Survival outcomes following salvage abdominoperineal resection for recurrent and persistent anal squamous cell carcinoma.

INTRODUCTION: The primary treatment for locoregional failure following chemoradiotherapy for squamous cell carcinoma of the anus (SCCA) is salvage abdominoperineal resection (APR). However, it is necessary to distinguish between recurrent and persistent diseases because of their varied pathologies. We aimed to clarify the survival outcomes following salvage APR for recurrent and persistent diseases and investigate the significance of salvage APR. MATERIALS AND METHODS: This multicentre retrospective cohort study used clinical data from 47 hospitals. All patients were diagnosed with SCCA and underwent definitive radiotherapy as the primary treatment between 1991 and 2015. Overall survival (OS) was compared between the following cohorts: salvage APR for recurrence, salvage APR for persistence, non-salvage APR for recurrence, and non-salvage APR for persistence. RESULTS: Five-year OS of salvage APR for recurrence, salvage APR for persistence, non-salvage APR for recurrence, and non-salvage APR for persistence were 75% (46%-90%), 36% (21%-51%), 42% (21%-61%), and 47% (33%-60%), respectively. OS of salvage APR for the recurrent disease was significantly higher than that for persistent disease (p = 0.00597). For recurrent disease, OS following salvage APR was significantly higher than that following non-salvage APR (p = 0.0204); however, for persistent disease, there was no significant difference between salvage and non-salvage APR (p = 0.928). CONCLUSION: Survival outcomes following salvage APR for persistent disease were significantly worse than that for recurrent disease. Salvage APR did not improve survival outcomes for persistent disease compared to non-salvage APR. These results will elicit a review of persistent disease treatment strategies.

Fecal microbiota in patients with a stoma decreases anaerobic bacteria and alters taxonomic and functional diversities.

Colorectal cancer (CRC) is one of the most common malignant diseases. Generally, stoma construction is performed following surgery for the resection of the primary tumor in patients with CRC. The association of CRC with the gut microbiota has been widely reported, and the gut microbiota is known to play an important role in the carcinogenesis, progression, and treatment of CRC. In this study, we compared the microbiota of patients with CRC between with and without a stoma using fecal metagenomic sequencing data from SCRUM-Japan MONSTAR-SCREEN, a joint industry-academia cancer research project in Japan. We found that the composition of anaerobes was reduced in patients with a stoma. In particular, the abundance of Alistipes, Akkermansia, Intestinimonas, and methane-producing archaea decreased. We also compared gene function (e.g., KEGG Orthology and KEGG pathway) and found that gene function for methane and short-chain fatty acids (SCFAs) production was underrepresented in patients with a stoma. Furthermore, a stoma decreased Shannon diversity based on taxonomic composition but increased that of the KEGG pathway. These results suggest that the feces of patients with a stoma have a reduced abundance of favorable microbes for cancer immunotherapy. In conclusion, we showed that a stoma alters the taxonomic and functional profiles in feces and may be a confounding factor in fecal microbiota analysis.

Retrospective cohort study of trifluridine/tipiracil (TAS-102) plus bevacizumab versus trifluridine/tipiracil monotherapy for metastatic colorectal cancer.

BACKGROUND: A previous phase I/II C-TASK FORCE study of trifluridine/tipiracil plus bevacizumab for patients with heavily pretreated metastatic colorectal cancer (mCRC) showed promising activity with an acceptable toxicity profile. This retrospective study aimed to investigate the safety and efficacy of trifluridine/tipiracil plus bevacizumab compared with trifluridine/tipiracil monotherapy in patients with heavily pretreated mCRC in clinical settings. METHODS: Records of patients with mCRC refractory to standard therapies who initiated trifluridine/tipiracil plus bevacizumab from January 2016 to March 2018 or trifluridine/tipiracil monotherapy from June 2014 to December 2015 were retrospectively reviewed at our institution. RESULTS: Totally, 60 patients received trifluridine/tipiracil plus bevacizumab and 66 received trifluridine/tipiracil monotherapy. All patients had previously received standard chemotherapy. Median progression-free survival (PFS) was 3.7 months [95% confidence interval (CI), 2.3-5.1] in the trifluridine/tipiracil plus bevacizumab group and 2.2 months (95% CI, 1.8-2.6) in the trifluridine/tipiracil monotherapy group [hazards ratio (HR) 0.69; 95% CI 0.48-0.99]. PFS rate at 16 weeks was 46.6% for the trifluridine/tipiracil plus bevacizumab group and 33.9% for the trifluridine/tipiracil monotherapy group. Although a relatively higher incidence of grade ≥ 3 neutropenia was observed in the trifluridine/tipiracil plus bevacizumab group than that in the other group (50.0% vs. 40.9%, p = 0.371), the incidence of febrile neutropenia was not high (3.3% vs. 7.8%, p = 0.444). CONCLUSIONS: In real-world settings, trifluridine/tipiracil plus bevacizumab prolonged PFS and helped achieve higher 16-week PFS rate compared with trifluridine/tipiracil monotherapy in patients with heavily pretreated mCRC with manageable toxicities. TRIAL REGISTRATION: Retrospectively registered.

[The Usefulness of Outpatient Pharmacy Services in Adjuvant Chemotherapy for Gastric Cancer].

Outpatient pharmacy services were established since June 2009 for educating about the signs and symptoms that required treatment, explaining how to receive an emergency service, improving a patient's adherence, and managing side effects. In this study, we evaluated the usefulness of one of our outpatient pharmacy services, which aims to help patients receiving adjuvant chemotherapy including S-1 monotherapy for gastric cancer. In total, 34 and 80 patients received S-1 monotherapy without or with the intervention of outpatient pharmacy services, respectively; additionally, the median ages of the former and latter were 68 and 65 years, respectively. The treatment completion rates(82.4% versus 67.5%)were similar between the 2 groups(odds ratio[OR]: 0.45, 95% confidence interval[CI]: 0.16-1.21, p=0.106). Their emergency visit rates were 23.5% and 8.8%(OR: 0.31, 95% Cl: 0.10-0.94, p<0.05). Emergency hospitalization was required for 8.8% and 0% of the population from each group(OR: 0.00, 95% CI: not significant, p<0.05). We suggest that outpatient pharmacy services are useful because they are likely to improve a patient's safety.

[Efficacy of Ipragliflozin in Patients with Steroid-Induced Hyperglycemia during Cancer Chemotherapy].

Steroid is a key drug in cancer chemotherapy-induced emesis. However, it may sometimes cause inadequately controlled hyperglycemia. Ipragliflozin is a novel selective sodium-dependent glucose cotransporter 2 inhibitor of urinary glucose excretion. In this case, we controlled steroid-induced hyperglycemia by administering ipragliflozin. The case was a 47-year-old man who was diagnosed with Stage IV esophageal cancer (T3N2M1). He had type 2 diabetes. He was treated with cisplatin (70 mg/m2; day 1) and 5-FU (700 mg/m2; days 1-4) as radiochemotherapy. Intravenous infusion of dexamethasone (9.9 mg) was administered on day 1, followed by additional doses (6.6 mg) for 3 days, as one of the emetic therapies. He received intensive insulin therapy during the first course of chemotherapy, but had Grade 3 hyperglycemia regardless. For the next treatment course, we additionally administered ipragliflozin along with dexamethasone. As a result, the hyperglycemia subsided to Grade 2. These findings suggest that ipragliflozin suppresses steroid-induced hyperglycemia.