- Email: [email protected]
Surgical concepts in the treatment of colorectal cancer
Surgical Concepts in the Treatment of Colorectal Cancer Brian W. Loggie
REATMENT OF colon and rectal cancer has evolved over the last decade.! This is particularly true for rectal cancer. 2 Rectalconservation (or colostomy sparing) treatment is being more widely applied and reflects changes in surgical thinking and surgical techniques as well as advances in combined modality treatment strategies. 34 These advances have been accompanied by the need for innovative endorectal-imaging techniques and increased interaction between surgeon and radiologist. This article will give our perspective on some of the management issues in the treatment of colorectal cancer and will emphasize the evolving approaches to the therapy of rectal cancer. Colon and rectal cancer is the third leading cancer site associated with cancer deaths for men and women, taking into account all ages. Colon and rectal cancer together will account for 138,200 new cancer cases in the United States in 1995. Between 1983 and 1990, the tumor stage at diagnosis was localized in only 37%, was associated with regional involvement in 38%, and was distant in 19%. A statistically significant improvement in survival has been noted over the last 30 years. 6 Staging is becoming more standardized and has dramatically improved. Colon cancers classified as unknown decreased from 79% in 1985 to 16% in 1992 with similar figures noted for rectal cancer. A higher ratio of males is observed for rectal cancer (male/female: 1.29), but not for colon cancer (0.98). A trend for more proximal bowel location has been noted for colon cancer with 27% of cases reported in 1971 arising in the ascending colon compared with 36% in 1992. More patients with both colon and rectal cancers are receiving combined modality therapy. 7,8
T
SURGICAL PERSPECTIVES ON TREATMENT
The treatment goals at surgery are well defined. Ideally, an en-bloc resection of tissue is performed. The involved bowel is resected with preferably at least 5-cm gross-tumor clearance from proximal and distal resection margins. If contiguous structures, such as the abdominal wall, are infiltrated, these are resected when feasible. Lymph-node removal is important for staging and treatment and this involves the removal of the appropriate mesenteric segment containing the vascular pedicle. Standardized surgical approaches are well-described elsewhere. The radiologist can provide information that may alter a surgical approach. A barium enema showing a small lesion in the sigmoid or right colon, and which is mobile, may allow the surgeon to use a limited incision or laparoscopic approach. For bulky or circumferential rectosigmoid tumors, the relationship of the tumor to the ureters and bladder base should be established by computed tomography (CT) or intravenous pyelogram (IVP). The benefit of routine preoperative CT in patients with resectable colon cancer is debated, but has been this investigator's practice. 9 At laparotomy, large polyps that cannot be removed colonoscopically or small proven cancers may be difficult to locate by palpation. Colonoscopic estimates for the location of the tumor are often just that--estimates. In such cases, a barium enema can provide a useful road map for the surgeon. While it is possible to perform colonoscopy at the time of surgery to confirm the exact location of a difficult-to-find lesion, this adds to the time, complexity, and cost of the procedure.
Rectal Cancer
Colon Cancer
Surgical considerations. Digital rectal examination is critical in the assessment of a patient
Surgery is the mainstay for the treatment of colon cancer. The initial consideration for the surgeon relates to the location of the primary tumor in the colon, because this is a primary determinant of which technical procedure will be used. In turn, these procedures are based on the vascular and lymphatic anatomy of the colon.
From the Department of Surgery, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC. Address reprint requests to Brian W. Loggie, MD, Department of Surgery, Bowman Gray School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157. Copyright © 1996 by W.B. Saunders Company 0037-198)(/96/3102-000555.00/0
Seminars in Roentgenology, Vol XXXI, No 2 (April), 1996: pp 111-117
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with rectal cancer. Typically, a lesion that is readily palpable on digital rectal examination lies within 7 to 10 cm of the anal verge. Lesions more than this level will be in the mid to upper rectum or rectosigmoid region. The implications for treatment by digital evaluation are simple. Upper rectal tumors can be treated by low anterior resection in most instances (ie, a permanent colostomy is not required). For more distal tumors, abdominoperineal resection (with a permanent colostomy mandated) was commonly practiced in the past. Rectal conservation therapy is possible in most cases of low rectal cancers without negatively impacting on local (pelvic) control and survival. An estimate is that only one patient in seven presenting with rectal cancer will require a colostomy. 1° Local pelvic control is a key treatment issue. Until they become bulky, hepatic, or pulmonary, metastases are often asymptomatic. Recurrent pelvic disease is usually symptomatic. Quality of life is rapidly eroded by constant pain or tenesmus. Most patients presenting with pelvic pain following treatment for rectal cancer will be found to have a pelvic recurrence (80%) and nearly all patients present with pain. 11Unfortunately, pelvic recurrences can only occasionally be salvaged and palliation is difficult2 2,13 The important issues relating to local control relate to the stage of the tumor and the relationship of the cancer to pelvic structures. The walls of the pelvis can be compared with the sides of a teacup in that a roughly circular opening in the true pelvis funnels down to the outlet. The walls are firmly fixed. On pathology reports, prominence is given to the report of proximal and distal resection margins. These margins usually correlate with gross margins at the time of surgery. Of greater significance is the depth-oftumor penetration relative to the bowel wall and surrounding tissues. This margin is the most difficult to characterize pathologically because of the ill-defined nature of the surrounding fatty tissues and because of the possibility of sampling error. Tumor penetration into the pelvic soft tissues constitutes the most likely cause for local failure. 14 This peripheral margin is no more effectively removed by low anterior resection than it is by abdominoperineal resection (APR). 15 This is because the dissection planes are determined by the walls of the pelvis and are
BRIAN W. LOGGtE
the same for either surgical dissection. A portion of the pelvic muscular floor, including the muscles of continence, is included to some extent in the abdominoperineal resection. If the tumor is not infiltrating the levator, there is no advantage for resecting this from an oncological standpoint and a permanent colostomy becomes mandated for the patient. It had previously been thought that a 5-cm distal margin was required to lessen the chance of recurrence. By this convention, most patients with lesions readily palpable on rectal examination required an APR; however, a much smaller distal margin is required for most tumorsJ 6,17In practice, our goal is to achieve a 1- to 2-cm distal margin for most tumors. The probability of local recurrence is greater if there is lymphatic involvement consistent with worse tumor biology. Bulky, advanced tumors (circumferential, ulcerated, poorly differentia t e d - T 3 ; fixed--T4) can be associated with extensive lymphatic permeation. Retrograde lymphatic distal extension can occur, especially if proximal lymphatics become filled with tumor. In these instances, tumors may extend in deep planes beyond visible mucosal margins. Patients with extensive lymphatic involvement are more likely to fail in the pelvis and distantly by virtue of more aggressive tumor biology. These locally advanced tumors are often deemed unresectable. Surgery can be done in many instances, but these patients are more likely to require APR or some form of pelvic exenterative procedure to achieve pelvic control. This is typically planned following radiation and chemotherapy, and complete surgical removal of the tumor is critical for good survival results. 18-24 Avoidance of a permanent colostomy, using rectal conservation treatment, is an important quality-of-life issue75 If rectal conservation is to be performed safely and effectively, a combined modality approach is usually required. Clinical staging is important in determining a treatment plan. In general, the more locally advanced a tumor is, the greater the likelihood exists for lymphatic involvement. 26 Local excision is probably best reserved for those patients with selected T1 and T2 tumors. Full thickness excision of a T1 tumor with negative margins likely constitutes definitive therapy in most instances. Local excision of T2 tumors, those involving the
SURGICAL TREATMENT OF COLORECTAL CANCER
muscular wall, without the addition of radiation therapy is associated with a higher recurrence rate. Our bias, and that of others, is to recommend combined chemotherapy and radiation therapy for these lesions. 27-3° When possible, such patients should be registered on ongoing national trials. 31 For T3 lesions, the tumor has invaded into the perirectal fat, which increases the possibility of local pelvic recurrence. Recurrence rates of 25% to 40% following surgery are anticipated in the absence of further therapy. All these patients should receive radiation therapy with chemotherapy.32 Whether this is best given preoperatively or postoperatively remains debated, but preoperative therapy is better tolerated and gives good local control. 33,34 Our preference and that of many others is to use combined full-dose radiation therapy with fluorouracil-(5-FU) based chemotherapy up front (neoadjuvant or induction therapy). This is followed by surgical resection, usually low anterior resection, at 4 to 6 weeks following completion of the neoadjuvant radiation therapy. Microscopic fingers of infiltrating peripheral tumor in the perirectal fat are sterilized and tissue planes become edematous in this time frame. This facilitates successful surgical resection. In almost all patients, a substantial clinical response, sometimes with downstaging, is appreciated with this approach. About 10% to 20% of patients will manifest a clinical complete response with aggressive neoadjuvant therapy. 35 Unless severe underlying medical conditions are present, some form of surgical resection is recommended because it is unclear how often a clinical complete response will translate into a pathological complete response. Some bulky low-lying tumors will respond well enough that rectal conservation therapy, usually a low anterior resection, becomes possible. 36Thus, preoperative treatment can facilitate rectal conservation in selected patients who would otherwise have required a permanent colostomy. Impact of radiological findings on treatment of rectal cancer. The importance of pre-therapy staging has become critical for treatment decisions to achieve rectal conservation or minimize surgery without compromising chances for cure. Treatment options are shown in Table 1. A number of radiological modalities are currently available for clinical staging.
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Table 1. Treatment of Rectal Cancer by Clinical Stage Rectal CancerT Stage T1, NO T2, NO T3, NO T1-T3, N1
Treatment Options 1"1-, 2 I + RT*1-, 2*, 2 + RT:I:,3 1 + RT§, 2 + RT*, 3 + RT[I 2 + RT*, 3 + RTII
Note: 1, local full-thickness rectal excision (endorectal excision or posterior approach); 2, low anterior resection (colorectal or coloanal anastomosis); 3, abdominoperineal resection (colostomy); RT, radiation therapy with chemotherapy. *Preferred treatment options. 1"Size <3 cm or one-third circumference; not high-grade or mucinous; not ulcerated. :l:Poorly differentiated, lymphovascular involvement, suboptimal surgery. §Medical-poor risk. ilTumor invades levator.
In most cases, CT scanning is used to stage the liver and abdomen. The anatomic information of the kidneys, ureters, and bladder is useful for the surgeon; it has not been my practice to obtain an IVP. CT can also detect incidental pathology or anatomic variations that may impact on treatment considerations, such as aortic aneurysms or gallstones. However, CT is not sensitive for the discrimination between T1, T2, and T3 lesions in the rectum. For bulky T3 tumors, a mass appreciated and stranding in the pelvic soft tissues is a common finding suggesting perireetal infiltration, but may represent inflammatory reaction. CT findings may be absent in a smaller rectal cancer. Because our treatment approach can vary importantly by exact tumor T-stage, other modalities have emerged in recent years. These tests must be correlated with clinical findings, particularly digital rectal examination. A learning curve is apparent for all endorectal radiological investigations. Communication between the radiologist and surgeon is vital. The surgeon must provide the radiologist with specific clinical information and, equally important, the radiologist should seek and use this information. It cannot be overstated that it is often necessary for the radiologist to perform a careful rectal examination so the probes or coils are correctly positioned and the radiological information is valid. Digital rectal examination requires experience and is about 60% to 80% accurate for staging. A clinical T1 designation is made where the rectal wall is mobile and the mucosal lesion
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is also mobile. T2 lesions are characterized by invasion into, but not beyond, the muscular wall. Discrimination between T1 and T2 lesions can be difficult but is less Critical than the discrimination between T2 and T3 lesions. For patients with tethering of the full rectal wall but without fixation on digital rectal examination, a clinical T3 status is accorded. Gross ulceration that is palpable is consistent with a T3 lesion. Fixation suggests invasion into the pelvic sidewall or adjacent structures and is classified as a T4 lesion. Both endorectal ultrasound and endorectal magnetic resonance imaging (MRI) have been used for the preoperative staging of rectal tumors. Correlation of physical examination by an experienced examiner with ultrasonography (US) or MRI findings has been good. When US or MRI suggest an early T3 tumor but the clinical stage is T2, the pathology has usually yielded evidence for a microscopic T3 stage. Both seem to provide accurate staging of the tumor through the rectal wall. 37,38 There is perhaps a slight bias in favor of over estimating stage using both these techniques and is preferable and safer than underestimation. Lymphnode metastases can sometimes be identified or strongly suspected. Both techniques have limitations. Endorectal ultrasound is limited in penetration beyond the rectal wall and the examination is observer dependent. Wall invasion is accurately predicted before radiation therapy but not postirradiation. 39 Hard-copy pictures usually do not provide orientation with respect to exact radial location or with respect to distance from the sphincter. We have also found that very low anorectal or anal lesions sometimes cannot be usefully assessed by ultrasound because of difficulties in probe placement. Advantages of endorectal MRI that may be appreciated by the surgeon are the ability to visualize the pelvic structures and their relationships to the rectal tumor. These relationships can be visualized by para:sagittal or coronal views. Further, gadolinium can enhance the tumor identification and clarify the status of a prominent, but not enlarged, lymph node. As wel l, endorectal imaging may be helpful in assessing for suspected extraluminal pelvic recurrence following rectal conservation therapy. 4° Liabilities associated with
BRIAN W, LOGGIE
MRI include: examination discomfort; cost; and availability. Discomfort can be minimized with new smaller coils but can sometimes result in refusal by the patient to undergo testing. Cost issues are pertinent but the quality of the information and the likelihood of changing therapy must be considered. Metastatic Cancer and Special Considerations Liver disease. As noted previously, about 19% of colorectal cancer patients will have synchronous metastatic disease. The likelihood of metastatic liver disease at the time of diagnosis is higher for patients with right-sided colon tumors (about 30%) when compared with more distal locations (about 13% to 22%). 41 The liver is the most common site of distant metastatic disease at the time of initial diagnosis and at relapse. Based on standard strict surgical criteria, only a minority of patients will be candidates for surgical resection. These cases are limited to instances in which no extrahepatic disease exists, only one to three lesions exist, and these lesions Can be safely resected with a minimum 1-cm tissue margin. It should be noted that the majority of well-selected patients will suffer disease relapse but about 20% to 25% will be disease-free at 5 years. Cryoablation of tumors is used by some groups to expand the treatment of patients with liver metastatic disease. 42 At surgery, blunt probes ranging in size from 3 to 10 mm are positioned in tumor deposits. Liquid nitrogen is circulated through the tips of these sealed probes and creates an ice ball centered on the tumor. This, in turn, is assoeiated with coagulative necrosis. Removal of the tumor is usually not performed. This approach is made feasible with the advent of intraoperative ultrasound (IOUS), which is used to identify tumor, guide probes, and monitor freezing. In our institution, the radiologist will typically scrub into the operation to perform this examination and will often assist the surgeon with cryoablation efforts. Cryoablation can be used in concert with resection. For example, a lesion in the lateral segment of the left lobe will be resected, whereas a lesion in the deep right lobe will be frozen. An advantage of cryoablation is that a large volume of normal liver parenchyma may be spared that would
SURGICAL TREATMENT OF COLORECTAL CANCER
otherwise be included in resection. Further, it is associated with low morbidity. Typically, lesions greater than 8 cm in size often cannot be frozen safely or adequately. It can sometimes be difficult to confirm adequate expansion of the freeze ball to incorporate all sides of the tumor. An unresolved issue is how many lesions can be treated with cryoablation in excess of strict surgical guidelines with expectations of reasonable outcome. Standard surgical selection and surgical resection remain the current gold standard. We use rapid CT arterial portography (CTAP) performed with contrast injections into the superior mesenteric or splenic artery for screening patients in whom surgical intervention for liver disease is being considered. The celiac vascular anatomy is defined at the time of placement of the arterial catheter before the CTAP. This permits definition of the hepatic vascular anatomy, which is useful to speed up dissection during liver resection or to easily identify the options for hepatic artery chemotherapy treatment. The logistics, costs, and additional risks associated with arterial catheter placement, which is necessary for CTAP, preclude its use as a routine screening or follow-up modality. In our hands, this is the most sensitive method for detection of metastatic liver disease. We generally do not use CTAP for patients who will require surgery anyway for their primary tumor. We routinely use I O U S during surgery where liver disease is known or suspected to be present. I O U S is not used as a routine screen for liver disease. It is helpful to define hepatic anatomy, identify nonpalpable lesions, and guide biopsy needles or cryoablation probes. Resection planes are determined using this information, particularly for nonanatomic resections. These studies arc carefully correlated with preoperative CT or M R images. I O U S has b e e n hailed as a very accurate method for examination of the liver. In reviewing our last 14 cases involving the use of cryosurgery, two patients had lesions identified on C T A P that we were unable to confirm with I O U S and that subsequently proved to be small metastatic deposits (unpublished observations). We have also noted that C T A P can overestimate the amount of disease in the liver, presumably with artifacts relating to factors such as dye streaming. These
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limitations need to be understood by the surgeon and acknowledged by the radiologist. M R I is less sensitive than C T A P in our hands. Peritoneal carcinomatosis. We have been involved in ongoing clinical studies for the treatment of patients with peritoneal carcinomatosis. Mucinous tumors compromise about 15% of colorectal tumors. These are seen more commonly in young patients, particularly patients under 30 to 40 years of age, and are by far the most frequent tumor type associated with peritoneal dissemination. A previous presentation with an obstructed or perforated cancer is common. It is critical that the surgeon and the radiologist work together with shared information to optimize patient care. CT scanning clearly underestimates disease in this circumstance. The signs of carcinomatosis can be very subtle on CT and can be easily missed without careful attention to scanning technique and clinical input. CONCLUSION
New treatment strategies have evolved for the treatment of both localized and advanced colorectal cancer. The intent of this article has been to stress the close working relationship necessary between the surgeon and the radiologist who are treating these patients. The impact of radiological findings on surgical treatment, especially localized rectal cancer, has been reviewed. APPENDIX
Glossary of terms used in the treatment of rectal cancer: Low anterior resection: This operation includes the full mobilization of the rectum and an anastomosisis performed below the peritoneal reflection. The anastomosis may be hand sewn or stapled. Typically,circular stapling devices are used for low colorectal anastomosis, These devices are referred to as end-to-end anastomosis (EEA) staplers. Very low anastomoses can be performed on selected patients between the proximal divided colon and the anal mucosa and is referred to as a coloanal anastomosis.A temporary or diverting colostomymay be used to protect the anastomosis in some instances. APR: Also known as the Miles procedure. This is a two-part procedure consisting of an abdominal portion and perineal dissection, usually performed synchronously. The rectum is mobilized via the abdominal route. Next, or simultaneously, the perineum around the anus is incised and dissection is deepened through the muscular pelvic floor. For anterior rectal cancers in women, the posterior vagina should be included in the resection. Because the muscles responsible for continence are included, a perma-
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BRIAN W. LOGGIE
nent colostomy is mandated. En-bloc rectal resection, including the bladder and prostate in men and the bladder, uterus, and ovaries in women, is known as a total pelvic exenteration. Abdominosacral resection includes partial sacral resection. Hartmann's procedure implies closure of the rectal stump and creation of a sigmoid colostomy following resection of a rectal cancer. Local excision may be performed using an endorectal approach. The technique involves the full thickness excision of the bowel wall with 1 cm margins. This is performed through the anus using a speculum or short endoscope and is suitable for low-lying, small carcinomas, mainly T1 or T2. A posterior approach, also known as a Kraske approach, is used by some, especially for villous adenomas. This involves
approaching via a posterior skin incision, resecting the coccyx, and splitting the muscles in the posterior midline. It is possible to open the bowel for a local excision or to excise and anastomose a short segment; this is referred to as a sleeve resection. An advantage is very low morbidity by avoiding an abdominal incision, but exposure is limited. Neoadjuvant therapy, or induction therapy, implies treatment administered before surgery to shrink large fixed tumors or downstage smaller tumors. This typically involves combination chemoradiotherapy. The chemotherapy drug 5-FU is most commonly used alone or in combination as a radiation sensitizer. Adjuvant therapy implies the use of chemotherapy or radiation therapy following complete, or so-called curative, resection.
REFERENCES
1. Moertel CG: Accomplishments in surgical adjuvant therapy for large bowel cancer. Cancer 70:1364-1371, 1992 (suppl) 2. Billingham RP: Conservative treatment of rectal cancer: Extending the indications. Cancer 70:1355-1363, 1992 (suppl) 3. RaubWF: Combinationtherapymostbeneficial against rectal cancer. JAMA 265:2173, 1991 4. Steele G: Combined-modality therapy for rectal carcin o m a - t h e time has come. N Engl J Med 324:764-766, 1991 5. Reynolds T: Combined treatment substantially improves outlook for rectal cancer patients. J Natl Cancer Inst 83:386-387, 1991 6. Wingo PA, Tong T, Bolden S: Cancer statistics, 1995. CA Cancer J Clin 45:8-30, 1995 7. Steele GD Jr, Jessup LM, Winchester DP, et al: Clinical highlights from the National Cancer Data Base. CA Cancer J Clin 45:102-111, 1995 8. Beart RW, Steele GD Jr, Menck HR, et al: Management and survival of patients with adenocarcinoma of the colon and rectum: A national survey of the commission of cancer. J Am Coll Surg 181:225-236, 1995 9. Cohen AM: Preoperative evaluation of patients with primary colorectal cancer. Cancer 70:1328-1332, 1992 (suppl) 10. DeCosse JJ, Cennerazzo W: Treatment options for the patient with colorectal cancer. Cancer 70:1342-1345, 1992 (suppl) 11. Boas RA, Schug SA, Acland RH: Perineal pain after rectal amputation: A 5-year follow-up. Pain 52:67-70, 1993 12. Wanebo HJ, Koness RJ, Turk PS, et al: Composite resection of posterior pelvic malignancy. Ann Surg 215:685695, 1992 13. Maetani S, Nishikawa T, Iijima Y, et al: Extensive en bloc resection of regionally recurrent carcinoma of the rectum. Cancer 69:2876-2883, 1992 14. Ng IOL, Luk ISC, Yuen ST, et al: Surgical lateral clearance in resected rectal carcinomas: A multivariate analysis of clinicopathologic features. Cancer 71:1972-1976, 1993 15. Graf W, Pahlman L, Enblad P, et al: Anterior versus abdominoperineal resections in the management of midrectal tumours. Acta Chir Scand 156:231-235, 1992 16. Shirouzo K, Hiroharu I, Kakegawa T: Distal spread of rectal cancer and optimal distal margin of resection for sphincter*preserving surgery. Cancer 76:388-392, 1995
17. Vernava AM III, Moran M, Rothenberger DA, et al: A prospective evaluation of distal margins in carcinoma of the rectum. Surg Gynecol Obstet 175:333-336, 1992 18. Whiting JF, Howes A, Osteen RT: Preoperative irradiation for unresectable carcinoma of the rectum. Surg Gynecol Obstet 176:203-207, 1993 19. Frykholm G, Glimelius B, Pahlman L: Preoperative irradiation with and without chemotherapy (raft) in the treatment of primarily non-resectable adenocarcinoma of the rectum. Results from two consecutive studies. Eur J Cancer Clin Oncol 25:1535-1541, 1992 20. Poulter CA: Radiation therapy for advanced colorectal cancer. Cancer 70:1434-1437, 1992 (suppl) 21. Minsky BD, Cohen AM, Enker WE, et al: Radiation therapy for unresectable rectal cancer. Int J Radiat Oncol Biol Phys 21:1283-1289, 1991 22. Tobin RL, Mohiuddin M, Marks G: Preoperative irradiation for cancer of the rectum with extrarectal fixation. Int J Radiat Oncol Biol Phys 21:1127-1132, 1991 23. Mohiuddin M, Ahmad NR: Pre-operative chemoradiation for advanced rectal cancer. Int J Radiat Oncol Biol Phys 25:923-924, 1993 24. Deneve W, Martijn H, Lybeert MM, et al: Incompletely resected rectum, recto-sigmoid, or sigmoid carcinoma-results of postoperative radiotherapy and prognostic factors. Int J Radiat Oncol Biol Phys 21:1297-1302, 1991 25. Frigell A, Ottander M, Stenbeck H, et al: Quality of life of patients treated with abdominoperineal resection or anterior resection for rectal carcinoma. Ann Chir Gynaecol 1990 79:26-30, 1992 26. Brodsky JT, Richard GK, Cohen AM, et al: Variables correlated with the risk of lymph node metastasis in early rectal cancer. Cancer 69:322-326, 1992 27. Cummings BJ: Adjuvant radiation therapy for colorectal cancer. Cancer 70:1372-1383, 1992 (suppl) 28. Bennett CJ Jr, Sombeck MD, Mendenhall WM, et al: Conservative alternatives in the management of early adenocarcinoma of the rectum. South Med J 86:409-413, 1993 29. Frazee RC, Patel R, Belew M, et al: Transanal excision of rectal carcinoma. Am Surg 61:714-717, 1995 30. Bailey HR, Huval WV, Max E, et al: Local excision of carcinoma of the rectum for cure. Surgery 111:555-561, 1992 31. Steele G Jr: Adjuvant therapy for patients with colon and rectal cancer: Clinical indications for multimodality
SURGICAL TREATMENT OF COLORECTAL CANCER
therapy in high-risk groups and specific surgical questions for future multimodality trials. Surgery 112:847-849, 1992 32. Krook JE, Moertel CG, Gunderson LL, et al: Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 324:709-715, 1991 33. Pahlman L, Glimelius B: Pre- or postoperative radiotherapy in rectal and rectosigmoid carcinoma. Report from a randomized multicenter trial. Ann Surg 211:187-195, 1992 34. Glimelius B, Pahlman L: The value of adjuvant therapy after radical surgery for colorectal cancer. Ann Med 24:9-14, 1992 35. Rouanet P: Conservative surgery for low rectal carcinoma after high-dose radiation: Functional and oncologic results. Ann Surg 221:67-73, 1995 36. Meade PG, Blatchford GJ, Thorson AG, et al: Preoperative chemoradiation downstages locally advanced ultrasound-staged rectal cancer. Am J Surg 170:609-613, 1995
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37. Wood M, Mitchell R, Zagoria R, et al: Staging of rectal carcinoma: A comparison of endoscopic ultrasound and endorectal magnetic resonance imaging. Am J Gastroentero189:1700, 1994 (abstr) 38. Allen C, Chert M, Wolfman N, et al: Endoscopic ultrasound (EUS) in the staging of rectal carcinoma: Efficacy and pitfalls. Am J Gastroenterol 90:1638, 1995 (abstr) 39. Napoleon B, Pujol B, Berger F, et al: Accuracy of endosonography in the staging of rectal cancer treated by radiotherapy. Br J Surg 78:785-788, 1991 40. Milsom JW, Lavery IC, Stolfi VM, et al: The expanding utility of endoluminal ultrasonography in the management of rectal cancer. Surgery 112:832-841, 1992 41. Martin MB, Fontrier T, Jarman W, et al: Colon and rectal carcinoma: Forty years and 1400 cases. Am Surg 53:146-148, 1987 42. Steele GD Jr: Cryoablation in hepatic surgery. Semin Liver Dis 14:120-125, 1994
REATMENT OF colon and rectal cancer has evolved over the last decade.! This is particularly true for rectal cancer. 2 Rectalconservation (or colostomy sparing) treatment is being more widely applied and reflects changes in surgical thinking and surgical techniques as well as advances in combined modality treatment strategies. 34 These advances have been accompanied by the need for innovative endorectal-imaging techniques and increased interaction between surgeon and radiologist. This article will give our perspective on some of the management issues in the treatment of colorectal cancer and will emphasize the evolving approaches to the therapy of rectal cancer. Colon and rectal cancer is the third leading cancer site associated with cancer deaths for men and women, taking into account all ages. Colon and rectal cancer together will account for 138,200 new cancer cases in the United States in 1995. Between 1983 and 1990, the tumor stage at diagnosis was localized in only 37%, was associated with regional involvement in 38%, and was distant in 19%. A statistically significant improvement in survival has been noted over the last 30 years. 6 Staging is becoming more standardized and has dramatically improved. Colon cancers classified as unknown decreased from 79% in 1985 to 16% in 1992 with similar figures noted for rectal cancer. A higher ratio of males is observed for rectal cancer (male/female: 1.29), but not for colon cancer (0.98). A trend for more proximal bowel location has been noted for colon cancer with 27% of cases reported in 1971 arising in the ascending colon compared with 36% in 1992. More patients with both colon and rectal cancers are receiving combined modality therapy. 7,8
T
SURGICAL PERSPECTIVES ON TREATMENT
The treatment goals at surgery are well defined. Ideally, an en-bloc resection of tissue is performed. The involved bowel is resected with preferably at least 5-cm gross-tumor clearance from proximal and distal resection margins. If contiguous structures, such as the abdominal wall, are infiltrated, these are resected when feasible. Lymph-node removal is important for staging and treatment and this involves the removal of the appropriate mesenteric segment containing the vascular pedicle. Standardized surgical approaches are well-described elsewhere. The radiologist can provide information that may alter a surgical approach. A barium enema showing a small lesion in the sigmoid or right colon, and which is mobile, may allow the surgeon to use a limited incision or laparoscopic approach. For bulky or circumferential rectosigmoid tumors, the relationship of the tumor to the ureters and bladder base should be established by computed tomography (CT) or intravenous pyelogram (IVP). The benefit of routine preoperative CT in patients with resectable colon cancer is debated, but has been this investigator's practice. 9 At laparotomy, large polyps that cannot be removed colonoscopically or small proven cancers may be difficult to locate by palpation. Colonoscopic estimates for the location of the tumor are often just that--estimates. In such cases, a barium enema can provide a useful road map for the surgeon. While it is possible to perform colonoscopy at the time of surgery to confirm the exact location of a difficult-to-find lesion, this adds to the time, complexity, and cost of the procedure.
Rectal Cancer
Colon Cancer
Surgical considerations. Digital rectal examination is critical in the assessment of a patient
Surgery is the mainstay for the treatment of colon cancer. The initial consideration for the surgeon relates to the location of the primary tumor in the colon, because this is a primary determinant of which technical procedure will be used. In turn, these procedures are based on the vascular and lymphatic anatomy of the colon.
From the Department of Surgery, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC. Address reprint requests to Brian W. Loggie, MD, Department of Surgery, Bowman Gray School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157. Copyright © 1996 by W.B. Saunders Company 0037-198)(/96/3102-000555.00/0
Seminars in Roentgenology, Vol XXXI, No 2 (April), 1996: pp 111-117
111
112
with rectal cancer. Typically, a lesion that is readily palpable on digital rectal examination lies within 7 to 10 cm of the anal verge. Lesions more than this level will be in the mid to upper rectum or rectosigmoid region. The implications for treatment by digital evaluation are simple. Upper rectal tumors can be treated by low anterior resection in most instances (ie, a permanent colostomy is not required). For more distal tumors, abdominoperineal resection (with a permanent colostomy mandated) was commonly practiced in the past. Rectal conservation therapy is possible in most cases of low rectal cancers without negatively impacting on local (pelvic) control and survival. An estimate is that only one patient in seven presenting with rectal cancer will require a colostomy. 1° Local pelvic control is a key treatment issue. Until they become bulky, hepatic, or pulmonary, metastases are often asymptomatic. Recurrent pelvic disease is usually symptomatic. Quality of life is rapidly eroded by constant pain or tenesmus. Most patients presenting with pelvic pain following treatment for rectal cancer will be found to have a pelvic recurrence (80%) and nearly all patients present with pain. 11Unfortunately, pelvic recurrences can only occasionally be salvaged and palliation is difficult2 2,13 The important issues relating to local control relate to the stage of the tumor and the relationship of the cancer to pelvic structures. The walls of the pelvis can be compared with the sides of a teacup in that a roughly circular opening in the true pelvis funnels down to the outlet. The walls are firmly fixed. On pathology reports, prominence is given to the report of proximal and distal resection margins. These margins usually correlate with gross margins at the time of surgery. Of greater significance is the depth-oftumor penetration relative to the bowel wall and surrounding tissues. This margin is the most difficult to characterize pathologically because of the ill-defined nature of the surrounding fatty tissues and because of the possibility of sampling error. Tumor penetration into the pelvic soft tissues constitutes the most likely cause for local failure. 14 This peripheral margin is no more effectively removed by low anterior resection than it is by abdominoperineal resection (APR). 15 This is because the dissection planes are determined by the walls of the pelvis and are
BRIAN W. LOGGtE
the same for either surgical dissection. A portion of the pelvic muscular floor, including the muscles of continence, is included to some extent in the abdominoperineal resection. If the tumor is not infiltrating the levator, there is no advantage for resecting this from an oncological standpoint and a permanent colostomy becomes mandated for the patient. It had previously been thought that a 5-cm distal margin was required to lessen the chance of recurrence. By this convention, most patients with lesions readily palpable on rectal examination required an APR; however, a much smaller distal margin is required for most tumorsJ 6,17In practice, our goal is to achieve a 1- to 2-cm distal margin for most tumors. The probability of local recurrence is greater if there is lymphatic involvement consistent with worse tumor biology. Bulky, advanced tumors (circumferential, ulcerated, poorly differentia t e d - T 3 ; fixed--T4) can be associated with extensive lymphatic permeation. Retrograde lymphatic distal extension can occur, especially if proximal lymphatics become filled with tumor. In these instances, tumors may extend in deep planes beyond visible mucosal margins. Patients with extensive lymphatic involvement are more likely to fail in the pelvis and distantly by virtue of more aggressive tumor biology. These locally advanced tumors are often deemed unresectable. Surgery can be done in many instances, but these patients are more likely to require APR or some form of pelvic exenterative procedure to achieve pelvic control. This is typically planned following radiation and chemotherapy, and complete surgical removal of the tumor is critical for good survival results. 18-24 Avoidance of a permanent colostomy, using rectal conservation treatment, is an important quality-of-life issue75 If rectal conservation is to be performed safely and effectively, a combined modality approach is usually required. Clinical staging is important in determining a treatment plan. In general, the more locally advanced a tumor is, the greater the likelihood exists for lymphatic involvement. 26 Local excision is probably best reserved for those patients with selected T1 and T2 tumors. Full thickness excision of a T1 tumor with negative margins likely constitutes definitive therapy in most instances. Local excision of T2 tumors, those involving the
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muscular wall, without the addition of radiation therapy is associated with a higher recurrence rate. Our bias, and that of others, is to recommend combined chemotherapy and radiation therapy for these lesions. 27-3° When possible, such patients should be registered on ongoing national trials. 31 For T3 lesions, the tumor has invaded into the perirectal fat, which increases the possibility of local pelvic recurrence. Recurrence rates of 25% to 40% following surgery are anticipated in the absence of further therapy. All these patients should receive radiation therapy with chemotherapy.32 Whether this is best given preoperatively or postoperatively remains debated, but preoperative therapy is better tolerated and gives good local control. 33,34 Our preference and that of many others is to use combined full-dose radiation therapy with fluorouracil-(5-FU) based chemotherapy up front (neoadjuvant or induction therapy). This is followed by surgical resection, usually low anterior resection, at 4 to 6 weeks following completion of the neoadjuvant radiation therapy. Microscopic fingers of infiltrating peripheral tumor in the perirectal fat are sterilized and tissue planes become edematous in this time frame. This facilitates successful surgical resection. In almost all patients, a substantial clinical response, sometimes with downstaging, is appreciated with this approach. About 10% to 20% of patients will manifest a clinical complete response with aggressive neoadjuvant therapy. 35 Unless severe underlying medical conditions are present, some form of surgical resection is recommended because it is unclear how often a clinical complete response will translate into a pathological complete response. Some bulky low-lying tumors will respond well enough that rectal conservation therapy, usually a low anterior resection, becomes possible. 36Thus, preoperative treatment can facilitate rectal conservation in selected patients who would otherwise have required a permanent colostomy. Impact of radiological findings on treatment of rectal cancer. The importance of pre-therapy staging has become critical for treatment decisions to achieve rectal conservation or minimize surgery without compromising chances for cure. Treatment options are shown in Table 1. A number of radiological modalities are currently available for clinical staging.
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Table 1. Treatment of Rectal Cancer by Clinical Stage Rectal CancerT Stage T1, NO T2, NO T3, NO T1-T3, N1
Treatment Options 1"1-, 2 I + RT*1-, 2*, 2 + RT:I:,3 1 + RT§, 2 + RT*, 3 + RT[I 2 + RT*, 3 + RTII
Note: 1, local full-thickness rectal excision (endorectal excision or posterior approach); 2, low anterior resection (colorectal or coloanal anastomosis); 3, abdominoperineal resection (colostomy); RT, radiation therapy with chemotherapy. *Preferred treatment options. 1"Size <3 cm or one-third circumference; not high-grade or mucinous; not ulcerated. :l:Poorly differentiated, lymphovascular involvement, suboptimal surgery. §Medical-poor risk. ilTumor invades levator.
In most cases, CT scanning is used to stage the liver and abdomen. The anatomic information of the kidneys, ureters, and bladder is useful for the surgeon; it has not been my practice to obtain an IVP. CT can also detect incidental pathology or anatomic variations that may impact on treatment considerations, such as aortic aneurysms or gallstones. However, CT is not sensitive for the discrimination between T1, T2, and T3 lesions in the rectum. For bulky T3 tumors, a mass appreciated and stranding in the pelvic soft tissues is a common finding suggesting perireetal infiltration, but may represent inflammatory reaction. CT findings may be absent in a smaller rectal cancer. Because our treatment approach can vary importantly by exact tumor T-stage, other modalities have emerged in recent years. These tests must be correlated with clinical findings, particularly digital rectal examination. A learning curve is apparent for all endorectal radiological investigations. Communication between the radiologist and surgeon is vital. The surgeon must provide the radiologist with specific clinical information and, equally important, the radiologist should seek and use this information. It cannot be overstated that it is often necessary for the radiologist to perform a careful rectal examination so the probes or coils are correctly positioned and the radiological information is valid. Digital rectal examination requires experience and is about 60% to 80% accurate for staging. A clinical T1 designation is made where the rectal wall is mobile and the mucosal lesion
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is also mobile. T2 lesions are characterized by invasion into, but not beyond, the muscular wall. Discrimination between T1 and T2 lesions can be difficult but is less Critical than the discrimination between T2 and T3 lesions. For patients with tethering of the full rectal wall but without fixation on digital rectal examination, a clinical T3 status is accorded. Gross ulceration that is palpable is consistent with a T3 lesion. Fixation suggests invasion into the pelvic sidewall or adjacent structures and is classified as a T4 lesion. Both endorectal ultrasound and endorectal magnetic resonance imaging (MRI) have been used for the preoperative staging of rectal tumors. Correlation of physical examination by an experienced examiner with ultrasonography (US) or MRI findings has been good. When US or MRI suggest an early T3 tumor but the clinical stage is T2, the pathology has usually yielded evidence for a microscopic T3 stage. Both seem to provide accurate staging of the tumor through the rectal wall. 37,38 There is perhaps a slight bias in favor of over estimating stage using both these techniques and is preferable and safer than underestimation. Lymphnode metastases can sometimes be identified or strongly suspected. Both techniques have limitations. Endorectal ultrasound is limited in penetration beyond the rectal wall and the examination is observer dependent. Wall invasion is accurately predicted before radiation therapy but not postirradiation. 39 Hard-copy pictures usually do not provide orientation with respect to exact radial location or with respect to distance from the sphincter. We have also found that very low anorectal or anal lesions sometimes cannot be usefully assessed by ultrasound because of difficulties in probe placement. Advantages of endorectal MRI that may be appreciated by the surgeon are the ability to visualize the pelvic structures and their relationships to the rectal tumor. These relationships can be visualized by para:sagittal or coronal views. Further, gadolinium can enhance the tumor identification and clarify the status of a prominent, but not enlarged, lymph node. As wel l, endorectal imaging may be helpful in assessing for suspected extraluminal pelvic recurrence following rectal conservation therapy. 4° Liabilities associated with
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MRI include: examination discomfort; cost; and availability. Discomfort can be minimized with new smaller coils but can sometimes result in refusal by the patient to undergo testing. Cost issues are pertinent but the quality of the information and the likelihood of changing therapy must be considered. Metastatic Cancer and Special Considerations Liver disease. As noted previously, about 19% of colorectal cancer patients will have synchronous metastatic disease. The likelihood of metastatic liver disease at the time of diagnosis is higher for patients with right-sided colon tumors (about 30%) when compared with more distal locations (about 13% to 22%). 41 The liver is the most common site of distant metastatic disease at the time of initial diagnosis and at relapse. Based on standard strict surgical criteria, only a minority of patients will be candidates for surgical resection. These cases are limited to instances in which no extrahepatic disease exists, only one to three lesions exist, and these lesions Can be safely resected with a minimum 1-cm tissue margin. It should be noted that the majority of well-selected patients will suffer disease relapse but about 20% to 25% will be disease-free at 5 years. Cryoablation of tumors is used by some groups to expand the treatment of patients with liver metastatic disease. 42 At surgery, blunt probes ranging in size from 3 to 10 mm are positioned in tumor deposits. Liquid nitrogen is circulated through the tips of these sealed probes and creates an ice ball centered on the tumor. This, in turn, is assoeiated with coagulative necrosis. Removal of the tumor is usually not performed. This approach is made feasible with the advent of intraoperative ultrasound (IOUS), which is used to identify tumor, guide probes, and monitor freezing. In our institution, the radiologist will typically scrub into the operation to perform this examination and will often assist the surgeon with cryoablation efforts. Cryoablation can be used in concert with resection. For example, a lesion in the lateral segment of the left lobe will be resected, whereas a lesion in the deep right lobe will be frozen. An advantage of cryoablation is that a large volume of normal liver parenchyma may be spared that would
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otherwise be included in resection. Further, it is associated with low morbidity. Typically, lesions greater than 8 cm in size often cannot be frozen safely or adequately. It can sometimes be difficult to confirm adequate expansion of the freeze ball to incorporate all sides of the tumor. An unresolved issue is how many lesions can be treated with cryoablation in excess of strict surgical guidelines with expectations of reasonable outcome. Standard surgical selection and surgical resection remain the current gold standard. We use rapid CT arterial portography (CTAP) performed with contrast injections into the superior mesenteric or splenic artery for screening patients in whom surgical intervention for liver disease is being considered. The celiac vascular anatomy is defined at the time of placement of the arterial catheter before the CTAP. This permits definition of the hepatic vascular anatomy, which is useful to speed up dissection during liver resection or to easily identify the options for hepatic artery chemotherapy treatment. The logistics, costs, and additional risks associated with arterial catheter placement, which is necessary for CTAP, preclude its use as a routine screening or follow-up modality. In our hands, this is the most sensitive method for detection of metastatic liver disease. We generally do not use CTAP for patients who will require surgery anyway for their primary tumor. We routinely use I O U S during surgery where liver disease is known or suspected to be present. I O U S is not used as a routine screen for liver disease. It is helpful to define hepatic anatomy, identify nonpalpable lesions, and guide biopsy needles or cryoablation probes. Resection planes are determined using this information, particularly for nonanatomic resections. These studies arc carefully correlated with preoperative CT or M R images. I O U S has b e e n hailed as a very accurate method for examination of the liver. In reviewing our last 14 cases involving the use of cryosurgery, two patients had lesions identified on C T A P that we were unable to confirm with I O U S and that subsequently proved to be small metastatic deposits (unpublished observations). We have also noted that C T A P can overestimate the amount of disease in the liver, presumably with artifacts relating to factors such as dye streaming. These
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limitations need to be understood by the surgeon and acknowledged by the radiologist. M R I is less sensitive than C T A P in our hands. Peritoneal carcinomatosis. We have been involved in ongoing clinical studies for the treatment of patients with peritoneal carcinomatosis. Mucinous tumors compromise about 15% of colorectal tumors. These are seen more commonly in young patients, particularly patients under 30 to 40 years of age, and are by far the most frequent tumor type associated with peritoneal dissemination. A previous presentation with an obstructed or perforated cancer is common. It is critical that the surgeon and the radiologist work together with shared information to optimize patient care. CT scanning clearly underestimates disease in this circumstance. The signs of carcinomatosis can be very subtle on CT and can be easily missed without careful attention to scanning technique and clinical input. CONCLUSION
New treatment strategies have evolved for the treatment of both localized and advanced colorectal cancer. The intent of this article has been to stress the close working relationship necessary between the surgeon and the radiologist who are treating these patients. The impact of radiological findings on surgical treatment, especially localized rectal cancer, has been reviewed. APPENDIX
Glossary of terms used in the treatment of rectal cancer: Low anterior resection: This operation includes the full mobilization of the rectum and an anastomosisis performed below the peritoneal reflection. The anastomosis may be hand sewn or stapled. Typically,circular stapling devices are used for low colorectal anastomosis, These devices are referred to as end-to-end anastomosis (EEA) staplers. Very low anastomoses can be performed on selected patients between the proximal divided colon and the anal mucosa and is referred to as a coloanal anastomosis.A temporary or diverting colostomymay be used to protect the anastomosis in some instances. APR: Also known as the Miles procedure. This is a two-part procedure consisting of an abdominal portion and perineal dissection, usually performed synchronously. The rectum is mobilized via the abdominal route. Next, or simultaneously, the perineum around the anus is incised and dissection is deepened through the muscular pelvic floor. For anterior rectal cancers in women, the posterior vagina should be included in the resection. Because the muscles responsible for continence are included, a perma-
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nent colostomy is mandated. En-bloc rectal resection, including the bladder and prostate in men and the bladder, uterus, and ovaries in women, is known as a total pelvic exenteration. Abdominosacral resection includes partial sacral resection. Hartmann's procedure implies closure of the rectal stump and creation of a sigmoid colostomy following resection of a rectal cancer. Local excision may be performed using an endorectal approach. The technique involves the full thickness excision of the bowel wall with 1 cm margins. This is performed through the anus using a speculum or short endoscope and is suitable for low-lying, small carcinomas, mainly T1 or T2. A posterior approach, also known as a Kraske approach, is used by some, especially for villous adenomas. This involves
approaching via a posterior skin incision, resecting the coccyx, and splitting the muscles in the posterior midline. It is possible to open the bowel for a local excision or to excise and anastomose a short segment; this is referred to as a sleeve resection. An advantage is very low morbidity by avoiding an abdominal incision, but exposure is limited. Neoadjuvant therapy, or induction therapy, implies treatment administered before surgery to shrink large fixed tumors or downstage smaller tumors. This typically involves combination chemoradiotherapy. The chemotherapy drug 5-FU is most commonly used alone or in combination as a radiation sensitizer. Adjuvant therapy implies the use of chemotherapy or radiation therapy following complete, or so-called curative, resection.
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