Tumor stroma-derived ANGPTL2 potentiates immune checkpoint inhibitor efficacy.

Use of immune checkpoint inhibitors (ICIs) as cancer immunotherapy has advanced rapidly in the clinic. We recently reported that tumor stroma-derived angiopoietin-like protein 2 (ANGPTL2) has tumor suppressive activity by enhancing dendritic cell-mediated CD8+ T cell anti-tumor immune responses. However, a direct impact of ANGPTL2 on ICI anti-tumor effect remains unclear. Here, we use a murine syngeneic model to show that host ANGPTL2 facilitates CD8+ T cell cross-priming and contributes to anti-tumor responses to ICIs in this context. Importantly, our analysis of public datasets indicated that ANGPTL2 expression is associated with positive responses to ICI therapy by human melanoma patients. We conclude that ANGPTL2-mediated stromal cell crosstalk facilitates anti-tumor immunity and ICI responsiveness. These findings overall provide novel insight into ANGPTL2 anti-tumor function and regulation of ICI-induced anti-tumor immunity.

Extracellular water to total body water ratio, a novel predictor of recurrence in patients with colorectal cancer.

Background: Total body water (TBW) fraction, which accounts for 60% of body weight, is an important indicator of body composition, and the extracellular water to TBW ratio (ECW/TBW) is reportedly useful in predicting clinical outcomes of patients with organ disorders. We aimed to clarify the clinical impact of preoperative ECW/TBW status on survival outcomes in cancer patients. Methods: We used a database of 320 colorectal cancer (CRC) patients who underwent potentially curative resections. Preoperative ECW/TBW was measured using a bioelectrical impedance analysis (BIA), and its correlation with patient survival outcomes, clinicopathological factors, laboratory data, and comorbidities were analyzed. Results: A high preoperative ECW/TBW was significantly associated with poorer relapse-free survival (RFS; p = 0.001) and overall survival (OS; p = 0.003). A high ECW/TBW ratio was significantly associated with older age (p < 0.001), low BMI (p = 0.009), and right-sided tumors (p = 0.03). In a multivariate analysis, a high ECW/TBW significantly predicted a higher RFS mortality (HR: 2.07, 95% CI: 1.10-3.88, p = 0.024) and OS mortality (HR: 3.23, 95% CI: 1.25-8.36, p = 0.016). Furthermore, a high ECW/TBW was significantly associated with lower hemoglobin (p < 0.001) and albumin levels (p < 0.001), but not comorbidities. Conclusions: A high preoperative ECW/TBW was a predictive factor for recurrence and poorer overall survival independent of the tumor, node, and metastasis (TNM) stage. Our data suggest that preoperative evaluation of ECW/TBW using BIA might serve as a novel tool for developing CRC treatment strategies.

Prognostic value of 18F-fluorodeoxyglucose uptake in the bone marrow on pretreatment positron emission tomography/computed tomography in patients with esophageal cancer who underwent esophagectomy.

BACKGROUND: Increased 18F-fluorodeoxyglucose (FDG) uptake in the bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) clinically reflects increased BM metabolism owing to systemic inflammation, bacterial infection, anemia, and cytokine-producing tumors. The association between FDG uptake in the BM and prognosis after esophagectomy for esophageal cancer has not been investigated. METHODS: This study included 651 patients who underwent PET/CT before any treatment and McKeown esophagectomy for esophageal cancer between June 2007 and August 2021. The pretreatment degree of FDG uptake in the BM was evaluated using a visual assessment criterion. Patients were divided into low- and high-FDG uptake groups. We retrospectively investigated whether the degree of FDG uptake in the BM was associated with clinicopathological and surgical backgrounds, blood parameters, and prognosis. RESULTS: High FDG uptake in the BM was significantly associated with elevated white blood cell and neutrophil counts, increased C-reactive protein levels, decreased hemoglobin, serum albumin, and total cholesterol levels. High FDG uptake in the BM was an independent predictor of worse overall survival in clinical stages 0-II esophageal cancer (hazard ratio, 2.27; 95% confidence interval, 1.097-4.695; P = 0.027). Worse overall survival was also associated with advanced age, low American Society of Anesthesiologists physical status, an advanced clinical stage, and high intraoperative blood loss. CONCLUSION: Increased FDG uptake in the BM on pretreatment PET/CT may be a surrogate indicator of various clinically disadvantageous backgrounds and may act as a predictor of poor prognosis after esophageal cancer surgery.

Repeated intestinal perforations in vascular Ehlers-Danlos syndrome: a case report of a novel mutation in the COL3A1 gene.

BACKGROUND: Ehlers-Danlos syndrome is an inherited connective-tissue disorder characterized by skin hyperextensibility, joint hypermobility, and tissue fragility. Intestinal perforation is one of the fatal manifestations of this syndrome, and its management is complicated. CASE PRESENTATION: A 58-year-old woman with a familial history of Ehlers-Danlos syndrome visited the emergency department due to a sudden onset of lower abdominal pain. Plain abdominal computed tomography showed abdominal free air. We found a perforated descending colon and subsequently resected this lesion and performed ileostomy. Fifty-one days after this first operation, the patient had transverse colon perforation and thus underwent the Hartmann procedure as the second operation. In addition, she was diagnosed with small bowel perforation 53 days after the first operation and consequently underwent a third operation-partial resection of the jejunum with functional end-to-end anastomosis. Fifty-eight days after the first operation, she complained of acute abdominal pain. Plain abdominal computed tomography showed fluid collection near the jejunojejunal anastomosis. We detected dehiscence at the entry hole of the linear stapler during the operation and thus performed partial resection of the affected jejunum, followed by jejunostomy. The postoperative course of the fourth operation was uneventful. Genetic testing revealed a novel missense mutation (c.2095G>T, p.Gly699Cys) in the COL3A1 gene, which is presumed to be a pathogenic variant of vascular Ehlers-Danlos syndrome. CONCLUSION: Vascular Ehlers-Danlos syndrome should be considered in the case of repeated intestinal perforation. The identified missense mutation in the COL3A1 gene (c.2095G>T, p.Gly699Cys) might be a novel pathogenic variation causing vascular Ehlers-Danlos syndrome. Careful postoperative screening and multidisciplinary management are required.

The impact of the advanced lung cancer inflammation index on the outcomes of patients with metastatic colorectal cancer who receive chemotherapy.

BACKGROUND: Advanced lung cancer inflammation index (ALI) is reported to be a prognosticator in various cancer patients with chemotherapy. However, the clinical impact of the ALI on treatment strategies in metastatic colorectal cancer (mCRC) patients remains unclear. METHODS: A total of 356 patients, who received first-line chemotherapy for mCRC between April 2005 and November 2019 in a single institution, were retrospectively enrolled. The association of pretreatment ALI (calculated as follows: BMI × albumin value/neutrophil-to-lymphocyte ratio) status with clinicopathological factors and patient survival outcome was analyzed, using subgroup analysis. RESULTS: The ALI-low cases were significantly associated with female sex, more synchronous metastasis, multiple metastatic sites, less primary tumor resection, less liver resection after chemotherapy, and poor overall survival (OS). A multivariate Cox proportional hazards analysis clarified that the ALI-low status was independently associated with poor OS (HR: 1.78, 95% CI 1.27-2.48, P = 0.001), in addition to right side tumor, multiple metastatic sites, and the non-performance of liver resection after chemotherapy. A subgroup analysis revealed that primary tumor resection and the resection of liver metastases after chemotherapy could not improve the prognosis of ALI-low cases in comparison with ALI-high cases, and the type of first-line chemotherapy did not significantly affect the association between the prognosis and the ALI status. CONCLUSION: ALI comprehensively evaluates the prognostic host status and is a reliable prognosticator for the mCRC patients with chemotherapy. Calculating pretreatment ALI may serve as a cost-effective and easily available tool for constructing treatment strategies.

Conversion Surgery After Atezolizumab Plus Bevacizumab for Primary and Peritoneal Metastasis After Hepatocellular Carcinoma Rupture.

BACKGROUND/AIM: Conversion surgery (CS) following atezolizumab plus bevacizumab (Atez+Bev) is a treatment strategy for unresectable hepatocellular carcinoma (UR-HCC). Herein, we report a case of CS after transcatheter arterial embolization (TAE) and Atez+Bev for primary HCC with peritoneal metastases and multiple liver metastasis after HCC rupture. CASE REPORT: A 75-year-old man with a suspected ruptured HCC in segment 4b was referred to the National Hospital Organization Kumamoto Medical Center. TAE was performed to stop the bleeding. Subsequently, 15 courses of Atez+Bev were administered for UR-HCC with primary tumor, peritoneal metastasis, and multiple liver metastases. Multiple liver metastases and peritoneal metastasis resolved 7 months after initiation of Atez+Bev. The primary HCC had shrunk, but the patient decided not to continue treatment because of severe numbness in his fingers. Six months after stopping Atez+Bev, CS was performed because no new lesions were observed, and the patient wished to become cancer-free by resection of the remaining tumor. HCC was successfully resected, and he was discharged without any complications. The pathological findings demonstrated that there was no remnant viable HCC. CONCLUSION: We herein present a case of CS following TAE and Atez+Bev for unresectable and ruptured HCC. The patient did not require chemotherapy after CS and is alive and recurrence-free for 7 months.

Shanghai fever, a fatal enteric illness, in an adult patient with neutropenia caused by treatment-related myelodysplastic syndrome: a case report.

BACKGROUND: Shanghai fever is a rare community-acquired enteric illness with sepsis caused by Pseudomonas aeruginosa. Cases of Shanghai fever in pediatric patients have been reported; however, to the best of our knowledge, there are no reports of adult cases. CASE PRESENTATION: A 65-year-old man visited the emergency department with sudden onset of abdominal pain. He was diagnosed as treatment-related myelodysplastic syndrome after treatment of follicular lymphoma. Moderate tenderness in the middle right abdominal quadrants was noted. Computed tomography showed abdominal free air with a small amount of effusion to the surrounding edematous small intestine, and we performed emergency exploration. During operation, we found multiple bowel perforations with patchy necrotic lesions. The patient was admitted to an intensive care unit postoperatively. Blood culture showed Pseudomonas aeruginosa. His condition improved; however, on the 8th postoperative day, the abdominal drain tube showed turbid drainage. We performed re-operation and found anastomotic leakage with two new bowel perforations. After the re-operation, the patient showed signs of septic shock and his general condition got worse, and the patient died due to multiple organ failure on the 12th postoperative day. CONCLUSION: Shanghai fever may occur in an adult patient with neutropenia.

The advanced lung cancer inflammation index is a novel independent prognosticator in colorectal cancer patients after curative resection.

BACKGROUND: The advanced lung cancer inflammation index (ALI), which comprehensively evaluates the patient body composition and inflammation/nutritional status, is reportedly associated with the patient outcome in lung cancer. However, the clinical significance in colorectal cancer (CRC) patients after curative resection remains unclear. METHODS: A total of 813 CRC patients after curative resection between April 2005 and June 2019 in a single institution were retrospectively enrolled. The association of the preoperative ALI (calculated as follows: body mass index × albumin value/neutrophil-to-lymphocyte ratio) with clinicopathological factors, postoperative complications, and survival was analyzed. RESULTS: A low ALI was significantly associated with male gender, older age, a higher depth of tumor invasion, progressed TNM stage, and preoperative carcinoembryonic antigen (CEA) positivity. Both postoperative complications and severe complications occurred more frequently in the ALI-low group than in the ALI-high group (P < .001 and P < .001, respectively), especially postoperative complications in stage III patients (P < .001) and severe complications in stages II and III patients (P = .024 and P = .004, respectively). In addition, a low ALI was an independent predictor of a poor overall survival (hazard ratio: 2.30, 95% confidence interval: 1.52-3.50, P < .001) and relapse-free survival (hazard ratio: 1.73, 95% confidence interval: 1.22-2.44, P = .002), especially in older patients, and in patients without lymph node metastasis or severe postoperative complications. CONCLUSION: This study suggests that preoperative ALI may serve as a novel independent predictive index for severe postoperative complications and recurrence in CRC patients after curative resection.

Port site recurrence of esophageal adenocarcinoma after minimally invasive esophagectomy: a case report.

BACKGROUND: Port site recurrence has been observed after a variety of oncologic resection procedures. However, few have reported port site recurrence of esophageal cancer. CASE PRESENTATION: A 51-year-old man underwent minimally invasive esophagectomy for pT3(AD)N3M0 adenocarcinoma of the esophagus. One year after surgery, he presented with a rapidly growing tumor on the right thoracic wall. Contrast computed tomography demonstrated an enhancing tumor with uptake on positron emission tomography. We performed resection of the thoracic wall, including the skin and subcutis. The pathologic diagnosis was poorly differentiated adenocarcinoma, consistent with metastasis of esophageal origin. CONCLUSION: This was the first report on thoracic port site recurrence of esophageal adenocarcinoma. We recommend elimination of leakage around the thoracoscopic ports to prevent such recurrence. We should provide prudent postoperative clinical surveillance.

Presacral lymph node recurrence of rectal intramucosal adenocarcinoma after endoscopic mucosal resection: a case report.

BACKGROUND: The recurrence of endoscopically resected intramucosal colorectal cancer (CRC) is quite rare, and data regarding metastasis in intramucosal tumors are still lacking. We herein report a case of presacral lymph node recurrence of intramucosal rectal cancer after curative endoscopic resection. CASE PRESENTATION: A 53-year-old man underwent endoscopic mucosal resection (EMR) for rectal intramucosal adenocarcinoma. Thirty-nine months after the procedure, follow-up computed tomography (CT) revealed a swollen anterior sacral lymph node with an abnormal fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). He underwent laparoscopic low anterior resection (LAR) and was discharged on postoperative day 11 without any complications. The pathological examination confirmed solitary lymph node metastasis (moderately differentiated adenocarcinoma) without a residual tumor in the rectal epithelium. We diagnosed him with lymph node metastasis of rectal cancer. Pathological examination of the resected lymph node confirmed moderately differentiated adenocarcinoma. He has not experienced any re-recurrence in the 6 months since surgery. CONCLUSIONS: This is a rare case of local lymph node recurrence of intramucosal rectal cancer after successful EMR that was salvaged with surgery. Surveillance after successful endoscopic resection of rectal cancer using both endoscopy and CT is necessary.