• 文章类型: Journal Article
    背景:HER2靶向治疗最近已成为治疗过表达HER2的转移性结直肠癌(mCRC)的一种选择。然而,有关原发性CRC及其相应肝转移的HER2状态的数据有限,潜在影响临床决策。因此,本研究的目的是比较原发性CRC和配对肝转移的HER2状态.
    方法:接受原发性大肠癌及其相应的同步或异发肝转移手术的mCRC患者,在贝桑松大学医院消化外科,1999年4月至2021年10月,包括在内。从匹配的原发性CRC和肝转移组织样品构建组织微阵列。根据Valtorta标准通过免疫组织化学和原位杂交评估HER2状态。
    结果:一系列108成对的原发性CRC和肝转移,包括一系列源自同一患者的多发性肝转移(n=24),被评估。在主要的CRC中,89(82.4%),17例(15.8%)和2例(1.8%)分别为0、1+和2+。在肝转移中,99(91.7%),7分(6.5%)和2分(1.8%)分别为0、1+和2分。总的来说,原发性CRC和转移之间的HER2状态差异率为19%,在给定患者中,在具有多个同步或异发肝转移的情况下,该比例增加到21%。在HER2状态方面,异时转移和同步转移之间没有发现显着差异(p=0.237)。
    结论:我们的研究强调了原发性CRC和相应肝转移之间HER2状态的时间和空间异质性。这些发现提出了在疾病进展期间对HER2状态进行顺序评估的问题。提供最合适的治疗策略。
    BACKGROUND: HER2-targeted therapies have recently emerged as an option in the management of metastatic colorectal cancer (mCRC) overexpressing HER2. However, data regarding HER2 status in primary CRC and its corresponding liver metastases are limited, potentially influencing clinical decisions. Therefore, the aim of this study was to compare the HER2 status in primary CRC and paired liver metastases.
    METHODS: Patients with mCRC who were operated from their primary colorectal cancer and their corresponding synchronous or metachronous liver metastases, in the digestive surgery department of Besançon University Hospital, between April 1999 and October 2021, were included. Tissue microarrays were constructed from matched primary CRC and liver metastastic tissue samples. HER2 status was assessed by immunohistochemistry and in situ hybridization according to Valtorta\'s criteria.
    RESULTS: A series of 108 paired primary CRC and liver metastases, including a series of multiple liver metastases originating from the same patients (n = 24), were assessed. Among the primary CRC, 89 (82.4%), 17 (15.8%) and 2 (1.8%) cases were scored 0, 1 + and 2 + respectively. In liver metastases, 99 (91.7%), 7 (6.5%) and 2 (1.8%) were scored 0, 1 + and 2, respectively. Overall, there was a 19% discrepancy rate in HER2 status between primary CRC and metastases, which increased to 21% in cases with multiple synchronous or metachronous liver metastases in a given patient. No significant difference was found between metachronous and synchronous metastases regarding the HER2 status (p = 0.237).
    CONCLUSIONS: Our study highlights the temporal and spatial heterogeneity of HER2 status between primary CRC and corresponding liver metastases. These findings raise the question of a sequential evaluation of the HER2 status during disease progression, to provide the most suitable treatment strategy.
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  • 文章类型: Journal Article
    目的:评估诊断和治疗算法在结直肠手术后出现高C反应蛋白(CRP)的患者管理中的可行性和益处。
    方法:前瞻性研究包括选择性结直肠手术后第4天CRP>125mg/L的患者。该方案涉及CT扫描,其结果是指导后续管理:抗生素,放射引流,内窥镜检查或手术重做。成功(主要终点)包括总住院时间少于15d的患者比例。次要终点是:协议在现实生活中的适用性,创建的气孔数量,重症监护病房的住院时间。
    结果:包括106例患者:51例患者(48%)出现术后并发症,其中21人(41%)严重。没有死亡发生。在纳入的患者中,68%的住院时间<15d。38%的案例发生了与管理算法的重大偏差。没有患者进行早期内窥镜检查。根据是否严格遵守方案,次要终点没有显着差异。
    结论:有必要制定治疗结直肠手术后CRP水平高的患者的方案,目的是减少并发症的影响,避免过度延长住院时间。协议从CT扫描开始,这是指导后续管理。
    OBJECTIVE: To evaluate the feasibility and benefit of a diagnostic and therapeutic algorithm for management of patients presenting with a high C-reactive protein (CRP) level after colorectal surgery.
    METHODS: Prospective study including patients with CRP>125mg/L at the 4th postoperative day following elective colorectal surgery. The protocol involved CT-scan of which the results were to orient subsequent management: antibiotics, radiological drainage, endoscopy or surgical redo. Success (primary endpoint) consisted in the proportion of patients with total duration of hospitalization fewer than 15d. Secondary endpoints were: applicability of the protocol in real-life conditions, number of stomas created, duration of hospitalization in an intensive care unit.
    RESULTS: One hundred and six (106) patients were included: 51 patients (48%) presented with postoperative complications, of which 21 (41%) were severe. No death occurred. Among the included patients, 68% had a hospital stay<15d. Major deviations from the management algorithm occurred in 38% of cases. No patients had an early endoscopy. There was no significant difference with regard to the secondary endpoints according to whether or not the protocol was strictly observed.
    CONCLUSIONS: It is necessary to define a protocol for management of patients presenting with high CRP levels after colorectal surgery, the objective being to reduce the impact of complications and to avoid excessive lengthening of hospital stay. The protocol begins with CT-scan, which is to orient subsequent management.
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  • 文章类型: Journal Article
    目的比较机器人直肠癌手术(RRCS)和腹腔镜直肠癌手术(LRCS)对患者泌尿和性功能的保护作用。我们在PubMed进行了系统的搜索,WebofScience,科克伦图书馆,和Embase用于比较RRCS和LRCS对泌尿功能和性功能的影响的研究。国际前列腺症状评分(IPSS)使用国际勃起功能指数(IIEF-5)和女性性功能指数(FSFI)的五项版本评估患者的排尿功能和性功能。共有13项研究包括1964名患者,包括3项随机对照试验,5项回顾性队列研究,3项前瞻性队列研究,和2项倾向得分匹配的研究。959例患者接受了RRCS,1005例患者接受了LRCS。IPSS评分的统计学分析表明,术后3、6和12个月,RRCS组的排尿功能明显优于LRCS组[平均差异(MD),-1.06,95%CI-1.85至-0.28;和MD,-0.96,95%CI-1.60至-0.32;和MD,-1.09,95%CI-1.72至-0.46]。IIEF-5评分的统计学分析表明,在术后3、6和12个月,RRCS组的男性性功能明显优于LRCS组(MD,1.76,95%CI0.80至2.72;和MD,1.83,95%CI0.34至3.33;和MD,1.05,95%CI0.09至2.01)。FSFI评分的统计分析表明,术后6个月和12个月,RRCS组的女性性功能明显优于LRCS组(MD,2.86;95%CI1.38至4.35;和MD,4.19;95%CI1.85至6.54)。RRCS比LRCS更有利于保持直肠癌患者的泌尿和性功能。
    The purpose of the study was to compare the protective effects of robotic rectal cancer surgery (RRCS) and laparoscopic rectal cancer surgery (LRCS) on urinary and sexual function of patients. We conducted a systematic search in the PubMed, Web of Science, Cochrane Library, and Embase for studies comparing the impact of RRCS and LRCS on urinary function and sexual function. The International Prostate Symptom Score (IPSS), the five-item version of the International Index of Erectile Function (IIEF-5) and the Female Sexual Function Index(FSFI) were used to evaluate the urinary function and sexual function of patients. A total of 13 studies comprising 1964 patients were included in this meta-analysis, including 3 randomized controlled trials, 5 retrospective cohort studies, 3 prospective cohort studies, and 2 propensity score-matched studies. Nine hundred and fifty-nine patients underwent RRCS and 1005 patients underwent LRCS. Statistical analysis of the IPSS scores indicated urinary function was significantly better in the RRCS group than in the LRCS group at 3, 6 and 12 months postoperatively [mean difference (MD), - 1.06, 95% CI - 1.85 to - 0.28; and MD, - 0.96, 95% CI - 1.60 to - 0.32; and MD, - 1.09, 95% CI - 1.72 to - 0.46]. Statistical analysis of the IIEF-5 scores indicated male sexual function was significantly better in the RRCS group than in the LRCS group at 3, 6 and 12 months postoperatively (MD, 1.76, 95% CI 0.80 to 2.72; and MD, 1.83, 95% CI 0.34 to 3.33; and MD, 1.05, 95% CI 0.09 to 2.01). Statistical analysis of the FSFI scores indicated female sexual function was significantly better in the RRCS group than in the LRCS group at 6 and 12 months postoperatively (MD, 2.86; 95% CI 1.38 to 4.35; and MD, 4.19; 95% CI 1.85 to 6.54). RRCS is more favorable than LRCS in preserving the urinary and sexual function of patients with rectal cancer.
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  • 文章类型: Journal Article
    四名直肠癌患者需要重建阴道后壁的缺损。所有患者均接受新辅助(化学)放疗,然后对直肠和阴道后壁进行会阴整块(腹部)切除。阴道缺损的程度需要使用带有皮肤岛的组织瓣进行闭合。臀部翻转皮瓣用于此目的,以替代常规的更具侵入性的肌皮瓣(gracilis,臀肌,或腹直肌)。臀翻皮瓣是通过一个弯曲的切口在距会阴伤口边缘2.5厘米的最大宽度创建的,从而创造了一个半月形的皮肤岛。皮下脂肪被解剖到臀肌,臀肌筋膜被切开了.此后,将皮瓣旋转到缺损中,并将皮肤岛缝合到阴道壁缺损中。动员对侧皮下脂肪在中线进行会阴闭合,之后没有供体部位可见。手术时间从77到392分钟不等,住院时间为3至16天。两名患者会阴伤口裂开,需要对一名患者进行额外的VY臀部成形术。所有患者均实现了阴道和会阴伤口的完全愈合。臀肌翻转皮瓣是一种最有前途的微创技术,可在直肠癌的腹部手术切除后重建阴道后壁缺损。
    Four patients with rectal cancer required reconstruction of a defect of the posterior vaginal wall. All patients received neoadjuvant (chemo)radiotherapy, followed by an en bloc (abdomino)perineal resection of the rectum and posterior vaginal wall. The extent of the vaginal defect necessitated closure using a tissue flap with skin island. The gluteal turnover flap was used for this purpose as an alternative to conventional more invasive myocutaneous flaps (gracilis, gluteus, or rectus abdominis). The gluteal turnover flap was created through a curved incision at a maximum width of 2.5 cm from the edge of the perineal wound, thereby creating a half-moon shape skin island. The subcutaneous fat was dissected toward the gluteal muscle, and the gluteal fascia was incised. Thereafter, the flap was rotated into the defect and the skin island was sutured into the vaginal wall defect. The contralateral subcutaneous fat was mobilized for perineal closure in the midline, after which no donor site was visible.The duration of surgery varied from 77 to 392 min, and the hospital stay ranged between 3 and 16 days. A perineal wound dehiscence occurred in two patients, requiring an additional VY gluteal plasty in one patient. Complete vaginal and perineal wound healing was achieved in all patients. The gluteal turnover flap is a promising least invasive technique to reconstruct posterior vaginal wall defects after abdominoperineal resection for rectal cancer.
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  • 文章类型: Journal Article
    慢性盆腔疼痛是一个隐藏的问题,需要涉及许多不同的通常不协调的专家。因此,治疗存在风险,在没有明确定义的途径的情况下,共同目标,和术语,可能效果不佳。本文的目的是总结肛门直肠盆腔疼痛的证据,为结直肠外科医生的日常活动提供有用的循证实践参数。慢性肛肠及盆腔疼痛综合征分析,诊断和临床最佳评估需求,目前可获得的大量低证据治疗和治疗方案表明,多模式个体化疼痛管理可能是最有希望的方法。专用中心的有限可用性仍然对这些原则的适用性产生负面影响。
    Chronic pelvic pain is a hidden issue which needs to involve many different usually uncoordinated specialists. For this reason there is a risk that treatments, in the absence of well-defined pathways, common goals, and terminology, may be poorly effective. The aim of the present paper is to summarize the evidence on anorectal pelvic pain, offering useful evidence-based practice parameters for colorectal surgeons\' daily activity. Analysis of chronic anorectal and pelvic pain syndromes, the diagnostic and clinical optimal needs for evaluation, and the innumerable low evidence treatments and therapeutic options currently available suggests that a multimodal individualized management of pain may be the most promising approach. The limited availability of dedicated centers still negatively affects the applicability of these principles.
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  • 文章类型: Journal Article
    结直肠癌(CRC)仍然是全球癌症相关死亡的主要原因。缺乏有效的生物标志物和治疗靶点。揭示CRC的关键致病因素和潜在机制将为临床应用提供潜在的治疗策略。G蛋白信号(RGS)蛋白家族调节剂在调节GPCR受体的下游信号中起重要作用,在癌症中的功能不清楚。我们的研究集中在CRC中RGS蛋白的表达模式,确定G蛋白信号调节因子16(RGS16)作为一个前瞻性的诊断和治疗靶标。分析899个CRC组织显示RGS16水平升高,通过免疫组织化学(IHC)结合微阵列与临床病理特征和CRC预后相关。我们证实了CRC中RGS16蛋白水平的升高,发现与RGS16低表达的患者相比,RGS16高肿瘤患者的疾病特异性生存率(DSS)和无病生存率(DFS)降低。功能测定表明RGS16促进CRC进展,RGS16的敲低导致CRC在体外和体内的凋亡率显着增加。值得注意的是,我们还证实了RGS16在源自切除的原发性人类CRC组织的类器官中的这些表型。机械上,RGS16通过破坏TAB2/TAK1募集至TRAF6来抑制JNK/P38介导的CRC细胞凋亡。这项研究提供了解决CRC带来的挑战的见解,为临床翻译提供途径。
    Colorectal cancer (CRC) remains a major global cause of cancer-related mortality, lacking effective biomarkers and therapeutic targets. Revealing the critical pathogenic factors of CRC and the underlying mechanisms would offer potential therapeutic strategies for clinical application. G protein signaling (RGS) protein family modulators play essential role within regulating downstream signaling of GPCR receptors, with function in cancers unclear. Our study focused on the expression patterns of RGS proteins in CRC, identifying Regulator of G protein signaling 16 (RGS16) as a prospective diagnostic and therapeutic target. Analyzing 899 CRC tissues revealed elevated RGS16 levels, correlating with clinicopathological features and CRC prognosis by immunohistochemistry (IHC) combined with microarray. We confirmed the elevated RGS16 protein level in CRC, and found that patients with RGS16-high tumors exhibited decreased disease-specific survival (DSS) and disease-free survival (DFS) compared to those with low RGS16 expression. Functional assays demonstrated that RGS16 promoted the CRC progression, knockdown of RGS16 led to significantly increased apoptosis rates of CRC in vitro and in vivo. Notably, we also confirmed these phenotypes of RGS16 in organoids originated from resected primary human CRC tissues. Mechanistically, RGS16 restrained JNK/P38-mediated apoptosis in CRC cells through disrupting the recruitment of TAB2/TAK1 to TRAF6. This study provides insights into addressing the challenges posed by CRC, offering avenues for clinical translation.
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  • 文章类型: Journal Article
    肠道菌群影响癌症患者对免疫检查点抑制剂(ICI)的临床反应。然而,有害生态失调没有一致的定义。基于宏基因组学(MG)对245例非小细胞肺癌(NSCLC)患者粪便进行测序,我们构建了物种水平的共丰度网络,这些网络被聚集成与总体存活相关的物种相互作用组(SIG).37和45个MG物种(MGS)与对ICIs的抗性(SIG1)和反应(SIG2)相关,分别。当与Akkermansia物种的定量相结合时,该程序允许基于人计算拓扑评分(TOPOSCORE),该评分在另外254例NSCLC患者和216例泌尿生殖系统癌症患者中得到验证.最后,该TOPOSCORE被转化为基于21细菌探针集的qPCR评分,该评分在NSCLC患者以及结直肠和黑色素瘤患者的前瞻性队列中得到了验证.这种方法可以代表肠道菌群失调的动态诊断工具,以指导以微生物群为中心的个性化干预措施。
    The gut microbiota influences the clinical responses of cancer patients to immunecheckpoint inhibitors (ICIs). However, there is no consensus definition of detrimental dysbiosis. Based on metagenomics (MG) sequencing of 245 non-small cell lung cancer (NSCLC) patient feces, we constructed species-level co-abundance networks that were clustered into species-interacting groups (SIGs) correlating with overall survival. Thirty-seven and forty-five MG species (MGSs) were associated with resistance (SIG1) and response (SIG2) to ICIs, respectively. When combined with the quantification of Akkermansia species, this procedure allowed a person-based calculation of a topological score (TOPOSCORE) that was validated in an additional 254 NSCLC patients and in 216 genitourinary cancer patients. Finally, this TOPOSCORE was translated into a 21-bacterial probe set-based qPCR scoring that was validated in a prospective cohort of NSCLC patients as well as in colorectal and melanoma patients. This approach could represent a dynamic diagnosis tool for intestinal dysbiosis to guide personalized microbiota-centered interventions.
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  • 文章类型: Case Reports
    背景:直肠鳞状细胞癌(rSCC)的治疗策略尚未建立,鉴于它的稀有性。尽管据报道鳞状细胞癌对西妥昔单抗和放射线高度敏感,尚无西妥昔单抗联合放疗治疗rSCC的报道.在这项研究中,我们首先报道了一例rSCC,其中最初的放化疗包括奥沙利铂,S-1西妥昔单抗,同时辐射。
    方法:一名46岁妇女因下腹痛和疲劳就诊。
    方法:基于肿瘤标志物分析,活检标本的组织学检查,和综合成像,患者被诊断为rSCC.
    方法:新辅助放化疗(50.4Gy)分28次进行,同时化疗包括SOX(S-1:80mg/m2,第1-5天和第8-12天,奥沙利铂:85mg/m2,第1天)和西妥昔单抗(400mg/m2,第1天,250mg/m2,第8天之后)。
    结果:放化疗后五周,患者接受了腹腔镜部分括约肌间切除术,实现完整的病理反应。
    结论:该病例首先强调了SOX联合西妥昔单抗联合放疗治疗局部晚期rSCC的有效性。然而,需要进行大规模研究以建立安全有效的治疗方案.
    BACKGROUND: Treatment strategies for rectal squamous cell carcinoma (rSCC) are yet to be established, given its rarity. Although squamous cell carcinoma has been reported to be highly sensitive to cetuximab and radiation, there is no report of combination therapy of cetuximab and radiation for rSCC. In this study, we firstly reported a case of rSCC in which a complete response was achieved with the original chemoradiotherapy comprising oxaliplatin, S-1, cetuximab, and simultaneous radiation.
    METHODS: A 46-year-old women presented to our hospital with lower abdominal pain and fatigue.
    METHODS: Based on tumor marker analyses, histological examination of biopsy specimens, and comprehensive imaging, the patient was diagnosed with rSCC.
    METHODS: Neoadjuvant chemoradiotherapy (50.4 Gy) was administered in 28 fractions, along with concurrent chemotherapy comprising SOX (S-1: 80 mg/m2, days 1-5 and 8-12, oxaliplatin: 85 mg/m2, day 1) and cetuximab (400 mg/m2, day 1, 250 mg/m2, after day 8).
    RESULTS: Five weeks after chemoradiation, the patient underwent laparoscopic partial intersphincteric resection, achieving a complete pathological response.
    CONCLUSIONS: This case firstly highlights the usefulness of SOX plus cetuximab combined with radiation in the treatment of locally advanced rSCC. However, a large-scale study is required to establish safe and effective treatment regimens.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    这项研究确定了正电子发射断层扫描/磁共振成像(PET/MRI)参数在预测接受术前放化疗(CRT)的局部直肠癌患者的治疗反应中的敏感性和特异性。
    招募计划于术前CRT后手术的I-III期直肠腺癌患者。患者在基线和CRT后6-8周进行PET/MRI扫描。评估功能MRI和PET参数对肿瘤消退等级(TRG)的诊断准确性。非参数受试者工作特性分析用于确定ROC曲线下面积(AUC),以及每个分位数截止的灵敏度和特异性。
    共招募了31名患者,其中20人完成了研究方案。包括的所有患者均患有直肠中部或下部肿瘤。有16名患者(80%)出现淋巴结阳性疾病。手术的中位时间为75.5天(范围52-106天)。组织病理学评估显示20%良好反应者(TRG1/2),其余80%的患者反应不佳(TRG3/4)。当预测好的反应者时,最大厚度减少百分比和表观扩散系数(ADC)变化百分比的AUC值分别为0.82和0.73。>47%的最大厚度减少截止值和>20%的ADC百分比变化产生75%/95%和75%/73%的灵敏度和特异性。分别。
    诸如最大厚度减少百分比和ADC变化百分比之类的参数可能有助于预测接受直肠癌术前CRT的患者的良好反应。需要更大规模的研究来确定PET/MRI在直肠癌分期中的实用性。
    UNASSIGNED: This study determines the sensitivity and specificity of positron emission tomography/magnetic resonance imaging (PET/MRI) parameters in predicting treatment response in patients with localised rectal cancer who have undergone preoperative chemoradiotherapy (CRT).
    UNASSIGNED: Patients with stage I-III adenocarcinoma of the rectum planned for preoperative CRT followed by surgery were recruited. Patients had PET/MRI scans at baseline and 6-8 weeks post-CRT. Functional MRI and PET parameters were assessed for their diagnostic accuracy for tumour regression grade (TRG). Nonparametric receiver operating characteristic analysis was employed to determine the area under the ROC curve (AUC), and the sensitivity and specificity of each quantile cut-off.
    UNASSIGNED: A total of 31 patients were recruited, of whom 20 completed study protocol. All patients included had mid or lower rectal tumours. There were 16 patients (80%) with node-positive disease at presentation. The median time to surgery was 75.5 days (range 52-106 days). Histopathological assessment revealed 20% good responders (TRG 1/2), and the remaining 80% of patients had a poor response (TRG 3/4). When predicting good responders, the AUC values for percent maximum thickness reduction and percent apparent diffusion coefficient (ADC) change were 0.82 and 0.73, respectively. A maximum thickness reduction cut-off of >47% and a percent ADC change of >20% yielded a sensitivity and specificity of 75%/95% and 75%/73%, respectively.
    UNASSIGNED: Parameters such as percent maximum thickness reduction and percent ADC change may be useful for predicting good responders in patients undergoing preoperative CRT for rectal cancer. Larger studies are warranted to establish the utility of PET/MRI in rectal cancer staging.
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