Age-Associated Reduction of Sinus Macrophages in Human Mesenteric Lymph Nodes.

There are numerous macrophages and dendritic cells in lymph nodes (LNs). Recent studies have highlighted that sinus macrophages (SMs) in LNs possess antigen-presenting capabilities and are related to anti-cancer immune responses. In this study, we assessed the distribution of SMs in mesenteric LNs removed during surgery for colorectal cancer. A marked reduction of SMs was noted in elderly patients, particularly those over 80 years old. We observed a disappearance of CD169-positive cells in LNs where SMs were reduced. In silico analysis of publicly available single-cell RNA sequencing data from LNs revealed that CD169-positive macrophages express numerous genes associated with antigen presentation and lymphocyte proliferation, similar to dendritic cells' functions. In conclusion, our study demonstrates that SMs, potentially crucial for immune activation, diminish in the LNs of elderly patients. This reduction of SMs may contribute to the immune dysfunction observed in the elderly.

Patient vulnerability is associated with poor prognosis following upfront hepatectomy for colorectal liver metastasis.

BACKGROUND: With the rapid aging of populations worldwide, the number of vulnerable patients with liver metastasis from colorectal cancer has increased. This study aimed to examine the association between vulnerability and clinical outcomes in patients with colorectal liver metastasis (CRLM). METHODS: Consecutive 101 patients undergoing upfront hepatectomy for CRLM between 2004 and 2020 were included. The preoperative vulnerability was assessed using the Clinical Frailty Scale (CFS) score ranging from one (very fit) to nine (terminally ill), and frailty was defined as a CFS score of ≥ 4. A multivariable Cox proportional hazard regression model was utilized to investigate associations of frailty with disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). RESULTS: Of the 101 patients, 12 (12%) had frailty. Associations between frailty and surgical outcomes, namely, the incidence of 90-day mortality and postoperative complications, were not statistically significant (P > 0.05). In the multivariable analyses, after adjusting for clinical risk scores calculated using six factors (timing of liver metastasis, primary tumor lymph node status, number of liver tumors, size of the largest tumor, extrahepatic metastatic disease, and carbohydrate antigen 19-9 level) to predict recurrence following hepatectomy for CRLM, preoperative frailty was found to be an independent risk factor for DFS (hazard ratio [HR]:2.37, 95% confidence interval [CI] 1.06-4.72, P = 0.036), OS (HR:4.17, 95% CI 1.43-10.89, P = 0.011), and CSS (HR:3.49, 95% CI 1.09-9.60, P = 0.036). CONCLUSION: Preoperative frailty was associated with worse DFS, OS, and CSS after upfront hepatectomy for CRLM. Assessment and improvement of patient vulnerability may provide a favorable prognosis for patients with CRLM.

CXCL10 Expression in Human Colorectal Cancer Tissue and its Correlation With Serum Levels of CXCL10.

BACKGROUND/AIM: CXCL10, a member of the CXC chemokine family, plays a crucial role in immune response by facilitating the chemotaxis of CXCR3-positive immune cells. We examined the expression of CXCL10 to unravel its functional significance in colorectal cancer. MATERIALS AND METHODS: Bioinformatics analysis was performed to investigate CXCL10 expression and its clinicopathological relevance. Subsequently, we examined the correlation between the serum levels of CXCL10 and its expression within cancer tissues. RESULTS: Analysis of the TCGA database revealed that elevated CXCL10 expression in CRC tissues correlates with improved long-term survival and is inversely associated with lymph node infiltration and metastasis. Insights from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes further established a connection between increased CXCL10 and co-regulated gene expression with enhanced immune activation and regulation, mediated by the inhibition of the NOD-like receptor signaling pathway. Single-cell analysis pinpointed myeloid cells and macrophages as the primary sources of CXCL10. Immunohistochemical assessments revealed that a subset of cancer cells and macrophages are positive for CXCL10 expression. CXCL10-positive cells are predominantly located at the invasive front of the tumor. Intriguingly, our findings reveal an inverse correlation between serum CXCL10 levels and its expression in cancer tissues. CONCLUSION: The expression of CXCL10 may play a role in mediating the inflammatory responses at the invasive front in colorectal cancer and is observed to be inversely correlated with serum CXCL10 levels. It is pivotal to elucidate the distinct roles of CXCL10 in colorectal cancer, particularly different functions of cancer-tissue CXCL10 from serum CXCL10.

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.

[The Usefulness of RFA as a Conversion Therapy after Molecular Targeted Therapy for Advanced Hepatocellular Carcinoma-A Case of Long-Term Survival with Multidisciplinary Treatment].

In this study, we report a case in which molecular-targeted agents have been shown to be effective in the treatment of unresectable hepatocellular carcinoma(HCC), which has enabled a radical treatment, conversion therapy, and long-term survival with multimodality treatment including RFA. Case: A 61-year-old male, abdominal ultrasonography revealed a large liver tumor and multiple lesions mainly in the right lobe of the liver. He was diagnosed as having unresectable HCC, and treatment with sorafenib was initiated. After treatment, the tumor was clearly reduced in size and the lung metastases disappeared. Five years later, recurrence was observed at the treated site of S7/8, and RFA was performed again after TACE. The patient has survived for 8 years without recurrence.

Self-expanding metal stent placement and pathological alterations among obstructive colorectal cancer cases.

BACKGROUND: Experimental studies suggest that self-expanding metal stents (SEMSs) enhance the aggressive behavior of obstructive colorectal cancer. The influence of SEMS placement on pathological alterations remains to be elucidated. AIM: To determine whether SEMS placement is associated with molecular or pathological features of colorectal carcinoma tissues. METHODS: Using a nonbiased molecular pathological epidemiology database of patients with obstructive colorectal cancers, we examined the association of SEMS placement with molecular or pathological features, including tumor size, histological type, American Joint Committee on Cancer (AJCC)-pTNM stage, and mutation statuses in colorectal cancer tissues compared with the use of transanal tubes. A multivariable logistic regression model was used to adjust for potential confounders. RESULTS: SEMS placement was significantly associated with venous invasion (P < 0.01), but not with the other features examined, including tumor size, disease stage, mutation status, and lymphatic invasion. In both the univariable and multivariable models with adjustment for potential factors including tumor location, histological type, and AJCC-pT stage, SEMS placement was significantly associated with severe venous invasion (P < 0.01). For the outcome category of severe venous invasion, the multivariable odds ratio for SEMS placement relative to transanal tube placement was 19.4 (95% confidence interval: 5.24-96.2). No significant differences of disease-free survival and overall survival were observed between SEMS and transanal tube groups. CONCLUSION: SEMS placement might be associated with severe venous invasion in colorectal cancer tissue, providing an impetus for further investigations on the pathological alterations by SEMSs in colorectal cancer development.

Endometrial stromal sarcoma of the sigmoid colon: a case report and literature review.

Endometrial stromal sarcoma (ESS) is a rare mesenchymal tumor of the uterus that accounts for 7-25% of uterine sarcomas and < 1% of uterine tumors. Previously reported sites include the ovary, bowel wall, abdomen, peritoneum, pelvis, and vagina; however, ESS in the extrauterine area is rare. We report a rare case of endometrial stromal sarcoma that developed in the sigmoid colon along the gonadal vasculature, which was difficult to distinguish from colon cancer. A large polyp was found in the sigmoid colon of a 74-year-old woman during a routine medical examination and was diagnosed as tubular adenoma. On colonoscopy 7 months later, the tumor had grown and blocked the lumen, causing stenosis. She was referred to our hospital for surgery. Although detailed examination at our hospital did not yield a definitive diagnosis, bowel obstruction was considered likely and we performed laparoscopic low anterior resection under a preoperative diagnosis of sigmoid colon cancer. The tumor protruded into the sigmoid colon from the stump of the ovarian arteries and veins outside the intestinal tract. As the left ovarian artery and vein were involved in the tumor, we extracted them as a lump. The tumor was diagnosed as low-grade ESS (LG-ESS). She had a history of hysterectomy and left salpingo-oophorectomy for uterine myoma 25 years ago, and radiation therapy was performed after surgery for an unknown reason. The postoperative course was uneventful, and follow-up was continued at the request of the patient. We report a rare case of ESS infiltrating the sigmoid colon, which was probably a lesion derived from endometriosis of the ovarian arteriovenous stump remaining after surgery 25 years ago.

Impairment of Activities of Daily Living is an Independent Risk Factor for Recurrence and Mortality Following Curative Resection of Stage I-III Colorectal Cancer.

BACKGROUND: With aging of the population, the number of colorectal cancer patients with impairment of activities of daily living (ADLs) has increased. The Barthel index is a validated tool for assessing functional levels of ADLs. In this retrospective study, we aimed to examine associations of Barthel index scores with recurrence and mortality after curative resection of colorectal cancer. METHODS: We retrospectively analyzed data of 815 consecutive patients who had undergone curative resection of stage I-III colorectal adenocarcinoma between January 2009 and December 2017. Preoperative functional levels of ADLs were assessed prospectively using the Barthel index (range, 0 to 100; higher scores indicate greater independence). Recurrence-free survival (RFS) and overall survival (OS) were compared according to Barthel index scores. The Cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders. RESULTS: Of the 815 patients, Barthel index scores were 40 or lower in 129 (16%), 41-85 in 110 (13%), and 86 or more in 576 (71%). In multivariable analyses adjusting for potential confounders including age and disease stage, scores of 85 or lower on the Barthel index were independently associated with shorter RFS (multivariable HR: 1.74, 95% confidence interval: 1.28-2.37, P<0.001) and OS (multivariable HR: 2.10, 95% confidence interval: 1.45-3.04, P<0.001). CONCLUSIONS: Lower scores on the Barthel index are associated with shorter RFS and OS following resection of nonmetastatic colorectal cancer. Further studies are needed to establish treatment strategies for colorectal cancer patients with poor functional capacity.

Surgical resection of a ruptured transverse pancreatic artery aneurysm.

BACKGROUND: Visceral artery aneurysms are rare, but they may cause heavy bleeding and high mortality. In addition, aneurysms originating from the superior mesenteric artery (SMA) account for only 1% of visceral artery aneurysms. We report the rare case of a ruptured transverse pancreatic artery aneurysm originating from the SMA that required urgent surgical treatment. CASE PRESENTATION: A 66-year-old woman presented with acute back pain after lunch, and she was transported by ambulance. She had upper quadrant spontaneous pain and moderate tenderness, but no guarding or rebound pain. She had rheumatoid arthritis, and was taking 10 mg of steroids per day. Contrast-enhanced computed tomography demonstrated a retroperitoneal hematoma spreading to the ventral side of the left kidney and extravasation of contrast agent from a branch of the SMA. We diagnosed rupture of aneurysm. We conferred with our IVR team on treatment strategy for the ruptured aneurysm. In addition, we finally selected operation, since the branch of the SMA to the aneurysm was too thin and complex to conduct IVR. For this reason, we performed emergency simple aneurysmectomy of the transverse pancreatic artery. The postoperative course was relatively smooth. CONCLUSION: Rupture of a transverse pancreatic artery aneurysm originating from the SMA is rare. However, when diagnosing patients with acute abdomen or back pain, we should consider rupture of a visceral artery aneurysm. Endovascular treatment may currently be common for ruptured visceral artery aneurysms, but we should flexibly treat them according to the patient's condition and facility considerations.

The efficacy of adjuvant chemotherapy for resected high-risk stage II and stage III colorectal cancer in frail patients.

BACKGROUND: The number of frail patients with colorectal cancer (CRC) has increased. Despite evidence-based treatment guidelines, a large proportion of patients with resected CRC do not receive adjuvant chemotherapy in daily practice. This retrospective study aimed to examine the effect of adjuvant chemotherapy for CRC according to frailty. METHODS: We retrospectively analyzed data from 507 consecutive patients with curatively resected high-risk stage II or stage III CRC between 2009 and 2016. Frailty was assessed using the Clinical Frailty Scale (CFS): 1 (very fit) to 9 (terminally ill), and frailty was defined as CFS ≥ 4. Recurrence-free survival (RFS) and overall survival (OS) were compared between surgery alone and adjuvant chemotherapy in frail and non-frail patients. A cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders. RESULTS: Of the 507 patients, 194 (38%) were frail. There were no significant interactions between frailty and adjuvant chemotherapy regarding RFS (Pinteraction = 0.59) and OS (Pinteraction = 0.81). In multivariable analyses, associations of adjuvant chemotherapy with longer RFS and OS in frail patients (RFS, HR: 0.33, 95% CI 0.15-0.63; OS, HR: 0.23, 95% CI 0.08-0.54) were comparable to non-frail patients (RFS, HR: 0.36, 95% CI 0.22-0.58; OS, HR: 0.34, 95% CI 0.15-0.69). Frail patients receiving adjuvant chemotherapy were younger and had better nutritional status than those undergoing surgery alone (all P < 0.005). CONCLUSION: Selected frail patients with CRC may experience a similar survival benefit from adjuvant chemotherapy as non-frail patients. Clinical trials are needed to establish adjuvant chemotherapy for CRC in frail patients.

Two Asian families with gastric adenocarcinoma and proximal polyposis of the stomach successfully treated via laparoscopic total gastrectomy.

Family 1: a 39-year-old woman and her sister were admitted to our hospital for fundic gland polyps (FGPs). Their mother died of gastric cancer with FGPs. We performed repeated biopsies at close intervals, suspecting gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). After a 1-year follow-up, the sisters were diagnosed with gastric cancer with FGP. We performed laparoscopic total gastrectomies with D1+lymph node dissection. Promoter 1B (exon 1B) of the APC gene (chr5: 112,043,224 T>C) contained a point mutation. The sisters were subsequently diagnosed with GAPPS as per the mutational analysis. Family 2 (unrelated to Family 1): a-24-year-old woman was referred for epigastralgia. EGD revealed FGPs localized in the proximal stomach. Pathological biopsy results showed severe dysplasia and adenocarcinoma in situ. Her father was simultaneously diagnosed with FGPs with GC localized in the proximal stomach. We performed laparoscopic total gastrectomies with D1+lymph node dissection. They had the same gene mutation as the family 1. Here, we report two Asian families with GAPPS successfully treated via laparoscopic total gastrectomy.