the importance of a periodic medical examination for individuals who have NBNC HCC risk factors.

Highlights • A single gallbladder with a double cystic duct is a very rare finding. • MRCP showed strong suspicion of a single gallbladder with a double cystic duct and the definite diagnosis of a double cystic duct was made by ERC. • Laparoscopic cholecystectomy could be successfully performed in combination with intraoperative cholangiography for double cystic duct., Introduction A single gallbladder with a double cystic duct is a very rare finding. In addition, few cases with this rare condition are preoperatively diagnosed. However, the preoperative confirmation or suspicion of this rare condition could facilitate safe laparoscopic cholecystectomy, which is a minimally invasive therapeutic modality for gallbladder disease. We herein present a case of gallstone disease in a patient with a double cystic duct who was preoperatively diagnosed and successfully treated with laparoscopic cholecystectomy. Presentation of case A 57-year-old woman was admitted to our hospital with epigastric pain. Gallstone disease in the gallbladder and common bile duct was diagnosed by ultrasonography and computed tomography. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiography (ERC) revealed that the aberrant cystic duct arose from the cystic duct and communicated with the intrahepatic bile duct of the posterior segmental branch. Laparoscopic cholecystectomy was successfully performed in combination with intraoperative cholangiography. Discussion If an anomaly of the biliary duct system is not identified during surgery, it may turn out to be a bile leak. The preoperative diagnosis of a double cystic duct allows laparoscopic cholecystectomy to be performed safely in combination with intraoperative cholangiography. Conclusions A single gallbladder with double cystic duct is a very rare anomaly. However, laparoscopic surgery can be facilitated by the use of preoperative and intraoperative images.

We investigated whether regular changes of the sire in a breeding farm of Hokkaido Native Horses (HKDs) enables the DNA-level genetic variation of the produced animals to be maintained. The genotypes of 31 microsatellite markers were identified and analyzed in 207 animals produced in a breeding farm in which the sire was replaced every 3 to 5 years. The mean allele number indicating the degree of genetic variation was 5.97 and was similar to those reported previously. The mean observed heterozygosity was 0.74 and was higher than the expected heterozygosity, 0.69; FIS was -0.07, indicating that the analyzed animals reflected frequent outbreeding and had maintained genetic variation. Based on genetic structural analysis, the number of genetic subpopulations of the animals was estimated to be as 6, and the majority (more than 50%) of each subpopulation corresponded to the progeny of one of the sires used in the breeding farm; these observations suggested that genetic variation in the analyzed animals reflected the genetic differences among sires. Pedigree records indicated that the average co-ancestry coefficient between sires used in the breeding farm was 0.015 corresponding to second cousin. This level of kinship among sires is acceptable for producing HKDs that maintain genetic variation.

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.

The prognosis of hepatocellular carcinoma (HCC) is unfavorable following complete tumor resection. The aim of the present study was to identify a molecule able to predict HCC prognosis through comprehensive protein profiling and to elucidate its clinicopathological significance. Comprehensive protein profiling of HCC was performed by liquid chromatography-tandem mass spectrometry. Through the bioinformatic analysis of proteins expressed differentially in HCC and non-HCC tissues, protein disulfide-isomerase A3 (PDIA3) was identified as a candidate for the prediction of prognosis. PDIA3 expression was subsequently examined in 86 cases of HCC by immunostaining and associations between PDIA3 expression levels and clinicopathological characteristics were evaluated. The Ki-67 index and apoptotic cell death of carcinoma cells were examined by immunostaining and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay in 24 cases. The results demonstrated that PDIA3 was expressed in all 86 HCC cases; 56 HCC cases (65%) exhibited high expression of PDIA3 and 30 (35%) exhibited low expression. The disease-free and overall survival times of HCC patients with high PDIA3 expression were significantly shorter than in HCC patients with low expression. Furthermore, increased expression of PDIA3 was associated with an elevated Ki-67 index, indicating increased cancer cell proliferation and a reduction in apoptotic cell death. Taken together, these results suggest that PDIA3 expression is associated with tumor proliferation and decreased apoptosis in HCC, and that increased expression of PDIA3 predicts poor prognosis. PDIA3 may therefore be a key molecule in the development of novel targeting therapies for patients with HCC.

Gallbladder rupture due to blunt abdominal injury is rare. There are few reports of traumatic gallbladder injury, and it is commonly associated with other concomitant visceral injuries. Therefore, it is difficult to diagnose traumatic gallbladder rupture preoperatively when it is caused by blunt abdominal injury. We report a patient who underwent laparoscopic cholecystectomy after an exact preoperative diagnosis of traumatic gallbladder rupture. A 43-year-old man was admitted to our hospital due to blunt abdominal trauma. The day after admission, abdominal pain and ascites increased and a muscular defense sign appeared. Percutaneous drainage of the ascites was performed, and the aspirated fluid was bloody and almost pure bile. He was diagnosed with gallbladder rupture by the cholangiography using the endoscopic retrograde cholangiopancreatography technique. Laparoscopic cholecystectomy was performed safely, and he promptly recovered. If accumulated fluids contain bile, endoscopic cholangiography is useful not only to diagnose gallbladder injury but also to determine the therapeutic strategy.

Transportal obliteration is a technique used in portal hypertension to embolize the collateral veins of the portal system. It is used to treat refractory esophagogastric varices, ectopic varices, or portal-systemic encephalopathy. After insertion of a 5-French long sheath introducer into the portal vein, a catheter is inserted directly into the vein, and the portal circulation is visualized by portography. A balloon catheter is inserted selectively into the inflow site of the veins feeding the varices. Sclerosant is injected to obliterate the feeding vein or veins, and steel coils are used to complete the obliteration. However, the rate of complete disappearance of varices is not high after transportal obliteration alone. Transportal obliteration combined with endoscopic treatment or balloon-occluded retrograde transvenous obliteration, or both, is useful for treating uncontrolled bleeding from varices. The most frequent complication of percutaneous transhepatic obliteration is intraperitoneal bleeding. Severe coagulopathy is a contraindication for both percutaneous transhepatic obliteration and transileocolic vein obliteration, and ascites is a contraindication for percutaneous transhepatic obliteration. The presence of collateral veins decreases portal venous pressure. Obliteration of these veins by transportal obliteration thus increases portal congestion and portal pressure, especially in patients with cirrhosis. Partial splenic embolization has been performed incrementally to reduce portal venous pressure to the level it was before obliteration of the collateral veins. Transportal obliteration in combination with endoscopic treatment or with other forms of interventional radiology is useful for treating refractory esophagogastric varices, ectopic varices, or portal-systemic encephalopathy.

Endoscopic variceal ligation (EVL) is being used increasingly to treat esophageal varices because of its safety and simplicity and because no sclerosant is required. However, early recurrence of esophageal varices after this procedure has been reported.

A number of surgical procedures have been developed for the management of esophagogastric varices. They can be broadry classified into shunting and nonshunting procedures. There are two types of shunting procedure, namely nonselective and selective. Nonselective shunts, such as portacaval or mesocaval shunts, effectively reduce the incidence of variceal bleeding, but they carry a high risk of postoperative encephalopathy as a result of hyperammonemia. Selective shunts such as the distal splenorenal shunt (DSRS) or left gastric venous caval shunt were developed to preserve portal blood flow through the liver and reduce esophagogastric variceal pressure. The DSRS effectively prevents rebleeding, but it still carries a risk of postoperative encephalopathy. In order to prevent both postoperative encephalopathy and bleeding, we have improved the DSRS procedure by additionally performing splenopancreatic disconnection and gastric transection.

Various complications, such as esophagogastric varices, ectopic varices, ascites, and hepatic encephalopathy, can occur in portal hypertension. Bleeding from esophagogastric or ectopic varices is the most critical complication of portal hypertension. In 1980, general rules for recording endoscopic findings of esophageal varices were initially proposed in Japan. Revised rules were proposed as “General Rules for Recording Endoscopic Findings of Esophagogastric Varices (1991)” and “General Rules for Recording Endoscopic Findings of Esophagogastric Varices (2010).” The revised rules are simpler and more straightforward than the former rules. In 2013, “General Rules for Study of Portal Hypertension” was proposed by the Japan Society for Portal Hypertension. These rules have widely been used in Japan and other countries.

Background Intrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension. Interventional radiology (IVR) is generally selected as the first-line therapeutic option. Surgical treatment for IAPF is required in refractory cases of IVR. As the treatment success rate with IVR is high, cases requiring surgical treatment are extremely rare. Case presentation A 54-year-old man was admitted to another hospital complaining of hematemesis due to rupture of the esophageal varices. A computed tomography revealed ascites and arterioportal fistula in the left lobe of the liver. Transcatheter arterial embolization (TAE) was performed to occlude the fistula; however, it could not reach complete occlusion. Thereafter, there were a total of four hematemeses, and six endoscopic variceal ligations were required. The second TAE also failed to reach complete occlusion. He was transferred to our hospital for further treatment. Because liver function was low due to frequent hematemeses and there was also uncontrollable ascites, it was confirmed that hepatectomy could not be performed safely at this time. Therefore, we ligated the left portal branch and ligated and dissected the left gastric vein to decrease portal vein pressure. However, on the 5th day after surgery, the esophageal varices reruptured. As the disappearance of ascites was observed in the postoperative course and the general condition also improved, left hepatectomy was performed to remove IAPF. There was no recurrence of portal hypertension for 1 year and 3 months since hepatectomy. Conclusions This case was difficult to treat with IVR and required surgical treatment. Our experience in the present case suggests that hepatectomy to remove arterioportal fistula was considered effective for improving portal hypertension due to IAPF. However, careful treatment selection according to the patient’s overall condition and clinical course is necessary for IAPF presenting with severe portal hypertension.

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.

At present the only method available to confirm microscopic infiltration of cancer into ductal margins during surgery, is intraoperative histological examination. In the present study, the status of the surgical margins and postoperative course were evaluated to determine any correlation between remnant carcinoma and postoperative survival. All consecutive patients who underwent resection for biliary tract cancer between January 2004 and May 2012 were identified from a database. Positive margin cases were divided into two groups, invasive carcinoma and carcinoma in situ (CIS). Immunohistochemical staining targeting Ki67 and p53 for positive margins was performed. Cases of major vessel invasion were significantly increased in the positive group compared with the negative group. The recurrence rate was significantly lower in the CIS group compared with the invasive group. The survival rate was significantly increased in the CIS group compared with the invasive group. The expression levels of p53 and Ki67 were significantly increased in the invasive group compared with the CIS group. No statistical correlations were observed between the expression of p53 or Ki67 and the survival or recurrence of disease. In the positive group, resected margin status was the principal factor associated with recurrence-free survival according to Cox-regression analysis. In conclusion, the status of the resected margins in the positive group was the most important factor for postoperative survival and recurrence in cholangiocarcinoma, not immunohistochemical staining targeting Ki67 and p53.

Previously, a single nucleotide polymorphism (SNP) related to gait type was identified at position 22 999 655 of chromosome 23 in the coding region of DMRT3 (DMRT3:Ser301Ter) by showing that a cytosine (C) to adenine (A) mutation of this SNP induced pace in the Icelandic horse. We investigated the effect of DMRT3:Ser301Ter on the gait of Hokkaido Native Horses, a Japanese native breed, and examined genetic factors other than DMRT3 by exploring genome-wide SNPs related to gait determination. All animals exhibiting pace were AA for DMRT3:Ser301Ter, confirming the association of DMRT3:Ser301Ter with gait determination; however, 14.3% of the animals exhibiting trot also had AA for DMRT3:Ser301Ter, suggesting the presence of another factor(s) cooperatively working with DMRT3:Ser301Ter for gait determination. SNPs on chromosomes 13 and 23 were detected by genome-wide association analysis (false discovery rate

Aim : The present study evaluated the safety and effectiveness of repeated injections of minocycline hydrochloride (MINO) for symptomatic polycystic liver disease (PLD). Methods : We retrospectively studied patients who received percutaneous MINO injections for symptomatic PLD and were followed up for at least 2 years between 2002 and 2015. Huge hepatic cysts (diameter > 10 cm) were treated by continuous drainage and multiple MINO injections. Small hepatic cysts underwent one-step drainage followed by a single injection of MINO. Only several cysts that caused complications were treated by percutaneous injection of MINO. Patients were discharged 1 day after treatment. Results : Ten patients, (4men and 6 women; mean age, 57.8 years) were studied. All patients had Type 2 PLD according to Gigot’s classification. The chief complaints were abdominal distension (n = 10), abdominal pain (n = 6), back pain (n = 4), and appetite loss (n = 8). Four patients had mild liver dysfunction. One patient complained of moderate right subscapular pain immediately after the injection, and another had pain at the site of catheter insertion. Liver dysfunction did not develop in any patient after treatment. The mean follow-up was 63.4 months. The interval from the first to last admission for MINO injection therapy was 14 to 148 months (mean, 40.8 months). The number of admissions for MINO injection therapy ranged from 2 to 12 times (mean, 4.0 times). The average interval for MINO injection therapy was 8.3 to 19 months (mean, 14.8 months).The hepatic cysts shrank in all patients after treatment. Complications improved consistently, and all patients were satisfied with the outcome of treatment. Conclusions : Symptomatic PLD was controllable by 14.8 months of repeated MINO injections on average. Repeated MINO injections are a safe, definitive treatment for symptomatic PLD.

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.