Complete Response To Tislelizumab In A Muscle-Invasive Urothelial Carcinoma After Surgery Associated With Tumor Mutational Burden High: A Case Report

Muscle-invasive urothelial carcinoma (MIUC) is a highly aggressive urothelial carcinoma. Radical cystectomy (RC) is standard of treatment, but still more than 50% patients with cancer invading the muscularis propria or involving the regional lymph nodes will have metastatic recurrence. In CheckMate274 study, programmed cell death-1 (PD-1) inhibitor nivolumab as adjuvant treatment has shown effective for patients with MIUC. Tislelizumab is an anti-human PD-1 monoclonal IgG4 antibody which was specifically engineered to minimize FcɣR macrophage binding to abrogate antibody-dependent phagocytosis. But there is no report of tislelizumab as adjuvant treatment in MIUC currently. Here, we report a case of MIUC in a patient with PD-L1-negative, microsatellite stable (MSS), high tumor mutational burden (TMB-H) obtained complete response (CR) receiving tislelizumab therapy after surgery. Progression-free survival (PFS) exceeded 6 months since tislelizumab treatment. To our knowledge, this is the first reported case of MIUC patient with PD-L1-negative, MSS and TMB-H who responded well to tislelizumab as adjuvant treatment. However, we still need more studies to assess the efficacy of tislelizumab as adjuvant treatment in MIUC and to confirm that TMB is a predicted biomarker of tislelizumab for efficacy.

Combination of extramural venous invasion and lateral lymph node size detected with magnetic resonance imaging is a reliable biomarker for lateral lymph node metastasis in patients with rectal cancer

Purpose Pathological extramural venous invasion (EMVI) is defined as the active invasion of malignant cells into veins beyond the muscularis propria in colorectal cancer. It is associated with poor prognosis and increases the risk of disease recurrence. Specific findings on MRI (termed MRI-EMVI) are reportedly associated with pathological EMVI. In this study, we aimed to identify risk factors for lateral lymph node (LLN) metastasis related to rectal cancer and to evaluate whether MRI-EMVI could be a new and useful imaging biomarker to help LLN metastasis diagnosis besides LLN size. Methods We investigated 67 patients who underwent rectal resection and LLN dissection for rectal cancer. We evaluated MRI-EMVI grading score and examined the relationship between MRI-EMVI and LLN metastasis. Results Pathological LLN metastasis was detected in 18 cases (26.9%), and MRI-EMVI was observed in 32 cases (47.8%). Patients were divided into two cohorts, according to LLN metastasis. Multivariate analyses demonstrated that higher risk of LLN metastasis was significantly associated with MRI-EMVI (P = 0.0112) and a short lateral lymph node axis (≥ 5 mm) (P = 0.0002). The positive likelihood ratios of MRI-EMVI alone, LLN size alone, and the combination of both factors were 2.12, 4.84, and 16.33, respectively. Patients negative for both showed better 2-year relapse-free survival compared to other patients (84.4% vs. 62.1%, P = 0.0374). Conclusions MRI-EMVI was a useful imaging biomarker for identifying LLN metastasis in patients with rectal cancer. The combination of MRI-EMVI and LLN size can improve diagnostic accuracy.

Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility via Opsin 3

Opsin photoreceptors outside of the central nervous system have been shown to mediate smooth muscle photorelaxation in several organs. We hypothesized that opsin receptor activation in the colon would have a similar effect and influence colonic motility. We detected Opsin 3 (OPN3) protein expression in the colonic wall and demonstrated that OPN3 was present in enteric neurons in the muscularis propria of the murine colon. Precontracted murine colon segments demonstrated blue light (BL) -mediated relaxation ex vivo. This photorelaxation was wavelength specific and was increased with the administration of the chromophore 9-cis retinal and a G protein receptor kinase 2 (GRK2) inhibitor. Light-mediated relaxation of the colon was not inhibited by L-NAME or tetrodotoxin (TTX). Furthermore, BL exposure in the presence of 9-cis retinal decreased the frequency of colonic migrating motor complexes (CMMC) in spontaneously contracting mouse colons ex vivo. These results demonstrate for the first time a receptor-mediated photorelaxation of colonic smooth muscle and implicate opsins as possible new targets in the treatment of spasmodic gastrointestinal dysmotility.

Efficacy and safety of a thermosensitive hydrogel for endoscopic submucosal dissection: An in vivo swine study

Injectable thermo-sensitive chitosan hydrogels have recently been developed for the use of submucosal fluids in endoscopic submucosal dissections (ESD). This study aimed to investigate the efficacy and safety of chitosan hydrogels during ESD. Submucosal fluids were administered as follows: 0.9% normal saline (NS), 0.4% hyaluronic acid (HA) and chitosan/β-glycerophosphate (CS/GP) hydrogel. Each solution was administered twice into the stomach and colon of a pig, with a total of 72 ESD procedures performed on 12 pigs. The injected volume and procedure-related parameters were recorded and analyzed. ESDs that created ulcers after 7 days were histologically compared. All ESD specimens were resected en bloc. The total injected volumes during ESD of the stomach (NS, 16.09±3.27 vs. HA, 11.17±2.32 vs. CS/GP, 9.44±2.33; p<0.001) and colon (NS, 9.17±1.80 vs. HA, 6.67±1.50 vs. CS/GP, 6.75±1.57; p = 0.001) were significantly different. Hydrogel showed significant differences from normal saline in terms of fluid power (mm2/vol; NS, 35.70±9.00 vs. CS/GP 57.48±20.77; p = 0.001) and consumption rate (vol/min; NS, 2.59±0.86 vs. CS/GP, 1.62±0.65; p = 0.013) in the stomach. Histological examination revealed preserved muscularis propria, although the chitosan hydrogel resulted in a partial inflammatory response, with a hypertrophied submucosal layer. Chitosan hydrogel was found to be superior to normal saline, with an efficacy similar to that of hyaluronic acid. Nonetheless, long-term histological changes should be evaluated before clinical implementation.

An adult case of a retroperitoneal isolated enteric duplication cyst with the imaging changes over time

Background Adult cases of retroperitoneal isolated enteric duplication cyst (IEDC) are rare, with only 17 case reports in the relevant literature. We herein present a case, which was characterized by changes in intra-cystic density on computed tomography (CT), which was safely resected by laparoscopic surgery. Case presentation The patient was a 60-year-old male who received abdominal CT to investigate the cause of increased serum CA19-9 levels. CT revealed a unilocular cystic mass located in the lower right retroperitoneum. The size increased from 5 to 10 cm in three and a half years and the CT value decreased from 101 Hounsfield Units (HU) to 20 HU. We performed laparoscopic surgical resection, because the possibility that the enlargement of the lesion represented malignant transformation could not be denied. The large cystic mass firmly adhered to the appendix and its mesentery via the retroperitoneum, the appendix was resected en bloc with the cystic lesion. Microscopically, it had no communication with the appendix, and had an intestinal wall structure of muscularis mucosae and muscularis propria. The final pathological diagnosis was IEDC in the retroperitoneal space. There was no histological evidence of malignancy. Conclusion When we encounter a retroperitoneal cystic lesion, we should consider the possibility of malignancy to determine the treatment strategy and perform a careful operation without breaking the cyst wall, irrespective of the preoperative diagnosis.

P-O06 A scoring system to support surgical decision-making for cardial submucosal tumors

Background Submucosal tunneling endoscopic resection (STER) and non-tunneling techniques are two alternative options for the treatment of cardial submucosal tumors (SMTs). We aimed to establish a regression model and develop a simple scoring system to help clinicians make surgical decisions for cardial submucosal tumors. Methods A total of 246 patients who suffered cardial SMTs and received endoscopic resection were included in this study. All of them were randomized into the training cohort (n = 147) or internal validation cohort (n = 99). Then, the scoring system was proposed based on multivariate logistic regression analysis in the training cohort and assessed in the validation cohort. Results Of 246 patients, 97 were treated with STER, and the others with non-tunneling endoscopic resection. In the training stage, four factors were weighted with points based on the β coefficient from the regression model, including irregular morphology (-2 points), ulcer (2 points), the direction of the gastroscope (-2 points for reversing direction and 1 point for entering direction), and originating from the muscularis propria (-2 points). The patients were categorized into low-score (&lt; -4), medium-score (-4 - -3) and high-score (&gt; -3) groups, and those with low scores were more likely to be treated with STER. Our score model performed satisfying discriminatory power in internal validation (Areas under the receiver-operator characteristic curve (AUC), 0.829; 95% confidence interval (CI), 0.694-0.964) and goodness-of-fit in the Hosmer-Lemeshow test (P = .4721). Conclusions This scoring system could provide clinicians the references for making decisions about the treatment of cardial submucosal tumors.

P-BN05 Solitary jejunal diverticulum: a rare unexpected cause of chronic pneumoperitoneum

Background Jejunal diverticula are rare acquired herniation of the mucosa and submucosa through the muscularis propria. They are asymptomatic in the majority of cases, however, they can present with non-specific abdominal symptoms and rarely complicate leading to acute abdomen. Perforation usually results in symptoms and signs of acute peritonitis and it is not an identifiable aetiology of chronic pneumoperitoneum. Computed tomography scan may identify intestinal wall oedema, air bubbles travelling through the mesentery, free intra-abdominal air and/or fluid . Radiological diagnosis requires high index of suspicion of such pathology. We report a case of an isolated jejunal diverticulum as a cause for aseptic chronic pneumoperitoneum . Methods A 77-year-old female was referred to the ambulatory emergency surgical unit (AESU) with a 4-month history of nonspecific abdominal pain, considerable weight loss, diarrhea, nausea and a few episodes of vomiting.Physical examination revealed no constitutional signs of sepsis and her abdomen was mildly distended but soft and nontender to palpation. Laboratory investigations were unremarkable. CT scan of her abdomen and pelvis on her first visit showed pneumoperitoneum with associated low volume ascites, which raised the possibility of sealed gastrointestinal perforation. In the absence of any clear signs of sepsis, a strategy of ambulatory, conservative management and follow up was chosen. Four months after her initial presentation our patient presented with ongoing vague abdominal symptoms with weight loss and failure to thrive. A CT colonogram described pneumoperitoneum and larger volume of ascites is in comparison to the previous CT scan. There was an unusual pattern of mural gas in some loops of small bowel in the left side of the abdomen that suggested pneumatosis. MDT decided to proceed with diagnostic laparoscopy. Results Laparoscopy exploration revealed odorless pneumoperitoneum, moderate amount of non-turbid bile stained serous ascites and thin fibrinous covering. We identified a jejunal diverticulum associated with mesenteric air bubbles and moderately enlarged reactive feeling lymph nodes in the diverticular segment . A small bowel resection with a primary side-to-side anastomosis, washout of the abdomen and cholecystectomy were done through a Kocher’s subcostal incision. She made an uneventful post-operative recovery and was discharged home well on day 4. Histopathological examination of the resected specimens confirmed the presence of a ruptured isolated jejunal diverticulum with a breach in muscularis propria and chronic cholecystitis in the gallbladder. Conclusions In summary, our case report highlights the importance of being aware of the possibility of perforated jejunal diverticula as a possible source of chronic pneumoperitoneum causing chronic nonspecific abdominal pain, diarrhea and unexplained weight loss. The surgical option of segmental resection and primary anastomosis was beneficial in this patient. However, calculating the risk benefit ratio remains the mainstay of the management plan, which, as ever, should be tailored to each patient’s general condition and fitness with appropriate counselling and consent.

Giant leiomyosarcoma of the transverse colon

Leiomyosarcoma (LMS) of the colon accounts for <1% of all colorectal malignancies. Our patient was a 72-year-old man with a history of aortic valvular disorder and congestive heart failure, who presented with an abdominal mass and no constitutional symptoms. The CT scan finding suggested a large tumour with both solid and cystic components. Intraoperatively, a portion of the involved colon was resected along with the tumour. Microscopically, the tumour was found to invade the muscularis propria layer of the transverse colon. The final diagnosis was LMS, FNCLCC grade 2 of 3 based on the histology and immunochemistry.