Palliative use of self-expanding metal stents in initially anticancer treatment-intolerant patients with esophageal cancer.

BACKGROUND: The post-insertion clinical course of esophageal self-expandable metal stents (SEMS) in initially frail patients with esophageal carcinoma (EC) with dysphagia remains unclear. This study aimed to assess dysphagia improvement and evaluate prognosis in initially frail patients with advanced EC following SEMS insertion. METHODS: We retrospectively reviewed EC patients with EC who underwent esophageal SEMS insertion at our institution between January 2014 and March 2023. Inclusion criteria comprised Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 3 or ECOG PS 2 for individuals aged ≥ 75 years and recommendation for best supportive care by a multidisciplinary team. RESULTS: Forty-six patients met the inclusion criteria. Among them, 37 patients (80.4%) were ≥ 75 years old, and 21 patients (45.7%) exhibited ECOG PS 3 or 4. Dysphagia score (DS) ≥ 3 was observed in 27 patients (58.7%). All esophageal SEMS insertions were successfully completed. Post-procedure, there were two fatal cases of aspiration pneumonia and one perforation incident. DS improved to ≤ 1 in 25 patients (54.3%), with multivariate analysis indicating DS 3-4 and Glasgow Prognostic Score (GPS) 1-2 as negative predictive factors. The median overall survival was 4.1 months (95% confidence interval 1.8-6.5). CONCLUSIONS: Esophageal SEMS insertion effectively alleviated dysphagia in initially frail EC patients, yet prognosis remained poor, with occurrences of some fatal adverse events. Careful selection of candidates for esophageal SEMS insertions is crucial in this demographic, particularly considering the challenges in improving dysphagia for patients with DS 3-4 and GPS 1-2.

Complete response induced by nivolumab monotherapy in gastric neuroendocrine carcinoma: a case report.

No standard treatment has been established for gastric neuroendocrine carcinoma (G-NEC). We present the case of a patient with recurrent G-NEC who achieved a complete response (CR) with nivolumab. A woman in her 70 s, with no significant medical or family history of illness, underwent an upper gastrointestinal endoscopy, which revealed a Borrmann type 2 tumor in the gastric antrum. Malignant tumor cells were not detected in the endoscopic biopsy samples; however, a malignant gastric tumor was strongly suspected. Therefore, surgical resection was performed, and the tumor was pathologically diagnosed as a G-NEC with liver metastases. Adjuvant etoposide plus carboplatin was administered for four cycles, but recurrence in the liver was observed 5 months after the completion of adjuvant chemotherapy. Ramucirumab plus paclitaxel and irinotecan were introduced as second and third-line treatments. After these treatments, the mesenteric lymph node metastases expanded. Tumor mutation burden (TMB) was low (five mutations/megabase), and microsatellite instability remained stable. However, programmed death-ligand 1 Combined Positive Score (CPS) was ≥ 5 in the resected sample. Therefore, nivolumab monotherapy was introduced as a fourth-line treatment. The mesenteric lymph node metastases exhibited swelling 3 weeks after the initiation of nivolumab; however, they rapidly shrank, and CR was later achieved. Treatment with nivolumab is currently ongoing for 12 months. This is the first report of nivolumab monotherapy in a patient with G-NEC who showed pseudo-progression. Even in TMB-low and microsatellite stable cases, nivolumab may be a viable option for patients with G-NEC.

An Evaluation of Renal Sinus Fat Accumulation Using the Anteroposterior Diameter of the Renal Sinus on a Computed Tomography Axial Image.

Backgrounds and objectives Renal sinus fat (RSF) is an indicator of obesity-related complications. However, the measurement and imaging process are complicated. For a simple measurement of RSF, we focused on the kidney's shape change caused by RSF accumulation. Thus, this study aimed to investigate whether the anteroposterior diameter of the renal sinus (APDRS) on a computed tomography (CT) axial image is useful for evaluating RSF accumulation. Materials and methods The correlation between APDRS and RSF was investigated in 98 outpatients who underwent abdominal CT. In addition, the correlation between APDRS or RSF and obesity indicators (estimated glomerular filtration rate from serum creatinine levels (eGFRcreat), body mass index (BMI), and visceral adipose tissue (VAT)) was also investigated. We classified patients based on the presence or absence of at least one underlying disease (chronic kidney disease (CKD), cardiovascular diseases (CVD), hypertension, and type 2 diabetes (T2D)) and investigated significant differences between the two groups at APDRS and RSF. The intraclass correlation coefficient (ICC) was also calculated for APDRS. Results There was a strong positive correlation between RSF and APDRS (r = 0.802, P < 0.01). The obesity indicators (eGFRcreat, BMI, and VAT) were correlated with RSF and APDRS (P < 0.01). Out of 98 outpatients, 48 had at least one underlying disease. There were statistically significant differences in APDRS and RSF between the patients with and without at least one of the underlying diseases caused by obesity (P < 0.01). The inter-reader ICC for the measurement of the APDRS was 0.98. Conclusions APDRS on a CT axial image may be useful for the evaluation of RSF accumulation.

Upper gastrointestinal endoscopic submucosal dissection using an ultrathin endoscope: a retrospective, single-center evaluation.

BACKGROUND: Recent studies have reported the therapeutic use of endoscopic submucosal dissection (ESD) using an ultrathin endoscope for targeting pharyngeal and distal side lesions in the stenosis or as a less invasive treatment via the nasal route. However, the effectiveness and safety of these treatments remain undetermined. Therefore, this study aimed to review treatment outcomes and discuss the advantages and precautions of the treatments based on our experience. METHODS: This study included 13 patients with 14 lesions who underwent 14 sessions of upper gastrointestinal ESD using an ultrathin endoscope between December 2021 and August 2023. The outcome measures included lesion background, en bloc resection rate, en bloc complete resection rates, and incidence of adverse events (including post-operative bleeding, intraoperative perforation, and delayed perforation). RESULTS: The lesions in the esophagus, stomach, and duodenum were eight, three, and three, respectively, and the median length (range) of each located lesion was 16.5 (6-26), 17 (9-36), and 10 (4-16) mm, respectively. En bloc resection and en bloc complete resection rates were 100 and 92.9%, respectively. The only adverse event was an intraoperative perforation observed during duodenal ESD, resulting from the assistant's inadvertent expansion of the SOUTEN at the final dissection stage. CONCLUSION: Our results demonstrate that ESD with an ultrathin endoscope effectively reaches lesions in difficult locations and enables treatment within a small working space. Therefore, ESD using an ultrathin endoscope is a treatment option for lesions located distally to gastrointestinal stenosis, highly fibrotic lesions, and duodenal tumors.

A case of an unreported point mutation in promoter 1B of the adenomatous polyposis coli gene, which is responsible for gastric adenocarcinoma and proximal polyposis of the stomach.

A 35-year-old woman of Asian descent with epigastralgia was referred to our hospital. Esophagogastroduodenoscopy revealed gastric cancer in the upper body and carpeting fundic gland polyposis in the fornix and body. Computed tomography revealed no metastases. Total colonoscopy and capsule endoscopy revealed no polyposis, except in the stomach. The patient was diagnosed with advanced gastric cancer and underwent open total gastrectomy. We speculated that her gastric cancer was a hereditary tumor due to its early onset and accompanying fundic gland polyposis. Germline multi-gene panel testing identified a single-nucleotide variant, c.-191 T > G, in exon 1B of the adenomatous polyposis coli gene, which can cause gastric adenocarcinoma and proximal polyposis of the stomach. To our knowledge, this is the first manuscript to report the variant (c.-191 T > G) in promoter 1B of the adenomatous polyposis coli gene, which is related to a predisposition to gastric adenocarcinoma and proximal polyposis of the stomach.

Efficacy of endoscopic submucosal resection with a ligation device for small rectal neuroendocrine tumor: study protocol of a multicenter open-label randomized control trial (BANDIT trial).

BACKGROUND: Endoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate. METHODS: This is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study. DISCUSSION: This is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022.

Combination of oligo-fractionated irradiation with nivolumab can induce immune modulation in gastric cancer.

BACKGROUND: Tumor-associated antigen (TAA)-specific CD8(+) T cells are essential for nivolumab therapy, and irradiation has been reported to have the potential to generate and activate TAA-specific CD8(+) T cells. However, mechanistic insights of T-cell response during combinatorial immunotherapy using radiotherapy and nivolumab are still largely unknown. METHODS: Twenty patients included in this study were registered in the CIRCUIT trial (ClinicalTrials.gov, NCT03453164). All patients had multiple distant metastases and were intolerance or had progressed after primary and secondary chemotherapy without any immune checkpoint inhibitor. In the CIRCUIT trial, eligible patients were treated with a total of 22.5 Gy/5 fractions/5 days of radiotherapy to the largest or symptomatic lesion prior to receiving nivolumab every 2 weeks. In these 20 patients, T-cell responses during the combinatorial immunotherapy were monitored longitudinally by high-dimensional flow cytometry-based, multiplexed major histocompatibility complex multimer analysis using a total of 46 TAAs and 10 virus epitopes, repertoire analysis of T-cell receptor ß-chain (TCRß), together with circulating tumor DNA analysis to evaluate tumor mutational burden (TMB). RESULTS: Although most TAA-specific CD8(+) T cells could be tracked longitudinally, several TAA-specific CD8(+) T cells were detected de novo after irradiation, but viral-specific CD8(+) T cells did not show obvious changes during treatment, indicating potential irradiation-driven antigen spreading. Irradiation was associated with phenotypical changes of TAA-specific CD8(+) T cells towards higher expression of killer cell lectin-like receptor subfamily G, member 1, human leukocyte antigen D-related antigen, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain, CD160, and CD45RO together with lower expression of CD27 and CD127. Of importance, TAA-specific CD8(+) T cells in non-progressors frequently showed a phenotype of CD45RO(+)CD27(+)CD127(+) central memory T cells compared with those in progressors. TCRß clonality (inverted Pielou's evenness) increased and TCRß diversity (Pielou's evenness and Diversity Evenness score) decreased during treatment in progressors (p=0.029, p=0.029, p=0.012, respectively). TMB score was significantly lower in non-progressors after irradiation (p=0.023). CONCLUSION: Oligo-fractionated irradiation induces an immune-modulating effect with potential antigen spreading and the combination of radiotherapy and nivolumab may be effective in a subset of patients with gastric cancer.