Crohn's Disease-Associated Anorectal Cancer Has a Poor Prognosis With High Local Recurrence: A Subanalysis of the Nationwide Japanese Study.

INTRODUCTION: Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC. METHODS: A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables. RESULTS: Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local. DISCUSSION: Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.

Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study.

INTRODUCTION: The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set. METHODS: The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC. RESULTS: In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001). DISCUSSION: Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

[A Case of Carcinomatosis of the Bone Marrow Due to Rectal Cancer].

A 33-year-old man was admitted due to dyschezia and melena. Colonoscopy revealed a circulating type 4 rectal tumor. Further examination revealed intestinal obstruction due to rectal cancer, paraaortic lymph node metastasis, and multiple bone metastases, and an ileus tube was transanally inserted for decompression. Bone scintigraphy revealed multiple abnormal uptake regions in the entire skeleton. We planned to perform primary tumor resection and postoperative adjuvant chemotherapy and radiotherapy administration. Peritoneal signs in the lower abdomen appeared after 6 days of tube insertion. Abdominal computed tomography demonstrated intestinal perforation, and emergency surgery was performed. During the surgery, tube penetration in the anterior abdominal wall was observed in the sigmoid colon proximal to the tumor. Postoperatively, the patient developed disseminated intravascular coagulation(DIC). The patient had multiple bone metastases and juvenile cells in peripheral blood figure analysis; therefore, we concluded that DIC was caused by carcinomatosis of the bone marrow. After an informed consent was obtained, FOLFOX4 with simultaneous DIC treatment was initiated, and DIC remission was observed. The patient was transferred to a different hospital near his home, but died 35 days postoperatively.

[A Case of Sinusoidal Obstruction Syndrome and Nodular Regenerative Hyperplasia after Using Oxaliplatin for Rectal Cancer].

We present a case of a 44-year-old woman with rectal cancer(cT2N3M0, cStage Ⅲb)treated with 4 capecitabine-oxaliplatin( CAPOX)therapy courses, followed by laparoscopic intersphincteric resection. The patient received 7 postoperative, adjuvant CAPOX therapy courses. After 16 months since the final CAPOX administration, computed tomography(CT) revealed multiple liver tumors, showing early enhancement, and a jejunal mesenteric mass suspected to be a gastrointestinal stromal tumor(GIST). To overcome the percutaneous needle biopsy limitation, laparoscopic partial hepatectomy and laparoscopic- assisted partial intestinal resection were performed. Two liver lesions were diagnosed as nodular regenerative hyperplasia( NRH)with sinusoidal obstruction syndrome(SOS), supported by the hyperplasia and sinusoidal dilatation pathological findings, consequential to using oxaliplatin. Considering the rarity of NRH, using oxaliplatin may be proven vital in the differential diagnosis.

[Successful Control of Hyperammonemia with BRTO of a Splenorenal Shunt Induced by CAPOX Therapy].

Among portosystemic shunts, splenorenal shunts can cause increased portal pressure, which in turn can bring about hyperammonemia, resulting in hepatic encephalopathy. In recent years, it has been reported that oxaliplatin(OX), a key chemotherapy drug in colorectal cancer, can precipitate splenorenal shunts due to sinusoidal injury. We report a case of hyperammonemia post oxaliplatin therapy. A 72-year-old male patient who had undergone surgical resection for(RS)rectal cancer with hepatic metastasis had been receiving capecitabine plus OX(CAPOX)as adjuvant chemotherapy. During his 7th course of treatment, he visited the outpatient clinic with complaints of weakness, dysarthria, and urinary incontinence. Laboratory findings showed an elevated NH3 level (200 µg/dL), and subsequent abdominal computed tomography revealed a splenorenal shunt, which was attributed to OX. Balloon-occluded retrograde transvenous obliteration(BRTO)was then performed. The patient has been routinely followed up in the outpatient clinic and has had no recurrence of hyperammonemia or cancer 14 months after the procedure. In retrospect, the splenorenal shunt was present on his first visit, therefore, hyperammonemia could have been prevented at the time of commencement of chemotherapy. We report our case, along with the relevant literature.

Severe immersion pulmonary edema in a novice elderly scuba diver after heavy alcohol intake.

BACKGROUND: There are no reports of immersion pulmonary edema induced by excessive alcohol intake. We describe the case of a novice scuba diver who developed apnea due to immersion pulmonary edema during scuba diving after heavy alcohol intake. CASE PRESENTATION: A 71-year-old hypertensive man, without regular antihypertensive therapy, performed diving after excessive alcohol intake (total amount, approximately 253 g) until the night before. When swimming at a depth of 12 m, the patient experienced chest discomfort and ascended immediately but became unconscious. Respiratory arrest was confirmed, and he spat pink foamy sputum. On hospital admission, hypoxemia was confirmed, and chest radiography revealed butterfly-shaped shadows. Therefore, mechanical ventilation was initiated. The next day, his blood oxygenation level improved, and the radiographic shadows disappeared. He was discharged on day 7 of hospitalization without sequelae. CONCLUSION: A scuba diver with untreated hypertension might develop immersion pulmonary edema during diving after heavy alcohol intake.

[A Case of Long-Term Survival of a Patient with a Nodal Recurrence of Intrahepatic Cholangiocarcinoma Who Attained Complete Remission with S-1 Monotherapy].

An 82-year-old man was referred to our hospital after a hepatic tumor was identified on ultrasonography.Computed tomography(CT)revealed a hypovascular tumor measuring 3 cm in diameter in the lateral section.He was diagnosed as having intrahepatic cholangiocarcinoma(ICC), and a left hemihepatectomy was performed in November 2012. During the postoperative follow-up in August 2013, CT revealed swollen lymph nodes around the greater curvature of the stomach and upper edge of the pancreas.By using endoscopic ultrasonography fine-needle aspiration(EUS-FNA), lymph node metastases of the ICC was diagnosed.S -1 monotherapy was initiated instead of gemcitabine and cisplatin regimens because of renal dysfunction.In July 2014, CT revealed that both lymph nodes were shrinking, and in January 2015, S-1 administration was discontinued upon the patient's request.However, the patient survived for 4 years without S-1 administration, and no recurrent tumors were recognized on CT in November 2018.O ur diagnosis indicates complete remission.

Changes in the rate of and trends in colectomy for ulcerative colitis during the era of biologics and calcineurin inhibitors based on a Japanese nationwide cohort study.

PURPOSE: We evaluated the recent incidence of surgery and the changing surgery trends for ulcerative colitis (UC) in Japan due to the increasing use of anti-tumor necrosis factor (TNF) agents. METHODS: A questionnaire survey was performed to assess the number of surgeries, surgical indications, surgical timing, and immunosuppressive treatments before surgery between 2007 and 2017. RESULTS: A total of 3801 surgical cases were reported over 11 years. The prevalence of UC surgery decreased over the period studied. The rate of prednisolone (PSL) use did not change. The prevalence of both calcineurin inhibitors (CNIs) and anti-TNF agents increased during the period studied (p < 0.01). The prevalence of urgent/emergent surgery did not change. The most distinctive change in surgical indications was the increase in cancer/dysplasia (CAC), the prevalence of which increased from 20.2% in 2007 to 34.8%. CONCLUSION: The prevalence of UC surgery seems to be decreasing according to the increasing rate of anti-TNF agent and CNI administration. However, the indication of CAC significantly increased. Further research should evaluate whether or not long-term remission maintained with several agents can lead to increasing CAC.

Antioxidative and modifying effects of a tropical plant Azadirachta indica (Neem) on azoxymethane-induced preneoplastic lesions in the rat colon.

The purpose of the present study was to examine whether Neem leaf (Azadirachta indica) has short-term chemopreventive effects on endpoint preneoplastic lesions involved in rat colon carcinogenesis and might also exert antioxidative activity. Forty- two male F344 rats were randomly divided into 6 experimental groups. Groups 1 to 4 were given a subcutaneous injection of azoxymethane (AOM, 20 mg/kg body weight) once a week for 2 weeks. Starting one week before the first injection of AOM, rats in groups 2 to 4 received an aqueous extract of Neem leaf (20, 100, and 250 mg/kg, respectively) by gavage 3 times per week, for 5 weeks. Rats in group 5 also were given the Neem extract by gavage feeding 3 times per week for 5 weeks, while group 6 served as untreated controls. The experiment was terminated 5 weeks after the start. Dietary feeding of the Neem extract at all dose levels significantly inhibited the induction of aberrant crypt foci (ACF) (P<0.0002), when compared to the AOM-treated group (group 1). In groups 2 to 4, treatment of rats with the Neem extract also significantly decreased the proliferating cell nuclear antigen (PCNA) labeling indices (P<0.0006) of colon epithelium and ACF. Moreover, the Neem extract also showed antioxidative activity. The finding that dietary Neem has possible chemopreventive effects in the present short-term colon carcinogenesis bioassay suggests that longer-term exposure may cause suppression of tumor development.

Anthraquinone derivative emodin inhibits tumor-associated angiogenesis through inhibition of extracellular signal-regulated kinase 1/2 phosphorylation.

An anthraquinone derivative, emodin, suppresses tumor development both in vitro and in vivo. In this study, we examined the anti-angiogenic activity of emodin and its modifying effect on the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. In cell cultures, emodin inhibited endothelial cell proliferation, migration, and tube formation in a dose-dependent manner. In addition, the mouse dorsal air sac assay revealed the vivo anti-angiogenic potential of emodin. Matrix metalloproteinase-9 (MMP-9) expression, which is critical for the angiogenic process, including migration and tube formation, decreased after exposure to emodin, as determined by polymerase chain reaction with reverse transcription (RT-PCR) and gelatin zymography. Moreover, the phosphorylation of ERK 1/2 decreased after exposure to emodin in a dose-dependent manner. These observations suggest that emodin has the potential to inhibit several angiogenic processes and that these effects may be related to suppression of the phosphorylation of ERK 1/2.

Reduced expression level of mgmt mRNA and beta-catenin gene mutation in rat colon tumors.

BACKGROUND: O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein and protects DNA from the biological effects of alkylating carcinogens. The purpose of this study was to investigate the association between the mRNA expression level of the Mgmt gene and mutation of the beta-catenin gene in rat colon tumors induced by azoxymethane (AOM) plus dextran sulfate sodium (DSS). MATERIALS AND METHODS: Eleven tumor samples from rat colon treated by AOM plus DSS were examined. Mutation of the beta-catenin gene was identified by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. The expression level of Mgmt mRNA was determined by reverse transcription-PCR (RT-PCR). RESULTS: Four out of five adeno-carcinoma samples bearing beta-catenin gene mutation (5 out of 11, 45%) displayed a decrease in expression levels of Mgmt mRNA (p<0.02). CONCLUSION: These results suggest that the reduced expression of Mgmt mRNA and beta-catenin gene mutation may contribute to the development of rat colon tumors.