Laparoscopic inguinal hernioplasty after robot-assisted laparoscopic radical prostatectomy.

PURPOSE: To evaluate the efficacy and safety of laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair in patients who have undergone robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: From July 2014 to December 2016, TAPP inguinal hernia repair was conducted in 40 consecutive patients who had previously undergone RALP. Their data were retrospectively analyzed as an uncontrolled case series. RESULTS: The mean operation time in patients who had previously undergone RALP was 99.5 ± 38.0 min. The intraoperative blood loss volume was small, and the duration of hospitalization was 2.0 ± 0.5 days. No intraoperative complications or major postoperative complications occurred. During the average 11.2-month follow-up period, no patients who had previously undergone prostatectomy developed recurrence. CONCLUSIONS: Laparoscopic TAPP inguinal hernia repair after RALP was safe and effective. TAPP inguinal hernia repair may be a valuable alternative to open hernioplasty.

FDG-PET predicts treatment efficacy and surgical outcome of pre-operative chemoradiation therapy for resectable and borderline resectable pancreatic cancer.

BACKGROUND: The efficacy of neoadjuvant chemoradiotherapy (NACRT) for resectable and borderline resectable pancreatic cancer is important for predicting outcomes after radical surgery, but few clinical indicators predict outcome before resection. This study examined the utility of FDG-PET in predicting the efficacy of NACRT and outcome after radical surgery. METHODS: Eighty-three pancreatic cancer patients who underwent FDG-PET before and after NACRT and had positive standard uptake values (SUVs) before NACRT were enrolled in this study. Peri-operative clinical factors, including FDG-PET findings, were examined to predict the efficacy of NACRT and outcome after surgery. RESULTS: Evans grade I, IIA, IIB, III, and IV was determined in 11, 31, 27, 11, and 3 patients, respectively. The maximum SUVs after NACRT (post SUV-max) and tumor size were significantly decreased compared to pretreatment values (p < 0.001 and p = 0.007, respectively). The post SUV-max and regression index were significantly related to grade III/IV (p = 0.04 and p < 0.001, respectively), but only the regression index predicted NACRT efficacy (p = 0.002). The AUC of the regression index for the detection of grade III/IV was 0.822, and 13 of 14 grade III/IV patients were picked up using 50% as the threshold (p < 0.001). Patients with a regression index >50% had a significantly better prognosis after radical resection than patients with <50% (p = 0.032). Regression index as well as pathological lymph node status and resectability status were independent prognostic factors in multivariate analysis (exp 2.086, p = 0.043). CONCLUSION: The regression index is potentially a good indicator of the efficacy of NACRT and outcome after radical resection for pancreatic cancer.

A retrospective analysis of the clinical effects of neoadjuvant combination therapy with full-dose gemcitabine and radiation therapy in patients with biliary tract cancer.

PURPOSE: This study aims to evaluate survival and the objective response to neoadjuvant combination therapy with gemcitabine and radiation therapy in patients with biliary tract cancer. METHODS: The chemoradiation therapy regimen consisted of 3 cycles of full-dose gemcitabine (1000 mg/m2 at days 1, 8, and 15, every 4 weeks) with 50-60 Gy radiation. We compared 27 patients who received neoadjuvant chemoradiation therapy and 79 patients who were treated without neoadjuvant therapy. Hemi-hepatectomy or pancreatoduodenectomy was planned for all of the patients in the study population. CT-based staging was used to adjust for the pre-treatment characteristics of the patients. RESULTS: After confirming the reproducibility of CT-based staging, we analyzed the survival of the patients. The multivariate analysis showed that the absence of arterial invasion on CT, the absence of lymph node swelling, and neoadjuvant therapy were independent prognostic factors. The three-year recurrence-free survival (RFS) rates in patients treated with and without neoadjuvant therapy were 78% and 58%, respectively (P = 0.0263). The adjusted overall survival (OS) (determined by the inverse probability of treatment weighting method using the inverse propensity score) was improved by neoadjuvant therapy (P = 0.00187); the hazard ratio was 0.3505. CONCLUSIONS: Neoadjuvant chemoradiation therapy might have the potential to improve RFS and OS. REGISTRATION: UMIN-CTR UMIN000015450.

Anatomical versus non-anatomical resection for hepatocellular carcinoma.

BACKGROUND: The optimal surgical resection method in patients with HCC to minimize the risk of local recurrence has not yet been determined. The aim of this study was to compare the prognosis following anatomical versus non-anatomical hepatic resection for hepatocellular carcinoma (HCC). METHODS: Consecutive patients with HCC without macroscopic vascular invasion, treated by curative resection between 1981 and 2012 at Osaka Medical Centre, were included in this retrospective study. The outcomes of patients selected by propensity score matching were compared. RESULTS: Some 1102 patients were included, 577 in the anatomical and 525 in the non-anatomical resection group. By propensity score matching, 329 patients were selected into each group. Demographic, preoperative and tumour variables were similar between the propensity score-matched groups, including tumour size, tumour multiplicity, α-fetoprotein level and 15-min indocyanine green retention rate at 15 min. The incidence of microvascular invasion was higher in the matched anatomical resection group (P = 0·048). Stratified analysis of recurrence-free and overall survival rates revealed no statistically significant differences between the two propensity score-matched groups (P = 0·704 and P = 0·381 respectively). There was also no significant difference in the early recurrence rate within 2 years after resection between these groups (P = 0·726). Subset analysis of the early recurrence-free survival rate in patients with and without microvascular invasion revealed no significant differences between the groups (P = 0·312 and P = 0·479 respectively). CONCLUSION: The resection method had no impact on the risk of HCC recurrence or survival.

Major joint replacement. A model for antithrombotic drug development: from proof-of-concept to clinical use.

AIM: Development of antithrombotic compounds has traditionally been performed in patients undergoing total hip and knee replacement surgery. A high number of asymptomatic deep-vein thromboses are radiologically detectable, and bleeding and other adverse events (AE) are easy to observe. However, standardization of study procedures and endpoints in early proof-of-concept studies and late pure clinical endpoint studies has been lacking. This has made comparison between studies difficult, economic analyses speculative and potential benefits of applying the drug regimen in non-selected patients uncertain. In this paper, the International Surgical Thrombosis Forum proposes a strategy for the clinical investigation of new pharmacological agents for the prophylaxis of postoperative thrombotic events. METHODS: First, dose titration safety studies of short duration, in highly selected patients using objective venographic endpoints are recommended. Bleeding should be divided into the quantified volume of surgical bleeding and other adjudicated clinical bleeding events. The number of AE should be described for each dose step and classified according to International Coding of Diagnoses (ICD). Second, a dose confirmatory study of moderate exposure period and sufficient follow-up time is recommended. The exclusion criteria should be restricted to contraindications of the compared drugs and technical procedure. RESULTS: The efficacy, bleeding and AE should be similar to those used in dose-titration studies. In addition, the failure rate of the drug to exert its effect and the net clinical benefit should be calculated. CONCLUSION: Finally, trials with simple clinical endpoints and long follow-up should be conducted to evaluate the potential benefits of the drug-regimen in non-selected populations.

Incidence of venous thromboembolism following major abdominal surgery: a multi-center, prospective epidemiological study in Japan.

BACKGROUND: Venous thromboembolism (VTE) has been considered to be a rare surgical complication in Japan. AIM: To investigate the incidence and risk factors of VTE in Japanese patients undergoing major abdominal surgery. METHODS: A prospective, multi-center epidemiological study was conducted from December, 2001 to August 2002 in 39 medical institutes throughout Japan. A total of 173 patients with general (n = 128), gynecologic (n = 23), and urologic (n = 22) surgery were analyzed. For the diagnosis of deep vein thrombosis (DVT), bilateral venography was performed in all patients. Lung ventilation/perfusion scintigraphy was carried out in patients suspected of pulmonary thromboembolism (PTE). RESULTS: There were 36 patients with distal DVT (20.8%) and five patients with proximal DVT (2.9%). One patient was diagnosed as PTE. Overall, VTE was diagnosed in 42 patients (24.3%). By univariate analysis, only age (60 years or older) was identified as a significant risk factor in the whole study population. When analyzed by the stepwise multiple logistic regression model, female gender, operation site, age, and operation time were four risk factors found to be significant. The incidence of VTE was closely related to the number of risk factors that patients had. As many as 44% of patients with three or four risk factors developed VTE while those with one or two risk factors showed about a 17% incidence of VTE. Four patients lacking any risk factors did not develop VTE. CONCLUSIONS: Venous thromboembolism is common in Japanese patients undergoing major abdominal surgery. Pharmacologic thromboprophylaxis is considered essential, particularly in those patients with multiple, potential risk factors.

Treatment of hepatocellular carcinoma with major portal vein thrombosis by combined therapy with subcutaneous interferon-alpha and intra-arterial 5-fluorouracil; role of type 1 interferon receptor expression.

We previously reported the beneficial effects of combination therapy of interferon (IFN)-alpha/5-fluorouracil (FU) for advanced hepatocellular carcinoma (HCC) with tumour thrombi in the major portal branches. This report describes the results of longer follow-up and includes more than double the number of patients relative to the original report, and evaluates the role of IFN-alpha/type 2 interferon receptor (IFNAR2) expression on the response to the combination therapy. The study subjects were 55 patients with advanced HCC and tumour thrombi in the major branches of the portal vein (Vp3 or 4). They were treated with at least two courses of IFN-alpha/5-FU without major complication. In the 55 patients, 24 (43.6%) showed objective response (eight (14.5%) showed complete response, 16 (29.1%) partial response), four (7.3%) showed no response, and 27 (49.1%) showed progressive disease. Immunohistochemically, IFNAR2 expression was detected in nine out of 13 (69.2%) patients. There was significant difference in the time-to-progression survival (P = 0.0002) and the overall survival (P < 0.0001) between IFNAR2-positive and -negative cases. There was a significant correlation between IFNAR2 expression and response to IFN-alpha/5-FU combination therapy in univariate analysis (P = 0.0070). IFN-alpha/5-FU combination therapy is a promising modality for advanced HCC with tumour thrombi in the major portal branches and could significantly depend on IFNAR2 expression.

Domino liver transplantation in living donors.

Domino liver transplantation (DLT) has been developed as a method to expand the donor pool. In living donors DLT, the prime concern is to avoid any disadvantage to the donor and the first recipient. Seven DLTs were performed among 211 patients who underwent living donor liver transplantation. The domino recipients included six with hepatocellular carcinoma and one with citrullinemia. The domino grafts were obtained from patients with familial amyloid polyneuropathy (FAP) including the left liver in three cases and the right liver in four. Among the seven domino recipients, a 64-year-old woman with advanced hepatocellular carcinoma died of lung metastasis. The other six domino recipients are alive without FAP symptoms. In living donor liver transplantation, because the vessels of the graft from the first donor are not long enough for anastomosis, the hepatic vessels must be left as long as possible when removing the liver from the FAP patients in order to ensure sufficient safety for vascular reconstruction. With careful decision making during the procedure, such as where to divide the vessels in the FAP patients, DLT may help address the shortage of liver grafts.

PCR-array gene expression profiling of hepatocellular carcinoma.

Many trials using DNA microarrays have been reported for various human malignancies, but an efficient molecular diagnostic system has yet to be established. Here, we adopted a high throughput quantitative PCR-array system based on adaptor-tagged competitive PCR (ATAC-PCR), as a novel technique for gene expression profiling of hepatocellular carcinoma (HCC). This PCR-array contained 3,072 genes derived from three different cDNA libraries, including 298 additional known genes suspected to be involved in hepatocarcinogenesis. Using this PCR-array with 20 pairs of liver tissues (20 HCC, 20 surrounding nontumor liver), we identified a total of 117 genes differing in expression levels in the two liver tissues. Hierarchical clustering analysis and principal component analysis with these genes revealed distinct gene expression patterns in the HBV-positive group and the HCV-positive groups. Among 117 genes, only 7 (GPAA1, TMEM9, FACL4, ADFP, MAWBP, PACE4, FOS) were common to both groups. In conclusion, this PCR-array analysis with an appropriate set of genes is considered useful for gene expression profiling of HCC, and we identified some genes which may play a common key role in hepatocarcinogenesis.

Role of cytoplasmic calcium in platelet aggregation.

BACKGROUND: Although adherence and aggregation of platelets on an active surface such as exposed subendothelial matrix or foreign surfaces is integral to the occlusion of blood vessels, its mode of action is not fully understood. METHODS: The role of cytoplasmic ionized Ca(2+) concentration ([Ca(2+)](i)) in platelet activation induced by contact with a glass surface under shear-stress was studied by employing confocal laser scanning microscopy (CLSM) in conjunction with a parallel plate flow chamber. Changes in [Ca(2+)](i) and morphology of aggregating platelets on glass surface was simultaneously examined. RESULTS: Under static condition, contact with glass caused platelet adhesion to the surface, which was associated with [Ca(2+)](i) rise and morphological change; however, platelets did not develop a large aggregation on the surface. Under lower shear-stress, the number of the single platelets adsorbed on the surface was less than that under static condition. Although shear-stress increased the number of single platelets involved and enhanced morphological change in aggregating platelets in a shear-stress related manner, the peak [Ca(2+)](i) value in individual platelets were not increased. CONCLUSIONS: These observations may suggest the crucial roles of shear-stress in platelet aggregate formation at the site of arterial stenosis. Shear-stress might enhances platelet aggregate growth not through the enhancement of [Ca(2+)](i) rise.

Angiomyolipoma of the liver with least amount of fat component: imaging features of CT, MR, and angiography.

We report two cases of angiomyolipoma of the liver, where small amounts of fat on computed tomography, magnetic resonance imaging, and angiography made distinguishing this tumor from other hypervascular tumors difficult. Recognizing the imaging features of no capsule, hypervascularity of the tumor including the fat component, and early venous drainage may be helpful for correctly diagnosing angiomyolipoma of the liver.

An immunohistochemical study of cyclooxygenase (COX)-2 expression in endocrine tumors of the pancreas.

Cyclooxygenase (COX) is a key rate-limiting enzyme in prostaglandin biosynthesis. There are two isoforms of COX, referred to as COX-1 and COX-2. COX-2, an inducible form of COX, is found to be overexpressed in various neoplasms and is believed to play an important role in tumorigenesis and tumor development. In this study, we investigated expression of the COX-2 protein in human endocrine tumors of the pancreas (N=23; 6 insulinomas, one glucagnoma, 2 gastrinomas, and 14 non-functioning tumors) using immunohistochemistry. Strong COX-2 expression was confirmed in normal islet tissue as previously reported. COX-2 immunoreactivity was detected in 65% (15 out of 23) of these tumors with a moderate to strong intensity. In all nine functioning tumors, COX-2 expressions were preserved with the weak or strong intensity. In contrast, COX-2 was present in 6 out of 14 nonfunctioning tumors. The correlation between COX-2 expression and their function was significant (p<0.05). We found that expression of this enzyme was detected in 11 out of 15 benign tumors and in 4 out of 8 malignant tumors, respectively. Our results suggest that COX-2 may play an important role in the endocrine function of islet tumors. Additionally, malignancy was not related to COX-2 expression.

[Significance of liver resection for multiple hepatic metastases from colorectal cancer].

In colorectal cancer, liver metastasis is the most common and most important prognostic factor. To elucidate the significance of liver resection, we examined 72 cases (H2: 29 cases, H3: 43 cases). The 3-year survival rate for H2 and H3 patients was 71.5% and 4.5%, respectively. The liver resection rate in H2 and H3 patients was 58.6% (17/29) and 16.3% (7/43), respectively. In H2 patients the 3-year survival rate of those with liver resection and non-resection was 71.3% and 9.2%, respectively (p < 0.001). However, in H3 patients the 3-year survival rate in liver resection and non-resection patients was 80.0% and 43.9%, respectively (not significant). Many therapies, such as liver resection, hepatic arterial infusion, and systemic chemotherapy, were attempted for patients with hepatic metastases. Our data show that liver resection can prolong the survival of H2 patients only. On the other hand, hepatic arterial infusion therapy prolongs the survival of H3 patients only. Systemic chemotherapy does not prolong the survival of either H2 or H3 patients.

[A case of postoperative multiple hepatic metastasis from esophageal cancer successfully treated by surgical resection and hepatic arterial infusion chemotherapy].

A 66-year-old male who underwent radical resection for esophageal cancer (stage IV) was diagnosed with multiple hepatic metastasis 1 year and 3 months after the surgery. He underwent hepatic resection and received systemic chemotherapy (FAP: 5-FU, ADR, CDDP), as the post-operative adjuvant therapy. One year and 3 months later, there was a huge recurrence in the residual liver and hepatic arterial infusion chemotherapy (FAP) was performed. The recurrent lesion disappeared completely after 3 sessions of arterial infusion chemotherapy. The arterial infusion chemotherapy was continued in the outpatient clinic and the recurrent lesion is well controlled. At present, this patient has returned to social life, 2 years and 3 months after the hepatic resection. The utility of hepatic arterial infusion chemotherapy and hepatectomy for postoperative multiple hepatic metastasis from esophageal cancer was shown in the present case.

[A patient with hepatocellular carcinoma and portal vein thrombosis in 1st branch who was treated by transcatheter arterial embolization].

We report a patient with hepatocellular carcinoma (HCC) with portal vein thrombosis in the 1st branch who was treated by transcatheter arterial embolization (TAE) and survived more than 3 years. A 58-year old male was diagnosed as having unresectable massive type HCC in the area of S8 with portal vein thrombosis from the P8 branch to the right portal branch. He was treated by TAE via the anterior branch of right hepatic artery. One week later, localized hepatic infarction in the anterior segment was recognized. Five months later, the portal vein thrombosis had disappeared and become necrotic. After 3 years and 4 months, he died of a relapse of a gastric varix, but with no portal thrombosis and a well controlled intra-hepatic recurrence that was treated by repeated TAE. This case suggests that TAE might be effective for cases of HCC with portal vein thrombosis in the 1st branch, if the liver function and portal flow are suitable.

Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial cells and bile duct neoplasm.

It is well known that chronic inflammatory conditions involving the bile ducts predispose to the development of bile duct carcinoma, although the relationship between chronic inflammation and malignant transformation is unclear. In this study, by combining immunohistochemistry and computer imaging techniques, we quantified and compared the cyclooxygenase-2 (COX-2) protein expression levels of epithelial cells according with their histopathological backgrounds. This technique revealed that the highest levels of COX-2 were expressed in bile duct carcinoma cells, mainly in cytoplasm, and the expression pattern was homogenous and abundant. Moderate levels of COX-2 protein expression were also observed in noncancerous epithelial cells with inflammatory reaction, but the staining intensity was heterogeneous among the positive cells exhibiting inflammation. In contrast, only scattered weak reactivity of COX-2 protein was observed in the noncancerous bile duct epithelial cells without inflammatory reaction. Moreover, bile duct epithelial cells in primary sclerosing cholangitis (PSC) showed very strong expression of COX-2 protein, that was comparable with carcinoma cells. On the other hand, primary biliary cirrhosis (PBC) epithelial cells showed moderate levels of COX-2 expression. In addition, specific COX-2 inhibitors, JTE-522 and NS-398, directly inhibited the growth of 4 bile duct carcinoma and 1 gall bladder carcinoma cell lines that expressed COX-2 protein, in vitro. These data suggest that COX-2 expression might regulate carcinogenesis of bile duct epithelial cells in inflammatory regions and tumor progression in this cancer. The data also suggest that COX-2 selective inhibitors might have therapeutic effects not only on bile duct carcinoma, but other hepatobiliary carcinomas.

Expression of p57/Kip2 protein in hepatocellular carcinoma.

Evaluation of the biological character of carcinomas requires understanding of cell cycle regulators. In the present study, we investigated the expression of p57 (Kip2) in 90 hepatocellular carcinomas and 66 noncancerous lesions. The average p57 labeling index in noncancerous lesions was 72.3 +/- 19.7. The labeling index significantly decreased (p < 0.0001) in hepatocellular carcinoma (54.9 +/- 19.7). It was significantly lower in hepatocellular carcinoma cases with high biological aggressiveness such as advanced stage (p = 0.0041), poor differentiation (p < 0.0001), larger size (p = 0.0400), portal invasion (p < 0.0001), satellite tumor (p = 0.0023), high proliferating activity (p = 0.0002) and cyclin D(1) overexpression (p = 0.0416). Furthermore, cases with low p57 expression showed worse outcomes for disease-free survival in univariate analysis (p = 0.0235), although p57 expression could not be recognized as an independent prognostic factor. These findings suggest that p57 contributes to the downregulation of cell proliferation and to the progression of hepatocellular carcinoma.

Human stomach-specific gene, CA11, is down-regulated in gastric cancer.

To reveal the implication in gastric cancer pathogenesis of the novel human gene referred to as CA11, which was recently isolated by a differential display technique using normal gastric mucosa and gastric cancer tissue, we examined CA11 expression in 50 primary gastric cancers and also introduced the CA11 gene into gastric cancer cells. RNA dot blot analysis against various human organs and developmental stages demonstrated that CA11 was intensively expressed especially in normal stomach tissue. Northern blot analysis showed that expression of the CA11 gene in cancer tissue was down-regulated compared with normal tissue. Semi-quantitative RT-PCR also demonstrated that CA11 gene expression was decreased in 41 out of 50 (82%) of the gastric cancer tissues, when compared with normal stomach tissues, while no relationship was found between CA11 expression and various clinicopathological characteristics including histological type, depth of invasion, lymph node metastasis, and clinical stage. Immunohistochemical analysis with anti CA11 antibody showed that CA11-positive staining was observed in the surface regions of normal gastric epithelium, but was found faintly or not at all in cancer tissues. CA11 transfected MKN28 cells also displayed a marked decrease in the number of colony formations when compared to double normal controls. These findings suggest that the loss of CA11 expression in gastric tissues may play an important role in gastric carcinogenesis.

Activation of c-Src gene product in hepatocellular carcinoma is highly correlated with the indices of early stage phenotype.

BACKGROUND/AIMS: The aim of this study was to investigate whether c-Src is involved in carcinogenesis and progression of human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. METHODS: We designed an immunohistochemical study using Clone 28, an antibody that specifically recognizes the activated form of c-Src. RESULTS: Hepatocytes in normal liver, chronic hepatitis with or without cirrhosis, atypical adenomatous hyperplasia, as well as bile ductular cells, and infiltrating mononuclear cells were all negative for immunohistochemical staining for the activated c-Src. Among 87 cases of HCC tested, 40 (46%) were positively stained for the activated c-Src, and this positive staining was inversely correlated with the Ki-67 labeling index (LI) (P = 0.0031), intrahepatic metastasis (P = 0.0099), TNM stage (P = 0.0062), alpha-fetoprotein (P = 0.0103) and epidermal growth factor-receptor expression (P = 0.0153). Positive staining for the activated c-Src was more frequently observed in well- or moderately-differentiated carcinoma (P = 0.0256). In multivariate analysis, the activated c-Src expression was independently related to the Ki-67 LI (P = 0.0197). In contrast to positive staining in HCC, cholangiocarcinoma were classified as negative in all 19 cases examined. CONCLUSIONS: These results strongly suggest the involvement of activated c-Src in early stages of HCC, and suggest that cholangiocarcinoma might employ different signaling mechanisms.

Pancreatic mass due to chronic pancreatitis: correlation of CT and MR imaging features with pathologic findings.

OBJECTIVE: The purpose of this study was to identify helical CT and MR imaging features of pancreatic masses (focal enlargement) due to chronic pancreatitis and their correlation with pathologic findings. CONCLUSION: When histologic fibrosis is uniformly present through the pancreas in patients with chronic pancreatitis, there is no demarcation of masses due to chronic pancreatitis. When there is a greater degree of histologic fibrosis in the masslike part of the pancreas, the mass is often demarcated from the remaining pancreas, and the enhancement pattern on two-phase helical CT and dynamic gadolinium-enhanced MR imaging mimics that of pancreatic adenocarcinoma.