Search

Elevated tumor-infiltrating T-cell density is associated with favorable outcomes in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). Here, we evaluated the significance of programmed cell death 1 (PD-1)-positive cells, regulatory T cells, and macrophages in response to CRT and prognosis.We assessed CD8+, PD-1+, FOXP3+, CD68+, and CD163+ intratumoral and stromal cell densities by immunohistochemistry using pre-treatment biopsies from 275 patients with rectal cancer treated with neoadjuvant CRT. We determined the impact of these measurements on response to CRT and survival. Response to CRT was determined by tumor regression grade (TRG) of surgical specimens, with good responders defined as TRG3-4.Intratumoral CD8+ and PD-1+ cell densities were significantly higher in good responders than in poor responders, whereas stromal CD68+ cell density was significantly lower in good responders as compared with poor responders. The multivariable analysis revealed high intratumoral CD8+ and PD-1+ cell densities to be independently associated with good responders (CD8: odds ratio [OR], 2.27; 95% confidence interval [CI], 1.21 - 4.34, P = .010; PD-1: OR, 1.97; 95%CI, 1.03 - 3.84, P = .039), and improved recurrence-free survival (CD8: hazard ratio [HR], 0.56; 95%CI, 0.32 - 0.98, P = .044; PD-1: HR, 0.37; 95%CI, 0.19 - 0.71, P = .002). Only high intratumoral CD8+ cell density was associated with improved overall survival (P = .022).Pre-treatment high intratumoral PD-1+ and CD8+ cell densities were independently associated with good response to CRT and improved recurrence-free survival, with high intratumoral CD8+ cell density additionally associated with improved overall survival. These values may serve as predictive and prognostic biomarkers in rectal cancer.

BACKGROUND The selection of endoscopic treatments for superficial non-ampullary duodenal epithelial tumors (SNADETs) is controversial. AIM To compare the efficacy and safety of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for SNADETs. METHODS We retrospectively analyzed the data of patients with SNADETs from a database of endoscopic treatment for SNADETs, which included eight hospitals in Fukuoka, Japan, between April 2001 and October 2017. A total of 142 patients with SNADETs treated with EMR or ESD were analyzed. Propensity score matching was performed to adjust for the differences in the patient characteristics between the two groups. We analyzed the treatment outcomes, including the rates of en bloc/complete resection, procedure time, adverse event rate, hospital stay, and local or metastatic recurrence. RESULTS Twenty-eight pairs of patients were created. The characteristics of patients between the two groups were similar after matching. The EMR group had a significantly shorter procedure time and hospital stay than those of the ESD group [median procedure time (interquartile range): 6 (3-10.75) min vs 87.5 (68.5-136.5) min, P < 0.001, hospital stay: 8 (6-10.75) d vs 11 (8.25-14.75) d, P = 0.006]. Other outcomes were not significantly different between the two groups (en bloc resection rate: 82.1% vs 92.9%, P = 0.42; complete resection rate: 71.4% vs 89.3%, P = 0.18; and adverse event rate: 3.6% vs 17.9%, P = 0.19, local recurrence rate: 3.6% vs 0%, P = 1; metastatic recurrence rate: 0% in both). Only one patient in the ESD group underwent emergency surgery owing to intraoperative perforation. CONCLUSION EMR has significantly shorter procedure time and hospital stay than ESD, and provides acceptable curability and safety compared to ESD. Accordingly, EMR for SNADETs is associated with lower medical costs.

Objectives: The colonic self-expandable metallic stent (C-SEMS) with a 9-French (Fr) delivery system allows for a small-caliber endoscope (SCE) to be used to treat malignant colonic obstruction. Despite the lack of evidence, the SCE has become popular because it is considered easier to insert than the large-caliber endoscope (LCE). We aimed to determine whether the SCE is more suitable than the LCE for C-SEMS placement. Methods: Between July 2018 and November 2019, 50 consecutive patients who were scheduled to undergo C-SEMS for colon obstruction were recruited in this study. Patients were randomized to the SCE or LCE group. The SCE and LCE were used with 9-Fr and 10-Fr delivery systems, respectively. The primary outcome was the total procedure time. Secondary outcomes were the technical success rate, complication rate, clinical success rate, insertion time, guidewire-passage time, stent-deployment time, and colonic obstruction-scoring-system score. Results: Forty-five patients (SCE group, n = 22; LCE group, n = 23) were analyzed. The procedure time in the LCE group (median, 20.5 min) was significantly ( p = 0.024) shorter than that in the SCE group (median, 25.1 min). The insertion time in the LCE group (median, 2.0 min) was significantly ( p = 0.0049) shorter than that in the SCE group (median, 6.0 min). A sub-analysis of the procedure difficulties showed that the insertion time in the LCE group (median, 5.0 min) was significantly shorter than that in the SCE group (median, 8.5 min). Conclusion: Both LCE and SCE can be used for C-SEMS; however, LCE is more suitable than SCE as it achieved a faster and equally efficacious C-SEMS placement as that of SCE. Clinical trial registration number: University Hospital Medical Information Network Clinical Trials Registry (UMIN 32748)

Background This study aimed to review and evaluate the surgical outcomes, particularly intraoperative severe blood loss and postoperative blood complications, of emergency gastrointestinal surgery in patients undergoing antithrombotic therapy (AT). Emergency surgeries for patients with antithrombotic medication have been increasing in the aging population. However, the effect of AT on intraoperative blood loss and perioperative complications remains unclear. Methods We retrospectively reviewed 732 patients who underwent emergency gastrointestinal surgery between April 2014 and March 2019. Patients were classified into AT group and Non-AT group, and propensity score-matched analysis was performed to compare the short surgical outcomes between the groups. Additionally, risk factors in severe estimated blood loss (EBL) and postoperative bleeding complications were assessed. Results Altogether, 64 patients received AT; 50 patients and 12, and 2 were given antiplatelet and anticoagulant, and both drugs, respectively. After propensity score matching, EBL (101 vs. 99 mL; p = 0.466) and postoperative complications (14 vs. 16 patients; p = 0.676) were similar between the groups (63 patients matched paired). Intraoperative severe bleeding (EBL ≥ 492 mL) occurred in 44 patients. Multivariate analysis using the full cohort revealed that antithrombotic drug use was not an independent risk factor for severe bleeding and postoperative bleeding complications. Conclusions This study demonstrated antithrombotic drugs do not adversely affect the perioperative outcomes of emergency gastrointestinal surgery.

Background This study aimed to evaluate the efficacy and the safety of polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G-CSF) for preventing neutropenia in metastatic colorectal cancer (mCRC) patients that received fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab (Bev) in clinical practice. Methods We retrospectively analyzed mCRC patients who received FOLFOXIRI plus Bev between December 2015 and December 2017. We evaluated the efficacy of PEG-G-CSF as preventing or treating grade 3 or 4 neutropenia, the overall response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.1, progression-free survival (PFS), overall survival (OS), and adverse events of FOLFOXIRI plus Bev based on the Common Terminology Criteria for Adverse Events version 4.0. Results A total of 26 patients (median age 53.5 years) were included. The ORR rate was 65.3%, the median PFS was 9.6 months (7.2–16.9), and the median OS was 24.2 months (13.6–NA). Grade 3 or 4 neutropenia occurred in 53.8% of the patients, and febrile neutropenia occurred in 7.7%. PEG-G-CSF was given to 77.0% of the patients, including prophylactically (n = 9) and after the development of grade 3 or 4 neutropenia (n = 11). No patients experienced grade 3 or 4 neutropenia after the administration of PEG-G-CSF. In seven of the nine patients who received PEG-G-CSF prophylactically (77.8%), no dose adjustment was required. Conclusions PEG-G-CSF is useful in preventing severe neutropenia in mCRC patients treated with FOLFOXIRI plus Bev.

Yusuke Kitagawa, Hiroki Osumi, Eiji Shinozaki, Yumiko Ota, Izuma Nakayama, Takeshi Suzuki, Takeru Wakatsuki, Takashi Ichimura, Mariko Ogura, Akira Ooki, Daisuke Takahari, Mitsukuni Suenaga, Keisho Chin, Kensei YamaguchiDepartment of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, JapanPurpose: Patients with gastrointestinal neuroendocrine carcinoma (GI-NEC) have poor prognoses. Although platinum-based combination chemotherapy is commonly used as first-line treatment, the benefit of amrubicin (AMR) and salvage chemotherapy in those who develop platinum-refractory GI-NEC remains unknown. This study aimed to evaluate the efficacy and safety of AMR monotherapy in patients with platinum-refractory GI-NEC.Patients and methods: Platinum-refractory GI-NEC patients who received AMR monotherapy between April 2012 and September 2017 were retrospectively analyzed. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. PFS and OS were estimated using Kaplan-Meier methods and compared using log-rank tests.Results: In total, 16 patients were enrolled. Of them, 13 (81.3%), 1 (6.2%), and 2 (12.5%) received cisplatin plus irinotecan, cisplatin plus etoposide, and fluoropyrimidine plus platinum, respectively, before AMR monotherapy. The primary sites of NEC included the esophagus (N=3, 18.8%), stomach (N=10, 62.5%), duodenum (N=1, 6.2%) and colorectum (N=2, 12.5%). Patients were administered a median of 3 (range, 1–15) cycles of AMR. The ORR was 6.3%, and the median PFS and OS were 2.9months (95% CI: 1.7–7.4) and 13.8months (95% CI: 7.9–23.5), respectively. Neutropenia was the most serious adverse event. Grade 3 or higher neutropenia and febrile neutropenia occurred in 50.0% and 6.2% of patients, respectively. Other nonhematological toxicities were not severe, and no treatment-related deaths occurred. The 10 patients who received subsequent chemotherapy after AMR had significantly longer OS than those who did not (17.3months vs 8.9months; p=0.018). The median PFS of those who received organ-specific subsequent chemotherapy after AMR was 3.8months, which was longer than that of those who received prior AMR.Conclusion: AMR is feasible with minimal side effects for platinum-refractory GI-NEC. Organ-specific subsequent chemotherapy after AMR may improve patient survival.Keywords: amrubicin monotherapy, platinum refractory, gastrointestinal neuroendocrine carcinoma

We describe a patient with a giant Brunner’s gland hamartoma in the duodenum who was safely treated by endoscopic mucosal resection (EMR). A 64-year-old woman visited our hospital for a workup of severe anaemia (haemoglobin level: 5 g/dL). Oesophagogastroduodenoscopy revealed a large pedunculated and elongated polypoid lesion measuring approximately 70 mm in longitudinal diameter, located at the anterior wall of the duodenal bulb . We diagnosed her as having gastrointestinal bleeding originating from this lesion. Although we considered surgical intervention initially, en bloc EMR, a less invasive treatment, was finally accomplished safely by placing endoclips before resection. The histological examination of the specimen revealed a hamartomatous lesion consisting of Brunner’s glands with cystic change and adipose tissue separated by the septa of smooth muscle fibers. Ultimately, we diagnosed her as having Brunner’s gland hamartoma. Notably, there were tiny foci of heterotopic pancreatic tissue containing islets and duct epithelium. Although this type of lesion is benign, a larger one may cause clinical symptoms such as obstruction or bleeding, and thus, local resection is preferable.