Janus kinase inhibitor overcomes resistance to immune checkpoint inhibitor treatment in peritoneal dissemination of gastric cancer in C57BL/6 J mice.

BACKGROUND: Cancer immunotherapy aims to unleash the immune system's potential against cancer cells, providing sustained relief for tumors responsive to immune checkpoint inhibitors (ICIs). While promising in gastric cancer (GC) trials, the efficacy of ICIs diminishes in the context of peritoneal dissemination. Our objective is to identify strategies to enhance the impact of ICI treatment specifically for cases involving peritoneal dissemination in GC. METHODS: The therapeutic efficacy of anti-PD1, CTLA4 treatment alone, or in combination was assessed using the YTN16 peritoneal dissemination tumor model. Peritoneum and peritoneal exudate cells were collected for subsequent analysis. Immunohistochemical staining, flow cytometry, and bulk RNA-sequence analyses were conducted to evaluate the tumor microenvironment (TME). A Janus kinase inhibitor (JAKi) was introduced based on the pathway analysis results. RESULTS: Anti-PD1 and anti-CTLA4 combination treatment (dual ICI treatment) demonstrated therapeutic efficacy in certain mice, primarily mediated by CD8 + T cells. However, in mice resistant to dual ICI treatment, even with CD8 + T cell infiltration, most of the T cells exhibited an exhaustion phenotype. Notably, resistant tumors displayed abnormal activation of the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway compared to the untreated group, with observed infiltration of macrophages, neutrophils, and Tregs in the TME. The concurrent administration of JAKi rescued CD8 + T cells function and reshaped the immunosuppressive TME, resulting in enhanced efficacy of the dual ICI treatment. CONCLUSION: Dual ICI treatment exerts its anti-tumor effects by increasing tumor-specific CD8 + T cell infiltration, and the addition of JAKi further improves ICI resistance by reshaping the immunosuppressive TME.

Gallbladder strangulation caused by a fibrotic band due to chlamydia infection: A case report.

Acute cholecystitis, a very common disease, is usually caused by gallstone obstruction of the cystic duct. Meanwhile, strangulated cholecystitis is extremely rare, and it develops when the gallbladder is strangled by a band. It is very similar to gallbladder torsion in terms of imaging findings and obstruction of blood and biliary flow, and it requires emergency surgery. We herein report a case of a 90-year-old woman with gallbladder strangulation caused by a fibrotic band due to a chlamydia infection, and we also reviewed some literature on strangulated cholecystitis.

[A Case of Pathological Complete Response Achieved with Neoadjuvant DCS Therapy in Gastric Cancer].

A 77-year-old man with appetite loss was referred to our hospital. Upper gastrointestinal endoscopy and computed tomography(CT)revealed advanced gastric cancer in the antrum with duodenal and pancreatic invasion. After 6 courses of neoadjuvant docetaxel, cisplatin, and S-1(DCS)therapy, CT revealed marked tumor shrinkage. Distal gastrectomy was performed. Histopathological examination showed no residual tumor cells or lymph node metastasis, and thus, finally, pathological complete response was considered to have been achieved. The patient was doing well and disease-free 3 years later. Thus, neoadjuvant DCS therapy can be a promising treatment option for borderline resectable advanced gastric cancer.

Protein-losing enteropathy caused by a jejunal ulcer after an internal hernia in Petersen's space: A case report.

BACKGROUND: The incidence of internal hernias has recently increased in concordance with the popularization of laparoscopic surgery. Of particular concern are internal hernias occurring in Petersen's space, a space that is surgically created after treatment for gastric cancer and obesity. These hernias cause devastating sequelae, such as massive intestinal necrosis, fatal Roux limb necrosis, and superior mesenteric vein thrombus. In addition, protein-losing enteropathy (PLE) is a rare syndrome involving gastrointestinal protein loss, although its relationship with internal Petersen's hernias remains unknown. CASE SUMMARY: A 75-year-old man with a history of laparotomy for early gastric cancer developed Petersen's hernia 1 year and 5 mo after surgery. He was successfully treated by reducing the incarcerated small intestine and closure of Petersen's defect without resection of the small intestine. Approximately 3 mo after his surgery for Petersen's hernia, he developed bilateral leg edema and hypoalbuminemia. He was diagnosed with PLE with an alpha-1 antitrypsin clearance of 733 mL/24 h. Double-balloon enteroscopy revealed extensive jejunal ulceration as the etiology, and it facilitated minimum bowel resection. Pathological analysis showed extensive jejunal ulceration and collagen hyperplasia with nonspecific inflammation of all layers without lymphangiectasia, lymphoma, or vascular abnormalities. His postoperative course was unremarkable, and his bilateral leg edema and hypoalbuminemia improved after 1 mo. There was no relapse over the 5-year follow-up period. CONCLUSION: PLE and extensive jejunal ulceration may occur after Petersen's hernia. Double-balloon enteroscopy helps identify and resect these lesions.

Evaluation of the safety and efficacy of suction-tip forceps, a new tool for laparoscopic surgery, for gastric cancer.

INTRODUCTION: Laparoscopic surgery is a minimally invasive surgery; however, obstacles to its functional optimization remain. Surgical ports can accommodate only one instrument at a time so complex exchange manipulations are necessary during surgery which increases operation times and patient risk. We developed a new laparoscopic instrument that functions as both forceps and a suction tube, which renders intraoperative tool exchange unnecessary. This pilot study was undertaken to evaluate the safety and efficacy of this novel dual-function device in laparoscopic surgery for gastric cancer. METHODS: This single-center pilot study assessed patient safety during and after laparoscopic distal gastrectomy for gastric cancer with the suction-forceps using intraoperative video and clinical follow-up, respectively. To evaluate instrument efficacy, we measured the time interval between the start of any bleeding and the start of aspiration ("suction access time") and compared this time with that of a conventional surgical setup. RESULTS: In total 15 patients participated, with all procedures being successful. No excess tissue damage occurred during surgery. Suction access time was significantly shorter in cases of bleeding when the suction-tip forceps were used for aspiration (2.01 seconds) compared to an ordinary suction tube (12.5 seconds; P < .01). CONCLUSION: These findings suggest that our new suction-tip forceps are a useful, safe, and efficacious operative tool. This surgical innovation may considerably simplify gastric laparoscopic surgery. This pilot study was registered with Japan Clinical Trial Registration on 22 June 2017 (registration number: UMIN000027879).

Endoscopic Detorsion for Early Postoperative Roux Limb Torsion after Laparoscopic Gastrectomy: A Case Report and Literature Review.

Various types of obstruction can occur after a gastrectomy for gastric cancer. If proper treatment is not performed, such obstructions can lead to serious conditions. Early postoperative Roux limb torsion is a rare complication, and few reports of endoscopic treatment for this complication have been made. In the present report, we describe the endoscopic detorsion of Roux limb torsion in two patients. The first case was a 77-year-old woman who underwent a laparoscopic distal gastrectomy with Roux-en-Y (R-Y) reconstruction for early gastric cancer and a laparoscopic ileocecal resection (ICR) for early colorectal cancer. On the 12th day after the gastrectomy, a Roux limb torsion was observed. Endoscopic detorsion was performed, and the patient recovered. She was discharged on postoperative day 40. The second case was a 73-year-old man who underwent a laparoscopic-assisted total gastrectomy with a R-Y reconstruction for early gastric cancer. On the 8th day after the gastrectomy, a Roux limb torsion occurred at the Y-shaped anastomosis (Y-anastomosis). Endoscopic detorsion was performed, and the patient recovered. He was discharged on postoperative day 17. In summary, we experienced two cases in which an endoscopic reduction of a Roux limb torsion was performed at the Y-anastomosis after gastrectomy with R-Y reconstruction. This study presents a further review of these cases and a summary of the existing literature.

[Pathological Complete Response in Multiple Advanced Rectal Cancers with Neoadjuvant CapeOX plus BV Therapy-A Case Report].

A 70-year-old male with defecation difficulties was referred to our hospital. A colonoscopy and computed tomography revealed multiple advanced rectal cancers in the rectosigmoid and lower rectum with swollen lymph nodes. After 6 courses of neoadjuvant capecitabine and oxaliplatin and bevacizumab without radiotherapy(CapeOX plus BV therapy), a colonoscopy revealed that the tumors had significantly reduced. A low anterior laparoscopic resection with diverting ileostomy was performed. Histopathological examination showed no residual tumor cells or lymph node metastasis. A final diagnosis of pathological complete response was made. The patient has currently survived 1-year disease-free. Neoadjuvant CapeOX plus BV therapy can be a promising therapeutic option for locally advanced rectal cancer.