[A Case of Rectal Neuroendocrine Carcinoma Treated with Multidisciplinary Therapy but with a Poor Prognosis].

A 70-year-old man presented to our hospital with weight loss. A colonoscopy revealed advanced cancer in the lower rectum. Computed tomography showed a tumor larger than 5 cm in the lower rectum with metastasis to the right lateral lymph node. The patient was diagnosed with advanced locally rectal cancer, and chemoradiotherapy(35 Gy plus S-1)was added after 6 courses of mFOLFOX6, and laparoscopic abdominal perineal resection and right lateral lymph nodes dissection were performed. Histopathological examination revealed endocrine cell carcinoma(pT3[A], pN0, M0, pStage Ⅱa). Four months after the operation, recurrence was found in the pelvis, lymph nodes, and lungs, and he died 9 months after the operation. Neuroendocrine carcinoma is relatively rare, so the further accumulation of cases and establishment of treatment methods are desired.

[A Case of Laparoscopic Abdominoperineal Resection of Anorectal Malignant Melanoma].

A 56-year-old woman with complaints of anal bleeding and pain visited our hospital, and an elastic soft mass was detected in the anal canal on digital examination.Colonoscopy showed a black Isp polypoid lesion with a black pit from the anal canal to the lower rectum(P-Rb).She was diagnosed with malignant melanoma based on colonoscopic biopsy.Tumor marker levels(CEA, CA19-9)were not increased.No distant metastasis was detected on abdominal CT.No direct invasion was detected on MRI of the pelvis.The patient underwent laparoscopic abdominoperineal resection and D2 lymph node dissection. Histopathology showed a malignant melanoma(pT4b, N0, M0, pStageⅡC).The patient received interferon therapy as adjuvant therapy.There is no sign of recurrence 2 years and 1 month after the surgery.Anorectal malignant melanoma is relatively rare, so establishment of therapy by the accumulation of cases is desired.

Effect of Abdominal Aortic Calcification on Recurrence Following Initial Hepatectomy for Colorectal Liver Metastases.

BACKGROUND/AIM: The aim of the study was to analyze the association between abdominal aortic calcification (AAC) and patient prognosis following resection of colorectal liver metastases (CRLM). AAC potentially reflects intrahepatic immunity and is involved in tumor development and progression. However, the clinical effects of AAC on colorectal cancer (CRC) prognosis after curative-intent liver resection for CRLM remain unclear. PATIENTS AND METHODS: We evaluated the effect of AAC on the clinical prognosis and metastatic patterns in 99 patients who underwent hepatectomy for CRLM between 2010 and 2019. RESULTS: The high-AAC group had significantly worse overall survival (OS) and remnant liver recurrence rate (RR) after propensity score matching to adjust for differences in baseline characteristics of patients and tumors. In multivariate Cox regression analyses, high AAC volume was an independent risk factor for poor OS and liver RR, but not poor lung RR. The expression of tumor necrosis factor-related apoptosis-inducing ligand, known as an anti-tumor marker, in liver natural killer (NK) cells was lower in the high-AAC group than in the low-AAC group. CONCLUSION: High AAC volume showed a strong relationship with remnant liver RR after curative resection of CRLM. High AAC volume may be responsible for the suppression of anti-tumor activity of liver NK cells, which results in an increased risk of liver recurrence and poor prognosis.

Impact of a new liver immune status index among patients with hepatocellular carcinoma after initial hepatectomy.

Aim: The anti-tumor effects of natural killer (NK) cells vary among individuals. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expressed on liver NK cells is a marker of anti-tumor cytotoxicity against hepatocellular carcinoma (HCC) in immune cell therapy. This study aimed to develop a liver immune status index (LISI) that predicts low TRAIL expression and validates its ability to predict recurrence after initial hepatectomy for primary HCC. Methods: A functional analysis of liver NK cells co-cultured with interleukin-2 for 3 days was performed of 40 liver transplant donors. The LISI, which predicted low TRAIL expression (25% quartile: <33%) in liver NK cells, was calculated using multiple logistic regression analysis. Next, 586 initial hepatectomy cases were analyzed based on the LISI. Results: Our model was based on the Fibrosis-4 index+0.1 (odds ratio [OR], 1.33), body mass index (OR, 0.61), and albumin levels+0.1 (OR, 0.54). The area under the receiver operating characteristic curve (AUC) of the LISI for low TRAIL expression was 0.89. Stratification of the recurrence rates (RR) revealed that LISI was an independent predictive factor of RR (moderate risk: hazard ratio, 1.44; high risk: hazard ratio, 3.02). The AUC was similar for the LISI, albumin-indocyanine green evaluation grade, albumin-bilirubin score, and geriatric nutritional risk index for predicting RR. Among the vascular invasion cases, the LISI was more useful than the other indexes. Conclusion: Our model facilitates the prediction of RR in high-risk patients by providing LISI to predict the anti-tumor effects of NK cells.

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis.

AIM: We investigated the chemotherapy effect of resectable colorectal cancer with liver metastasis (CRLM) on the function of intrahepatic immune cells. METHODS: We classified patients into adjuvant chemotherapy (bevacizumab+CapeOX) after hepatectomy group (group A) and neoadjuvant chemotherapy followed by hepatectomy group (group B), and collected peripheral blood mononuclear cells (PBMC) and liver mononuclear cells (LMNC) to ascertain phenotypic and functional differences. RESULTS: There were no significant differences in lymphocyte fractions of either PBMC or LMNC between groups, except for the significantly lower percentage of natural killer (NK) cells in LMNC in group B than in group A. Significantly higher percentage of natural-killer group 2, member D (NKG2D)- positive NK cells in PBMC and percentage of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-, NKp30-, and signal regulatory protein ß (SIRPß)-positive NK cells in LMNC were found in group B. Furthermore, significantly higher expressions of NKG2D and SIRPß in peripheral blood NK cells and of NKp46 and CD122 in liver NK cells were found in group B. When LMNC were incubated with interleukin (IL)-2 in vitro, no difference was observed in the expression of these molecules in NK cells between groups. Consistently, there was no difference in the cytotoxic activity of those LMNC against a colon adenocarcinoma cell line between groups. CONCLUSION: Colorectal cancer with liver metastasis patients treated with neoadjuvant chemotherapy showed enhanced expression of activation markers on peripheral blood and liver NK cells in comparison with patients who did not receive therapy; however, the difference in those function remains unclear. These results suggest that neoadjuvant chemotherapy does not have a negative impact on intrahepatic immune cells in resectable CRLM patients.