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10.1245/s10434-006-9311-6
Annals of Surgical Oncology 14:1735-1743 (2007)
© 2007 Society of Surgical Oncology
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Original Article

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

Bridget N. Fahy1, Laura H. Tang2, David Klimstra2, W. Douglas Wong1, Jose G. Guillem1, Philip B. Paty1, Larissa K. F. Temple1, Jinru Shia2 and Martin R. Weiser1

1 Department of Surgery, Division of Colorectal Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
2 Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Correspondence: Address correspondence and reprint requests to: Martin R. Weiser; E-mail: weiser1{at}mskcc.org


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Predicting rectal carcinoid behavior based exclusively on tumor size is imprecise. We sought to identify factors associated with outcome and incorporate them into a pre-operative risk stratification scheme.

Methods: Seventy rectal carcinoid patients 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 female. The mean tumor size was 1.3 cm (range: 0.1–5 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 elevated mitotic rate (≥ 2/50 HPF). Eleven patients (17%) had distant metastases at presentation. Sixty-one patients were followed for a median of 22 months (2–308 months), during which seven patients developed recurrence and seven died of disease (2/7 who developed recurrence). Poor outcome was associated with large tumor size, deep invasion, presence of LVI, and elevated 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 elevated mitotic rate. The CaRRS score incorporates these features and accurately predicts outcome. Because the CaRRS score is based upon values available on pre-operative biopsy, it can identify patients with very favorable prognosis as well as those with poor prognosis that may benefit from additional staging or surveillance.

Key Words: Carcinoid • Rectum • Outcome • Risk assessment


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Rectal carcinoids are rare, accounting for approximately 15% of all gastrointestinal tract carcinoids and 1.3% of all rectal tumors. Rectal carcinoids tend to exhibit more indolent behavior when compared with carcinoids at other sites. A recent study by Rorstad1 reported that 5-year survival rates for rectal carcinoids varied from 62 to 100%, while those for small intestine were 52–77%, and for colon (excluding appendix) 33–75%.

The wide variability in survival for patients with rectal carcinoids challenges the assumption that these tumors behave in an indolent fashion. Available reports are conflicting regarding what constitutes a virulent carcinoid tumor. Several factors have been studied as possible predictors of behavior in rectal carcinoids. Size of the primary tumor has been most thoroughly examined. The risk of metastasis has been shown to correlate with size by several authors.2–4 According to a report by Mani et al.3 metastases were found in 2% of patients with tumors <1.0 cm, 10–15% in patients with tumors measuring 1.0–1.9 cm, and 60–80% in patients with tumors measuring >2 cm. Similar findings were reported by Schindl et al.,4 where size of the rectal carcinoid was found to correlate with the presence of regional (lymph node) or distant metastases. However, Jetmore5 found that for 1–2 cm tumors, size is not as predictive of behavior.

Depth of invasion has also been implicated as an important prognostic factor in rectal carcinoids. Naunheim et al.6 reported that the interaction between size and depth of invasion was important in predicting the behavior of rectal carcinoids. For small tumors <2 cm, metastases were seen in 2% of patients if the tumor was contained within the submucosa; the risk of metastases rose to 48% if the tumor invaded the muscularis propria. These findings were corroborated by Soga et al.,2 who reported a stepwise increase in the risk of metastases with increasing depth of invasion.

Eleven to 36% of patients with rectal carcinoids present with distant metastases at the time of diagnosis.7,8 The existing literature is consistent regarding the significance of distant metastases and outcome in patients with rectal carcinoids; no single criterion other than existing distant metastases accurately predicts the behavior of these tumors.

Pathologic features believed to be associated with aggressive behavior include DNA ploidy, invasion of the muscularis propria, increased mitotic figures, vascular or lymphatic invasion, perineural invasion (PNI), and mucin production. Two authors reported that atypical histopathology was correlated with increased tumor size and/or depth of invasion, which was associated with decreased disease-free survival and increased risk of distant metastases.4,8 Rectal carcinoid tumors were classified as atypical if they manifested one of the following features, according to Koura et al.:8 lymphatic invasion, anaplasia, frequent mitotic cells, cellular pleomorphism, mucin production. The relative importance of these individual factors and their impact on clinical outcome has not been studied.

The aims of the current study were (1) to identify clinical or pathologic variables associated with distant disease, recurrence, and disease-related outcome in rectal carcinoids, and (2) to develop a pre-operative strategy for stratifying rectal carcinoid into low, intermediate, and high risk based upon the above variables.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
All patients evaluated at our institution from 1957 to 2004 with a pathologically-confirmed diagnosis of rectal carcinoid were retrospectively reviewed. During this period, a total of 70 cases of rectal carcinoid tumors were identified. The study design was reviewed and approved by the Institutional Review Board at Memorial Sloan-Kettering Cancer Center. Specific data extracted from the charts included patient age, past medical history, family history, presenting signs or symptoms, clinical and pathologic features of the tumor, radiographic and laboratory evaluation, methods of treatment, and outcomes.

Pathologic Evaluation
All cases were reviewed by a single pathologist (LT). Carcinoid tumors were defined as having one or more of the typical organoid growth patterns characteristic of well-differentiated endocrine neoplasms along with relatively uniform nuclei having coarsely clumped chromatin. The presence of neuroendocrine differentiation was evidenced by positive immunohistochemical staining for chromogranin or synaptophysin. Importantly, the mitotic rate was consistently less than 10/10 HPF (or 50/50 HPF), and neuroendocrine neoplasms with a higher mitotic rate were regarded as representing high grade neuroendocrine carcinomas. For each available case, the size of the primary lesion, depth of invasion, presence of lymphovascular invasion (LVI) or PNI, and mitotic rate were evaluated. The size of each tumor was determined from chart review and was not confirmed. The margin status following excision/resection was determined from review of the pathology report but was not confirmed. Seven patients required an additional procedure because of close or indeterminate excision margin status; all resection margins were reported as negative.

Surgical Management
The method of diagnosing and/or surgically treating the rectal carcinoids was noted for each patient. Patients whose tumors were removed either endoscopically or via transanal excision were grouped together and classified as having undergone local excision. Radical resections included either low anterior resection or abdominoperineal resection. Due to the retrospective nature of our study, we were unable to definitively determine why a certain method of surgical management was chosen.

Additional surgical procedures required to treat the primary rectal carcinoid were recorded for each patient, when possible. The frequency and types of non-surgical treatments provided following surgical biopsy or treatment were noted. Due to the small number of patients who received adjuvant therapies, specific details regarding the type of chemotherapy or dosage of radiation are not presented.

Follow-up
Sixty-one patients were available for follow-up and were followed for a median of 22 months, with a range of 2–308 months. The method(s) used to follow patients after initial excision or resection was noted for each (e.g. physical exam, endoscopy, computed tomography, octreotide scan, and endorectal ultrasound). Disease recurrence was defined as local or distant disease diagnosed more than 3 months after the date of the initial excision or resection. In most cases, the diagnosis of recurrent or metastatic disease was made based upon the results of a biopsy of the new lesion or radiographic findings consistent with metastases.

Statistical Analysis
Categorical groups were compared using Chi-square. Kaplan–Meier methodology was used for time-to-event analysis, and comparisons made with log-rank test. Outcome was measured as recurrence-free survival (RFS) and disease-specific survival (DSS). Differences of P < 0.05 were considered significant. Time to recurrence or death was calculated from the date of surgery to date of first recurrence, death, or last follow-up. Statistical analysis was performed using SPSS 12.0TM software (Chicago, IL, USA).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
A total of 70 patients with rectal carcinoids were evaluated at our institution between 1957 and 2004. The demographic, clinical, and pathologic characteristics of these patients are shown in Table 1Go. There was a slight female predominance in our population. A majority of the tumors were located in the mid-rectum. Metastatic disease was present in 17.5% of patients at the time of initial presentation; the liver was the most common site of distant metastasis. A slight majority of patients presented with symptoms possibly referable to their rectal carcinoids, with bright red blood per rectum being the most common symptom. No patient presented with symptoms consistent with carcinoid syndrome. Most of the tumors were small; the average tumor size was 1.3 cm. In those for whom depth of invasion data was available (n = 63), most tumors were limited to the submucosa. Information regarding LVI was available for 58 of the tumors, of which 24% had evidence of LVI. Twelve patients underwent a radical resection (see below); 11/12 patients had information available regarding lymph node involvement by rectal carcinoid. Nine of eleven patients had lymph node metastases. The number of involved nodes ranged from two to eight, with a median of three nodes involved. Data regarding PNI were available for 59 of the tumors; 12% were found to have PNI. Tumors were divided into those with low (<2/50 HPF) and elevated (≥ 2/50 HPF) mitotic rate. Mitotic rate data were available for 60 of the tumors; 28% had an elevated mitotic rate. Tumors with an elevated mitotic rate had a mean rate of 10.4/50 HPF (range: 2–50/50 HPF).


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  		TABLE 1. Characteristics of 70 patients with rectal carcinoids
 
The method of treatment is summarized in Fig. 1Go. Surgical treatment information was available for 69 patients. The majority of patients, 70%, underwent local excision of their tumors. Additional operative procedures were performed in 11 patients, and 10 patients received some form of additional non-surgical management (chemotherapy or radiation).


Figure 1
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  		FIG. 1. Treatment strategies for all patients.

 
Nine patients were not available for follow-up and were excluded from the survival analysis. Seven patients developed recurrent disease at a median of 29 months after diagnosis. Two patients developed local recurrence and five patients developed hepatic recurrence. At the time of last follow-up, 75% of patients were without evidence of disease, while an equal percentage of patients were either alive with disease or dead of disease (11.5%).

Distant Metastasis at Presentation
The key clinical and pathologic characteristics of rectal carcinoids in patients with and without distant metastases at presentation are summarized in Table 2Go. Patients with metastatic disease were significantly more likely to have larger tumors, deeper tumors, tumors with LVI, and an elevated mitotic rate. Although a majority of patients who presented with metastatic disease were dead of disease at last follow-up, 40% of patients who initially presented with metastatic disease were still alive after a median follow-up of 20 months.


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  		TABLE 2. Clinicopathologic and outcomes in patients with and without distant metastases at initial presentation
 
Patients Who Developed Recurrent Disease
A total of seven patients developed recurrent disease during the course of follow-up; the clinical and pathological features of their tumors are illustrated in Table 3Go. Two patients had tumors <2 cm; these same two patients had tumors confined to the submucosa. Three of five patients with available data had LVI present in their tumors. PNI was present in 1/5 patients in whom these data were available. An elevated mitotic rate was found in 5/6 tumors. Two patients treated by local excision experienced a local recurrence, while one of these patients developed a distant recurrence. The site of recurrence in patients initially managed by radical resection was the liver. Recurrence occurred between 10 and 92 months following initial resection and tended to occur at a later date following radical resection (10–92 months, average 43.3 months) than following local excision (14–29 months, average 20.3 months). The majority of patients were alive with disease at last follow-up (n = 4); only one patient was without disease and two patients had died of their disease.


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  		TABLE 3. Clinical and pathological profile of patients who developed recurrent disease
 
Size of Primary
Because size of the primary tumor has historically been considered the most important factor predicting the behavior of rectal carcinoids, we sought to examine the interrelationship between size and other clinical and pathologic variables included in the current study. Patients were divided based upon the size of their primary lesion (<1, 1–1.9, ≥ 2 cm) and then analyzed for differences in demographic, clinical, and pathologic factors (Table 4Go). There was no association between size of the primary and any of the demographic variables. Only one patient with a tumor <2 cm presented with metastatic disease. The pathologic variables significantly associated with the size of the primary lesion included: depth of invasion, presence of LVI, and mitotic rate. Two patients with tumors <2 cm (4.5%) developed recurrent disease during the period of follow-up, while 4/11 (36%) of patients with tumors ≥ 2 cm developed recurrent disease. No patient with a tumor <2 cm died of disease during the period of follow-up, while 46% of patients with tumors ≥ 2 cm were dead of disease at last follow-up.


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  		TABLE 4. Clinicopathologic and outcomes in patients based upon size of tumor
 
Factors Associated with Recurrence-Free and Disease-Specific Survival
Univariate analysis of RFS and DSS is shown in Table 5Go. Five-year RFS was associated with tumor size, depth of penetration into the intestinal wall, and mitotic rate. Five-year DSS was associated with the above factors as well as LVI. Due to the small numbers in the study, multivariate analysis was not performed.


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  		TABLE 5. Factors associated with recurrence-free survival (RFS) and disease-specific survival (DSS)
 
Carcinoid of the Rectum Risk Stratification (CaRRS)
The results of the analyses above demonstrated that the factors that correlated most closely and consistently with poor outcome included size, depth of invasion, presence of LVI, and mitotic rate. In addition to being reliably associated with virulent behavior or poor outcome, these factors have the advantage of being determined at the time of an initial biopsy and can therefore be used as part of a pre-operative risk stratification. We incorporated these four factors into a risk score by assigning points to the various features as outlined in Table 6Go. Features assigned 0 points were characterised by size <1 cm, invasion confined to the mucosa/submucosa, no LVI, mitotic rate <2/50 HPF. Features assigned one point were characterised by size between 1 and 1.9 cm, invasion into the muscularis propria or deeper, presence of LVI, and mitotic rate ≥ 2/50 HPF. Two points were assigned to tumors ≥ 2 cm. The points were totaled to yield an overall risk score. Patients were then categorized into low, medium, and high risk based on total scores of 0, 1–2, and ≥ 3 points, respectively. The CaRRS score accurately predicted RFS and DSS outcome. As seen in Fig. 1Go, patients with low risk tumors enjoyed a significantly higher 5-year RFS than patients with either intermediate or high risk tumors. Figure 2Go contains the 5-year DSS curve based upon the CaRRS groups and shows a significantly increased 5-year DSS for patients with low risk tumors, compared to those with high risk tumors. Patients with intermediate risk tumors did not differ significantly from the other two groups in terms of 5-year DSS (Fig. 3Go).


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  		TABLE 6. CaRRS: carcinoid of the rectum risk stratification
 

Figure 2
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  		FIG. 2. Recurrence-free survival for patients based upon carcinoid of the rectum risk stratification (CaRRS) scores.

 

Figure 3
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  		FIG. 3. Disease-specific survival for patients based upon CaRRS scores.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Not all rectal carcinoids behave in an indolent fashion. There appear to be a subset of tumors which behave aggressively, either due to distant metastasis, or a tendency toward recurrence. The aim of the current study was to determine which demographic, clinical, and histopathologic features are associated with distant metastases, recurrence, or death. Our secondary aim was to combine these features into a pre-operative risk assessment score which could identify patients with aggressive tumors so that they might be considered for more extensive staging evaluation and/or follow-up.

No demographic factors were capable of identifying patients with aggressive rectal carcinoids. In the current study, the four factors that proved to correlate most closely with aggressive behavior and/or poor outcome were size of the primary tumor, depth of invasion, presence of LVI, and mitotic rate. Tumor size correlated with the presence of metastatic disease; only one patient with a tumor <2 cm (n = 56) presented with distant metastasis while 64% of patients with tumors ≥ 2 cm presented with metastatic disease. This trend is consistent with the frequency of meta-static disease reported by Soga9 in his analysis of 849 rectal carcinoids. The risk of metastases was 10% for rectal carcinoids ≤ 1 cm, 18% for tumors 1.1–2.0 cm, and 57% for tumors ≥ 3 cm. Of note, however, both in our study and in the reports by Soga9 and Naunheim et al.6 metastases were occasionally seen in tumors <2 cm, illustrating that the risk of distant metastases is not governed by size of the primary tumor alone.

Size of the rectal carcinoid was also significantly associated with 5-year RFS and DSS. Patients with tumors <1 cm had a markedly higher 5-year RFS (92%) than patients with tumors ≥ 2 cm (30%). Five-year DSS was also significantly higher in patients with tumors <1 or 1–1.9 cm compared to those with tumors ≥ 2 cm. Our findings are consistent with those of Koura et al.8 who reported a significant correlation between tumor size and metastasis-free survival. Five-year metastasis-free survival was 100% in patients with tumors <1 cm, 65% in patients with tumors 1–1.9 cm, and 25% in patients with tumors ≥ 2 cm.

Depth of tumor invasion was also significantly associated with the presence of distant metastases at presentation, RFS and DSS. Seven of 16 patients with deep lesions presented with metastatic disease compared to only one of 39 patients with superficial invasion. The 5-year RFS in patients whose tumors invaded into the muscularis propria or deeper was 30%, compared to an 88% 5-year RFS in those whose tumors were limited to the mucosa/submucosa. A 68% decrease in 5-year DSS was seen in patients with deeper tumors, compared to those whose tumors were limited to the mucosa/submucosa (32% vs. 100%, respectively). Several other authors have also noted the importance of depth of invasion in predicting the behavior of rectal carcinoids.3,7,10 Soga9 reported a 5-year overall survival for all patients with rectal carcinoids of 88%, while that for patients whose tumors were confined to the submucosa was 98%.

Aside from size and depth of invasion, few other features of rectal carcinoids have been systematically examined for their impact on outcome. The results of the current study showed that LVI and mitotic rate were consistently associated with poor outcomes such as distant metastases, recurrence, and diminished survival. All patients who presented with distant metastases had LVI in their tumors, in contrast to the 18% incidence of LVI found among patients who did not present with distant metastases. The presence of LVI was also associated with a 30% reduction in RFS and DSS. Koura et al.8 are among the few authors who have studied the impact of features such as LVI and PNI on behavior of rectal carcinoids. "Typical" carcinoids, in their study, had no or rare mitotic cells and did not invade the lymphatics, blood vessels, perineurium or muscularis propria. "Atypical" carcinoids, in contrast, had at least one of these features present. Five-year metastasis-free survival was 100% in 16 patients with "typical" carcinoids versus 50% in four patients with "atypical" carcinoids.

We chose to study the mitotic rate of rectal carcinoid tumors because previous studies have demonstrated the prognostic significance of mitotic rate in distinguishing low grade from intermediate grade pancreatic endocrine neoplasms11 and pulmonary carcinoids.12 Additionally, mitotic rate is widely considered one of the most important measures of aggressiveness in well-differentiated endocrine neoplasms. We found that 6/7 patients who presented with distant metastases had a mitotic rate ≥ 2/50 HPF in contrast to only 24% (11/46) of patients who did not present with metastases. Similarly, 5/6 patients who developed recurrence had an elevated mitotic rate. Decreased 5-year RFS and DSS was seen in patients with an elevated mitotic rate (57 and 70%, respectively).

Federspiel et al.7 was among the first to evaluate mitotic rate in colorectal carcinoids in a cohort of 35 patients. Only three of their patients (9%) had a mitotic rate >0/10 HPF. All of their patients who did not present with metastases and were alive at last follow-up had amitotic carcinoids. Although other authors have included mitotic rate under a general categorization of "atypical" versus "typical" carcinoids,4,8 to our knowledge we are the first to independently evaluate the significance of mitotic rate on outcome in patients with rectal carcinoid, and were able to show its consistent and significant association with distant metastases, RFS, and DSS.

Our small sample size prevented us from performing multivariate analyses, which could determine the independent risk factors for poor outcome in rectal carcinoids. Instead, we examined the frequency of adverse clinical and histopathologic features in relationship to tumor size, which has traditionally been considered the primary governor of rectal carcinoid behavior. Our results are consistent with the existing literature; although size is an important factor in predicting the behavior of rectal carcinoids, it does not tell the whole story.2,8,13 We found multiple instances in which poor histopathologic features were seen in small tumors: 3/7 tumors that recurred were <2 cm, 25% of patients with tumors that invaded into the muscularis propria or deeper were <2 cm, 43% of tumors with LVI were <2 cm, and 50% of tumors with a mitotic rate ≥ 2/50 HPF were <2 cm in size. Additionally, there was generally a stepwise increase in the frequency of poor prognostic features with increasing tumor size, such that tumors 1–1.9 cm had an increased frequency of poor characteristics compared to tumors <1 cm, and a lower frequency of these characteristics compared with tumors ≥ 2 cm. Other investigators have also found that factors other than size alone impact outcome and behavior in rectal carcinoids. Naunheim et al.6 reported that the risk of metastases for tumors <2 cm was 6% overall and ranged from 2% if the tumor was contained within the submucosa to 48% if the tumor invaded into the muscularis. Koura et al.8 found that the frequency of atypical histopathology increased with increasing size of the tumor. Twenty-five percent (4/16) patients with tumors <1 cm had atypical carcinoids compared to 50% (4/8) in patients with tumors 1–1.9 cm and a 75% incidence of "atypical" carcinoids in patients with tumors ≥ 2 cm (1/4).

The second aim of our study was to develop a strategy for stratifying rectal carcinoids into low, intermediate, and high risk groups based upon the factors found to be associated with distant metastases, recurrence, and survival. The CaRRS score was determined by assigning points to the four variables identified as important in determining the behavior of rectal carcinoids: size, depth of invasion, LVI, and mitotic rate. We found that our risk groups were capable of distinguishing patients in terms of RFS and DSS (Figs. 1Go, 2Go). We were able to show that patients in the low risk group had essentially no risk of recurrence and a 100% 5-year DSS.

Schindl et al.4 are among the few investigators to attempt to stratify rectal carcinoids by more than a single factor (e.g. size, depth of invasion). They classified rectal carcinoids as either benign (<2 cm, had a typical growth pattern, local invasion, and no regional or distant metastases) or malignant (>2 cm, or had atypical histology, or regional or distant metastases). Sixteen patients with benign tumors underwent local excision, with no local recurrence or death from disease after a mean follow-up of 98 months. In contrast, 4/14 (28.5%) patients with malignant tumors developed local recurrence and 5/14 (36%) died of disease.

The universally good outcome of our low risk patients has implications for pre-operative staging and follow-up. In patients with tumors <1 cm, limited to the mucosa/submucosa, without LVI, and with a mitotic rate <2/50 HPF, no additional staging appears necessary since the risk of distant disease is negligible. Additionally, no unique follow-up is required in these patients since they are at no appreciable risk for recurrence or disease-related death. For patients with intermediate risk tumors, closer follow-up appears justified and should be continued long-term, as recurrence was seen in our patients up to 7.5 years after initial resection. In addition, these patients should be considered for additional staging tests (e.g. computed tomography, endorectal ultrasound, scintigraphy) to identify occult metastases, as was seen in one of our patients with an intermediate risk tumor. Finally, in patients with high risk lesions, both rigorous pre-treatment staging evaluation and close follow-up appears warranted, given their significant risk for distant metastases (7/15, 47%), recurrence (4/13, 31%) and disease-related death (4/15, 27%).

We are unable to make specific surgical treatment recommendations based upon the results of the current study, due to its retrospective nature. However, given the excellent outcome in patients with low risk lesions (as defined above) following local excision, it appears that these patients can be safely managed by local excision alone. The optimal method of surgical management is a more challenging question for patients with intermediate and high risk lesions. Of the 14 patients with intermediate risk lesions who underwent local excision, two patients developed local recurrence (14%). While a radical procedure would have resulted in over-treatment if all patients with intermediate risk lesions were subjected to a radical procedure, consideration of a radical procedure appears justified, given the demonstrated risk of local recurrence in this group following local excision. Of the 15 patients with high risk lesions, three were treated by local excision; one of these patients recurred distantly. The ability of a radical resection to reduce such a patient’s risk of distant recurrence is unknown; therefore, radical resection cannot be routinely recommended in all patients with high risk rectal carcinoids.

The optimal method for following these patients post-excision/resection is currently unknown. Patients in the current study were followed using a variety of modalities: physical exam, computed tomography, lower endoscopy, octreotide scan, endorectal ultrasound. The most common surveillance methods were lower endoscopy followed by computed tomography and physical examination alone. Endorectal ultrasound has only recently been incorporated into our surveillance program for these patients, but is currently being utilized by the majority of the surgeons in our group. Unfortunately, only eight patients in the current study have been followed by endorectal ultrasound, so we are unable to comment on its utility in following patients with rectal carcinoids. Serum chromogranin A has been found by some investigators to be a useful tumor marker for following patients with gastrointestinal carcinoids,14 but was not used routinely in our patients.

The findings of the current study highlight several important features of rectal carcinoids: (1) not all rectal carcinoids behave in an indolent fashion; (2) size alone is an inadequate indicator upon which to predict the behavior of rectal carcinoids; and (3) depth of invasion, LVI, and mitotic rate are important histopathologic features in these tumors. Additionally, we propose a simple risk stratification scheme which can help predict the risk of RFS and DSS, based upon four clinical and histopathological variables readily available from biopsy or endoscopic excisional material.

Received for publication March 30, 2006. Accepted for publication July 13, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Rorstad O. Prognostic indicators for carcinoid neuroendocrine tumors of the gastrointestinal tract. J Surg Oncol 2005; 89(3):151–60.[CrossRef][Medline]
  2. Soga J. Carcinoids of the rectum: an evaluation of 1271 reported cases. Surg Today 1997; 27(2):112–9.[CrossRef][Medline]
  3. Mani S, et al. Carcinoids of the rectum. J Am Coll Surg 1994; 179(2):231–48.[Medline]
  4. Schindl M, et al. Stage-dependent therapy of rectal carcinoid tumors. World J Surg 1998; 22(6):628–33; discussion 634.[CrossRef][Medline]
  5. Jetmore AB, et al. Rectal carcinoids: the most frequent carcinoid tumor. Dis Colon Rectum 1992; 35(8):717–25.[CrossRef][Medline]
  6. Naunheim KS, et al. Rectal carcinoid tumors–treatment and prognosis. Surgery 1983; 94(4):670–6.[Medline]
  7. Federspiel BH, et al. Rectal and colonic carcinoids. A clinicopathologic study of 84 cases. Cancer 1990; 65(1):135–40.[CrossRef][Medline]
  8. Koura AN, et al. Carcinoid tumors of the rectum: effect of size, histopathology, and surgical treatment on metastasis free survival. Cancer 1997; 79(7):1294–8.[CrossRef][Medline]
  9. Soga J. Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases. Cancer 2005; 103(8): 1587–95.[CrossRef][Medline]
  10. Shirouzu K, et al. Treatment of rectal carcinoid tumors. Am J Surg 1990; 160(3):262–5.[Medline]
  11. Hochwald SN, et al. Prognostic factors in pancreatic endocrine neoplasms: an analysis of 136 cases with a proposal for low-grade and intermediate-grade groups. J Clin Oncol 2002; 20(11):2633–42.[Abstract/Free Full Text]
  12. Travis WD, et al. Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol 1998; 22(8):934–44.[CrossRef][Medline]
  13. Heah SM, et al. Tumor size is irrelevant in predicting malignant potential of carcinoid tumors of the rectum. Tech Coloproctol 2001; 5(2):73–7.[CrossRef][Medline]
  14. Nikou GC, et al. Current diagnosis and treatment of gastrointestinal carcinoids in a series of 101 patients: the significance of serum chromogranin-A, somatostatin receptor scintigraphy and somatostatin analogues. Hepatogastroenterology 2005; 52(63):731–41.[Medline]



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