The presurgical controlling nutritional status (CONUT) score is independently associated with severe peristomal skin disorders: a single-center retrospective cohort study.

While nutritional interventions may potentially lower the risk of peristomal skin disorders (PSDs) and their exacerbation, no previous studies have evaluated the relationship between PSDs and nutritional status using the Controlling Nutritional Status (CONUT) score. The purpose of this study was to assess the impact of preoperative nutritional status on stoma health, and determine risk factors for postoperative PSDs, including severe PSDs. A retrospective analysis was performed of 116 consecutive patients with rectal cancer who underwent radical surgery with ileostomy or colostomy creation. PSDs were diagnosed in 32 patients (27.6%); including 10 cases (8.7%) that were defined as severe based on the ABCD-stoma score. Multivariable logistic regression showed that smoking (odds ratio [OR] 3.451, 95% confidence interval [CI] 1.240-9.607, p = 0.018) and ileostomy (OR 3.287, 95% CI 1.278-8.458, p = 0.014) were independent risk factors for PSDs. A separate multivariable logistic regression analysis of risk factors for severe PSDs, found that the only independent risk factor was the CONUT score (OR 10.040, 95% CI 1.191-84.651, p = 0.034). Severe PSDs are associated with preoperative nutritional disorders, as determined by the CONUT score. Furthermore, nutritional disorders may increase the severity of PSDs, regardless of the stoma type.

PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer.

Ulcerative colitis (UC) is a DNA damage-associated chronic inflammatory disease; the DNA double-strand break (DSB) repair pathway participates in UC-associated dysplasia/colitic cancer carcinogenesis. The DSB/interferon regulatory factor-1 (IRF-1) pathway can induce PD-L1 expression transcriptionally. However, the association of PD-L1/DSB/IRF-1 with sporadic colorectal cancer (SCRC), and UC-associated dysplasia/colitic cancer, remains elusive. Therefore, we investigated the significance of the PD-L1/DSB repair pathway using samples from 17 SCRC and 12 UC patients with rare UC-associated dysplasia/colitic cancer cases by immunohistochemical analysis. We compared PD-L1 expression between patients with SCRC and UC-associated dysplasia/colitic cancer and determined the association between PD-L1 and the CD8+ T-cell/DSB/IRF-1 axis in UC-associated dysplasia/colitic cancer. PD-L1 expression in UC and UC-associated dysplasia/colitic cancer was higher than in normal mucosa or SCRC, and in CD8-positive T lymphocytes in UC-associated dysplasia/colitic cancer than in SCRC. Moreover, PD-L1 upregulation was associated with γH2AX (DSB marker) and IRF-1 upregulation in UC-associated dysplasia/colitic cancer. IRF-1 upregulation was associated with γH2AX upregulation in UC-associated dysplasia/colitic cancer but not in SCRC. Multicolour immunofluorescence staining validated γH2AX/IRF-1/PD-L1 co-expression in colitic cancer tissue sections. Thus, immune cell-induced inflammation might activate the DSB/IRF-1 axis, potentially serving as the primary regulatory mechanism of PD-L1 expression in UC-associated carcinogenesis.

Low level of stromal lectin-like oxidized LDL receptor 1 and CD8+ cytotoxic T-lymphocytes indicate poor prognosis of colorectal cancer.

BACKGROUND: Lectin-like oxidized LDL receptor-1 (LOX-1) has been identified as a new marker for functional myeloid-derived suppressor cells (MDSCs) that exhibit an immunosuppressive phenotype in the tumor microenvironment (TME). However, the role of LOX-1+ cells in the TME of colorectal cancer (CRC) remains unknown. AIM: This study aimed to determine the expression and significance of LOX-1 in the TME of clinical CRC specimens. METHODS AND RESULTS: We performed immunohistochemical and genetic analyses of LOX-1, CD8, KRAS, and BRAF in 128 resected CRC specimens and determined the expression of IFN-γ and IL-10 using real-time reverse transcription-polymerase chain reaction. We analyzed the correlation between LOX-1, TME factors, gene alteration, clinicopathological factors, and disease prognosis. The co-expression pattern of LOX-1, hematopoietic markers, and a fibroblast marker was evaluated using multiplex immunofluorescence staining. Low stromal LOX-1 expression and low intratumoral CD8+ cytotoxic T-lymphocyte (CTL) status correlated with poor prognosis. Moreover, stromal LOX-1-low/CD8+ CTL-low status was the most important independent prognostic factor of poor overall survival. Most of the LOX-1+ stromal cells were positive for CD163+ , indicating they were CD163+ M2 macrophages. CONCLUSIONS: The MDSC marker, LOX-1, was mainly expressed by M2 macrophages in CRC tissues. LOX-1+ macrophages and CD8+ CTLs may serve as useful biomarkers for predicting the prognosis of CRC.

Bowel obstruction due to Chlamydia trachomatis: a case report and review of literature.

BACKGROUND: Chlamydial infection is a difficult-to-diagnose type of sexually transmitted disease that occurs mainly in young people. We report a case of bowel obstruction caused by intrapelvic adhesions formed by chlamydial infection. CASE PRESENTATION: This patient was a 23-year-old woman who had been suffering from acute abdominal pain. She had been previously treated several times for intrapelvic abscesses and had a history of chlamydial infection. Endometriosis was thought to be the cause of her pelvic abscess based on endoscopic findings. Computed tomography demonstrated a small bowel obstruction caused by a pelvic abscess. However, the diagnosis could not be confirmed. She underwent laparoscopic surgery and was diagnosed with bowel obstruction due to adhesion of chlamydial infection based on the intraoperative findings and Chlamydia trachomatis antibody test. She was discharged 5 days after surgery. CONCLUSIONS: It is necessary to consider the possibility of chlamydial infection as a cause for lower abdominal pain and unexplained bowel obstruction in female patients.

Outcomes of surgical treatment in patients with anorectal fistula cancer.

BACKGROUND: No standard treatment for anorectal fistula cancer, such as multidisciplinary therapy, has been established due to the rarity of the disease. Herein, we investigated patients with cancer associated with anorectal fistula who underwent surgery to clarify the clinicopathological characteristics and to propose future perspectives for treatment strategies. CASE PRESENTATION: Seven patients with cancer associated with anorectal fistula who underwent rectal amputation in our institute were analyzed with regard to clinical characteristics, pathological findings, surgical results, and prognosis. Four cases had Crohn's disease as an underlying cause. All seven cases were diagnosed as advanced stage. Preoperative [18F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computed tomography (FDG-PET/CT) showed abnormal FDG accumulation in six cases including four mucinous adenocarcinomas. Three cases that received preoperative hyperthermo-chemoradiotherapy achieved pathological R0 resection. Postoperative recurrence was observed in four cases including three with Crohn's disease and one resulting in death. CONCLUSIONS: Anorectal fistula cancer is rare and difficult to be diagnosed at early stages. Mucinous adenocarcinoma associated with anorectal fistula tends to exhibit abnormal FDG accumulation by FDG-PET/CT unlike common colorectal mucinous adenocarcinoma. Preoperative hyperthermo-chemoradiotherapy may be effective in obtaining pathological complete resection.

A case of colorectal large cell neuroendocrine carcinoma accompanied by disseminated peritoneal leiomyomatosis.

BACKGROUND: Neuroendocrine carcinomas (NECs) of the colon are among the rarest types of colorectal cancers. Among these, large cell type neuroendocrine carcinoma (LCNEC) is particularly rare. Colorectal NEC is an aggressive disease, and there are few reports of long-term survivors. Here, we report a case of LCNEC accompanied by disseminated peritoneal leiomyomatosis that was difficult to diagnose. CASE PRESENTATION: The case involves a 62-year-old female found to be positive for fecal occult blood by medical examination. An endoscopy revealed a tumor in the ascending colon, and the biopsy revealed poorly differentiated cancer. Abnormal FDG accumulation with peritoneal thickening was visible on 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) and suspected to be peritoneal dissemination. Laparoscopic ileocecal resection was performed for the tumor of the ascending colon with abdominal wall invasion. At that time, numerous intra-abdominal nodules were observed, indicating peritoneal dissemination. The pathological diagnosis of the primary lesion was LCNEC, and the patient requested to undergo total peritoneal resection. After one course of chemotherapy with irinotecan plus cisplatin, she underwent total peritoneal resection, uterine annex resection, left inguinal lymph node resection, and intra-abdominal hyperthermic intraperitoneal chemotherapy with mitomycin C. Because a postoperative pathological examination revealed that the intra-abdominal nodules were leiomyomas, we diagnosed the patient with disseminated peritoneal leiomyomatosis. The left inguinal lymph node was diagnosed with a metastatic tumor. In summary, the final diagnosis was LCNEC in the ascending colon with inguinal lymph node metastasis. Postoperative chemotherapy has been administered to date. She is currently 18 months post-primary surgery and 15 months post-peritonectomy without apparent recurrence or metastatic findings. CONCLUSION: We experienced a case of Stage IVa colorectal LCNEC accompanied by disseminated peritoneal leiomyomatosis. Although the prognosis is generally poor, multidisciplinary treatment for advanced colorectal LCNEC may result in a favorable outcome for some patients. If peritoneal dissemination is suspected during operation, sampling of the nodule to confirm the pathological diagnosis is advisable.

Prognostic significance of ß2-adrenergic receptor expression in patients with surgically resected colorectal cancer.

PURPOSE: The ß2-adrenergic receptor (ß2AR) is highly expressed in various human cancers. The prognostic significance of its expression in patients with colorectal cancer (CRC) remains unclear. The aim of this study was to assess the prognostic role of ß2AR expression in patients with surgically resected CRC. METHODS: One hundred and forty-seven patients with surgically resected CRC were examined using immunohistochemistry. The expression of ß2AR was assessed in the specimens of resected primary tumors. RESULTS: ß2AR was expressed in 52.3% of the patients' tumors. ß2AR expression was significantly associated with T factor, N factor, and tumor cell proliferation (Ki-67 labeling index). Univariate analysis demonstrated that T factor, N factor, tumor stage, lymphatic permeation, vascular invasion, perineural invasion, ß2AR expression, and Ki-67 labeling index were significant prognostic factors for worse disease-free survival (DFS); all but T factor were also significant predictors for worse overall survival (OS). Multivariate analysis confirmed that expression of ß2AR was a significant prognostic marker for predicting worse DFS and OS. CONCLUSION: ß2AR expression was identified as a significant independent prognostic factor in patients with surgically resected CRC.

STMN1 accumulation is associated with dysplastic and neoplastic lesions in patients with ulcerative colitis.

Ulcerative colitis (UC) is thought to be associated with precancerous lesions that can ultimately lead to colon cancer. Therefore, diagnostic markers for colorectal dysplasia and cancer are urgently needed for patients with UC. Stathmin 1 (STMN1) is a novel cancer biomarker that is also a novel target for treatment in several cancers, including colon cancer. However, few studies have investigated the relationship between STMN1 expression and clinical features in colorectal dysplasia and cancer in patients with UC. The present study examined the clinical significance of STMN1 expression in colorectal dysplasia and cancer with UC. The present study performed an immunohistochemical analysis of 31 clinical colorectal samples from eight patients with colorectal dysplasia and/or cancer to assess the relationships between STMN1 expression and clinicopathological features including mismatch repair protein expression, rate of Ki-67 positivity, differentiation level, TNM stage, and UC duration. STNM1 expression was detected in 95.7% of dysplastic and cancerous lesions, whereas p53, the current diagnostic marker, was not expressed in 39.1% of dysplastic and cancerous lesions. Furthermore, STMN1 expression was associated with a high rate of positivity for Ki-67, a proliferation marker. Our data suggest that STMN1 in the colonic mucosa of UC patients may be useful as an early diagnostic marker of dysplasia and colitic cancer.

Role of Amino Acid Transporter Expression as a Prognostic Marker in Patients With Surgically Resected Colorectal Cancer.

BACKGROUND/AIM: L-type amino acid transporter 1 (LAT1) is highly expressed in various human cancers. However, the clinicopathological significance of LAT1 and 4F2 cell surface antigen (4F2hc) in patients with colorectal cancer (CRC) is unknown. The aim of this study was to clarify the prognostic significance of LAT1 expression in CRC patients who underwent surgical resection. MATERIALS AND METHODS: Samples from one hundred and forty-seven patients were examined by immunohistochemistry. The expression of LAT1 and 4F2hc, and the Ki-67 labeling index were assessed using resected tumor specimens. RESULTS: The positive expression of LAT1 and 4F2c was 80% (118/147) and 58% (86/147) (p<0.01), respectively. The expression of LAT1 was identified as an independent significant marker linked to worse prognosis in patients with CRC, and was correlated with tumor cell proliferation, tumor aggressiveness, and metastasis. Moreover, LAT1 was closely associated with the expression of 4F2hc and phosphorylation of the mTOR pathway. CONCLUSION: LAT1 is a significant molecular marker used to predict prognosis after surgical resection of CRC patients.

Preparation of 1L-myo-Inositol 1-Phosphate as a Substrate of Phosphatidylinositol Phosphate Synthase.

Novel drugs possessing a mechanism of action specific to pathogenic mycobacteria, including Mycobacterium tuberculosis, are needed. In 2010, we discovered that the biosynthetic pathway of phosphatidylinositol, which is a membrane phospholipid, differs between humans and mycobacteria. The key enzyme responsible for this difference is phosphatidylinositol phosphate (PIP) synthase, which is present only in a few bacteria belonging to the phylum Actinobacteria. Discovering compounds that inhibit the activity of this enzyme will lead to the development of new drugs specific to pathogenic mycobacteria. Measuring PIP synthase activity requires the isotope-labeled substrate 1l-myo-inositol 1-phosphate (1l-Ino-1P). Because this substrate is not commercially available, we synthesized it from [14C] glucose 6-phosphate ([14C] Glc-6P), using a crude enzyme solution isolated from the methanoarchaeon 1l-Ino-1P synthase. The activity of 1l-Ino-1P synthase in the crude enzyme mixture was low, and quantitative analysis of the synthesized 1l-Ino-1P was inaccurate due to impurities present in the crude enzyme mixture. In the present study, we describe a method for synthesizing 1l-Ino-1P using a solution containing recombinant 1l-Ino-1P synthase derived from the hyperthermophilic archaeon Aeropyrum pernix. In addition, we elucidate the conditions leading to the almost complete conversion of Glc-6P into 1l-Ino-1P using this enzyme. Quantitation of the synthesized 1l -Ino-1P was performed by colorimetry and gas liquid chromatography. Further, we confirmed that isotope-labeled 1l-Ino-1P, which is difficult to quantitate by gas liquid chromatography, can be accurately quantified by colorimetry. We also confirmed that 1d-inositol 1-phosphate cannot be a substrate for PIP synthase.

A novel one-step lens cleaning device using air and water flow for endoscopic surgery.

In a surgical operation requiring endoscopy, it is essential to obtain a clear endoscopic view. However, it is often disturbed by the contamination on the lens during the surgery. No device can clean the lens surface simply and completely. Many surgeons are hampered by the impaired view and the distraction by the repeated cleaning of the lens. Therefore, we developed a novel endoscope cleaning device to address this problem. The device was made of 3D-printed rubber-like plastic. It contains a syringe filled with saline and an aspiration system. It would be used intraoperatively to wash the lens surface in a few seconds with rapid flow of water and air. The cleaning ability of the device was evaluated using mayonnaise with adenosine triphosphate (ATP) as a model contaminant. The gauze-wiping maneuver was selected as control. After each maneuver, the clarity of the endoscopic view was evaluated, and residual contaminants were assessed quantitatively with ATP assay. The cleaning device obtained a crisp and clear view and eliminated the contaminant on the lens every time after a single cleaning maneuver. The gauze-wiping maneuver required for the lens to be wiped at least three times to obtain a clear view, and even then, some contaminants remained. Repeated contamination and cleaning using gauze led to accumulation of contaminants on the lens, which resulted in difficulty in cleaning the lens as the operation proceeded. The cleaning device did not show such accumulation. Our novel cleaning device with air and water flow has been shown to wash out the lens contaminants completely and immediately in a simple manner. It is expected to improve the safety and cost-effectiveness of endoscopic surgery.