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BACKGROUND: The standard treatment for colorectal cancer consists of surgery and chemotherapy, which can be combined to improve outcomes. Immune checkpoint inhibitors (ICI) are a significant advancement in the standard treatment of metastatic, unresectable colorectal cancer with deficient mismatch repair (dMMR). However, limited data are available about the use of ICI in the neoadjuvant and conversion settings. Here, we present two cases treated with ICI. CASE PRESENTATION: Case 1: A 75-year-old male with a large, borderline resectable rectal cancer diagnosed as cT4bN1bM0 who underwent neoadjuvant chemotherapy, followed by combination ICI consisting of ipilimumab and nivolumab. After four courses of ICI, the tumor significantly shrank, but positron emission tomography still showed a positive result and R0 resection was performed. Pathological analysis revealed no residual cancer cells. The patient has been monitored without adjuvant chemotherapy, and no recurrences have occurred after one year. Case 2: A 60-year-old male with locally advanced sigmoid colon cancer who received neoadjuvant treatment with pembrolizumab. The tumor partially shrank after three courses, and continued pembrolizumab monotherapy resulted in further tumor shrinkage which still showed positive positron emission tomography. Curative sigmoidectomy with partial resection of the ileum and bladder was performed, and the pathological outcome was pCR. There was no viable tumor in the specimen. The patient has been monitored without adjuvant chemotherapy for six months, and no recurrence has been observed. CONCLUSIONS: The present study reports two cases, including a large, borderline resectable rectal cancer after failure of chemotherapy followed by combination treatment with nivolumab and ipilimumab and one case of sigmoid colon cancer after pembrolizumab treatment, which resulted in pathological complete response. However, it remains unknown whether ICI therapy can replace surgery or diminish the optimal extent of resection, or whether adjuvant chemotherapy is needed after surgery in the case of achieving pCR after ICI therapy. Overall, this case report suggests that ICI before colorectal surgery can be effective and potentially a 'watch-and-wait" strategy could be used for cases in which ICI is effective.
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INTRODUCTION: Carbohydrate restriction in diet is becoming a popular means of losing weight nowadays, although it has been reported that excessive intake of low-carbohydrate and high-protein (LCHP) diet causes an adverse effect on cardiovascular function. AIM: To investigate the influence of LCHP on erectile function in rats. METHODS: A total of 48, 12-week-old rats were divided into 2 groups and either fed a LCHP diet (LCHP group) or a normal diet (Control group). Hematological examination, blood pressure evaluation, erectile function assessments as well as evaluations of the relaxation and contractile responses of corpus cavernosum were carried out in these rats by using standardized methods. Statistical analysis using 2-way ANOVA and Welch's t-test was conducted to examine the obtained data. MAIN OUTCOME MEASURE: At the end of the study period, the evaluated outcomes to assess erectile function were intracavernosal pressure , mean arterial pressure , endothelial functions, nitric oxide (NO)-operated nerve functions and the expressions of endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and sphingosine-1-phosphate receptor 1 (S1P1). RESULTS: The intracavernosal pressure / mean arterial pressure ratio was significantly lower in the LCHP group (P < .05) at 4 weeks. Compared to the Control group, the LCHP group exhibited significantly lower responses to ACh and EFS and a decreased nNOS mRNA expression. The results based on this animal model indicate that extreme carbohydrate restricted diet may affect erectile function. Our study identified that LCHP decreased erectile function in rats. A major limitation of this study is, due to the extreme condition of completely replacing carbohydrates with protein, that carbohydrate intake will be gradually increased in the future. CONCLUSION: Extreme carbohydrate restriction and high protein in diet may cause ED with vascular endothelial dysfunction and a decrease in the relaxation response of the corpus cavernosum smooth muscle via NO-operated nerves. Kataoka T, Hidaka J, Suzuki J, et al. Evaluating the Effects of Low Carbohydrate and High Protein Diet on Erectile Function in Rats. Sex Med 2021;10:100500.
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Stress is a risk factor for erectile dysfunction (ED); however, the pathology of stress-induced ED remains unclear. Accordingly, in this study, we investigated the mechanisms of stress-induced ED using a rat model. Ten-week-old male Wistar/ST rats were maintained in a cage filled with water to a height of 2 cm (stress group) or a normal cage (control group). We found that water immersion stress significantly enhanced the contractile response to noradrenaline in the corpus cavernosum (CC) (p < 0.05). Moreover, stress significantly decreased erectile function, as assessed by changes in intracavernous pressure (p < 0.01). In addition, Rho kinase-1 (ROCK-1) protein expression was significantly upregulated under stress conditions (p < 0.05), and phosphorylated myosin light chain (phospho-MLC) levels, contribute to smooth muscle contraction, were also upregulated (p < 0.01). Treatment with fasudil hydrochloride, a Rho kinase inhibitor, for 5 days significantly improved erectile function (p < 0.01) and normalized ROCK-1 and phospho-MLC levels (p < 0.01). Thus, the RhoA/Rho kinase pathway may be associated with stress-induced ED via contraction of CC. Stress also decreased the smooth muscle/collagen ratio of CC (p < 0.01), and fasudil treatment did not alleviate these effects (p = 0.50). These findings suggested that penile fibrosis gradually progressed under stress conditions and that fibrosis may be independent of the RhoA/Rho kinase pathway, implying that longer exposure to stress may promote ED. We conclude that stress-induced ED was caused by contraction of CC mediated by the RhoA/Rho kinase pathway.