Carcinoid of the Rectum Risk Stratification (CaRRS): A Strategy for Preoperative Outcome Assessment

Background Predicting rectal carcinoid behavior exclusively on the basis of tumor size is imprecise. We sought to identify factors associated with outcome and incorporate them into a preoperative risk stratification scheme. Methods Seventy patients with rectal carcinoid evaluated at our institution were identified. Demographic, clinical, and histopathologic data were collected and correlated with recurrence and survival. Results The mean age of our cohort was 53.6 years. Fifty-seven percent of patients were women. The mean tumor size was 1.3 cm (range, .1–5 cm). Twenty-five percent of patients had deeply invasive tumors (into the muscularis propria or deeper); an equal percentage had tumors with lymphovascular invasion (LVI) or an increased mitotic rate (two or more mitoses per 50 high-power fields). Eleven patients (17%) had distant metastases at presentation. Sixty-one patients were followed for a median of 22 months (range, 2–308 months), during which seven patients developed recurrence and seven died of disease (including two of seven whose disease recurred). Poor outcome was associated with large tumor size, deep invasion, presence of LVI, and increased mitotic rate. These factors were incorporated into a Carcinoid of the Rectum Risk Stratification (CaRRS) score. CaRRS predicted recurrence-free and disease-specific survival better than any single factor alone. Conclusions Poor prognostic features of rectal carcinoids include large size, deep invasion, LVI, and increased mitotic rate. The CaRRS score incorporates these features and accurately predicts outcome. Because the CaRRS score is based on values available by preoperative biopsy, it can identify patients with favorable prognosis and those with poor prognosis who may benefit from additional staging or surveillance.     

直肠类癌预后影响因素分析

目的探讨直肠类癌的临床病理特点及影响预后的因素。方法回顾性分析31例直肠类癌患者的临床资料,所有病例均经手术和病理检查证实。将其按肿瘤直径大小和肌层是否有浸润分别分组,比较不同肿瘤直径各组和肌层是否浸润各组的手术治疗效果。结果本组31例直肠类癌患者的中位年龄49岁(22～83岁),中位随访时间36个月(15～86个月),随访率为80.6%(25/31)。随访期内,肿瘤直径≤l.0 cm的15例手术切除肿瘤后无复发,直径1.0～2.0 cm的7例中复发1例,直径>2.0 cm的3例中2例因类癌肝转移死亡。直肠类癌是否浸润肌层或全层以及是否有转移均与肿瘤大小有关(P<0.05);肿瘤的浸润深度与转移有关(P<0.05)。随着直肠类癌直径的增大,肿瘤浸润深度加深,转移发生率增高。结论直肠类癌的大小和肌层浸润可能是影响患者生存的重要因素,是选择手术方式时需参考的重要依据。     

直肠类癌36例外科治疗体会

目的:探讨直肠类癌外科治疗的合理方法及疗效。方法:回顾性分析36例直肠类癌病例的临床资料。结果:随访（82.6±63.4）个月。小于1cm的20例手术切除后无一复发，1~2cm的9例有3例复发，大于2cm的7例中3例因类癌肝转移死亡。结论:肿瘤直径大小可粗略地判断直肠类癌潜在恶性程度, 以TNM分期来决定手术方式简单、实用,值得推荐。     

Long-Term Outcome of Patients with Locally Resected High- and Low-Risk Rectal Carcinoid Tumors

Background

Tumor size and lymphovascular invasion are known high-risk factors for lymph node and distant metastasis in patients with rectal carcinoid tumors. However, the optimal treatment for these tumors remains controversial.

Aim

The aim of this paper is to compare the outcome of local or radical resection between patients with high-risk (tumor size >10 mm or lymphovascular invasion) disease and those with low-risk (tumor size ≤10 mm, no lymphovascular invasion) disease.

Methods

Patients with rectal carcinoid tumors treated between January 1990 and March 2010 were identified retrospectively and classified into low- and high-risk groups.

Results

In total, 83 patients with rectal carcinoid tumors were included, 53 (64 %) of whom were identified as low-risk and 30 (36 %) as high-risk. Local resection was performed in 50 (60 %) low-risk and 24 (29 %) high-risk patients, and postoperative recurrence was observed in one (1 %) of the high-risk patients who underwent local resection and one (11 %) who underwent radical resection. No recurrence was observed in the low-risk group. Kaplan–Meier analysis of the patients who underwent local resection revealed that the 10-year disease-free survival rate was 100 % in the low-risk group and 83.3 % in the high-risk group.

Conclusions

There was no significant difference in outcome between local and radical resection.     

Usefulness of transanal endoscopic surgery for carcinoid tumor in the upper and middle rectum

Background This study evaluated the indications and outcome for transanal endoscopic surgery (TES) used to manage rectal carcinoid tumor as compared with those of conventional transanal local resection (TAR). Methods The retrospective study subjects were 28 patients with rectal carcinoid tumor treated by TES (n = 17) or TAR (n = 11) between January 1995 and December 2001. Patient and tumor characteristics, operative results, and postoperative outcomes were compared between the two groups. Results The distance from the anal verge to the distal tumor margin in the TES group (range, 4–12 cm; median, 6.8 cm) was significantly greater than in the TAR group (range, 3–6 cm; median, 4.5 cm) (p = 0.001). The median tumor diameter was 5.5 mm (range, 3–11 mm) in the TES group and 5.0 mm (range, 3–8 mm) in the TAR group, showing no statistical difference. Microscopically, resected specimens in both groups were typical carcinoid tumors restricted to the submucosal layer. No recurrence was noted in either group. Conclusion Whereas TES is useful for patients with small rectal carcinoid tumor of typical histology within the submucosal layer in the upper and middle rectum, TAR is effective for accessing the lower rectum.     

内镜治疗直肠类癌的长期疗效

目的探讨内镜下治疗直肠类癌的长期疗效。方法总结分析2000年1月至2007年7月间采用内镜治疗的91例直肠类癌患者的临床资料。结果本组患者肿瘤病理结果均为典型类癌，均未突破黏膜下层，均未侵及周围淋巴结及血管。有80例（87．9％）患者获随访，随访时间6～96（32．5±24．1）个月。肿瘤直径小于1．0cm的65例患者，术后无1例复发；1．0-2．0cm的25例患者，术后有3例（12％）复发，复发时间分别为3个月、2年和6个月，其中1例再行Dixon术后3个月又出现肝脏转移（4％）：肿瘤直径大于2．0cm的1例患者术后未见复发。本组1、3、5年累计生存率分别为100％、98．0％和91．4％。结论肿瘤直径小于1cm、未侵犯肌层的直肠类癌患者内镜下治疗长期疗效较为理想。     

Novel nomograms to predict muscle invasion and lymph node metastasis in upper tract urothelial carcinoma

ObjectivesTo develop accurate preoperative nomograms for prediction of muscle-invasive disease and lymph node metastasis in upper tract urothelial carcinoma (UTUC), to assist surgeons in risk stratifying patients and help guide treatment decisions.Materials/MethodsThe National Cancer Database was used to identify all patients from 2004 to 2016 with UTUC who underwent extirpative surgery and lymphadenectomy. Univariate and multivariate logistic regression was performed to identify variables predicting muscle-invasive and node-positive disease. The data set was split 80:20 into a derivation and validation cohort and used to generate and test two nomograms. Nomograms were assessed using area under the curve (AUC) and calibration plots.ResultsA total of 6,143 patients met inclusion criteria. Predictors of muscle-invasive disease were age, grade, lymphovascular invasion (LVI), tumor size, and positive clinical lymph node status. Predictors of node-positive disease were grade, LVI, tumor size, and positive clinical lymph node status. The accuracy of the final nomogram predicting muscle-invasive disease was 80.0% (AUC 0.800, corrected C-index 0.813), and the accuracy of the nomogram predicting node-positive disease was 87.8% (AUC 0.878, corrected C-index 0.887).ConclusionsWith data readily available after imaging and biopsy (age, tumor grade, LVI status, tumor size, and clinical lymph node status), we developed the first preoperative nomograms to quantitatively predict muscle-invasive disease and lymph node metastasis in UTUC, with an accuracy of 80.0% and 87.8% respectively. This information could be helpful to assist surgeons with pre-operative risk stratification.     

Tumor invasion of muscular vessels predicts poor prognosis in patients with pancreatic ductal adenocarcinoma who have received neoadjuvant therapy and pancreaticoduodenectomy

Lymphovascular invasion (LVI) is a prognostic factor in many types of human malignancies, including pancreatic ductal adenocarcinoma (PDAC). However, the prognostic significance of LVI in patients with PDAC who have received neoadjuvant therapy and pancreaticoduodenectomy is unclear. In this study, we analyzed LVI in 212 patients who had received neoadjuvant chemoradiation and subsequent pancreaticoduodenectomy at our institution between January 1999 and December 2007. LVI was present in 61.8% (131/212) of the patients. Of the 131 patients who were positive for LVI, 67 (31.6%) had tumor invasion into lymphovascular spaces without muscle layer (nonmuscular lymphovascular spaces), and 64 (30.2%) had tumor invasion into muscular vessels. Tumor invasion into muscular vessels correlated with higher frequencies of positive resection margin, lymph node metastasis, and locoregional/distant recurrence. Patients with tumor invasion into muscular vessels had significantly shorter disease-free survival and overall survival than did patients who had no LVI or who had tumor invasion of nonmuscular lymphovascular spaces (P<0.01). Tumor invasion into muscular vessels is an independent prognostic factor in patients with PDAC who have received neoadjuvant therapies. Our results showed that tumor invasion into muscular vessels plays an important role in the progression of PDAC and in predicting prognosis in this group of patients.     

Lymph node status combined with lymphovascular invasion creates a more powerful tool for predicting outcome in patients with invasive breast cancer

BACKGROUND: Multiple clinical, biologic, and pathologic factors are known to correlate with outcome in patients with invasive breast cancer. The utility of lymphovascular invasion as an additional useful prognostic indicator has been heretofore ill defined. The purpose of the current study was to determine whether the presence or absence of peritumoral lymphovascular invasion (LVI) contribute further significant information in assessing survival. METHODS: Using a prospective database of 1,258 patients with invasive breast cancer followed up for as long as 12 years, eight factors were evaluated for their impact on patient survival: lymph node status, LVI, age at diagnosis, tumor size, tumor palpability, estrogen and progesterone receptor status, and nuclear grade. RESULTS: Multivariate analysis revealed that both lymph node status and the presence or absence of LVI were highly significant independent predictors of outcome. CONCLUSIONS: Knowledge of both lymph node status and the presence or absence of LVI can be used to predict which subset of patients will do extremely well (node negative + LVI absent) or extremely poorly (node positive + LVI present). The combination of the two factors is most meaningful in patients with 1 to 3 positive nodes.     

Improved methods of detection of lymphovascular invasion demonstrate that it is the predominant method of vascular invasion in breast cancer and has important clinical consequences

The presence of vascular invasion (VI), encompassing both lymphovascular invasion (LVI) and blood vascular invasion (BVI), in breast cancer has been found to be a poor prognostic factor. It is not clear, however, which type of VI plays the major role in metastasis. The aims of this study were to use an endothelial subtype specific immunohistochemical approach to distinguish between LVI and BVI by comparing the differential expression of blood vascular (CD34 and CD31) and lymphatic markers (podoplanin/D2-40) to determine their prognostic role in a well-characterized group of breast cancer patients with known long-term follow-up. Sections from 177 consecutive paraffin-embedded archival specimens of primary invasive breast cancer were stained for expression of podoplanin, D2-40, CD31, and CD34. BVI and LVI were identified and results were correlated with clinicopathologic criteria and patient survival. VI was detected in 56/177 specimens (31.6%); 54 (96.4%) were LVI and 2 (3.5%) were BVI. The presence of LVI was significantly associated with the presence of lymph node metastasis, larger tumor size, development of distant metastasis, regional recurrence and worse disease-free interval and overall survival. In multivariate analysis, LVI retained significance association with decreased disease-free interval and overall survival. In conclusion, VI in breast cancer is predominantly of lymph vessels and is a powerful independent prognostic factor, which is associated with risk of recurrence and death from the disease. The use of immunohistochemical staining with a lymphendothelial specific marker such as podoplanin/D2-40 increases the accuracy of identification of patients with tumor associated LVI.     

Pathologic Characteristics of Breast Cancer that Predict for Local Recurrence After Lumpectomy Alone

▪ Abstract: Breast conservation surgery (BCS) plus irradiation has been shown to be equivalent to mastectomy in controlling ipsilateral breast cancer recurrence. The purpose of this study is to evaluate the factors that determine the rate of local recurrence in a group of patients treated with partial mastectomy without postoperative radiation, adjuvant hormonal therapy, or chemotherapy. We also assess the role of standard pathologic features, specifically lymphovascular invasion (LVI) in identifying high- and low-risk subsets of patients. We have a cohort of 293 patients treated with partial mastectomy followed prospectively for a median of 8 years. Data collected included patient's age, tumor size, tumor morphology, tumor grade, the extent of ductal carcinoma in situ (DCIS), the presence of LVI, lymph node status, and hormone receptors. Statistical analyses carried out were Kaplan–Meier plots with Wilcoxon (Peto–Prentice) test statistics for univariate analysis and Cox stepwise regression for multivariate analysis; the end point was local recurrence. The relapse rate in this cohort was 26%. In univariate analysis the significant factors associated with prolonged disease-free survival included older age, negative nodes, positive estrogen receptor (ER) status, and absence of LVI. Small tumor size was significant only in the univariate analysis. In the multivariate analysis, absence of comedocarcinoma entered the model in addition to the other variables. If the variables are stratified, a group of 66 patients with 6% local recurrence rate was identified. These were node-negative women 50 years of age with no LVI, no comedo DCIS, and ER-positive tumors. This study clearly indicates the important role of pathologic parameters in assessing the risk of recurrence.  ▪     

Prognostic Significance of Immunohistochemically Detected Blood and Lymphatic Vessel Invasion in Colorectal Carcinoma: Its Impact on Prognosis

Background The prognostic significance of blood vessel invasion (BVI) and lymphatic vessel invasion (LVI) is unclear. Because of the absence of specific markers for venous and lymphatic vessels, earlier studies could not reliably distinguish between BVI and LVI. Methods By immunostaining for podoplanin and CD34 antigen, we retrospectively investigated LVI and BVI in 419 tissue specimens of colorectal carcinoma. We performed univariate and multivariate analysis of the clinicopathologic features, frequency of recurrence, and outcome of patients with or without LVI and BVI. Results The use of hematoxylin and eosin (H&E) staining to identify BVI and LVI yielded a false positive rate of 9.1% and false negative rate of 12.6%. The incidence of BVI was significantly higher among tumors with LVI than tumors without LVI (P <.001). In logistic multivariate analysis, only LVI (P < .001) was associated with lymph node metastasis and BVI (P = .015) was associated with distant recurrence. Calculating the prognostic relevance, both two invasion types correlated with decreased survival in univariate analysis (both P <.001). In multivariate analysis, BVI (P =.024), lymph node status (P =.003) and tumor stage (P <.001) remained statistically significant factors for survival. Conclusions Our results suggest that immunohistologic evaluation of BVI and LVI could be useful in colorectal carcinoma indicating the risk of lymph node metastasis and recurrence, thereby contributing to prognostic evaluation.     

Treatment of rectal carcinoid tumors

We investigated the treatment of 24 rectal carcinoid tumors from both the clinicopathologic and prognostic viewpoints. All tumors less than 2 cm in diameter had neither muscle layer invasion nor lymph node metastasis, except for an atypical carcinoid tumor that had both lymphatic permeation and intramural metastasis. One typical carcinoid tumor larger than 2 cm had both several lymphatic permeations and urinary bladder invasion. All cases had a good prognosis with no recurrence and no new metastases. For rectal carcinoid tumors less than 2 cm in diameter, local resection is sufficient, whereas radical operation is required for tumors larger than 2 cm in diameter. For atypical rectal carcinoid tumors, radical operation should be considered even if the diameter is less than 2 cm.     

Prognostic analysis for carcinoid tumours of the rectum: a single institutional analysis of 106 patients

Aim Rectal carcinoid is a rare rectal tumour with a good prognosis. The aim of this study was to assess its clinicopathological characteristics and prognostic factors in a single institution. Method Clinical and pathological information was retrospectively collected in a single institution, and patients’ outcomes were determined. Multivariate analyses were performed to find independent prognostic factors attributed to overall survival. Results A total of 106 patients with rectal carcinoid were included. In all, 66% of the patients underwent transanal local excision and 34% had transabdominal surgery. The 5‐year survival rate was 87%. Muscularis invasion was the only independent prognostic factor for predicting 5‐year survival (P = 0.00046). Tumour size was found to be significantly associated with muscular invasion (P = 0.00003). The area under the curve of tumour size in the receiver operating characteristic curve for predicting muscular invasion was 0.92. Conclusion Patients with rectal carcinoid have a good prognosis. Muscular invasion is an independent risk factor of survival.     

Transanal endoscopic microsurgery in the treatment of rectal carcinoid tumor

Background This study aimed to assess the efficacy of transanal endoscopic microsurgery (TEM) in the treatment of rectal carcinoid tumor. Methods Between May 1994 and April 2006, 27 patients with rectal carcinoid tumor underwent TEM, and their clinical data were reviewed retrospectively. Results The TEM procedure was performed as a primary excision (n = 14) or as completion surgery after incomplete resection by endoscopic polypectomy (n = 13). The average size of a primary tumor was 9.1 mm (range, 5–13 mm), and the average distance of the tumor from the anal verge was 8.5 cm. The mean duration of the operation was 51.6 min. Minor morbidities, transient soilage, and mild dehiscence occurred in two cases (7.4%). Histopathologically, all tumors were localized within the submucosal layer showing typical histology without lymphatic or vessel infiltration, and both deep and lateral surgical margins were completely free of tumors. Among 13 cases of completion surgery after endoscopic polypectomy, 4 (30.8%) were histologically shown to have a residual tumor in the specimens obtained by TEM. No additional radical surgery was performed. The mean follow-up period was 70.6 months, and no recurrence was noted. Conclusion The results indicate that TEM is a safe, minimally invasive procedure for the local excision of rectal carcinoid tumors, particularly those in the proximal rectum. Furthermore, for patients with microscopic positive margins after endoscopic polypectomy, TEM can be an effective surgical option for complete removal of residual tumors.     

Prognostic impact of lymphatic and/or blood vessel invasion in patients with node-negative advanced gastric cancer

Background Heterogeneous survival rates in patients with similar clinicopathologic characteristics or molecular prognostic markers have been noted. This study was conducted to evaluate the prognostic effect of lymphatic and/or blood vessel invasion (LBVI), identified by routine hematoxylin and eosin staining, on the outcome of patients with node-negative advanced gastric cancer. Methods A total of 280 patients who underwent curative gastrectomy for advanced gastric cancer without lymph node metastasis were retrospectively reviewed. Univariate and multivariate analyses of the clinicopathological features, recurrences, and prognoses of patients with and without LBVI were performed. Results Lymphatic vessel invasion (LVI) was noted in 20.0%, blood vessel invasion (BVI) in 5.4%, and either LVI or BVI in 22.5%. None of the clinicopathologic features was related to LBVI. Patients with LBVI had a recurrence rate of 26.8%, whereas patients without LBVI had a recurrence rate of 13.5% (P=.018). The 5-year survival rates were 82.4% for patients without LBVI and 67.1% for patients with LBVI (P=.0222). LBVI was shown to be an independent risk factor for recurrence (relative risk, 2.30; 95% confidence interval, 1.06–4.99) and poor prognosis (relative risk, 1.88; 95% confidence interval, 1.07–3.29). Conclusions LBVI is an adverse prognostic indicator and the presence of LBVI seems to provide useful information for the prognosis and clinical management of patients with node-negative advanced gastric carcinoma.     

Prognostic impact of lymphovascular invasion in radical prostatectomy specimens

OBJECTIVE: To estimate the prognostic value of lymphovascular invasion (LVI) in patients with node-negative prostate cancer treated by radical prostatectomy (RP). PATIENTS AND METHODS: In all, 412 patients with prostatic adenocarcinoma who had RP and pN0 status were analysed for all established standard pathological factors and LVI. The influence of these pathological findings on biochemical failure was evaluated by multivariate analysis with the Cox model. The mean (range) follow-up was 52.5 (10-116) months. RESULTS: LVI was identified in 42 patients (10.2%) and significantly associated with a high preoperative prostate-specific antigen (PSA) level, a high PSA density, high percentage of positive biopsy cores, high Gleason score, and seminal vesicle invasion. Of the 42 patients with LVI, 33 (79%) had a Gleason score of > or = 7 and 27 (64%) had pathological stage pT3. The 5-year biochemical-free survival was 87.3% for patients with no LVI and 38.3% with LVI on the RP specimen (P < 0.001). By multivariate analysis, LVI and Gleason score were independent predictors of biochemical failure. CONCLUSION: These results show that in addition to the Gleason score, only LVI is strongly correlated with biochemical failure after RP. These findings support the routine evaluation of LVI status in RP specimens and provide the option for its incorporation into nomograms predictive of oncological outcome.     

Lymph-node metastases in rectal carcinoids

Background

Colorectal carcinoids are described as low-grade malignancy in the WHO classification. However, the survival is equally poor between carcinoids and adenocarcinomas if the tumors have lymph node metastasis or distant metastasis.

Patients and methods

We reviewed 17 patients with rectal carcinoid, who underwent surgical resection with lymph node dissection at our institution between March 2005 and November 2007. Our criteria for surgical resection were: tumor size of 10 mm or larger and positive resection margin or the presence of lymphovascular invasion in lesions to which endoscopic or surgical local treatment was carried out.

Results

Lymph node metastases were present in 12 patients. Three of them were with tumors less than 10 mm in size, of whom two patients had lymphovascular invasion. In eight out of the 12 with lymph node metastases, preoperative computed tomography (CT) identified lymph nodes of 5 mm or larger in size.

Conclusions

The present study demonstrated that rectal carcinoids with lymph node metastasis are common. Previously reported risk factors of lymph node metastasis in rectal carcinoid such as tumor size >?=?10 mm and lymphovascular invasion are useful in predicting lymph node metastasis. In addition, lymph nodes 5 mm or larger in size identified on preoperative CT suggest the presence of metastasis.     

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??Objective:To evaluate the outcome and the prognosis of transanal local excision in the treatment of patients with benign and malignant lower rectal tumors. Methods:From January 2003 to July 2006,86 patients (49 man,37 women) with benign (n=55) and malignant (n=31) rectal tumors underwent transanal local excision.Data were analyzed retrospectively and 69 patients obtained follow??up. Results:Among 86 patients,there were 26 cases of adenocarcinomas??30.2%??,39 cases of adenoma ??45.3%??,3 cases of carcinoid ??3.5%??,1 case of GIST ??1.2%??,and 17 cases of others ??19.8%??.All tumors located 1 to 12cm from the dentate line.The tumor size was less than 3cm in 68 patients (79.1%),and more than 3cm in 18 patients (21.9%).During the follow??up of 69 patients,tumor recurrence was observed in 6 of 57 patients with the tumor size ??3cm,in 5 of 12 patients with ≥3cm,and the difference was significance (P??0.01).Among the assessable patients of adenocarcinoma,there were 19 cases in T1 and 7 cases in T2.The tumor recurrence was observed in 2 of 16 patients for T1 and in 4 of 7 patients for T2 (P??0.05). Conclusion:Transanal local excision for low rectal tumor is appealing for its less morbidity and excellent functional results.It may be used in the curative management of benign rectal tumors and selected early malignant neoplasm with small tumor size.It is also a treatment option for patients who would be unable to tolerate radical surgery.     

直肠类癌29例的外科治疗

目的 探讨直肠类癌的临床、病理及影响预后的因素.方法 回顾性分析两家医院29例直肠类癌患者的临床资料.所有病例均经手术和病理证实,其中内镜黏膜下切除5例,经肛门局部切除14例、局部扩大切除4例,经骶尾直肠部分切除2例,根治性切除4例.结果 本组29例直肠类癌患者的年龄32～71(54±11)岁,随访时间3至136个月,平均(61±4)个月,随访率为76%.随访期内,直径小于1 cm的13例手术切除后无复发,直径1～2 cm的5例复发1例,直径大于2 cm的4例中3例因类癌肝转移死亡.5年、10年肿瘤相关生存率为87%、80%.结论 手术治疗是直肠类癌的最佳治疗方法,手术切除范围取决于原发肿瘤的大小、浸润程度、淋巴结受累及是否存在肝脏转移等情况.