Retroportal Hepaticojejunostomy for Extended Resection of Hilar Bile Ducts

High hepatic duct resection sometimes is unavoidable in achieving curative resection of hilar cholangiocarcinoma, as tumor cells can extend further than expected along the bile ducts from the macroscopically evident cancer. In patients undergoing left hemihepatectomy with caudate lobectomy whose bile duct must be severed at the subsegmental bile duct levels, the orifices of the posterior bile ducts would lie behind the right portal vein. Conventional hepaticojejunostomy would be risky in such cases because an anastomosis performed in the usual manner would be subjected to strain. Instead, between 2002 and 2004, three patients underwent retroportal hepaticojejunostomy using a jejunal limb mobilized and positioned behind the hepatoduodenal ligament. Primary tumors were classified as type IV in the Bismuth–Corlette classification. Tension-free hepaticojejunal anastomosis was performed successfully in all three patients; insufficiency of the hepaticojejunostomy did not develop. Neither early nor late complications directly related to this method occurred. Retroportal hepaticojejunostomy, thus, permits more peripheral resection of the hepatic duct while providing a sufficient operative field for safe, tension-free anastomosis. This technique is very useful for patients undergoing left hemihepatectomy requiring high hilar resection of the bile duct.     

Applicability of the Milan Criteria for Determining Liver Transplantation as a First-Line Treatment for Hepatocellular Carcinoma

Background To determine whether or not the Milan criteria (MC) should be used to determine the applicability of liver transplantation (LT) as a first-line treatment for patients with cirrhosis with hepatocellular carcinoma (HCC) who are able to endure hepatectomy.Methods Retrospective analysis of 82 patients with cirrhosis with HCC who were treated by hepatectomy without LT at our institution between 1990 and 2003.Results Of these 82 patients, 48 met the MC. Proportional hazard regression analyses to determine the independent prognostic factors for postoperative cumulative patient and disease-free survival showed that meeting the MC is the strongest prognostic factor for both patient and disease-free survival. The cumulative patient and disease-free survival rates were 76.7% and 28.9%, respectively, at 5 years in patients who met the MC. The cumulative disease-free survival was markedly inferior to those in previously reported series of LT for HCC who met the MC, but the cumulative patient survival was comparable to those in the previously reported series. A comparison of cumulative postoperative survival between patients who met the MC and fulfilled all five factors listed below and patients who met the MC but did not fulfill any of the five factors demonstrated that the latter patients showed statistically significantly worse postoperative patient survival than the former. The five factors included: Model for End-Stage Liver Disease score <10, indocyanine green retention rate at 15 minutes <20%, absence of microscopic fibrous capsular invasion and microscopic intrahepatic metastases, and earlier grade (T1 or T2) of American Joint Committee on Cancer tumor classification.Conclusions The MC should not be used to determine the applicability of LT as a first-line treatment for patients with HCC considered able to endure hepatectomy. However, modifying MC with some clinicopathological factors could satisfy the appropriate criteria for applying LT as a first-line treatment for these patients.     

Prognostic Significance of Complications after Curative Surgery for Gastric Cancer

Background

Postoperative complications such as anastomotic leakage were reported to be a major independent prognostic factor for long-term survival in gastrointestinal malignancies. This study sought to clarify the prognostic significance of postoperative inflammatory complications specifically for patients with gastric cancer.

Methods

This study included 1,395 patients who underwent curative resection for gastric cancer from 2005 to 2008. Complications were evaluated according to the Clavien-Dindo classification. Overall survival (OS) and disease-specific mortality (DSM) were compared between complication and no-complication groups. Presence of complications was modeled by the Cox proportional hazard model for OS and the Fine and Gray competing risk regression model for DSM to assess the correlation between complication and prognosis.

Results

The median follow-up time was 3.1 years. Two hundred seven patients (14.8 %) had complications of grade 2 or higher. Of 131 patients who died within this period, 87 died of gastric cancer. The 3-year OS in the complication group was 84.1 % compared to 93.1 % in the no-complication group (P < 0.0001). The cumulative incidence of DSM was also significantly worse in patients with complications (P < 0.0001). Multivariate analysis identified the same significant increasing risk of complication for both OS (hazard ratio 1.88; 95 % confidence interval 1.26–2.80) and DSM (hazard ratio 1.90; 95 % confidence interval 1.19–3.02).

Conclusions

Postoperative complications that can cause prolonged inflammation have an obvious impact not only on the OS but also on the DSM of patients with gastric cancer even if the tumor is resected curatively.     

Risk factors for small intestinal adenocarcinomas that are common in the proximal small intestine

The frequency of primary small intestinal adenocarcinoma is increasing but is still low. Its frequency is approximately 3% of that of colorectal adenocarcinoma. Considering that the small intestine occupies 90% of the surface area of the gastrointestinal tract, small intestinal adenocarcinoma is very rare. The main site of small intestinal adenocarcinoma is the proximal small intestine. Based on this characteristic, dietary animal proteins/lipids and bile concentrations are implicated and reported to be involved in carcinogenesis. Since most nutrients are absorbed in the proximal small intestine, the effect of absorbable intestinal content is a suitable explanation for why small intestinal adenocarcinoma is more common in the proximal small intestine. The proportion of aerobic bacteria is high in the proximal small intestine, but the absolute number of bacteria is low. In addition, the length and density of villi are greater in the proximal small intestine. However, the involvement of villi is considered to be low because the number of small intestinal adenocarcinomas is much smaller than that of colorectal adenocarcinomas. On the other hand, the reason for the low incidence of small intestinal adenocarcinoma in the distal small intestine may be that immune organs reside there. Genetic and disease factors increase the likelihood of small intestinal adenocarcinoma. In carcinogenesis experiments in which the positions of the small and large intestines were exchanged, tumors still occurred in the large intestinal mucosa more often. In other words, the influence of the intestinal contents is small, and there is a large difference in epithelial properties between the small intestine and the large intestine. In conclusion, small intestinal adenocarcinoma is rare compared to large intestinal adenocarcinoma due to the nature of the epithelium. It is reasonable to assume that diet is a trigger for small intestinal adenocarcinoma.     

Characteristics and Treatment Outcomes of Small-bowel Angioectasia in Systemic Sclerosis Patients: A Retrospective Observational Study

Objective Systemic sclerosis (SSc) is defined as an autoimmune disease presenting with fibrosis of various organs and vascular endothelial damage. Vascular lesions, including small-bowel angioectasias, are also frequently detected in SSc patients. Polidocanol injection (PDI) is a safe and effective hemostatic treatment for gastrointestinal bleeding. We evaluated the outcomes of PDI for small-bowel angioectasia in SSc patients. Methods We retrospectively evaluated 65 consecutive SSc patients (61 women; mean age, 64.3 years old) who underwent capsule endoscopy (CE) and/or double-balloon endoscopy at Hiroshima University Hospital between April 2012 and December 2019. Patients Patients were stratified according to the presence of small-bowel angioectasia. Among patients who underwent CE during the same period, those with small-bowel angioectasia without concomitant diseases were compared with SSc patients with small-bowel angioectasia. Clinical and endoscopic characteristics, treatment outcomes, and the incidence of metachronous small-bowel angioectasia after PDI were evaluated. Results SSc patients with small-bowel angioectasia exhibited significantly lower hemoglobin levels and a significantly higher incidence of skin telangiectasia than those without small-bowel angioectasia. On a multivariate analysis of the presence of small-bowel angioectasia, anemia and skin telangiectasia were significant independent factors. SSc patients with small-bowel angioectasia included a higher proportion of women and exhibited a significantly higher incidence of metachronous small-bowel angioectasia than X. The characteristics of small-bowel angioectasia and outcomes of PDI were not significantly different between the two groups. No post-treatment rebleeding cases or adverse events were noted. Conclusion CE should be performed for SSc patients with anemia and/or skin telangiectasia. PDI is effective for SSc patients with small-bowel angioectasia.     

Modified SH2 domain to phototrap and identify phosphotyrosine proteins from subcellular sites within cells

Spatial regulation of tyrosine phosphorylation is important for many aspects of cell biology. However, phosphotyrosine accounts for less than 1% of all phosphorylated substrates, and it is typically a very transient event in vivo. These factors complicate the identification of key tyrosine kinase substrates, especially in the context of their extraordinary spatial organization. Here, we describe an approach to identify tyrosine kinase substrates based on their subcellular distribution from within cells. This method uses an unnatural amino acid-modified Src homology 2 (SH2) domain that is expressed within cells and can covalently trap phosphotyrosine proteins on exposure to light. This SH2 domain-based photoprobe was targeted to cellular structures, such as the actin cytoskeleton, mitochondria, and cellular membranes, to capture tyrosine kinase substrates unique to each cellular region. We demonstrate that RhoA, one of the proteins associated with actin, can be phosphorylated on two tyrosine residues within the switch regions, suggesting that phosphorylation of these residues might modulate RhoA signaling to the actin cytoskeleton. We conclude that expression of SH2 domains within cellular compartments that are capable of covalent phototrapping can reveal the spatial organization of tyrosine kinase substrates that are likely to be important for the regulation of subcellular structures.     

DIRECT CHOLANGIOSCOPY USING A DOUBLE‐BALLOON ENTEROSCOPE: CHOLEDOCHOJEJUNOSTOMY WITH INTRADUCTAL BILIARY CARCINOMA

A 75‐year‐old man who underwent choledochojejunostomy for gallstones 30 years ago was hospitalized for general malaise. Abdominal computed tomography revealed marked dilation of the intrahepatic bile duct in the right lobe and an image of a hypervascular tumor. Endoscopic retrograde cholangiography using double‐balloon enteroscopy (DBE) showed a filling defect that was localized to the right hepatic bile duct. Furthermore, the scope was able to readily pass through the anastomosed site of the choledochojejunostomy and, therefore, we observed the interior of the bile duct using the same scope. We obtained an image showing a whitish, papillary‐like tumor, and a biopsy of the tumor rendered the pathology of intraductal papillary mucinous carcinoma. Direct cholangioscopy using DBE is a useful diagnostic tool, particularly in patients with a past history of choledochojejunostomy.     

Symptoms Predictive for Efficacy of Naftopidil in Patients with Benign Prostate Hyperplasia

Objectives: To evaluate the lower urinary tract symptoms predicting the efficacy of the α1‐adrenoreceptor (AR) antagonist naftopidil in patients with benign prostate hyperplasia. Methods: The efficacy of naftopidil was examined on the basis of changes in the international prostate symptom score (IPSS). All patients received naftopidil (50 mg/day) for 12 weeks. We defined a “responder” as a patient whose total IPSS improved by five or more points and assessed the lower urinary tract symptoms predicting the efficacy of treatment by performing multivariate and probit analyses. Results: Among 132 patients whose data could be analyzed, the efficacy rate was 50.8%. All IPSS items except the urgency score were significantly higher in the responders than the non‐responders before treatment, and all IPSS items were lower in the responders after treatment. In the responder group, significant improvements were observed in the total IPSS score, quality of life (QOL) index, maximum flow rate (Q_max), residual urine volume, and all IPSS items after treatment. In contrast, in the non‐responder group, no parameter except the QOL index improved significantly. The probit analysis demonstrated that the score for weak stream (≥3) or nocturia (≥4) in the IPSS were factors predicting an effective response to naftopidil treatment. Conclusions: Weak stream and/or nocturia are the key symptoms that predict the efficacy of naftopidil treatment in patients with benign prostatic hyperplasia. Those with a score of ≥3 for weak stream or of ≥4 for nocturia are expected to achieve a good response in the subjective symptoms with administration of naftopidil.