Exosomal miR-493 suppresses MAD2L1 and induces chemoresistance to intraperitoneal paclitaxel therapy in gastric cancer patients with peritoneal metastasis.

Intraperitoneal (IP) chemotherapy with paclitaxel (PTX) for gastric cancer (GC) with peritoneal metastasis (PM) is considered a promising treatment approach, however, there are no useful biomarkers to predict the efficacy of IP therapy. We examined the association between intra-peritoneal exosomes, particularly exosomal micro-RNAs (exo-miRNAs), and IP-chemo sensitivity. MKN45 cells that were cultured with intra-peritoneal exosomes from patients who did not respond to IP therapy with PTX (IPnon-respond group) exhibited resistance to PTX compared with exosomes from responding patients (IPrespond group) (p = 0.002). A comprehensive search for exo-miRNAs indicated that miR-493 was significantly up-regulated in exosomes from the IPnon-respond group compared with those collected from the IPrespond group. The expression of miR-493 in PTX-resistant MKN45 cells (MKN45PTX-res) was higher compared with that in MKN45. In addition, MKN45PTX-res cells exhibited lower MAD2L1 gene and protein expression compared with MKN45. Finally, miR-493 enhancement by transfection of miR-493 mimics significantly down-regulated MAD2L1 expression in MKN45 cells and reduced PTX sensitivity. Our results suggest that intra-peritoneal exo-miR-493 is involved in chemoresistance to PTX by downregulating MAD2L1 in GC with PM. Exo-miR-493 may be a biomarker for chemoresistance and prognosis of GC patients with PM and may also be a promising therapeutic target.

A gastroduodenal artery that branched from the celiac artery in gastrectomy: A rare case of an anatomical variant.

Understanding anatomical anomalies of the branch of the celiac artery for safe gastrectomy is important. We report a case of laparoscopic distal gastrectomy with D1+ lymph node dissection for early gastric cancer with a vascular anatomical anomaly of the celiac artery. A 45-year-old woman was referred to our hospital because of early gastric cancer. Computed tomography showed an anatomical variation of the gastroduodenal artery, which branched from the celiac artery. The celiac artery also branched into the left gastric artery, the splenic artery, and the common hepatic artery. Preoperative understanding of an unusual branch of the celiac artery enabled a safe laparoscopic surgery. There were no postoperative complications. The Adachi classification or Michel classification is used for an anatomical anomaly of the celiac artery, but to the best of our knowledge, this case has not been previously classified and is the first reported case.

Prognostic significance of the cachexia index in patients with unresectable advanced gastric cancer receiving palliative chemotherapy: a retrospective single-center study.

PURPOSE: To investigate the prognostic utility of the cachexia index (CXI) in unresectable advanced gastric cancer (UAGC). METHODS: The relationship between CXI and the outcomes was evaluated in 102 patients with UAGC who had received first-line palliative 5-fluorouracil-based chemotherapy between January 2012 and December 2021. RESULTS: The median survival time (MST) from first-line chemotherapy initiation was 16.2 months, and the cohort included 60 and 42 patients with high and low CXIs, respectively, based on the optimal CXI cutoff. The rates of patients with a performance status score of 0, recurrence, third-line chemotherapy, and all grade 3-4 side effects, including febrile neutropenia (FN), were significantly higher in the CXIhigh group than in the CXIlow group. The prognosis based on MST was significantly better in the CXIhigh group than in the CXIlow group (22.5 vs. 11.6 months, p < 0.001). According to a multivariate analysis, a low CXI and performance status score of 1-2 were poor prognostic factors. CONCLUSIONS: Patients with UAGC and a low CXI had poorer prognoses and more frequent grade 3-4 side effects, including FN, than those with a high CXI. Patients with UAGC and a low CXI should be carefully managed to control for side effects to receive subsequent treatment.

Perioperative Infusion Management for Adhesive Bowel Obstruction with Congenital Nephrogenic Diabetes Insipidus: A Case Report.

Congenital nephrogenic diabetes insipidus (CNDI) is a rare disease that results in polyuria due to decreased responsiveness to the antidiuretic hormone in the collecting ducts of the kidney. Without compensation by drinking large amounts of water, dehydration and hypernatremia can rapidly develop. We present a case of a patient originally diagnosed with CNDI who required surgery and a fasting period due to adhesive bowel obstruction. The patient was a 46-year-old man who was originally diagnosed with CNDI. He was prescribed trichlormethiazide but self-discontinued treatment in the process. His normal urine output was about 7,000-8,000 mL/day. He underwent robot-assisted radical cystectomy and uretero-cutaneostomy for bladder cancer. Two years later, he was hospitalized due to adhesive bowel obstruction. A 5% glucose solution was infused, and the dose was adjusted according to the urine volume and electrolytes. An adhesiotomy was performed due to recurrent bowel obstruction in a short period of time. A 5% glucose solution was used as the main infusion during the perioperative period. Once drinking water was resumed after surgery, urinary output and electrolytes were easily controlled. In conclusion, patients with CNDI should be given a 5% glucose solution as the primary infusion, and the infusion volume should be adjusted by monitoring daily urine output, electrolytes, and blood glucose levels. Infusion management is easier if oral intake is initiated as early as possible.

Impact of Robot-Assisted Minimally Invasive Esophagectomy for Esophageal Cancer: A Propensity Score-Matched Short-Term Analysis.

Background: We compared short-term clinical outcomes between robotic-assisted minimally invasive esophagectomy (RAMIE) and video-assisted thoracic esophagectomy (VATS-E) using propensity score-matched analysis. Methods: We enrolled 114 patients with esophageal cancer who underwent esophagectomy at our institution from January 2013 to January 2022. Propensity score matching was performed to minimize selection bias between the RAMIE and VATS-E groups. Results: After propensity score matching, 72 patients (RAMIE group, n = 36; VATS-E group, n = 36) were selected for analysis. No significant differences in clinical variables were observed between the two groups. The RAMIE group had a significantly longer thoracic operation time (313 ± 40 vs. 295 ± 35 min, P = 0.048), a higher number of right recurrent laryngeal nerve lymph nodes (4.2 ± 2.7 vs. 2.9 ± 1.9, P = 0.039), and a shorter postoperative hospital stay (23.2 ± 12.8 vs. 30.4 ± 18.6 days, P = 0.018) than the VATS-E group. The RAMIE group tended to have a lower rate of anastomotic leakage (13.9% vs. 30.6%) than the VATS-E group, although the difference was not statistically significant (P = 0.089). No significant differences were found in recurrent laryngeal nerve paralysis (11.1% vs. 13.9%, P = 0.722) or pneumonia (13.9% vs. 13.9%, P = 1.000) between the RAMIE group and the VATS-E group. Conclusion: Although RAMIE for esophageal cancer requires a longer thoracic surgery time, it might be a feasible and safe alternative to VATS-E for treating esophageal cancer. Further analysis is needed to clarify the advantages of RAMIE over VATS-E, especially in terms of long-term surgical outcomes.

A low cumulative perioperative prognostic nutritional index predicts poor long-term outcomes in patients with gastric cancer: A single-center retrospective study in Japan.

PURPOSE: Perioperative surgical stress and systemic inflammation resulting from complex interactions between cancer and the host play an important role in cancer progression. This retrospective study compared the prognostic impact of various perioperative cumulative inflammation- and nutrition-based markers in patients with gastric cancer (GC). METHODS: This study included 301 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery. Perioperative cumulative markers were calculated using the newly developed trapezoidal area method. RESULTS: The cumulative prognostic nutritional index (cum-PNI) had the highest area under the receiver operating characteristic (ROC) curve for predicting the overall survival (OS) as well as the relapse-free survival (RFS). The cum-PNI was significantly correlated with tumor-related factors, including tumor size, depth of invasion, lymph node metastasis, lymphatic involvement, vascular involvement, and TNM stage classification. The cum-PNI was also significantly correlated with surgical factors, including surgical approach, gastrectomy, lymphadenectomy, intraoperative blood loss, and postoperative complications. Furthermore, the OS and RFS were poorer in patients with a low cum-PNI (< 236.3) than in those with a high cum-PNI (> 236.3). A multivariate analysis indicated that a low cum-PNI was an independent prognostic indicator in patients with GC. CONCLUSIONS: The cum-PNI might be useful for predicting the prognosis and guiding the perioperative management of patients with GC.

Right thoracoscopic resection in the supine position for recurrent pretracheal lymph nodes after esophagectomy.

Mediastinal lymph node recurrence is often observed following esophageal cancer surgery; however, no treatment has been established for the same. Surgical resection is often considered for cases of recurrence in a single lymph node region, although the procedures and approaches vary depending on the recurrence site. Right thoracoscopic resection is rarely opted for owing to its high surgical difficulty. Herein, we report a successful case of right thoracoscopic resection in the supine position for recurrent pretracheal lymph nodes following esophagectomy. The intraoperative findings revealed few adhesions around the recurrent lymph nodes due to the initial surgery, and the recurrent lymph nodes were safely resected within a short period. The patient was discharged on postoperative day 4 without any complications, and there was no recurrence after 20 months. Thus, right thoracoscopic resection may be a promising treatment option for recurrent pretracheal lymph nodes after esophagectomy.

Usefulness of the Modified Frailty Index for Predicting Pneumonia Occurrence After Esophagectomy.

Background: Esophagectomy is an invasive and complication-prone surgical procedure. Therefore, a tool that can predict the occurrence of postoperative complications may be useful for perioperative management. In this study, we investigated whether the modified frailty index (mFI) could be a useful tool for predicting the postoperative complications of esophagectomy. Methods: In this study, 162 patients who underwent curative esophagectomy for esophageal squamous cell carcinoma from 2004 to 2019 at our institution were included. The patients were divided into the high mFI (≥ 0.27) and low mFI (< 0.27) groups, and the short-term postoperative outcomes of each group were examined retrospectively. Results: Regarding background factors, age and the American Society of Anesthesiologists physical status classification were significantly higher in the high mFI group (P = 0.049 and P = 0.002, respectively); however, the other items were not significantly different between the two groups. Regarding surgical outcomes, no significant differences in operative time, blood loss, and hospital stay were observed between the two groups. Regarding postoperative complications, pneumonia was significantly more common in the high mFI group (P = 0.035). In multivariate analysis, high mFI (P = 0.034) was an independent predictor of pneumonia, along with operative time ≥ 613 min (P = 0.03) and preoperative BMI < 20.48 (P = 0.006). Conclusion: The mFI is useful for predicting pneumonia after esophagectomy.

[A Case of Palliative Abdominoperineal Resection and Perineal Reconstruction by Gluteus Maximus Flap following Regrowth of Primary Anal Canal Cancer with the Perianal Skin Infiltration after CRT].

An 85-year-old woman who visited the hospital with sores on the perianal skin was diagnosed with squamous cell carcinoma of the anal canal(cT3N1aM0, cStage ⅢC). She received chemoradiotherapy(radiation total 54 Gy/30 Fr, mitomycin C/capecitabine). The tumor initially shrank, but regrowth of the primary lesion, extensive perianal skin infiltration, and the appearance of para aortic lymph node metastases was observed 6 months later. Laparoscopic abdominoperineal resection was performed to mitigate strong local symptoms. The perineal defect was repaired with bilateral gluteus maximus flap(V- Y flap). The operation prevented anal pain and improved ADL. The patient is currently undergoing chemotherapy 7 months after surgery. We report the case with a review of the literature in which ADL was improved by salvage surgery for tumor regrowth with severe local symptoms and distant metastases after chemoradiotherapy for squamous cell carcinoma of the anal canal.

Hybrid approach with laparoscopic wall-inversion surgery and single-incision intragastric surgery for intraluminal gastrointestinal stromal tumor: A case report.

Laparoscopic wedge resection (LWR) for intraluminal gastrointestinal stromal tumor (GIST) leads to excessive resection of normal gastric wall. We report a case of GIST around the cardia successfully treated with full-thickness partial resection using a hybrid approach of laparoscopic surgery and single-incision intragastric surgery (SIIGS). A 69-year-old woman had a 5 cm intraluminal GIST at the posterior wall around the cardia. Submucosal injection of glycerin and indigo carmine was performed with transoral endoscopy. Circumferential seromuscular incision followed by placement of seromuscular sutures to invert the lesion into the stomach was performed under laparoscopy. By SIIGS, resection of the inverted mucosa and retrieval of the tumor were completed. A hybrid approach consisting of laparoscopic wall-inversion surgery and SIIGS was useful for intraluminal GIST and may expand the indications for laparoscopic wall-inversion surgery by removing size limitations.

[A Case of Advanced Gastric Cancer-Recurrence of Skin Metastasis Nine Years after Surgery and Rectal Stenosis Due to Peritoneal Dissemination Ten Years Later].

A 70-year-old man previously underwent laparoscopic total gastrectomy for gastric cancer in 2010 and pathological diagnoses were pT4a, pN3, M0, pStage ⅢC. The postoperative adjuvant chemotherapy was interrupted due to nausea, but the patient had no apparent recurrence within 5 years after gastrectomy. In 2019, a swelling appeared from the left inguinal region to the scrotum, and MRI scan showed subcutaneous edematous changes in the same region. Biopsy showed adenocarcinoma and we diagnosed a recurrence of gastric cancer with skin metastasis. In November 2020, the patient complained of defecation disorder, and CT scan showed a circumferential wall thickening with contrast effect in the rectum. Although colonoscopy revealed rectal stenosis, biopsy specimen showed no malignant findings. We suspected rectal stenosis due to peritoneal dissemination of gastric cancer and performed a colostomy. Intraoperative findings showed that the rectal wall was remarkably thickened with serosal erythema. Adenocarcinoma cells were found from the cytology of ascites. The patient was treated with nab-paclitaxel plus ramucirumab, then treated with nivolumab after failure of first-line therapy.