REVIEW
Local Excision of Rectal Carcinoma Roger A. Graham, MD, Boston, Massachusetts, Lisa Garnsey, MS, Houston, Texas, J. M i l b u r n Jessup, MD, Boston, Massachusetts
Sixteen published series were reviewed in which local excision was used as definitive treatment for patients with invasive rectal carcinoma located within 6 cm of the anal verge. Ninety-four percent of tumors were T1 or T2 adenocarcinomas with no identified regional metastases. Five-year cancerspecific survival was 89%. Local recurrence was 19%, although more than half of these patients were cured with additional surgery. These results were comparable with those for historical controls treated with abdominoperineal resection (APR). Four pathologic features of the surgical specimen were analyzed to assess their correlation with patient outcome. Positive surgical margins, poorly differentiated histology, and increasing depth of bowel wall invasion were associated with increased local recurrence and decreased survival. Tumor size greater than 3 cm was not a significant factor. When criteria for appropriate patient selection are followed, local excision may provide survival and recurrence rates comparable with those achieved with APR with less morbidity and operative mortality.
he standard treatment for rectal carcinoma located within 6 cm of the anal verge is abdominoperineal T resection (APR). There has been recent interest, however, in the use of sphincter-saving procedures for rectal carcinoma [1]. Lesions in the middle or upper rectum can be managed with the end-to-end anastomosing stapler, but low rectal carcinomas require local excision if the anal sphincters are to be spared. Since local excision of the primary tumor does not remove the areas of lymphatic spread, either the risk of metastases must be minimal or Fromthe Departmentof Surgery(RAG),New England MedicalCenter, Boston,Massachusetts, and the Departmentsof General Surgery (JMJ) and Biomathematics(LG), The Universityof Texas M.D. Anderson Cancer Center, Houston,Texas.Supportedin part by Training Grant 1 T32 CA09599-01 from the National Institutes of Health, Bethesda,Maryland,and a grant fromthe Kelsey-SeyboldFoundation, Houston,Texas. Requests for reprints should be addressed to Roger A. Graham, MD, New EnglandMedicalCenter,750 WashingtonStreet,Box 1043, Boston,Massachusetts02111. Manuscript submittedNovember17, 1989,revisedApril24, 1989, and acceptedAugust 14, 1989. 306
additional treatment must be administered to control regional disease. Our purpose in this study is to review the use of local excision for rectal carcinoma, to analyze the factors associated with the development of locoregional metastases, and to suggest criteria by which patients with low rectal carcinomas may be selected for sphincter-sparing surgery. Local excision of rectal carcinoma is performed by a transsacral, transsphincteric, or transanal approach. Kraske [2] introduced the transsacral approach in 1885, using a midline incision from the lower sacrum to the upper border of the external anal sphincters. The coccyx was excised, often with the lower portion of the sacrum, and the posterior rectum was approached either above or through the levator ani muscle. The technical details of this operation are outlined by O'Brien [3]. Mason [4,5] popularized the transsphincteric approach for carcinomas in the distal rectum. Approaching the rectum through a left parasacral incision, he carefully divided and resutured the individual sphincters and preserved normal fecal continence in all of his patients. Both posterior approaches provide excellent exposure and allow for evaluation of the mesorectum so that lymph nodes can be sampled to determine whether metastatic disease is present. However, rectal fistulas occur in up to 21% of patients, although most heal without significant sequelae [6,7]. A temporary colostomy may be necessary in some patients to protect an anastomosis or to allow for fistula closure. Wound infections are uncommon but can result in fibrosis of the sphincter mechanism. As a result, many surgeons have recommended a transanal approach, either through an operating anoscope or by dilating the anus and using retractors [8]. However, the transanal approach is often difficult, provides limited exposure of the tumor, and does not allow for examination of the pararectal lymph nodes. Alternative forms of local therapy have also been employed. Papillon [9] reported his initial experience with endocavitary radiation in 1973. Five-year survival for 123 patients with early rectal carcinoma was 72%, with only a 7% incidence of local recurrence. Papillon [9-11] and Sischy et al [12-14] have since confirmed these results in carefully selected low-risk patients. Electrocoagulation of rectal carcinoma was introduced by Strauss and co-workers [15] in 1935. This technique has been used to palliate patients with advanced disease and to cure those with early lesions or those who are medically unfit to undergo a radical operation. Survival was 52% to 68% for patients with invasive rectal carcinoma who were treated for cure and followed for a minimum of 4 years [16-19]. Neither endocavitary radiation nor electrocoagulation, however, provides a complete specimen for pathologic examination. Histologic grading is based on a random biopsy that is subject to sampling errors. Rectal wall invasion and involvement of adjacent lymph nodes are
THE AMERICAN JOURNAL OF SURGERY VOLUME160 SEPTEMBER1990
LOCAL E X C I S I O N O F R E C T A L CARCINOMA
No Patient Or~acteristie v.Ffeet ( 6.07
(Negative vs. Positive)
I/
1.87
Depth of Invasiong (TI vs. T2)
9185
( .50
3107
(
(TI art 1"2 vs. 1"3)
123.~
Tutor Size w
(
(< 3o~ vs. >3~)
21.61
0.35
1__1__
0
0.5
1.0
1.5
/ / - - ) 51.95
!1
) 18.93
I
//
2.18
10.86
//
)
//
54
) 19.30
__[__I 2.5
3.0
l~oled4~Is Ratio
[ 19,22,25,27,28].
determined by physical examination alone. Since accurate pathologic staging cannot be obtained, results with endocavitary radiation and electrocoagulation cannot be compared with results from other treatment modalities. Thus, patients treated with either endocavitary radiation or electrocoagulation are not included in our analysis of local excision of rectal carcinoma. MATERIAL AND METHODS Patients: To ensure that data were not obscured by problems inherent in learning how to perform local excision, this analysis was limited to published series with 10 or more patients who underwent local excision with curative intent. There were 16 series of curative local excisions for invasive rectal adenocarcinoma that met this criterion [4,6,20-33]. Six institutions reported their experience more than once. Since only the most recent report from each institution was analyzed, there were 10 series available for study [4,6,20,23,26,28-31,33]. All tumors were staged according to the T N M staging system [34]: T1, tumor invades submucosa; T2, tumor invades muscularis propria; T3, tumor invades through muscularis propria into subserosa or into nonperitonealized pericolic or perirectal tissues. Patients treated with local excision for palliation were excluded, as were patients with carcinomatous polyps treated by snare excision. Parameters: Estimates of absolute survival, cancerspecific survival, and local recurrence were determined. Absolute survival summarized the survival experience of patients without regard to the cause of death, while cancer-speeific survival referred to the survival of patients who did not die of recurrent disease. Local recurrence was the recurrence of tumor either in the rectum or the pelvis. Two additional parameters were measured: salvage, including those patients with a local recurrence who were subsequently cured with additional surgery, and persistent local recurrence, including those patients with local recurrence who could not be rendered free of disease. Statistics: Subset analyses were performed to investiTHE AMERICAN
//-------)
r 27.33
(
ltlstologie Differentiation+ (WeI3. or Moderate vs. Poor)
Figure 1. Survival by various patienl characteristics: pooled odds ratios together with approximate 95% confidence intervals. Asterisk indicates data from [19,20,25]; dagger indicates data from [5,19,25,27,29,32]; not-equal-to sign indicates data from [3,5, 10,25, 27,28]; section indicates data from
//
gate the relationship between pathologic criteria and prognosis. Four pathologic features were analyzed: surgical margins, histologic differentiation, depth of bowel wall invasion, and tumor size. There were too few patients to analyze for the effects of other pathologic features. The relationships between these four pathologic criteria and patient outcome (absolute survival or local recurrence) were explored using the pooled odds ratio [35], and the results are presented graphically (Figure 1). The odds ratio (relative risk) is the rate of failure (death or local recurrence) among patients with a certain pathologic criterion compared with the rate of failure among patients without this criterion. Each horizontal line represents the point estimate (relative risk) and the 95% confidence limit of the pooled odds ratio for each pathologic criterion. The solid vertical lines represent an odds ratio of 1.0, indicating that the pathologic criterion had no effect [36]. If the 95% confidence interval around the pooled odds ratio of a pathologic criterion does not encompass an odds ratio of 1.0, the criterion is considered to have a significant effect on outcome. Overall results were not affected by the type of local excision (transanal, transsacral, or transsphincteric); therefore, all three are analyzed together. In an overview of this nature, estimates of survival and local recurrence may be somewhat imprecise due to the variability of patient foUow-up. To minimize this problem, results are presented both for the 3 series with a minimum of 5 years of follow-up [20,23,26] and for the 10 series combined. Potential publication bias of studies with more favorable outcomes may also affect the statistical analyses of pathologic criteria and their effect on patient outcome. If outcomes by various patient characteristics were not reported in some studies because no relationship was observed, then the risks associated with given pathologic criteria may be overestimated. RESULTS Individual series: The characteristics of the 10 individual series are presented in Table I. The series ranged in
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TABLE I
Patient Characteristics
Series
No. of Patients
Biggers e t a / [ 2 3 ] (1956-80) Whiteway eta/[20] (1948-78) Stearns e t a / [ 2 6 ] (1954-78) Hager et al [28] (1969-80)
141" 33 31 59
T1
Depth of Invasion T2
T3
Local Recurrence
Salvagew
Follow-up
Killingback [29] (1969-84) Wilson [30] (1948-69)
39 30
0
28 NG
6
NG NG
82% 100%
23% 7%
22% 100%
Cuthbertson and Simpson [31] (1970-84) Mason [5] (1962-70) Grigg et al [33] (1950-80) Bergman and Solhang [6] (1977-83) Overall
28
16
12
0
NG
100%
21%
100%
>-5 years >--5 years >-5 years Median 33-40.5 months > 1 8 months 18/30 > 5 years 12/30 < 5 years Average 51 months
14 16 13
0 16 7
14 0 5
0 0 1
100% NG 85%
100% 100% 85%
14% 6% 0%
100% 100% --
1-8 years NG 18-76 months
69% (161/232)
94% (247/263)
19% (76/404)
--
12 15 39
404
105 (46%)
NG 16 14 20
Survival CancerAbsolute t Specific~
5 2 0
109 (48%)
14 (6%)
65% 55% 84% NG
NG 88% 90% 97%
27% 12% 26% 10%
NG 25% 50% NG
--
* An unspecified number of these patients had polyps with invasive cancer. Also, a small percentage (--5 Yrs Follow-up 66% 89% 24% 42% 11%
(55-84%) (88-90%) (12-27%) (25-50%) (9-13%)
* Values in parentheses indicate ranges. t Percentage of patients in the combined series who were cured by additional surgery after a Iocoregional recurrence.
TABLE IIl Effect of Pathologic Criteria upon Patient Outcome
Mortality
Local Recurrence
(%)
(%)
Surgical margins*
Negative Positive Histologic differentiation t Well to moderate Poor Depth of invasion t T1 T2 T3 Size of tumorw - 3 cm
1
6
35
52
3 26
11 33
1 8 20
5 18 22
4 18
11 33
* [ 19,20,25] t [5, 19,25,27,29,32] t, [3,5, 10,25,27,28] w [ 19,22,25,27,28]
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THE A M E R I C A N J O U R N A L OF SURGERY
size from 13 to 141 patients. Three series had 5-year follow-up of all patients (series 1-3, Table I). Most tumors were either T1 (105 of 227; 46%) or T2 (109 of 117; 48%) lesions, while 6% were T3 lesions (Table I). Overall, local recurrence occurred in 19% of patients and ranged from 0% to 27%. Results with local excision: In the series with 5-year follow-up, two thirds of patients survived for 5 years, and the cancer-specific survival was 89% (Table II). Although 24% of patients developed a local recurrence, nearly half of these patients were cured with additional surgery (Table II). This included several patients who were considered by the authors to be poor candidates for local excision because they had positive surgical margins, poorly differentiated cancers, or tumor invasion into the perirectal tissues. The series by Biggers et al [23] had a 27% local recurrence, but the authors did not specify how many of these patients had successful salvage therapy. Effect of pathologic criteria on outcome: When the effects of the four pathologic criteria upon patient outcome were analyzed, positive margins in the surgical specimen, poorly differentiated histology, and increasing depth of bowel wall invasion were associated with a significant increase in mortality and local recurrence (Table III, Figures 1 and 2). Higher rates of mortality and local recurrence were also observed in patients whose tumors were greater than 3 cm in diameter, although the association was not significant. COMMENTS Since its introduction in 1908, Miles' [37] APR has been accepted as the standard of care for patients with invasive rectal carcinoma located within 6 cm of the anal verge. Morbidity and mortality from this operation, however, are significant. Operative mortality ranges from 1%
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NoPatient O~araeteristie Effect
(
//
5.81
( l ~ a t i ~ vs. Positive) ( 1.18
Kistologic Diffexentiation+ 6,'ell or l~xterate vs. Poor)
//
//
) 7.82
2149
//--)
( 1.03 Tumor size w (_ 3~)
3173
0.70 (--
I
I
0.5
o
3q26. // 1.0
I
I
1.5
2.0
I
13.49
15.15 )
i
2.5
3.0
Pooled-0dds
data f r o m [ 19,22,25,27,28].
to 5% [38-42] and is markedly increased in patients over 70 years of age. Sexual dysfunction occurs in the majority of male patients [43-46]. While this is more common in the elderly, 15% of patients under the age of 50 are rendered impotent by an APR, and 10% are unable to ejaculate [47]. Bladder dysfunction is similarly common [48-54]. Marks and Ritchie [54] found a 34% incidence of urinary retention, often requiring surgical relief for symptoms of bladder outlet obstruction. An APR also results in a permanent colostomy with its attendant mechanical and psychosocial problems. Although a trial that compares local excision with radical surgery has not been performed, the results in these 10 series are similar to results achieved with APR for similarly staged tumors. Dukes and Bussey [55], in the first detailed analysis of survival and its relationship to histologic grade and extent of spread, reported a 98% 5-year survival for 261 patients with well- and moderately differentiated (grades 1 and 2) tumors and no extrarectal disease. Two recent series have confirmed these results: Wilson and Beahrs [56] (362 patients) and Grigg et al [33] (268 patients) reported 85% and 88% 5-year survival, respectively, in patients with TI and T2 lesions. Local recurrence rates were also similar. McDermott and coworkers [57], in reviewing 276 patients who underwent an APR for T1 and T2 carcinomas, found a 10% incidence of local recurrence [57]. Since none of these patients were rendered disease-free with additional surgery, this figure is identical to the persistent local recurrence rate after local excision. Appropriate candidates for local excision should be at minimal risk for local or regional spread of cancer. In reviewing the 10 series of local excisions (Table III, Figures 1 and 2), positive surgical margins significantly increased the rates of local recurrence (relative risk = 19) and mortality (relative risk -- 27). Poorly differentiated histology also resulted in higher rates of local recurrence (relative risk -- 6) and mortality (relative risk --- 10). Depth of bowel wall invasion had a smaller, but still THE AMERICAN
) 62.71
32.31
(T1 and 'r2 vs. T3)
Figure 2. Local recurrence by various patient characteristics: pooled odds ratios together with approximate 95% confidence intervals. Asterisk indicates data from [ 19,20,25]; dagger indicates data from [5, 19,25,27,29,32]; note q u a l - t o sign indicates data f r o m [3,5, 10,25,27,28]; section indicates
//
//--) 6119
(-0.79
Depth of Invasion# (I"1vs. T2)
. 19110
significant, impact. As tumor invasion extended from the submucosa (T1) into the muscularis propria (T2), local recurrence rates increased from 5% to 18% (relative risk = 2.5) and mortality increased from 1% to 8% (relative risk = 3). As tumors extended into the perirectal fat (T3), local recurrence rates increased to 22% (relative risk = 4) and mortality increased to 20% (relative risk = 11). Tumor size greater than 3 cm showed a trend toward higher rates of local recurrence (relative risk = 3) and mortality (relative risk = 2.5), but the results were not significant, This finding is supported by Spratt and Spjut [58] who reviewed 1,137 consecutive patients with colorectal carcinoma and found that both the risk of nodal metastases and the overall prognosis were independent of tumor size. When Whiteway and co-workers [20] reviewed the St. Marks' experience with local excision, they similarly found that size was not an independent prognostic factor when tumor pathology was corrected for histologic differentiation and depth of invasion. Other pathologic features may be important in predicting the natural biology of the tumor. Several studies suggest that ulcerative tumors and those with lymphatic, vascular, or perineural invasion are all associated with an increased risk of nodal metastases and decreased survival [58-62]. Recent data from flow cytometry show that aneuploid tumors with high S-phase fractions have a worse prognosis than diploid tumors [63-65]. Although these factors may be important in selecting appropriate candidates for local excision, this review did not analyze their significance. In addition to these pathologic criteria, careful preoperative examination is necessary to identify patients at high risk for intramural or extramural extension of disease. Intramural spread is rare in patients with T1 and T2 rectal carcinomas and favorable histology. Grinnell [66] examined 93 rectal specimens and identified significant (more than 0.5 mm) distal spread in 18 (19%), In only one of these cases was the primary tumor confined to the bowel wall, and intramural spread in that case was limit-
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T A B L E IV
Guidelines for Local Excision Preoperative A. Absolute indications 1. Mobile tumor 2. T1 tumor (by ultrasound) 3. Well- or moderately differentiated histology (by biopsy) 4. Size - 3 cm C. Contraindic~tions 1. Fixed tumor 2. T3 tumor (by ultrasound) 3. Poorly differentiated histology (by biopsy)
Postoperative Indications
for abdominoperineal
resection
and/or adjuvant
therapy 1. 2. 3. 4.
Positive surgical margins T3 tumor Poorly differentiated histology Positive perirectal lymph node(s)
ed to 1 cm. Quer et al [67] demonstrated intramural spread in 4 of 91 patients with rectal carcinoma. Two were poorly differentiated carcinomas, and two were moderately differentiated with limited (1 cm, 1.5 cm) spread in submucosal veins. Williams and co-workers [68] examined 50 specimens following curative APR. Only 5 of 50 specimens had intramural spread greater than 1 cm, and all 5 were poorly differentiated Dukes' stage C tumors. Thus, intramural spread is unlikely in patients with T1 and T2 lesions and should be detected by frozen-section analysis of the margins. Extramural spread occurs by direct extension into the perirectal fat, metastases to regional lymph nodes, or both. Since extension beyond the bowel wall is associated with a 50% risk of nodal metastases [69,70], and since local excision does not systematically remove the adjacent lymph nodes, neither group of patients should be offered local excision alone. It is difficult, however, to preoperatively determine which patients have extrarectal disease. Direct extension of the primary tumor can be difficult to assess. In a prospective study of 70 patients, clinical predictions that disease was confined to the bowel wall based on digital examination were confirmed pathologically in only 44% to 83% of cases [71]. Computed tomography (CT) scanning and magnetic resonance imaging (MRI) have been unable to demonstrate microscopic spread [72-80]. Intralumenal ultrasound, on the other hand, has been very accurate in defining bowel wall infiltration [81-83]. In reviewing 90 patients who were examined with endorectal ultrasound, staging was accurate in more than 90% of cases, and only one patient had more extensive disease than was demonstrated by ultrasound. As final confirmation, local excision provides a full-thickness excision of the tumor, and the exact extent of extrarectal spread can be determined [26]. There are no preoperative tests that adequately detect metastases in perirectal lymph nodes. Clinical examination is not reliable [69,84-86]. CT scanning and MRI 310
reveal grossly enlarged nodes only (greater than 1 to 1.5 cm), with little sensitivity (22% to 39%) and variable specificity (61% to 96%) [72-75]. Normal-sized lymph nodes containing micrometastases are missed. Examination of operative specimens indicates that two thirds of lymph node metastases are less than 5 mm in diameter [87]. Monoclonal imaging methods have been unable to detect positive lymph nodes; one study showed greater uptake in normal mesenteric nodes than in tumor-bearing nodes [88]. Careful patient selection can minimize the risk of nodal metastases, but this risk is still 11% to 23% in patients with T1 and T2 rectal carcinomas [69,70,89]. The majority of these metastases, however, occur with poorly differentiated tumors. Dukes and Bussey [55] showed that the frequency of lymph node metastases increases as tumors become less differentiated (30% in well-differentiated, 47% in moderately differentiated, and 81% in poorly differentiated neoplasms). Cohen et al [59] confirmed this in a recent study at the Massachusetts General Hospital (25% in well-differentiated, 33% in moderately differentiated, and 77% in poorly differentiated neoplasms). In Morson's [70] series, all five T1 cancers with lymph node metastases were poorly differentiated neoplasms. One solution to the problem of detecting lymph node metastases is to sample the perirectal lymph nodes at the time of surgery. Since lymphatic metastases occur in an orderly and predictable pattern [55], the first nodes to receive metastases are those situated adjacent to or immediately cephalad to the primary tumor. As a result, if these lymph nodes are negative, a lymph node dissection is not necessary. If these nodes are positive, additional therapy is needed to control regional disease. The choice of such additional therapy is often difficult. A completion APR can be safely performed and combined with adjuvant radiotherapy and/or chemotherapy. No published data exist on the efficacy of adjuvant therapy alone following local excision for rectal carcinoma, but radiotherapy is clearly effective in the adjuvant setting for more advanced rectal tumors [9093], and recent results from the Gastrointestinal Tumor Study Group [94] and the National Surgical Adjuvant Breast Project [95] suggest a similar benefit from adjuvant chemotherapy. At the present time, M.D. Anderson Cancer Center is combining local excision with postoperative radiotherapy and 5-fluorouracil for patients with T2 and T3 lesions [96]. Although follow-up has been short, 19 patients have been treated in this program with no local recurrences and no cancer-related mortality. The role of adjuvant therapy following local excision awaits further analysis of such carefully controlled studies. Current guidelines for local excision are provided in Table IV. CONCLUSIONS Local excision of T 1 and T2 invasive rectal carcinomas within 6 cm of the anal verge results in survival and local control comparable to those obtained with radical resection. A permanent colostomy is avoided, and the operative mortality (less than 1% in these series) and morbidity are significantly lowered. Selection of patients
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LOCAL EXCISIONOF RECTALCARCINOMA
for local excision requires a careful digital examination, endoscopy, biopsy of the tumor, intralumenal ultrasound, a n d CT. Local excision may be attempted if the tumor is mobile, well or moderately differentiated, and shows no evidence of extrarectal spread. A transsacral or transsphincteric approach is recommended to evaluate perirectal lymph nodes. The operative specimen must then be reviewed for confirmation of favorable histology and absence of regional spread. Positive surgical margins, poorly differentiated histology, and extension into perirectal fat are associated with increased local recurrence and decreased survival. T u m o r size greater than 3 cm does not appear to be significant. Local excision is adequate for rectal carcinoma that is well or moderately differentiated and limited to the submucosa (T1). Lesions involving the muscularis propria (T2) may require adjuvant radiotherapy a n d / o r chemotherapy to limit local recurrence. Tumors that are poorly differentiated or penetrate the perirectal fat (T3) may be radically resected or treated with multimodality therapy in an experimental trial, given the high risk of nodal metastases. REFERENCES 1. Yeatman TJ, Bland K. Sphincter-saving procedures for distal carcinoma of the rectum. Ann Surg 1989; 209: 1-18. 2. Kraske P. Zur Exstirpation Hochsitzender Mastdarmkrebse. Verh Dtsch Ges Chir 1885; 14: 464-74. 3. O'Brien PH. Kraske's posterior approach to the rectum. Surg Gynecol Obstet 1976; 142: 412-4. 4. Mason AY. Surgical access to the rectum: a trans-sphincteric exposure. Proc R Soc Med 1970; 63: 91-4. 5. Mason AY. Trans-sphincteric approach to rectal lesions. Surg Annu 1977; 9: 171-94. 6. Bergman L, Solhaug JH. Posterior trans-sphincteric resection for small tumours of the lower rectum. Acta Chir Scand 1986; 152: 313-6. 7. Westbrook KC, Lang NP, Broadwater JR, Thompson BW. Posterior surgical approaches to the rectum. Ann Surg 1982; 195: 677-85. 8. Olsen WR. Transanal excision of sessile rectal polyps. Surg Gynecol Obstet 1975; 140: 766-8. 9. Papillon J. Endocavitary irradiation of early rectal cancers for cure: a series of 123 cases. Proc R Soc Med 1973; 66: 1179-81. 10. Papillon J. Endocavitary irradiation in the curative treatment of early rectal cancers. Dis Colon Rectum 1974; 17: 172-80. 11. PapiUon J. New prospects in the conservative treatment of rectal cancer. Dis Colon Rectum 1984; 27: 695-700. 12. Sischy B, Remington JH. Treatment of carcinoma of the rectum by intracavitary irradiation. Surg Gynecol Obstet 1975; 141: 562-4. 13. Sischy B, Remington JH, Sobel SH. Treatment of rectal carcinomas by means of endocavitary irradiation. Cancer 1978; 42: 1073-6. 14. Sischy B, Remington JH, Sobel SH. Treatment of rectal carcinomas by means of endocavitary irradiation: a progress report. Cancer 1980; 46: 1957-61. 15. Strauss AA, Strauss SF, Crawford RA, Strauss HA. Surgical diathermy of carcinoma of the rectum. JAMA 1935; 104: 1480-4. 16. Madden JL, Kandalaft S. Electrocoagulation in the treatment of cancer of the rectum: a continuing study. Ann Surg 1971; 174: 530-40. 17. Crile G, Turnbull RB. The role of electrocoagulation in the treatment of carcinoma of the rectum. Surg Gynecol Obstet 1972; 135: 391-6. 18. Eisenstat TE, Deak ST, Rubin R J, Salvati EP, Greco RS. Five
year survival in patients with carcinoma of the rectum treated by electrocoagulation. Am J Surg 1982; 143: 127-32. 19. Hoekstra H J, Verschueren RCJ, Oldhoff J, van der Ploeg E. Palliative and curative electrocoagulation for rectal cancer: experience and results. Cancer 1985; 55: 210-3. 20. Whiteway J, Nicholls R J, Morson BC. The role of surgical local excision in the treatment of rectal cancer. Br J Surg 1985; 72: 694-7. 21. Morson BC, BusseyH JR, Samoorian S. Policy of local excision for early cancer of the colorectum. Gut 1977; 18: 1045-50. 2 2 . Lock MR, Cairns DW, Ritchie JK, Lockhart-Mummery HE. The treatment of early colorectal cancer by local excision.Br J Surg 1978; 65: 346-9. 23. Biggers OR, Beart RW, Ilstrup DM. Local excision of rectal cancer. Dis Colon Rectum 1986; 29: 374-7. 24. Wittoesch JH, Jackman RJ. Results of conservative management of cancer of the rectum in poor risk patients. Surg Gynecol Obstet 1958; 107: 648-50. 25. Jackman RJ. Conservative management of selected patients with carcinoma of the rectum. Dis Colon Rectum 1961; 4: 429-34. 26. Stearns MW, Sternberg SS, DeCosse JJ. Treatment alternatives: localized rectal cancer. Cancer 1984; 54: 2691-4. 27. Deddish MR. Local excision. Surg Clin North Am 1974; 54: 877-80. 28. Hager T, Gall FP, Hermanek P. Local excisionof cancer of the rectum. Dis Colon Rectum 1983; 26: 149-51. 29. Killingbak MJ. Indications for local excision of rectal cancer. Br J Surg 1985; 72: $54-6. 30. Wilson E. Local treatment of cancer of the rectum. Dis Colon Rectum 1973; 16: 194-9. 31. Cuthbertson AM, Simpson RL. Curative local excision of rectal adenocarcinoma. Aust NZ J Surg 1986; 56: 229-31. 32. Cuthbertson AM, Kaye AH. Local excision of carcinomas of the rectum, anus, and anal canal. Aust N Z J Surg 1978;48: 412-5. 33. Grigg M, McDermott FT, Pihl EA, Hughes ESR. Curative local excision in the treatment of carcinoma of the rectum. Dis Colon Rectum 1984; 27: 81-3. 34. UICC, International Union Against Cancer. TNM classification of malignant tumours. Hermanek P, Sobin LH, eds. Berlin: Springer-Verlag, 1987: 47-9. 35. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. JNCI 1959; 22: 719-48. 36. Peto R. Why do we need systematic overview of randomized trials? Stat Med 1987; 6: 233-40. 37. Miles WE. A method of performing abdominoperineal excision for carcinoma of the rectum and terminal portion of the pelvic colon. Lancet 1908; 2: 1812-3. 38. Lea JW, Covington K, McSwain B, Scott HW. Surgical experience with carcinoma of the colon and rectum. Ann Surg 1982; 195: 600-7. 39. Hughes ESR, McDermott FT, Masterton JP, Cunningham IGE, Polglase AL. Operative mortality following excision of the rectum. Br J Surg 1980; 67: 49-51. 40. Payne JE, Chapuis PH, Pheils MT. Surgery for large bowel cancer in people aged 75 years and older. Dis Colon Rectum 1986; 29: 733-7. 41. Mason AY. The place of local resection in the treatment of rectal carcinoma. Proc R Soc Med 1970; 63: 1259-62. 42. Ohman U. Colorectal carcinoma: trends and results over a 30year period. Dis Colon Rectum 1982; 25: 431-40. 43. Weinstein M, Roberts M. Sexual potency followingsurgery for rectal carcinoma. Ann Surg 1977; 185: 295-300. 44. Danzi M, Ferulano GP, Abate S, Califano G. Male sexual function after abdominoperineal resection for rectal cancer. Dis Colon Rectum 1983; 26: 665-8. 45. Balslev I, Hurling H. Sexual dysfunction following operation for carcinoma of the rectum. Dis Colon Rectum 1983; 26: 785-8. 46. Williams JT, Slack WW. A prospective study of sexual function after major colorectal surgery. Br J Surg 1980; 67: 772-4. 47. Yeager ES, Van Heerden JA. Sexual dysfunction following
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proctocolectomy and abdominoperineal resection. Ann Surg 1980; 191: 169-70. 4,8. Kinn A-C, Ohman U. Bladder and sexual function after surgery for rectal cancer. Dis Colon Rectum 1986; 29: 43-8. 49. Fowler JW, Bremner DN, Moffat LEF. The incidence and consequencesof damage to the parasympathetic nerve supply to the bladder after abdominoperineal resection of the rectum for carcinoma. Br J Urol 1978; 50: 95-8. 50. Eickenberg H-U, Amin M, Klompus W, Lich R. Urologic complications following abdominoperineal resection. J Urol 1976; 115: 180-2. 51. Ward JN, Nay HR. Immediate and delayed urologiccomplications associated with abdominoperineal resection. Am J Surg 1972; 123: 642-8. 52. Kontturi M, Larmi TKI, Tuononen S. Bladder dysfunction and its manifestations following abdominoperineal extirpation of the rectum. Ann Surg 1974; 179: 179-82. 53. Gerstenberg TC, Nielsen ML, Clausen S, Blaabjerg J, Lindenberg J. Bladder function after abdominoperineal resection of the rectum for anorectal cancer: urodynamic investigation before and after operation in a consecutive series. Ann Surg 1980; 191: 81-6. 54. Marks CG, Ritchie JK. The complications of synchronous combined excision for adenocarcinoma of the rectum at St. Mark's Hospital. Br J Surg 1975; 62: 901-5. 55. Dukes CE, Bussey H JR. The spread of rectal cancer and its effect on prognosis. Cancer 1958; 11: 309-20. 56. Wilson SM, Beahrs OH. The curative treatment of carcinoma of the sigmoid, rectosigmoid, and rectum. Ann Surg 1976; 183: 556-65. 57. McDermott FT, Hughes ESR, Pihl E, Johnson WR, Price AB. Local recurrence after potentially curative resection for rectal cancer in a series of 1008 patients. Br J Surg 1985; 72: 34-7. 58. Spratt JS Jr, Spjut HJ. Prevalence and prognosisof individual clinical and pathologic variables associated with colorectal carcinoma. Cancer 1967; 20: 1976-85. 59. Cohen AM, Wood WC, Gunderson LL, Shinnar M. Pathological studies in rectal cancer. Cancer 1980; 45: 2965-8. 60. Montessori GA, Donald JC. Invasion profile of colorectal carcinoma. Dis Colon Rectum 1978; 21: 26-8. 61. Rankin FW, Olsen PF. The hopeful prognosis in cases of carcinoma of the colon. Surg Gynecol Obstet 1933; 56: 366-74. 62. Spratt JS Jr, Watson FR, Pratt JL. Characteristics of variants of colorectal carcinoma that do not metastasize to lymph nodes. Dis Colon Rectum 1970; 13: 243-6. 63. Wolley RC, Schreiber K, Koss LG, Karas M, Sherman A. DNA distribution in human colon carcinomas and its relationship to clinical behavior. JNCI 1982; 69: 15-22. 64. Armitage NC, Robins RA, Evans DF, Turner DR, Baldwin RW, Hardcastle JD. The influence of tumour cell DNA abnormalities on survival in colorectal cancer. Br J Surg 1985; 72: 828-30. 65. Kokal W, Sheibani K, Terz J, Harada JR. Tumor DNA content in the prognosis of colorectal carcinoma. JAMA 1986;255: 3123-7. 66. Grinnell RS. Distal intramural spread of carcinoma of the rectum and rectosigmoid. Surg Gynecol Obstet 1954; 99: 421-30. 67. Quer EA, Dahlin DC, Mayo CW. Retrograde intramural spread of carcinoma of the rectum and rectosigmoid: a microscopic study. Surg Gynecol Obstet 1953; 96: 24-30. 68. Williams NS, Dixon MF, Johnston D. Reappraisal of the 5 centimetre rule of distal excision for carcinoma of the rectum: a study of distal intramural spread and of patients' survival. Br J Surg 1983; 70: 150-4. 69. Astler VB, Coller FA. The prognostic significance of direct extension of carcinoma of the colon and rectum. Ann Surg 1954; 139: 846-51. 70. Morson BC. Factors influencing the prognosis of early cancer of the rectum. Proc R Soc Med 1966; 59: 607-8. 71. Nicholls R J, Mason AY, Morson BC, Dixon AK, Fry IK. The clinical staging of rectal cancer. Br J Surg 1982; 69: 404-9. 72. Dixon AK, Fry 1K, Morson BC, Nicholls ILl, Mason AY. Pre312
THE AMERICAN JOURNAL OF SURGERY
operative computed tomography of carcinoma of the rectum. Br J Radiol 1981; 54: 655-9. 73. Freeny PC, Marks WM, Ryan JA, Bolen JW. Colorectal carcinoma evaluation with CT: preoperative staging and detection of postoperative recurrence. Radiology 1986; 158: 347-53. 74. Thompson WM, Halvorsen RA, Foster WL, Roberts L, Gibbons R. Preoperative and postoperative CT staging of rectosigmoid carcinoma. AJR 1986; 146: 703-10. 75. Adalsteinsson B, Glimelius B, Graffman S, Hemmingsson A, Pahlman L. Computed tomography in staging of rectal carcinoma. Acta Radiol [Diagn] (Stockh) 1985; 26: 45-55. 76. Grabbe E, Lierse W, Winkler R. The perirectal fascia: morphology and use in staging of rectal carcinoma. Radiology 1983; 149: 241-6. 77. van Waes PFGM, Koehler PR, Feldberg MAM. Management of rectal carcinoma: impact of computed tomography. AJR 1983; 140:1137-42. 78. Clark J, Bankoff M, Carter B, Smith TJ. The use of computerized tomography scan in the staging and follow-upstudy of carcinoma of the rectum. Surg Gynecol Obstet 1984; 159: 335-42. 79. Butch R J, Stark DD, Wittenberg J, et al. Staging rectal cancer by MR and CT. AJR 1986; 146: 1155-60. 80. Thoeni RF, Moss AA, Schnyder P, Margulis AR. Detection and staging of primary rectal and rectosigmoidcancer by computed tomography. Radiology 1981; 141: 135-8. 81. Hildebrandt U, Feifel G. Preoperative staging of rectal cancer by intrarectal ultrasound. Dis Colon Rectum 1985; 28: 42-6. 82. Dragsted J, Gammelgaard J. Endoluminal ultrasonic scanning in the evaluation of rectal cancer: a preliminary report of 13 cases. Gastrointest Radiol 1983; 8: 367-9. 83. Aecarpio G, Scopinaro G, Claudiani F, Davini D, Mallarini G, Saitta S. Experience with local rectal cancer excision in light of two recent preoperative diagnostic methods. Dis Colon Rectum 1987; 30: 296-8. 84. Gabriel WB, Dukes C, Bussey H JR. Lymphatic spread in cancer of the rectum. Br J Surg 1935; 23: 395-413. 85. McVay JR. Involvement of the lymph nodes in carcinoma of the rectum. Ann Surg 1922; 76: 755-67. 86. Coller FA, Kay EB, Maclntyre RS. Regional lymphatic metastases in carcinoma of the colon. Ann Surg 1941; 114: 56-63. 87. Herrera-Ornelas L, Justiniano J, Castillo N, Petrelli N J, Steele JP, Mittelman A. Metastases in small lymph nodes from colon cancer. Arch Surg 1987; 122: 1253-6. 88. Beatty JD, Duda RB, Williams LE, et al. Preoperative imaging of colorectal carcinoma with rain-labeled anticarcinoembryonic antigen monoclonal antibody. Cancer Res 1986; 46: 6494-502. 89. Cuthbertson AM, Hughes ESR, Pihl E. Metastatic "early" colorectal cancer. Aust NZ J Surg 1984; 54: 549-51. 90. Gerard A, Berrod J-L, Pene F, et al. Interim analysis of a phase III study on preoperative radiation therapy in resectable rectal carcinoma: trial of the gastrointestinal tract cancer cooperative group of the European Organization for Research on Treatment of Cancer (EORTC). Cancer t985; 55: 2373-9. 91. Cummings BJ. Adjuvant radiation therapy for rectal adenocarcinoma. Dis Colon Rectum 1984; 27: 826-36. 92. Mohiuddin M, Derdel J, Marks G, Kramer S. Results of adjuvant radiation therapy in cancer of the rectum: Thomas Jefferson University Hospital experience. Cancer 1985; 55: 350-3. 93. Hoskins RB, Gunderson LL, Dosoretz DE, et al. Adjuvant postoperative radiotherapy in carcinoma of the rectum and rectosigmoid. Cancer 1985; 55: 61-71. 94. Gastrointestinal Tumor Study Group. Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med 1985; 312: 1465-72. 95. Wolmark N, Fisher B, Rockette H, et al. Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP Protocol C-01. JNCI 1988; 80: 30-6. 96. McCready DR, Ota DM, Rich TA, Thielvoldt D, Jessup JM. Prospective phase I trial of conservative management of low rectal lesions. Arch Surg 1989; 124: 67-70.
VOLUME 160 SEPTEMBER 1990
Local Excision of Rectal Carcinoma Roger A. Graham, MD, Boston, Massachusetts, Lisa Garnsey, MS, Houston, Texas, J. M i l b u r n Jessup, MD, Boston, Massachusetts
Sixteen published series were reviewed in which local excision was used as definitive treatment for patients with invasive rectal carcinoma located within 6 cm of the anal verge. Ninety-four percent of tumors were T1 or T2 adenocarcinomas with no identified regional metastases. Five-year cancerspecific survival was 89%. Local recurrence was 19%, although more than half of these patients were cured with additional surgery. These results were comparable with those for historical controls treated with abdominoperineal resection (APR). Four pathologic features of the surgical specimen were analyzed to assess their correlation with patient outcome. Positive surgical margins, poorly differentiated histology, and increasing depth of bowel wall invasion were associated with increased local recurrence and decreased survival. Tumor size greater than 3 cm was not a significant factor. When criteria for appropriate patient selection are followed, local excision may provide survival and recurrence rates comparable with those achieved with APR with less morbidity and operative mortality.
he standard treatment for rectal carcinoma located within 6 cm of the anal verge is abdominoperineal T resection (APR). There has been recent interest, however, in the use of sphincter-saving procedures for rectal carcinoma [1]. Lesions in the middle or upper rectum can be managed with the end-to-end anastomosing stapler, but low rectal carcinomas require local excision if the anal sphincters are to be spared. Since local excision of the primary tumor does not remove the areas of lymphatic spread, either the risk of metastases must be minimal or Fromthe Departmentof Surgery(RAG),New England MedicalCenter, Boston,Massachusetts, and the Departmentsof General Surgery (JMJ) and Biomathematics(LG), The Universityof Texas M.D. Anderson Cancer Center, Houston,Texas.Supportedin part by Training Grant 1 T32 CA09599-01 from the National Institutes of Health, Bethesda,Maryland,and a grant fromthe Kelsey-SeyboldFoundation, Houston,Texas. Requests for reprints should be addressed to Roger A. Graham, MD, New EnglandMedicalCenter,750 WashingtonStreet,Box 1043, Boston,Massachusetts02111. Manuscript submittedNovember17, 1989,revisedApril24, 1989, and acceptedAugust 14, 1989. 306
additional treatment must be administered to control regional disease. Our purpose in this study is to review the use of local excision for rectal carcinoma, to analyze the factors associated with the development of locoregional metastases, and to suggest criteria by which patients with low rectal carcinomas may be selected for sphincter-sparing surgery. Local excision of rectal carcinoma is performed by a transsacral, transsphincteric, or transanal approach. Kraske [2] introduced the transsacral approach in 1885, using a midline incision from the lower sacrum to the upper border of the external anal sphincters. The coccyx was excised, often with the lower portion of the sacrum, and the posterior rectum was approached either above or through the levator ani muscle. The technical details of this operation are outlined by O'Brien [3]. Mason [4,5] popularized the transsphincteric approach for carcinomas in the distal rectum. Approaching the rectum through a left parasacral incision, he carefully divided and resutured the individual sphincters and preserved normal fecal continence in all of his patients. Both posterior approaches provide excellent exposure and allow for evaluation of the mesorectum so that lymph nodes can be sampled to determine whether metastatic disease is present. However, rectal fistulas occur in up to 21% of patients, although most heal without significant sequelae [6,7]. A temporary colostomy may be necessary in some patients to protect an anastomosis or to allow for fistula closure. Wound infections are uncommon but can result in fibrosis of the sphincter mechanism. As a result, many surgeons have recommended a transanal approach, either through an operating anoscope or by dilating the anus and using retractors [8]. However, the transanal approach is often difficult, provides limited exposure of the tumor, and does not allow for examination of the pararectal lymph nodes. Alternative forms of local therapy have also been employed. Papillon [9] reported his initial experience with endocavitary radiation in 1973. Five-year survival for 123 patients with early rectal carcinoma was 72%, with only a 7% incidence of local recurrence. Papillon [9-11] and Sischy et al [12-14] have since confirmed these results in carefully selected low-risk patients. Electrocoagulation of rectal carcinoma was introduced by Strauss and co-workers [15] in 1935. This technique has been used to palliate patients with advanced disease and to cure those with early lesions or those who are medically unfit to undergo a radical operation. Survival was 52% to 68% for patients with invasive rectal carcinoma who were treated for cure and followed for a minimum of 4 years [16-19]. Neither endocavitary radiation nor electrocoagulation, however, provides a complete specimen for pathologic examination. Histologic grading is based on a random biopsy that is subject to sampling errors. Rectal wall invasion and involvement of adjacent lymph nodes are
THE AMERICAN JOURNAL OF SURGERY VOLUME160 SEPTEMBER1990
LOCAL E X C I S I O N O F R E C T A L CARCINOMA
No Patient Or~acteristie v.Ffeet ( 6.07
(Negative vs. Positive)
I/
1.87
Depth of Invasiong (TI vs. T2)
9185
( .50
3107
(
(TI art 1"2 vs. 1"3)
123.~
Tutor Size w
(
(< 3o~ vs. >3~)
21.61
0.35
1__1__
0
0.5
1.0
1.5
/ / - - ) 51.95
!1
) 18.93
I
//
2.18
10.86
//
)
//
54
) 19.30
__[__I 2.5
3.0
l~oled4~Is Ratio
[ 19,22,25,27,28].
determined by physical examination alone. Since accurate pathologic staging cannot be obtained, results with endocavitary radiation and electrocoagulation cannot be compared with results from other treatment modalities. Thus, patients treated with either endocavitary radiation or electrocoagulation are not included in our analysis of local excision of rectal carcinoma. MATERIAL AND METHODS Patients: To ensure that data were not obscured by problems inherent in learning how to perform local excision, this analysis was limited to published series with 10 or more patients who underwent local excision with curative intent. There were 16 series of curative local excisions for invasive rectal adenocarcinoma that met this criterion [4,6,20-33]. Six institutions reported their experience more than once. Since only the most recent report from each institution was analyzed, there were 10 series available for study [4,6,20,23,26,28-31,33]. All tumors were staged according to the T N M staging system [34]: T1, tumor invades submucosa; T2, tumor invades muscularis propria; T3, tumor invades through muscularis propria into subserosa or into nonperitonealized pericolic or perirectal tissues. Patients treated with local excision for palliation were excluded, as were patients with carcinomatous polyps treated by snare excision. Parameters: Estimates of absolute survival, cancerspecific survival, and local recurrence were determined. Absolute survival summarized the survival experience of patients without regard to the cause of death, while cancer-speeific survival referred to the survival of patients who did not die of recurrent disease. Local recurrence was the recurrence of tumor either in the rectum or the pelvis. Two additional parameters were measured: salvage, including those patients with a local recurrence who were subsequently cured with additional surgery, and persistent local recurrence, including those patients with local recurrence who could not be rendered free of disease. Statistics: Subset analyses were performed to investiTHE AMERICAN
//-------)
r 27.33
(
ltlstologie Differentiation+ (WeI3. or Moderate vs. Poor)
Figure 1. Survival by various patienl characteristics: pooled odds ratios together with approximate 95% confidence intervals. Asterisk indicates data from [19,20,25]; dagger indicates data from [5,19,25,27,29,32]; not-equal-to sign indicates data from [3,5, 10,25, 27,28]; section indicates data from
//
gate the relationship between pathologic criteria and prognosis. Four pathologic features were analyzed: surgical margins, histologic differentiation, depth of bowel wall invasion, and tumor size. There were too few patients to analyze for the effects of other pathologic features. The relationships between these four pathologic criteria and patient outcome (absolute survival or local recurrence) were explored using the pooled odds ratio [35], and the results are presented graphically (Figure 1). The odds ratio (relative risk) is the rate of failure (death or local recurrence) among patients with a certain pathologic criterion compared with the rate of failure among patients without this criterion. Each horizontal line represents the point estimate (relative risk) and the 95% confidence limit of the pooled odds ratio for each pathologic criterion. The solid vertical lines represent an odds ratio of 1.0, indicating that the pathologic criterion had no effect [36]. If the 95% confidence interval around the pooled odds ratio of a pathologic criterion does not encompass an odds ratio of 1.0, the criterion is considered to have a significant effect on outcome. Overall results were not affected by the type of local excision (transanal, transsacral, or transsphincteric); therefore, all three are analyzed together. In an overview of this nature, estimates of survival and local recurrence may be somewhat imprecise due to the variability of patient foUow-up. To minimize this problem, results are presented both for the 3 series with a minimum of 5 years of follow-up [20,23,26] and for the 10 series combined. Potential publication bias of studies with more favorable outcomes may also affect the statistical analyses of pathologic criteria and their effect on patient outcome. If outcomes by various patient characteristics were not reported in some studies because no relationship was observed, then the risks associated with given pathologic criteria may be overestimated. RESULTS Individual series: The characteristics of the 10 individual series are presented in Table I. The series ranged in
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TABLE I
Patient Characteristics
Series
No. of Patients
Biggers e t a / [ 2 3 ] (1956-80) Whiteway eta/[20] (1948-78) Stearns e t a / [ 2 6 ] (1954-78) Hager et al [28] (1969-80)
141" 33 31 59
T1
Depth of Invasion T2
T3
Local Recurrence
Salvagew
Follow-up
Killingback [29] (1969-84) Wilson [30] (1948-69)
39 30
0
28 NG
6
NG NG
82% 100%
23% 7%
22% 100%
Cuthbertson and Simpson [31] (1970-84) Mason [5] (1962-70) Grigg et al [33] (1950-80) Bergman and Solhang [6] (1977-83) Overall
28
16
12
0
NG
100%
21%
100%
>-5 years >--5 years >-5 years Median 33-40.5 months > 1 8 months 18/30 > 5 years 12/30 < 5 years Average 51 months
14 16 13
0 16 7
14 0 5
0 0 1
100% NG 85%
100% 100% 85%
14% 6% 0%
100% 100% --
1-8 years NG 18-76 months
69% (161/232)
94% (247/263)
19% (76/404)
--
12 15 39
404
105 (46%)
NG 16 14 20
Survival CancerAbsolute t Specific~
5 2 0
109 (48%)
14 (6%)
65% 55% 84% NG
NG 88% 90% 97%
27% 12% 26% 10%
NG 25% 50% NG
--
* An unspecified number of these patients had polyps with invasive cancer. Also, a small percentage (--5 Yrs Follow-up 66% 89% 24% 42% 11%
(55-84%) (88-90%) (12-27%) (25-50%) (9-13%)
* Values in parentheses indicate ranges. t Percentage of patients in the combined series who were cured by additional surgery after a Iocoregional recurrence.
TABLE IIl Effect of Pathologic Criteria upon Patient Outcome
Mortality
Local Recurrence
(%)
(%)
Surgical margins*
Negative Positive Histologic differentiation t Well to moderate Poor Depth of invasion t T1 T2 T3 Size of tumorw - 3 cm
1
6
35
52
3 26
11 33
1 8 20
5 18 22
4 18
11 33
* [ 19,20,25] t [5, 19,25,27,29,32] t, [3,5, 10,25,27,28] w [ 19,22,25,27,28]
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THE A M E R I C A N J O U R N A L OF SURGERY
size from 13 to 141 patients. Three series had 5-year follow-up of all patients (series 1-3, Table I). Most tumors were either T1 (105 of 227; 46%) or T2 (109 of 117; 48%) lesions, while 6% were T3 lesions (Table I). Overall, local recurrence occurred in 19% of patients and ranged from 0% to 27%. Results with local excision: In the series with 5-year follow-up, two thirds of patients survived for 5 years, and the cancer-specific survival was 89% (Table II). Although 24% of patients developed a local recurrence, nearly half of these patients were cured with additional surgery (Table II). This included several patients who were considered by the authors to be poor candidates for local excision because they had positive surgical margins, poorly differentiated cancers, or tumor invasion into the perirectal tissues. The series by Biggers et al [23] had a 27% local recurrence, but the authors did not specify how many of these patients had successful salvage therapy. Effect of pathologic criteria on outcome: When the effects of the four pathologic criteria upon patient outcome were analyzed, positive margins in the surgical specimen, poorly differentiated histology, and increasing depth of bowel wall invasion were associated with a significant increase in mortality and local recurrence (Table III, Figures 1 and 2). Higher rates of mortality and local recurrence were also observed in patients whose tumors were greater than 3 cm in diameter, although the association was not significant. COMMENTS Since its introduction in 1908, Miles' [37] APR has been accepted as the standard of care for patients with invasive rectal carcinoma located within 6 cm of the anal verge. Morbidity and mortality from this operation, however, are significant. Operative mortality ranges from 1%
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LOCAL EXCISION OF RECTAL CARCINOMA
NoPatient O~araeteristie Effect
(
//
5.81
( l ~ a t i ~ vs. Positive) ( 1.18
Kistologic Diffexentiation+ 6,'ell or l~xterate vs. Poor)
//
//
) 7.82
2149
//--)
( 1.03 Tumor size w (_ 3~)
3173
0.70 (--
I
I
0.5
o
3q26. // 1.0
I
I
1.5
2.0
I
13.49
15.15 )
i
2.5
3.0
Pooled-0dds
data f r o m [ 19,22,25,27,28].
to 5% [38-42] and is markedly increased in patients over 70 years of age. Sexual dysfunction occurs in the majority of male patients [43-46]. While this is more common in the elderly, 15% of patients under the age of 50 are rendered impotent by an APR, and 10% are unable to ejaculate [47]. Bladder dysfunction is similarly common [48-54]. Marks and Ritchie [54] found a 34% incidence of urinary retention, often requiring surgical relief for symptoms of bladder outlet obstruction. An APR also results in a permanent colostomy with its attendant mechanical and psychosocial problems. Although a trial that compares local excision with radical surgery has not been performed, the results in these 10 series are similar to results achieved with APR for similarly staged tumors. Dukes and Bussey [55], in the first detailed analysis of survival and its relationship to histologic grade and extent of spread, reported a 98% 5-year survival for 261 patients with well- and moderately differentiated (grades 1 and 2) tumors and no extrarectal disease. Two recent series have confirmed these results: Wilson and Beahrs [56] (362 patients) and Grigg et al [33] (268 patients) reported 85% and 88% 5-year survival, respectively, in patients with TI and T2 lesions. Local recurrence rates were also similar. McDermott and coworkers [57], in reviewing 276 patients who underwent an APR for T1 and T2 carcinomas, found a 10% incidence of local recurrence [57]. Since none of these patients were rendered disease-free with additional surgery, this figure is identical to the persistent local recurrence rate after local excision. Appropriate candidates for local excision should be at minimal risk for local or regional spread of cancer. In reviewing the 10 series of local excisions (Table III, Figures 1 and 2), positive surgical margins significantly increased the rates of local recurrence (relative risk = 19) and mortality (relative risk -- 27). Poorly differentiated histology also resulted in higher rates of local recurrence (relative risk -- 6) and mortality (relative risk --- 10). Depth of bowel wall invasion had a smaller, but still THE AMERICAN
) 62.71
32.31
(T1 and 'r2 vs. T3)
Figure 2. Local recurrence by various patient characteristics: pooled odds ratios together with approximate 95% confidence intervals. Asterisk indicates data from [ 19,20,25]; dagger indicates data from [5, 19,25,27,29,32]; note q u a l - t o sign indicates data f r o m [3,5, 10,25,27,28]; section indicates
//
//--) 6119
(-0.79
Depth of Invasion# (I"1vs. T2)
. 19110
significant, impact. As tumor invasion extended from the submucosa (T1) into the muscularis propria (T2), local recurrence rates increased from 5% to 18% (relative risk = 2.5) and mortality increased from 1% to 8% (relative risk = 3). As tumors extended into the perirectal fat (T3), local recurrence rates increased to 22% (relative risk = 4) and mortality increased to 20% (relative risk = 11). Tumor size greater than 3 cm showed a trend toward higher rates of local recurrence (relative risk = 3) and mortality (relative risk = 2.5), but the results were not significant, This finding is supported by Spratt and Spjut [58] who reviewed 1,137 consecutive patients with colorectal carcinoma and found that both the risk of nodal metastases and the overall prognosis were independent of tumor size. When Whiteway and co-workers [20] reviewed the St. Marks' experience with local excision, they similarly found that size was not an independent prognostic factor when tumor pathology was corrected for histologic differentiation and depth of invasion. Other pathologic features may be important in predicting the natural biology of the tumor. Several studies suggest that ulcerative tumors and those with lymphatic, vascular, or perineural invasion are all associated with an increased risk of nodal metastases and decreased survival [58-62]. Recent data from flow cytometry show that aneuploid tumors with high S-phase fractions have a worse prognosis than diploid tumors [63-65]. Although these factors may be important in selecting appropriate candidates for local excision, this review did not analyze their significance. In addition to these pathologic criteria, careful preoperative examination is necessary to identify patients at high risk for intramural or extramural extension of disease. Intramural spread is rare in patients with T1 and T2 rectal carcinomas and favorable histology. Grinnell [66] examined 93 rectal specimens and identified significant (more than 0.5 mm) distal spread in 18 (19%), In only one of these cases was the primary tumor confined to the bowel wall, and intramural spread in that case was limit-
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T A B L E IV
Guidelines for Local Excision Preoperative A. Absolute indications 1. Mobile tumor 2. T1 tumor (by ultrasound) 3. Well- or moderately differentiated histology (by biopsy) 4. Size - 3 cm C. Contraindic~tions 1. Fixed tumor 2. T3 tumor (by ultrasound) 3. Poorly differentiated histology (by biopsy)
Postoperative Indications
for abdominoperineal
resection
and/or adjuvant
therapy 1. 2. 3. 4.
Positive surgical margins T3 tumor Poorly differentiated histology Positive perirectal lymph node(s)
ed to 1 cm. Quer et al [67] demonstrated intramural spread in 4 of 91 patients with rectal carcinoma. Two were poorly differentiated carcinomas, and two were moderately differentiated with limited (1 cm, 1.5 cm) spread in submucosal veins. Williams and co-workers [68] examined 50 specimens following curative APR. Only 5 of 50 specimens had intramural spread greater than 1 cm, and all 5 were poorly differentiated Dukes' stage C tumors. Thus, intramural spread is unlikely in patients with T1 and T2 lesions and should be detected by frozen-section analysis of the margins. Extramural spread occurs by direct extension into the perirectal fat, metastases to regional lymph nodes, or both. Since extension beyond the bowel wall is associated with a 50% risk of nodal metastases [69,70], and since local excision does not systematically remove the adjacent lymph nodes, neither group of patients should be offered local excision alone. It is difficult, however, to preoperatively determine which patients have extrarectal disease. Direct extension of the primary tumor can be difficult to assess. In a prospective study of 70 patients, clinical predictions that disease was confined to the bowel wall based on digital examination were confirmed pathologically in only 44% to 83% of cases [71]. Computed tomography (CT) scanning and magnetic resonance imaging (MRI) have been unable to demonstrate microscopic spread [72-80]. Intralumenal ultrasound, on the other hand, has been very accurate in defining bowel wall infiltration [81-83]. In reviewing 90 patients who were examined with endorectal ultrasound, staging was accurate in more than 90% of cases, and only one patient had more extensive disease than was demonstrated by ultrasound. As final confirmation, local excision provides a full-thickness excision of the tumor, and the exact extent of extrarectal spread can be determined [26]. There are no preoperative tests that adequately detect metastases in perirectal lymph nodes. Clinical examination is not reliable [69,84-86]. CT scanning and MRI 310
reveal grossly enlarged nodes only (greater than 1 to 1.5 cm), with little sensitivity (22% to 39%) and variable specificity (61% to 96%) [72-75]. Normal-sized lymph nodes containing micrometastases are missed. Examination of operative specimens indicates that two thirds of lymph node metastases are less than 5 mm in diameter [87]. Monoclonal imaging methods have been unable to detect positive lymph nodes; one study showed greater uptake in normal mesenteric nodes than in tumor-bearing nodes [88]. Careful patient selection can minimize the risk of nodal metastases, but this risk is still 11% to 23% in patients with T1 and T2 rectal carcinomas [69,70,89]. The majority of these metastases, however, occur with poorly differentiated tumors. Dukes and Bussey [55] showed that the frequency of lymph node metastases increases as tumors become less differentiated (30% in well-differentiated, 47% in moderately differentiated, and 81% in poorly differentiated neoplasms). Cohen et al [59] confirmed this in a recent study at the Massachusetts General Hospital (25% in well-differentiated, 33% in moderately differentiated, and 77% in poorly differentiated neoplasms). In Morson's [70] series, all five T1 cancers with lymph node metastases were poorly differentiated neoplasms. One solution to the problem of detecting lymph node metastases is to sample the perirectal lymph nodes at the time of surgery. Since lymphatic metastases occur in an orderly and predictable pattern [55], the first nodes to receive metastases are those situated adjacent to or immediately cephalad to the primary tumor. As a result, if these lymph nodes are negative, a lymph node dissection is not necessary. If these nodes are positive, additional therapy is needed to control regional disease. The choice of such additional therapy is often difficult. A completion APR can be safely performed and combined with adjuvant radiotherapy and/or chemotherapy. No published data exist on the efficacy of adjuvant therapy alone following local excision for rectal carcinoma, but radiotherapy is clearly effective in the adjuvant setting for more advanced rectal tumors [9093], and recent results from the Gastrointestinal Tumor Study Group [94] and the National Surgical Adjuvant Breast Project [95] suggest a similar benefit from adjuvant chemotherapy. At the present time, M.D. Anderson Cancer Center is combining local excision with postoperative radiotherapy and 5-fluorouracil for patients with T2 and T3 lesions [96]. Although follow-up has been short, 19 patients have been treated in this program with no local recurrences and no cancer-related mortality. The role of adjuvant therapy following local excision awaits further analysis of such carefully controlled studies. Current guidelines for local excision are provided in Table IV. CONCLUSIONS Local excision of T 1 and T2 invasive rectal carcinomas within 6 cm of the anal verge results in survival and local control comparable to those obtained with radical resection. A permanent colostomy is avoided, and the operative mortality (less than 1% in these series) and morbidity are significantly lowered. Selection of patients
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for local excision requires a careful digital examination, endoscopy, biopsy of the tumor, intralumenal ultrasound, a n d CT. Local excision may be attempted if the tumor is mobile, well or moderately differentiated, and shows no evidence of extrarectal spread. A transsacral or transsphincteric approach is recommended to evaluate perirectal lymph nodes. The operative specimen must then be reviewed for confirmation of favorable histology and absence of regional spread. Positive surgical margins, poorly differentiated histology, and extension into perirectal fat are associated with increased local recurrence and decreased survival. T u m o r size greater than 3 cm does not appear to be significant. Local excision is adequate for rectal carcinoma that is well or moderately differentiated and limited to the submucosa (T1). Lesions involving the muscularis propria (T2) may require adjuvant radiotherapy a n d / o r chemotherapy to limit local recurrence. Tumors that are poorly differentiated or penetrate the perirectal fat (T3) may be radically resected or treated with multimodality therapy in an experimental trial, given the high risk of nodal metastases. REFERENCES 1. Yeatman TJ, Bland K. Sphincter-saving procedures for distal carcinoma of the rectum. Ann Surg 1989; 209: 1-18. 2. Kraske P. Zur Exstirpation Hochsitzender Mastdarmkrebse. Verh Dtsch Ges Chir 1885; 14: 464-74. 3. O'Brien PH. Kraske's posterior approach to the rectum. Surg Gynecol Obstet 1976; 142: 412-4. 4. Mason AY. Surgical access to the rectum: a trans-sphincteric exposure. Proc R Soc Med 1970; 63: 91-4. 5. Mason AY. Trans-sphincteric approach to rectal lesions. Surg Annu 1977; 9: 171-94. 6. Bergman L, Solhaug JH. Posterior trans-sphincteric resection for small tumours of the lower rectum. Acta Chir Scand 1986; 152: 313-6. 7. Westbrook KC, Lang NP, Broadwater JR, Thompson BW. Posterior surgical approaches to the rectum. Ann Surg 1982; 195: 677-85. 8. Olsen WR. Transanal excision of sessile rectal polyps. Surg Gynecol Obstet 1975; 140: 766-8. 9. Papillon J. Endocavitary irradiation of early rectal cancers for cure: a series of 123 cases. Proc R Soc Med 1973; 66: 1179-81. 10. Papillon J. Endocavitary irradiation in the curative treatment of early rectal cancers. Dis Colon Rectum 1974; 17: 172-80. 11. PapiUon J. New prospects in the conservative treatment of rectal cancer. Dis Colon Rectum 1984; 27: 695-700. 12. Sischy B, Remington JH. Treatment of carcinoma of the rectum by intracavitary irradiation. Surg Gynecol Obstet 1975; 141: 562-4. 13. Sischy B, Remington JH, Sobel SH. Treatment of rectal carcinomas by means of endocavitary irradiation. Cancer 1978; 42: 1073-6. 14. Sischy B, Remington JH, Sobel SH. Treatment of rectal carcinomas by means of endocavitary irradiation: a progress report. Cancer 1980; 46: 1957-61. 15. Strauss AA, Strauss SF, Crawford RA, Strauss HA. Surgical diathermy of carcinoma of the rectum. JAMA 1935; 104: 1480-4. 16. Madden JL, Kandalaft S. Electrocoagulation in the treatment of cancer of the rectum: a continuing study. Ann Surg 1971; 174: 530-40. 17. Crile G, Turnbull RB. The role of electrocoagulation in the treatment of carcinoma of the rectum. Surg Gynecol Obstet 1972; 135: 391-6. 18. Eisenstat TE, Deak ST, Rubin R J, Salvati EP, Greco RS. Five
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