Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy.

The mammalian target of rapamycin (mTOR) is often activated in several cancers. We focused on two mTOR regulatory mechanisms: oxaliplatin-induced mTOR signaling and L-type amino acid transporter 1 (LAT1)-induced mTOR activation. High LAT1 expression in several cancers is associated with mTOR activation and resistance to chemotherapy. However, the significance of LAT1 has not yet been elucidated in colorectal cancer (CRC) patients treated with post-operative adjuvant chemotherapy. Immunohistochemistry was conducted to examine the significance of membrane LAT1 expression in 98 CRC patients who received adjuvant chemotherapy, including oxaliplatin. In vitro analysis was performed using CRC cell lines to determine the effects of LAT1 suppression on proliferation, oxaliplatin sensitivity, and mTOR signaling. LAT1 expression was associated with cancer aggressiveness and poor prognosis in 98 CRC patients treated with adjuvant chemotherapy. We found that positive LAT1 expression correlated with shorter survival in 43 patients treated with the capecitabine-plus-oxaliplatin (CAPOX) regimen. LAT1 suppression in CRC cells inhibited the proliferation potency and oxaliplatin-induced activation of mTOR signaling, and improved oxaliplatin sensitivity. LAT1 evaluation before adjuvant treatment may therefore be a sensitive marker for oxaliplatin-based regimens. Moreover, LAT1 may be a promising target for patients with refractory CRC.

Gangrenous ischemic colitis localized to the cecum: a case report.

BACKGROUND: Ischemic colitis affects the left colon in elderly individuals and localization on the right side, especially in the cecum, is rare. We report a case of gangrenous ischemic colitis localized in the cecum of a patient undergoing hemodialysis. CASE PRESENTATION: A 73-year-old man had been undergoing hemodialysis for chronic renal failure caused by diabetic nephropathy. He experienced frequent vomiting, diarrhea, and abdominal pain. Contrast-enhanced computed tomography revealed thickening of the cecal wall, poor enhancement, dilation of the cecum, and intrahepatic portal emphysema. No obvious abnormal findings were observed in the appendix. The patient was diagnosed with cecal necrosis and ileocecal resection was performed. Histopathological examination revealed gangrenous ischemic colitis of the cecum. He was discharged 12 days after surgery without postoperative complications. CONCLUSION: It is important to consider the possibility of ischemic colitis of the right colon in the event of renal failure requiring dialysis, to ensure that opportunities for surgical intervention are not missed.

Significance of routine preoperative prone computed tomography for predicting intractable cases of inguinal hernias treated by transabdominal preperitoneal repair.

Physical examination is the standard diagnostic approach for adult inguinal hernias. We aimed to evaluate the clinical utility of routine preoperative computed tomography scans in the prone position for predicting intractable cases of inguinal hernias before performing transabdominal preperitoneal repairs. We retrospectively analyzed 56 lesions in 48 patients with inguinal hernias who underwent prone computed tomography scans prior to transabdominal preperitoneal repairs. To assess the ability of prone computed tomography to enable the accurate preoperative diagnosis of inguinal hernias, we compared preoperative hernia types as classified through hernia computed tomography and intraoperative diagnosis. We also analyzed the relationship between operation time and hernia type in unilateral cases (n = 40). The overall hernia computed tomography detection and classification accuracy rates were 81.0% and 83.9%, respectively, using the Japan Hernia Society classification system (2009 version) and 84.3% and 91.2%, respectively, using the European Hernia Society classification system. There were no differences in the hernia type frequencies between the shorter (n = 20) and longer (n = 20) operation time groups. Two patients had sliding inguinal hernias with prolapsing bladders, both of which were detectable using preoperative prone computed tomography. Although transabdominal preperitoneal repairs were completed in both cases, the operation times were exceptionally long (185 and 291 minute). Preoperative prone computed tomography is useful for predicting intractable cases of inguinal hernias. Prone computed tomography can play a significant role in not only typing and differentiating hernias from other diseases, but also in helping surgeons appropriately treat unexpected intractable cases with laparoscopic surgery.

Risk and Protective Factors for Postoperative Complications in Elderly Patients With Colorectal Cancer.

AIM: This study aimed to evaluate perioperative factors, including nutritional status and sarcopenia on short-term postoperative complications, determine the risk factors for postoperative complications, and clarify potential preoperative interventions and optimal surgical procedures to improve short-term outcomes in elderly patients with colorectal cancer (CRC). PATIENTS AND METHODS: This retrospective, single-centre cohort study analysed the factors and short-term postoperative complications of CRC in a cohort of 101 patients aged ≥80 years who underwent radical resection between 2013 and 2020. Nutritional status was evaluated by calculating the controlling nutritional status. RESULTS: The median age was 83 years, and the frequency of sarcopenia was 39.6%. Short-term postoperative complications occurred in 24 patients. Risk factors for short-term postoperative complications in multivariate analysis were sarcopenia combined with nutritional disorders and open surgical approach. CONCLUSION: The status of nutrition and sarcopenia must be considered in order to predict and improve postoperative outcomes. If possible, a laparoscopic approach should be selected to prevent poor postoperative outcomes.

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.

Large retroperitoneal leiomyoma developed from the pelvic floor to the buttocks.

Retroperitoneal leiomyoma is a very rare disease, with little reported information on its origin. Herein, we report a case of a large retroperitoneal leiomyoma that developed from the pelvic floor. A 44-year-old woman had a large mass protruding outside the body from the right hip. Imaging revealed a large tumor developing from the pelvic floor to the buttocks. It was difficult to identify the place of origin. Upon preoperative biopsy, the patient was diagnosed with retroperitoneal leiomyoma. Tumor removal with abdominoperineal and partial vaginal resection was performed. Based on the histological findings of the surgical specimens, she was diagnosed with a retroperitoneal leiomyoma (gynecologic type) via immunohistochemistry, the tumor cells were positive for αSMA, desmin, estrogen receptor(ER), and progesterone receptor(PgR), but negative for myoglobin, S-100, CD34, and MIB-1.This is a case of a large retroperitoneal leiomyoma that was successfully removed via abdominoperineal and partial vaginal resection.

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.