Prognostic Factors After Surgical Resection for Intrahepatic, Hilar, and Distal Cholangiocarcinoma

Background

The prognosis of patients with cholangiocarcinoma is unsatisfactory. Therefore, evaluation of prognostic factors and establishment of new therapeutic strategies are needed to improve their long-term survival. The aim of this study was to identify useful prognostic factors for patients with intrahepatic, hilar, and distal cholangiocarcinoma.

Materials and Methods

Records of 127 patients with cholangiocarcinoma (21 with intrahepatic cholangiocarcinoma, 50 with hilar cholangiocarcinoma, and 56 with distal cholangiocarcinoma) who underwent surgical resection were reviewed retrospectively. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate analysis.

Results

For all 127 patients, overall 1-, 3-, 5-year survival rates were 80, 51, and 40%, respectively. Univariate analysis revealed that adjuvant chemotherapy (P = .049), tumor differentiation (P = .014), lymph node metastasis (P < .001), surgical margin status (P < .001), UICC pT factor (P < .001), and UICC stage (P < .001) were associated significantly with survival. UICC pT factor (P = .007), adjuvant chemotherapy (P = .009), surgical margin status (P = .012), and lymph node metastasis (P = .014) remained independently associated with long-term survival by multivariate analysis. The 5-year survival rates of patients with or without positive surgical margins were 13 and 49%, respectively. The 5-year survival rates of patients treated with or without adjuvant chemotherapy were 47 and 36%, respectively.

Conclusions

R0 resection and adjuvant chemotherapy may be mandatory to achieve long-term survival for patients with cholangiocarcinoma.     

Treatment of iliac artery rupture during percutaneous transluminal angioplasty: a report of three cases

We report three cases of iliac artery rupture during percutaneous transluminal angioplasty (PTA). In all three cases, bleeding was temporarily controlled by inflating an angioplasty balloon at the site of bleeding. Two patients underwent subsequent surgical revascularization, and one underwent endovascular stent grafting but ultimately required a surgical bypass. Arterial rupture is a rare but potentially fatal complication of PTA. Although stent grafts for peripheral arteries are not yet covered by Japanese medical insurance, it is a useful treatment for arterial injury during PTA.     

Novel mesoporous silica-based antibiotic releasing scaffold for bone repair

Tissue engineering scaffolds with a micro- or nanoporous structure and able to deliver special drugs have already been confirmed to be effective in bone repair. In this paper, we first evaluated the biomineralization properties and drug release properties of a novel mesoporous silica–hydroxyapatite composite material (HMS–HA) which was used as drug vehicle and filler for polymer matrices. Biomineralization can offer a credible prediction of bioactivity for the synthetic bone regeneration materials. We found HMS–HA exhibited good apatite deposition properties after being soaked in simulated body fluid (SBF) for 7 days. Drug delivery from HMS–HA particle was in line with Fick’s law, and the release process lasted 12 h after an initial burst release with 60% drug release. A novel tissue engineering scaffold with the function of controlled drug delivery was developed, which was based on HMS–HA particles, poly(lactide-co-glycolide) (PLGA) and microspheres sintering techniques. Mechanical testing on compression, degradation behavior, pH-compensation effect and drug delivery behavior of PLGA/HMS–HA microspheres sintered scaffolds were analyzed. Cell toxicity and cell proliferation on the scaffolds was also evaluated. The results indicated that the PLGA/HMS–HA scaffolds could effectively compensate the increased pH values caused by the acidic degradation product of PLGA. The compressive strength and modulus of PLGA/HMS–HA scaffolds were remarkably high compared to pure PLGA scaffold. Drug delivery testing of the PLGA/HMS–HA scaffolds indicated that PLGA slowed gentamycin sulfate (GS) release from HMS–HA particles, and the release lasted for nearly one month. Adding HMS–HA to PLGA scaffolds improved cytocompatibility. The scaffolds demonstrated low cytotoxicity, and supported mesenchymal stem cells growth more effectively than pure PLGA scaffolds. To summarize, the data supports the development of PLGA/HMS–HA scaffolds as potential degradable and drug delivery materials for bone replacement.     

Combined Analysis of Dihydropyrimidine Dehydrogenase and Human Equilibrative Nucleoside Transporter 1 Expression Predicts Survival of Pancreatic Carcinoma Patients Treated with Adjuvant Gemcitabine Plus S-1 Chemotherapy after Surgical Resection

Background

Although postoperative adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) improves survival in some patients, the effectiveness varies by individual, and the results remain unsatisfying. The aim of this study was to investigate whether intratumoral dihydropyrimidine dehydrogenase (DPD) and human equilibrative nucleoside transporter 1 (hENT1) expression can predict the survival of PDAC patients treated with adjuvant gemcitabine plus S-1 (GEM+S-1) chemotherapy.

Methods

Intratumoral DPD and hENT1 expression were examined by immunohistochemistry in 86 PDAC patients who received adjuvant GEM+S-1 chemotherapy after surgical resection (all R0 or R1). Relationships between clinicopathologic factors, including DPD and hENT1 expression, and disease-free or overall survival were evaluated by univariate and multivariate analyses.

Results

DPD and hENT1 expression had no significant relationship with any other clinicopathologic factors. A multivariate disease-free survival analysis revealed that lymph node metastasis (hazard ratio [HR], 2.90: 95% confidence interval [CI], 1.51–5.90; P = 0.001), DPD expression (HR 2.47; 95% CI 1.37–4.44; P = 0.003), and hENT1 expression (HR 2.55; 95% CI 1.37–4.64; P = 0.004) as independent factors. Multivariate overall survival analysis also identified pT factor (HR 3.47; 95% CI 1.08–15.8; P = 0.03), lymph node metastasis (HR 2.08; 95% CI 1.01–4.57; P = 0.04), DPD expression (HR 1.98; 95% CI 1.06–3.71; P = 0.03), and hENT1 expression (HR 2.18; 95% CI 1.10–4.19; P = 0.02) as independent factors.

Conclusions

Combined analysis of DPD and hENT1 expression predicts the survival of PDAC patients treated with adjuvant GEM+S-1 chemotherapy.

     

Genetic Basis of Type 1 Diabetes: Similarities and Differences between East and West

Type 1 diabetes is a multifactorial disease caused by a complex interaction of genetic and environmental factors. The genetic factors involved consist of multiple susceptibility genes, at least five of which, HLA, INS, CTLA4, PTPN22 and IL2RA/CD25, have been shown to be associated with type 1 diabetes in Caucasian (Western) populations, as has recently been confirmed by genome-wide association studies. It has been proposed, however, that the contribution of these genes to type 1 diabetes susceptibility may be different in Asian (Eastern) populations. HLA and INS genes are consistently associated with type 1 diabetes in both Caucasian and Asian populations, but apparent differences in disease-associated alleles and haplotypes are observed between Japanese and Caucasian subjects. The association of CTLA4 with type 1 diabetes is concentrated in a subset of patients with autoimmune thyroid disease (AITD) in both Japanese and Caucasian populations, while the association of PTPN22 with type 1 diabetes in Japanese and most Asian populations is not as clear as in Caucasians. IL2RA/CD25 genes seem to be similarly distributed in type 1 diabetes patients in the two populations, whereas genetic heterogeneity may exist regarding SUMO4, with an association of the M55V variant with type 1 diabetes observed in Asians, but not in Caucasians. Genome-wide association studies (GWA) are largely outstanding for Asian populations but they are now underway in Japan. This review reports on the discovered similarities and differences in susceptibility genes for type 1 diabetes between East and West and discusses the most recent observations made by the involved investigators.     

Survival impact of distal pancreatectomy with en bloc celiac axis resection combined with neoadjuvant chemotherapy for borderline resectable or locally advanced pancreatic body carcinoma

BackgroundThe survival benefit associated with distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for patients with borderline resectable or locally advanced pancreatic body carcinoma is controversial. The aim of this study was to evaluate the impact of DP-CAR following neoadjuvant chemotherapy on survival in patients with borderline resectable or locally advanced pancreatic body carcinoma.MethodsMedical records of patients with pancreatic ductal adenocarcinoma who underwent distal pancreatectomy (DP, n = 102) and DP-CAR following neoadjuvant chemotherapy (n = 32) between 2008 and 2019 were analyzed retrospectively. Short- and long-term outcomes were compared between the two groups.ResultsAll patients who underwent DP-CAR had tumor contact with the celiac axis. Of these, 30 patients underwent preoperative embolization of the common hepatic artery. The pretreatment tumor size of patients who underwent DP-CAR was larger (P < 0.001), and rates of blood transfusion (P = 0.003) and postoperative complications (P = 0.016) were higher in patients who underwent DP-CAR compared with patients who underwent DP. The 5-year survival rate of patients who underwent DP and DP-CAR were 50.6% and 41.1%, respectively (median survival time, 65.9 vs 37.0 months). For all 134 patients, pretreatment serum CA19-9 levels (P < 0.001), adjuvant chemotherapy (P < 0.001), and lymph node status (P = 0.035) were independent prognostic factors of overall survival by multivariate analysis.ConclusionsDP-CAR following neoadjuvant chemotherapy for patients with borderline resectable or locally advanced pancreatic body carcinoma may bring the same survival impact as DP, despite increased morbidity.     

Obstruction of St. Jude Medical Valves in the Aortic Position: Plasma Transforming Growth Factor Type Beta 1 in Patients With Pannus Overgrowth

The study investigated the hypothesis that plasma transforming growth factor type beta 1 (TGF‐β1) initiated pannus overgrowth in cases with aortic prosthetic valve dysfunction (PVD). Patients with obstruction of an aortic St. Jude Medical valve in 26 cases (PVD group) and without obstruction in 48 cases (control group) were studied. Plasma TGF‐β1, the intensity of the prothrombin time–international normalized ratio (PT‐INR), and the interruption of an oral anticoagulant medicine were conducted. Plasma TGF‐β1 levels in the PVD group (87.7 ± 29.2 ng/mL) were significantly higher (P < 0.05) than in the control group (73.7 ± 25.2 ng/mL). The interruption of an oral anticoagulant medicine in 54% of the PVD group versus 12% of the control group was identified (P < 0.001). The mean value of the PT‐INR in the PVD group (1.75 ± 0.30) and control group (1.75 ± 0.30) was not significantly different (P = 0.82). In conclusion, elevated levels of plasma TGF‐β1 may play a role in pannus overgrowth.