Fifty-Year Trend Towards Suppression of Wolbachia-Induced Male-Killing by Its Butterfly Host, Hypolimnas bolina

Some intracellular symbionts of arthropods induce a variety of reproductive alterations in their hosts, and the alterations tend to spread easily within the host populations. A few cases involving the spread of alteration-inducing Wolbachia bacteria in natural populations with time have been reported, but the investigations on the increasing trend in counteracting the bacterial effect on hosts in natural populations (i.e., increased resistance in hosts against the alterations) have been limited. In the present study, the prevalence of an alteration, killing of male Hypolimnas bolina (L.) (Lepidoptera: Nymphalidae) butterflies by their inherited Wolbachia strain in the wild in Japan, was surveyed over a continuous 50-year period, which is far longer than ever before analyzed in studies of dynamics between reproductive alteration-inducing symbionts and their host arthropods. Thus, the results in this study provide the first instance of a long-term trend involving a change in reproductive alteration; and it strongly suggests a change in the opposite direction (i.e., suppression of male-killing) in natural populations. This change in the current combination of the Wolbachia and butterflies appears to be dependent upon the host taxon (race)

Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations

Background & Aims Biliary tract cancers (BTCs) are clinically and pathologically heterogeneous and respond poorly to treatment. Genomic profiling can offer a clearer understanding of their carcinogenesis, classification and treatment strategy. We performed large-scale genome sequencing analyses on BTCs to investigate their somatic and germline driver events and characterize their genomic landscape. Methods We analyzed 412 BTC samples from Japanese and Italian populations, 107 by whole-exome sequencing (WES), 39 by whole-genome sequencing (WGS), and a further 266 samples by targeted sequencing. The subtypes were 136 intrahepatic cholangiocarcinomas (ICCs), 101 distal cholangiocarcinomas (DCCs), 109 peri-hilar type cholangiocarcinomas (PHCs), and 66 gallbladder or cystic duct cancers (GBCs/CDCs). We identified somatic alterations and searched for driver genes in BTCs, finding pathogenic germline variants of cancer-predisposing genes. We predicted cell-of-origin for BTCs by combining somatic mutation patterns and epigenetic features. Results We identified 32 significantly and commonly mutated genes including TP53 , KRAS , SMAD4 , NF1 , ARID1A , PBRM1 , and ATR , some of which negatively affected patient prognosis. A novel deletion of MUC17 at 7q22.1 affected patient prognosis. Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes such as BRCA1 , BRCA2 , RAD51D , MLH1 , or MSH2 were detected in 11% (16/146) of BTC patients. Conclusions BTCs have distinct genetic features including somatic events and germline predisposition. These findings could be useful to establish treatment and diagnostic strategies for BTCs based on genetic information. Lay summary We here analyzed genomic features of 412 BTC samples from Japanese and Italian populations. A total of 32 significantly and commonly mutated genes were identified, some of which negatively affected patient prognosis, including a novel deletion of MUC17 at 7q22.1 . Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes were detected in 11% of patients with BTC. BTCs have distinct genetic features including somatic events and germline predisposition

FoundationOne CDx detected an uncovered variant of epidermal growth factor receptor exon 19 deletion by Oncomine Dx target test in a patient with lung adenocarcinoma

A non-smoker woman with advanced lung adenocarcinoma was referred to us. The Oncomine Dx target test (ODxTT), a next-generation sequencing (NGS)-based hot spots panel test, did not detect any driver mutations, so we treated her with chemo-immunotherapy. After second-line chemotherapy, we performed FoundationOne CDx, a NGS-based comprehensive genomic profiling (CGP) test, and identified a rare variant of epidermal growth factor receptor exon 19 deletion that had not been covered by ODxTT. This case highlights the importance of considering the indication of a CGP test for patients who are likely to harbor driver mutations, even when ODxTT fails to detect any

Postoperative Concurrent Daily Low-dose Cisplatin-based Chemoradiation Improves the Prognosis of Patients with Pathologic T2b or N1 Cervical Cancer

Aim: To determine the effectiveness of postoperative concurrent daily low-dose cisplatin-based chemoradiation (CCRT) in patients with high-risk cervical cancer. Patients and Methods: Patients with stage IB, IIA, or IIB cervical cancer who were initially treated with radical hysterectomy and pelvic lymphadenectomy, and were proven to have pelvic lymph node metastasis (pN1) or microscopic involvement of the parametrium (pT2b), participated in this study. Thirty-one patients received adjuvant CCRT with daily low-dose (6-8.5 mg/m2) cisplatin (daily CCRT group). A non-randomised control group of 44 patients received adjuvant radiotherapy alone (RT group). Results: Overall survival (OS) at 4 years was 61% in the RT group and 91% in the daily CCRT group (p=0.004). Hazard ratio for poorer recurrence-free survival (RFS) in the RT group vs. the CCRT group was 7.9 (p=0.006). In the daily CCRT group, daily cisplatin chemotherapy was successfully completed in 27 out of 31 patients, although toxicity of grade ≥3 was found in 29% for neutropenia and 17% for gastrointestinal tract toxicity. Conclusion: Postoperative adjuvant CCRT with daily low-dose cisplatin improved RFS and OS of pT2b or pN1 patients, with acceptable compliance

Magnesium Hydroxide Nanoparticles Improve the Ocular Hypotensive Effect of Twice Daily Topical Timolol Maleate in Healthy Dogs

Timolol maleate (TM), a beta-adrenergic receptor antagonist, is widely used for canine antiglaucoma eye drops; however, its bioavailability is <5%. Our previous study revealed that magnesium hydroxide nanoparticles (nMH) have potency in improving the bioavailability of fixed-combined TM in rodent models. This study aimed to investigate whether the fixed combination with nMH improves the ocular hypotensive effect of TM and affects pupil size (PS), heart rate (HR), and mean arterial pressure (MAP) in clinically healthy dogs. Five clinically healthy dogs were administered topical saline, commercial 0.5% TM, and a 0.01% or 0.1% nMH–0.5% TM fixed combination (0.01% or 0.1% nMH–TM) twice daily in one eye for 7 days with at least a 28-day interval. The changes from baseline were calculated and were statistically analyzed for each drug. IOP was significantly reduced in both 0.01% and 0.1% nMH–TM-treated-dogs compared with saline- and TM-treated dogs. Meanwhile, 0.01% and 0.1% nMH did not exacerbate the side effects of TM. From these results, nMH improved the ocular hypotensive effect of TM without enhancing side effects. Topical nMH–TM is potentially more effective for canine ocular hypotensive eye drops than TM

Transperineal total mesorectal excision for rectal cancer on the residual rectum after multiple abdominal surgeries in a patient with Crohn's disease: a case report

Background: The improved prognosis of Crohn's disease may increase the opportunities of surgical treatment for patients with Crohn's disease and the risk of development of colorectal cancer. We herein describe a patient with Crohn's disease and a history of multiple surgeries who developed rectal stump carcinoma that was treated laparoscopically and transperineally. Case presentation: A 51-year-old man had been diagnosed with Crohn's disease 35 years earlier and had undergone several operations for treatment of Crohn's colitis. Colonoscopic examination was performed and revealed rectal cancer at the residual rectum. The patient was then referred to our department. The tumor was diagnosed as clinical T2N0M0, Stage I. We treated the tumor by combination of laparoscopic surgery and concomitant transperineal resection of the rectum. While the intra-abdominal adhesion was dissected laparoscopically, rectal dissection in the correct plane progressed by the transperineal approach. The rectal cancer was resected without involvement of the resection margin. The duration of the operation was 3 h 48 min, the blood loss volume was 50 mL, and no intraoperative complications occurred. The pathological diagnosis of the tumor was type 5 well- and moderately differentiated adenocarcinoma, pT2N0, Stage I. No recurrence was evident 3 months after the operation, and no adjuvant chemotherapy was performed. Conclusion: The transperineal approach might be useful in patients with Crohn's disease who develop rectal cancer after multiple abdominal surgeries