Increased insulin sensitivity and hypoinsulinemia in APS knockout mice

A tyrosine kinase adaptor protein containing pleckstrin homology and SH2 domains (APS) is rapidly and strongly tyrosine phosphorylated by insulin receptor kinase upon insulin stimulation. The function of APS in insulin signaling has heretofore remained unknown. APS-deficient (APS(-/-)) mice were used to investigate its function in vivo. The blood glucose-lowering effect of insulin, as assessed by the intraperitoneal insulin tolerance test, was increased in APS(-/-) mice. Plasma insulin levels during fasting and in the intraperitoneal glucose tolerance test were lower in APS(-/-) mice. APS(-/-) mice showed an increase in the whole-body glucose infusion rate as assessed by the hyperinsulinemic-euglycemic clamp test. These findings indicated that APS(-/-) mice exhibited increased sensitivity to insulin. However, overexpression of wild-type or dominant-negative APS in 3T3L1 adipocytes did not affect insulin receptor numbers, phosphorylations of insulin receptor, insulin receptor substrate-1, or Akt and mitogen-activated protein kinase. The glucose uptake and GLUT4 translocation were not affected by insulin stimulation in these cells. Nevertheless, the insulin-stimulated glucose transport in isolated adipocytes of APS(-/-) mice was increased over that of APS(+/+) mice. APS(-/-) mice also showed increased serum levels of leptin and adiponectin, which might explain the increased insulin sensitivity of adipocytes.     

Prognostic Factors in Endodontic Surgery Using an Endoscope: A 1 Year Retrospective Cohort Study

This retrospective study clarified the success rate of endoscopic endodontic surgeries and identified predictors accounting for successful surgeries. In this retrospective study, 242 patients (90 males, 152 females) who underwent endoscopic endodontic surgery at a single general hospital and were diagnosed through follow-up one year later were included. Risk factors were categorized into attributes, general health, anatomy, and surgery. Then, the correlation coefficient was calculated for the success or failure of endodontic surgery for each variable, the odds ratio was calculated for the upper variable, and factors related to the surgical prognosis factor were identified. The success rate of endodontic surgery was 95.3%, showing that it was a highly predictable treatment. The top three correlation coefficients were post, age, and perilesional sclerotic signs. Among them, the presence of posts was the highest, compared with the odds ratio, which was 9.592. This retrospective study revealed the success rate and risk factors accounting for endoscopic endodontic surgeries. Among the selected clinical variables, the presence of posts was the most decisive risk factor determining the success of endodontic surgeries.     

Laparoscopic pancreaticoduodenectomy combined with minilaparotomy

Laparoscopic pancreatic surgery is evolving rapidly; however, the surgical treatment of periampullary tumors is still fraught with challenges, such as technical difficulty and the appropriateness of oncologic treatment for these patients. We describe how we performed laparoscopic pancreaticoduodenectomy (LPD) combined with minilaparotomy successfully in six consecutive patients. This procedure consisted of two surgical phases: safe laparoscopic surgery, including the Kocher maneuver, tunneling behind the pancreatic neck, and dissecting along the uncinate process with magnified vision; and a secure open approach with complete skeletonization of the hepatoduodenal ligament and alimentary tract reconstruction, performed similarly to conventional pancreaticoduodenectomy, under direct visualization through the minilaparotomy. By performing this procedure, we combined a safe and secure minilaparotomy approach under direct vision with a less invasive laparoscopic approach providing a magnified image. Our experience demonstrates that LPD combined with minilaparotomy is technically feasible for selected patients with periampullary tumors.     

Clinical outcomes of definitive radiotherapy for patients with cT1aN0M0 esophageal cancer unsuitable for endoscopic resection and surgery

BackgroundStudies on the clinical outcomes of radiotherapy for clinical (c)T1aN0M0 (UICC-TNM Classification, Eighth Edition) esophageal cancer (EC) are limited. Therefore, this retrospective study aimed to clarify the clinical outcomes of definitive radiotherapy (RT) or chemoradiotherapy (CRT) for cT1aN0M0 EC unsuitable for endoscopic resection and surgery.MethodsPatients with cT1aN0M0 esophageal squamous cell carcinoma who underwent definitive RT or CRT between January 2009 and December 2020 were retrospectively reviewed. The initial response, toxicities, survival rates, recurrence patterns, and salvage treatments of the patients were evaluated. Initial response was measured using the Response Evaluation Criteria in Solid Tumors guideline. Toxicity was assessed and documented following the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Survival rates from the date of initiation of treatment were measured using the Kaplan–Meier method.ResultsTwenty patients treated with definitive RT or CRT were included in the study. The median follow-up duration was 55 months (range, 13–131 months). All patients achieved complete response to the initial treatment. Grade 3 acute toxicities observed esophagitis (10%), pneumonitis (5%), and leukopenia (5%). Late toxicities higher than grade 3 were not observed. The 1-, 3-, and 5-year overall and disease-specific survival rates were 100% and 100%, 83% and 100%, and 67% and 100%, respectively. No treatment-related deaths occurred. Among the 20 patients, 6 showed local recurrence and 2 showed metachronous recurrence. Seven patients underwent salvage endoscopic submucosal dissection (ESD), and one underwent argon plasma coagulation treatment. After the endoscopic treatment, no recurrences were observed.ConclusionsDefinitive RT or CRT was considered an alternative initial treatment for patients with cT1aN0M0 EC who were unsuitable for endoscopic resection and surgery.     

The dosimetric impact of respiratory breast movement and daily setup error on tangential whole breast irradiation using conventional wedge,field-in-field and irregular surface compensator techniques

To evaluate the dosimetric impact of respiratory breast motion and daily setup error on whole breast irradiation (WBI) using three irradiation techniques; conventional wedge (CW), field-in-field (FIF) and irregular surface compensator (ISC). WBI was planned for 16 breast cancer patients. The dose indices for evaluated clinical target volume (CTV_evl), lung, and body were evaluated. For the anterior-posterior (AP) respiratory motion and setup error of a single fraction, the isocenter was moved according to a sine function, and the dose indices were averaged over one period. Furthermore, the dose indices were weighted according to setup error frequencies that have a normal distribution to model systematic and random setup error for the entire treatment course. In all irradiation techniques, AP movement has a significant impact on dose distribution. CTV_evlD₉₅ (the minimum relative dose that covers 95 % volume) and V₉₅ (the relative volume receiving 95 % of the prescribed dose) were observed to significantly decrease from the original ISC plan when simulated for the entire treatment course. In contrast, the D₉₅, V₉₅ and dose homogeneity index did not significantly differ from those of the original plans for FIF and CW. With regard to lung dose, the effect of motion was very similar among all three techniques. The dosimetric impact of AP respiratory breast motion and setup error was largest for the ISC technique, and the second greatest effect was observed with the FIF technique. However, these variations are relatively small.     

Poor responses to tyrosine kinase inhibitors in a child with precursor B‐cell acute lymphoblastic leukemia with SNX2‐ABL1 chimeric transcript

In addition to BCR, various rare fusion partners for the ABL1 gene have been reported in leukemia. We have identified the fusion gene SNX2‐ABL1 in a pediatric case of acute lymphoblastic leukemia (ALL), which has only once previously been reported in an adult patient. Cytogenetic analysis detected this fusion gene arising from a t(5;9)(q22;q34) translocation. ALL cells carrying a SNX2‐ABL1 fusion exhibited a BCR‐ABL1+ ALL‐like gene expression profile. The patient poorly responded to dasatinib but partially responded to imatinib. Treatment using tyrosine kinase inhibitors requires further investigation to optimize the genotype‐based treatment stratification for patients with SNX2‐ABL1 fusion.