Annals of Surgical Oncology Cite Track
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
10.1245/s10434-006-9221-7
Annals of Surgical Oncology 14:478-483 (2007)
© 2007 Society of Surgical Oncology
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mullen, J. T.
Right arrow Articles by Feig, B. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mullen, J. T.
Right arrow Articles by Feig, B. W.

Original Article

Results of Surgical Salvage after Failed Chemoradiation Therapy for Epidermoid Carcinoma of the Anal Canal

John T. Mullen1, Miguel A. Rodriguez-Bigas1, George J. Chang1, Carlos H. Barcenas3, Christopher H. Crane2, John M. Skibber1 and Barry W. Feig1

1 Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
2 Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
3 Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

Correspondence: Address correspondence and reprint requests to: Barry W. Feig; Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Boulevard, Unit 444, Houston, TX 77030-1402, USA; E-mail: bfeig{at}mdanderson.org


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: The standard treatment for epidermoid carcinoma of the anal canal consists of combined radiation and chemotherapy. For patients who present with persistent or locally recurrent disease, salvage abdominoperineal resection is the treatment of choice. The purpose of this study is to review our experience with salvage surgery in this group of patients.

Methods: From 1990–2002, 31 patients underwent radical salvage surgery with curative intent after failure of initial sphincter-conserving therapy, and the medical records of these patients were retrospectively reviewed. Clinicopathologic variables were determined and comparisons performed with the Cox proportional hazards model. Survival was calculated by the Kaplan–Meier method.

Results: Eleven patients underwent radical salvage surgery for persistent disease and 20 patients for recurrent disease. The median follow-up time was 29 months. The actuarial 5-year overall survival was 64%. Twelve patients developed recurrent disease after radical salvage surgery. Patients who received an initial radiation dose of less than 55 Gy had a significantly worse survival than those who received at least 55 Gy as part of their initial treatment (5-year overall survival 37.5% vs. 75%; age-adjusted hazard ratio 8.2 [95% CI: 1.1–59.8], P = .037). The presence of positive lymph nodes at presentation also adversely affected survival (P < .05). Factors that were not found to have an impact on survival included the presence of persistent versus recurrent disease, tumor (T) stage, and margin status of resection.

Conclusions: Long-term survival following salvage surgery for persistent or locally recurrent epidermoid carcinoma of the anal canal can be achieved in the majority of patients. However, patients who initially present with node-positive disease and patients who receive a radiation dose of less than 55 Gy as part of their initial chemoradiation therapy regimen have a worse prognosis after radical salvage surgery.

Key Words: Anal cancer • Recurrence • Salvage surgery • Abdominoperineal resection • Chemoradiation therapy


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Epidermoid carcinoma of the anal canal serves as a paradigm for the multimodality treatment of solid tumors. Since the pioneering work by Nigro in the 1970s, the primary therapy of anal cancer has shifted from one of radical surgery to one of combined chemoradiation therapy (CRT).1–5 Randomized trials have confirmed this work in larger numbers of patients, with 5-year survival in the range of 60–80%.6–9 Locoregional failure remains a problem, however, in up to 40% of patients.4,10–14 For patients who develop a local failure after CRT, radical salvage surgery is the treatment of choice. Several groups have reported their experience with salvage surgery with quite variable outcomes.15–24 Many of these studies consist of rather small, heterogeneous patient populations extending over several decades. The aim of this study was to present our experience with salvage surgery in a contemporary population of patients treated at a single institution.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
From 1990 to 2002, 327 patients with biopsy-proven epidermoid carcinoma of the anal canal were identified in our database at the University of Texas M.D. Anderson Cancer Center (MDACC). Sixty-one patients were identified as having persistent or recurrent disease after initial therapy and received further treatment at MDACC. Patients who received surgery as their initial therapy were excluded and only those who received CRT with curative intent were included. Initial clinical stage was assigned in accordance with the 2002 American Joint Committee on Cancer (6th edition) tumor node metastasis (TNM) staging system for cancer of the anal canal based on the physical examination described in the medical records, including those records available from referring institutions. The tumor T stage was assigned based on the size in centimeters of the primary lesion. Similarly, the nodal N stage was assigned based on the presence or absence and location of clinically palpable or radiographically enlarged lymph nodes at the time of initial patient presentation, prior to the administration of CRT.

Patients with histologically proven epidermoid carcinoma detected within 6 months of the termination of CRT were classified as having persistent disease. Those patients who had an initial complete response to CRT but whose recurrence was diagnosed 6 months or more after CRT were classified as having recurrent disease. CRT, when delivered at MDACC, was administered as previously described.25 Patients who received CRT at MDACC were seen weekly during treatment, monthly after the completion of treatment until a complete response was confirmed, and then routinely every 3 – 6 months. Patients were evaluated with a history and physical examination at each visit and underwent a chest X-ray and an abdominopelvic CT scan annually. Post-treatment biopsies were not routinely performed. Only clinically suspicious lesions, such as those accompanied by mucosal ulceration, were biopsied.

Thirty-one patients with isolated locoregional failure after CRT underwent radical salvage surgery at MDACC and were retrospectively reviewed. Patients with distant disease, patients who underwent a palliative operation, and patients who underwent local excision either because of patient refusal or medical comorbidities that precluded radical surgery, were excluded from this review.

Survival curves were calculated from the time of salvage surgery until the most recent follow-up using the Kaplan–Meier method.26 Comparisons of survival between persistent and recurrent disease and according to initial dose of radiation were performed with the log-rank test. The Cox proportional hazards model was used to examine the effect on survival of tumor (T) stage (T1/2 vs. T3/4), initial nodal status (N– vs. N+), margin status of resection, type of failure (persistent vs. recurrent disease), and initial dose of radiation (<55 Gy vs. ≥ 55 Gy). A P value <.05 was considered statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Patient Characteristics
The characteristics of the 31 patients who underwent radical salvage surgery are shown in Table 1Go. There were 25 women and 6 men ranging in age from 31 to 75 years. The mean age at diagnosis was 51 years. The initial clinical TNM staging of the patients and type of CRT are as shown in Table 1Go. Seventeen patients received a combination of 5-FU and cis-platin, 12 patients received 5-FU and mitomycin C, one patient received 5-FU only, and in one patient the regimen was not known. Ten patients were treated with an XRT dose of less than 55 Gy, 19 patients were treated with an XRT dose equal to or greater than 55 Gy, and in two patients the initial XRT dose was unknown. The initial prescribed CRT regimen was completed by all but three patients who experienced excessive toxicity. Eleven patients were classified as having persistent disease and 20 were classified as having recurrent disease.


View this table:
[in this window]
[in a new window]

  		TABLE 1. Characteristics of patients undergoing radical salvage surgery
 
Operative Data
Twenty-nine patients underwent an abdominoperineal resection (APR), including eight women who underwent an APR with a posterior vaginectomy, and nine women who had a posterior or total pelvic exenteration. Two patients underwent an iliac lymph node dissection as part of their procedure. Two patients underwent a low anterior resection with primary anastomosis for recurrent disease in peri-rectal lymph nodes.

Primary closure of the perineal wound alone was performed in seven patients. In eight patients, an omental pedicle alone was placed in the pelvis. The remaining 16 patients underwent primary myocutaneous flap reconstruction of the pelvis and perineum. Eleven patients had a vertical rectus adbominis muscle (VRAM) flap alone, three patients had a combination of a VRAM flap and omental pedicle, and two patients had other muscle flap reconstruction.

Complications
There were no postoperative deaths. A total of 28 complications occurred in 20 patients, including perineal wound infection or breakdown (n = 11), perineal hernia (n = 1), and parastomal hernia (n = 5). Of the 11 perineal wound complications, five occurred in patients who had an omental pedicle alone placed within the pelvis and the other six occurred in patients with primary myocutaneous flap reconstruction of the perineum.

Outcome
The median length of follow-up was 29 months (range, 4–144 months). At the time of last follow-up, seven patients had died as a result of disease progression, three patients were alive with disease, and 21 patients were alive without evidence of recurrent disease. The median follow-up for survivors was 31 months (range 3–132), with eight of them followed now for greater than 5 years. The actuarial 5-year overall survival was 64% (Fig. 1Go).


Figure 1
View larger version (6K):
[in this window]
[in a new window]

  		FIG. 1. Actuarial overall survival in patients undergoing radical salvage surgery with curative intent (n = 31).

 
Patients who received an initial radiation dose of at least 55 Gy as part of their initial CRT had a significantly better 5-year overall survival rate after radical salvage surgery than those who received less than 55 Gy (75% vs. 37.5%; P = 0.037) (Fig. 2Go). In addition, the presence of clinically positive lymph nodes at presentation adversely affected survival (P < .05). There was no difference in survival comparing those patients classified as having persistent disease with those classified as having recurrent disease (Fig. 3Go). Other factors not found to have an impact on survival by univariate analysis included the initial tumor stage (T1/T2 vs. T3/T4) and the margin status of resection (P = NS).


Figure 2
View larger version (6K):
[in this window]
[in a new window]

  		FIG. 2. Survival after radical salvage surgery in patients with recurrent (n = 20) and persistent (n = 11) disease.

 

Figure 3
View larger version (7K):
[in this window]
[in a new window]

  		FIG. 3. Survival after radical salvage surgery according to the dosage of radiation (XRT) administered with initial chemoradiation therapy. XRT ≥ 55 Gy (n = 19) and XRT < 55 Gy (n = 10); P = .037.

 
There were 12 secondary failures after salvage surgery—six locoregional failures alone, three distant failures alone, and three combined locoregional and distant failures. Four patients developed liver metastasis, one in combination with a local recurrence, and all have died of their disease. Four patients recurred in the inguinal nodes. One patient remains disease-free 5 years after an inguinal node dissection and postoperative cisplatin-based chemotherapy, and another patient has developed concurrent lung and brain metastases. Three additional patients recurred locoregionally in the pelvis and a final patient recurred in the lungs as well as locally. All of these patients who have recurred after radical salvage surgery, with the exception of the one aforementioned patient, have either died of their disease or were alive with disease at the time of their last follow-up. The median survival for patients with secondary failure was 33 months.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Epidermoid carcinoma of the anal canal accounts for only 1–2% of all large bowel cancers and nearly 4% of anorectal carcinomas.27 Nonetheless, this disease has served as a model for the superiority of a multimodality treatment approach to solid tumors. Historically, radical surgery alone achieved overall 5-year survival rates in the range of 30–70%.28–32 With the introduction of combined CRT as the primary treatment modality, 5-year survival rates improved to 60–90%6–9,25 in conjunction with decreased morbidity as well as sphincter preservation.

Despite the success of combined CRT, a substantial proportion of patients will fail treatment. Some have advocated salvage CRT with cisplatin-containing regimens, reporting 50% survival at 4 years,7 whereas others have reported more disappointing results with salvage CRT.16 There has been much greater experience with radical surgery as salvage therapy after failed CRT, however, making radical rectal resection the treatment of choice. Previous investigators have reported 5-year survival rates after salvage APR in the range of 24–53%.15–22 In the present series, the 5-year overall survival rate was 64%, perhaps the result of careful patient selection as well as meticulous surgical technique to include total mesorectal and wide perineal resections.

Of the 30% of patients who fail initial CRT, approximately half of the failures can be classified as persistent disease and the other half as recurrent disease.12,13,33 In this study, 20 (65%) of 31 patients were operated on for recurrent disease. There was no difference in survival between patients with persistent disease versus those with recurrent disease (Fig. 3Go). This finding is in agreement with what several other groups have reported.17,18,20 Others, however, have found that patients with persistent disease fare significantly worse than those who recur.19,22,23 Perhaps these contradictory findings are a consequence of the rather arbitrary selection of 6 months as the dividing line between the two types of failure as well as the timing and accuracy of the biopsy. For instance, a patient classified as having recurrent disease may simply have presented to a clinician more than 6 months after CRT despite the fact that his response was much less than complete, or perhaps the initial biopsy within the 6-month window represented a sampling error and did not capture the presence of persistent disease. Likewise, a patient classified as having persistent disease may simply have been biopsied too soon following the completion of CRT to allow for a complete tumor response to occur. Thus, survival differences between patients with persistent disease compared with those with recurrent disease may simply be due to the timing of the clinical evaluation rather than the underlying tumor biology.

Patients who received a radiation dose of less than 55 Gy as part of their initial CRT had a significantly worse survival than those who received at least 55 Gy as part of their initial treatment (Fig. 2Go). This finding is in keeping with the results of Hughes et al., 34 who reported on our experience with radiotherapy for anal cancer from 1979 to 1987. They reported a local control rate of 50% for all stages receiving 45–49 Gy and 90% for those patients receiving greater than or equal to 55 Gy. Accordingly, it is the standard of care at our institution to administer at least 55 Gy as part of the initial CRT for epidermoid cancer of the anal canal. Many of the patients in this series, however, received their initial CRT elsewhere, and thus ten (32%) patients received less than 55 Gy. In our modest experience, patients with persistent or recurrent anal cancer after an initial dose of XRT of less than 55 Gy are more difficult to salvage with radical surgery. This may be due to inferior local control that leads to microscopic nodal and distant disease that is not apparent at the time of salvage surgery. Alternatively, since most of the patients that received 55 Gy were treated at MDACC and thus were followed closely by a multidisciplinary team specializing in the treatment of this cancer, perhaps their recurrences were detected at an earlier, more curable stage.

Similar to the findings of others,17,35 we found that the presence of inguinal lymphadenopathy at presentation adversely affected survival. The presence of nodal involvement is likely a reflection of microscopic disseminated disease. Indeed, the majority of patients with N+ disease developed secondary failures after salvage APR in the pelvis and/or distantly. The clinical tumor (T) stage at presentation, however, did not have an impact on survival, and this finding is also in agreement with what others have reported.17,20,23

Perineal wound infection and breakdown is a well-documented complication of salvage APR following radiation therapy. In this series, the incidence of perineal wound complications was 35% (11 of 31 patients). Interestingly, all of the perineal complications occurred in patients who underwent omental pedicle or muscle flap reconstruction of the perineum, albeit the majority of our patients had a perineal reconstruction (24 of 31 patients). Perhaps the higher incidence of perineal complications seen in our reconstructed patients compared with those who had a primary perineal closure is a consequence of the small sample size and/or more diligent follow-up of the reconstructed group by two sets of surgeons (plastic and colorectal surgeons).

Nearly 40% (12 of 31) of the patients who underwent radical salvage surgery developed a secondary failure, and all but one of these patients have either died of their disease or is alive with disease today. Six of these failures were locoregional alone and six involved distant failure––four in the liver, one in the lungs alone, and one in the lungs and brain. This fact supports the notion that adjuvant chemotherapy in conjunction with salvage surgery may be warranted in selected patients.

The limitations of this study include its retrospective nature, the small sample size, and the relatively short follow-up. Unfortunately, when one studies a disease process as rare as locally persistent or recurrent anal cancer it is difficult to obtain a large population of patients. In addition, since we are a tertiary referral center, the initial CRT regimens of the patients are variable and long-term follow-up to 5 or 10 years is difficult. In addition, we wished to limit our study to a modern population of patients, all but one of whom received at least 45 Gy of radiation as part of their initial CRT and in whom we could evaluate the more recent advances in surgical technique, such as the importance of total mesorectal excision.

In conclusion, long-term survival can be achieved in the majority of patients who undergo radical salvage surgery after failed CRT for epidermoid carcinoma of the anal canal. However, patients who initially present with node-positive disease and patients who receive a radiation dose of less than 55 Gy as part of their initial CRT regimen have a worse prognosis after radical salvage surgery.

Received for publication July 13, 2006. Accepted for publication July 15, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Nigro ND, Vaitkevicius VK, Considine B Jr. Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum 1974; 17:354–356.[Medline]
  2. Nigro ND, Seydel HG, Considine B, Vaitkevicius VK, Leichman L, Kinzie JJ. Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal. Cancer 1983; 51:1826–1829.[CrossRef][Medline]
  3. Cummings B, Keane T, Thomas G, Harwood A, Rider W. Results and toxicity of the treatment of anal canal carcinoma by radiation therapy or radiation therapy and chemotherapy. Cancer 1984; 54:2062–2068.[CrossRef][Medline]
  4. Cummings BJ, Keane TJ, O’Sullivan B, Wong CS, Catton CN. Epidermoid anal cancer: treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C. Int J Radiat Oncol Biol Phys 1991; 21:1115–1125.[Medline]
  5. Cho CC, Taylor CW 3rd, Padmanabhan A, et al. Squamous-cell carcinoma of the anal canal: management with combined chemo-radiation therapy. Dis Colon Rectum 1991; 34:675–678.[CrossRef][Medline]
  6. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet 1996; 348:1049–1054.[CrossRef][Medline]
  7. Flam M, John M, Pajak TF, et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 1996; 14:2527–2539.[Abstract]
  8. Martenson JA, Lipsitz SR, Wagner H Jr., et al. Initial results of a phase II trial of high dose radiation therapy, 5-fluorouracil, and cisplatin for patients with anal cancer (E4292): an Eastern Cooperative Oncology Group study. Int J Radiat Oncol Biol Phys 1996; 35:745–749.[CrossRef][Medline]
  9. Bartelink H, Roelofsen F, Eschwege F, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 1997; 15:2040–2049.[Abstract/Free Full Text]
  10. Meeker WR Jr., Sickle-Santanello BJ, Philpott G, Kenady D, Bland KI, Hill GH, Popp MB. Combined chemotherapy, radiation, and surgery for epithelial cancer of the anal canal. Cancer 1986; 57:525–529.[CrossRef][Medline]
  11. Sischy B, Doggett RL, Krall JM, Taylor DG, Sause WT, Lipsett JA, Seydel HG. Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314. J Natl Cancer Inst 1989; 81:850–856.[Abstract/Free Full Text]
  12. Habr-Gama A, da Silva e Sousa Junior AH, Nadalin W, Gansl R, da Silva JH, Pinotti HW. Epidermoid carcinoma of the anal canal. Results of treatment by combined chemotherapy and radiation therapy. Dis Colon Rectum 1989; 32:773–777.[Medline]
  13. Cummings BJ. Concomitant radiotherapy and chemotherapy for anal cancer. Semin Oncol 1992; 19:102–108.[Medline]
  14. Renehan AG, Saunders MP, Schofield PF, O’Dwyer ST. Patterns of local disease failure and outcome after salvage surgery in patients with anal cancer. Br J Surg 2005; 92:605–614.[CrossRef][Medline]
  15. Zelnick RS, Haas PA, Ajlouni M, Szilagyi E, Fox TA Jr. Results of abdominoperineal resections for failures after combination chemotherapy and radiation therapy for anal canal cancers. Dis Colon Rectum 1992; 35:574–577; discussion 577–578.[CrossRef][Medline]
  16. Longo WE, Vernava AM 3rd, Wade TP, Coplin MA, Virgo KS, Johnson FE. Recurrent squamous cell carcinoma of the anal canal. Predictors of initial treatment failure and results of salvage therapy. Ann Surg 1994; 220:40–49.[Medline]
  17. Ellenhorn JD, Enker WE, Quan SH. Salvage abdominoperineal resection following combined chemotherapy and radiotherapy for epidermoid carcinoma of the anus. Ann Surg Oncol 1994; 1:105–110.[Abstract]
  18. Pocard M, Tiret E, Nugent K, Dehni N, Parc R. Results of salvage abdominoperineal resection for anal cancer after radiotherapy. Dis Colon Rectum 1998; 41:1488–1493.[CrossRef][Medline]
  19. Allal AS, Laurencet FM, Reymond MA, Kurtz JM, Marti MC. Effectiveness of surgical salvage therapy for patients with locally uncontrolled anal carcinoma after sphincter-conserving treatment. Cancer 1999; 86:405–409.[CrossRef][Medline]
  20. van der Wal BC, Cleffken BI, Gulec B, Kaufman HS, Choti MA. Results of salvage abdominoperineal resection for recurrent anal carcinoma following combined chemoradiation therapy. J Gastrointest Surg 2001; 5:383–387.[CrossRef][Medline]
  21. Smith AJ, Whelan P, Cummings BJ, Stern HS. Management of persistent or locally recurrent epidermoid cancer of the anal canal with abdominoperineal resection. Acta Oncol 2001; 40:34–36.[CrossRef][Medline]
  22. Nilsson PJ, Svensson C, Goldman S, Glimelius B. Salvage abdominoperineal resection in anal epidermoid cancer. Br J Surg 2002; 89:1425–1429.[CrossRef][Medline]
  23. Akbari RP, Paty PB, Guillem JG, et al. Oncologic outcomes of salvage surgery for epidermoid carcinoma of the anus initially managed with combined modality therapy. Dis Colon Rectum 2004; 47:1136–1144.[Medline]
  24. Ghouti L, Houvenaeghel G, Moutardier V, et al. Salvage abdominoperineal resection after failure of conservative treatment in anal epidermoid cancer. Dis Colon Rectum 2005; 48:16–22.[CrossRef][Medline]
  25. Hung A, Crane C, Delclos M, et al. Cisplatin-based combined modality therapy for anal carcinoma: a wider therapeutic index. Cancer 2003; 97:1195–1202.[CrossRef][Medline]
  26. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53:457–481.[CrossRef]
  27. Fuchshuber PR, Rodriguez-Bigas M, Weber T, Petrelli NJ. Anal canal and perianal epidermoid cancers. J Am Coll Surg 1997; 185:494–505.[CrossRef][Medline]
  28. Klotz RG Jr., Pamukcoglu T, Souilliard DH. Transitional cloacogenic carcinoma of the anal canal. Clinicopathologic study of three hundred seventy-three cases. Cancer 1967; 20:1727–1745.[CrossRef][Medline]
  29. Hardcastle JD, Bussey HJ. Results of surgical treatment of squamous cell carcinoma of the anal canal and anal margin seen at St. Mark’s Hospital 1928–66. Proc R Soc Med 1968; 61:629–630.[Medline]
  30. Boman BM, Moertel CG, O’Connell MJ, et al. Carcinoma of the anal canal. A clinical and pathologic study of 188 cases. Cancer 1984; 54:114–125.[CrossRef][Medline]
  31. Greenall MJ, Quan SH, DeCosse JJ. Epidermoid cancer of the anus. Br J Surg 1985; 72(Suppl):S97–103.[Medline]
  32. Clark J, Petrelli N, Herrera L, Mittelman A. Epidermoid carcinoma of the anal canal. Cancer 1986; 57:400–406.[CrossRef][Medline]
  33. Leichman L, Nigro N, Vaitkevicius VK, et al. Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy. Am J Med 1985; 78:211–215.[CrossRef][Medline]
  34. Hughes LL, Rich TA, Delclos L, Ajani JA, Martin RG. Radiotherapy for anal cancer: experience from 1979–1987. Int J Radiat Oncol Biol Phys 1989; 17:1153–1160.[Medline]
  35. Stearns MW Jr., Quan SH. Epidermoid carcinoma of the anorectum. Surg Gynecol Obstet 1970; 131:953–957.[Medline]



This article has been cited by other articles:


Home page
 Ann. Surg. Oncol.Home page
K. G. Sunesen, S. Buntzen, T. Tei, J. C. Lindegaard, M. Norgaard, and S. Laurberg
Perineal Healing and Survival After Anal Cancer Salvage Surgery: 10-Year Experience with Primary Perineal Reconstruction Using the Vertical Rectus Abdominis Myocutaneous (VRAM) Flap
Ann. Surg. Oncol., January 1, 2009; 16(1): 68 - 77.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mullen, J. T.
Right arrow Articles by Feig, B. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mullen, J. T.
Right arrow Articles by Feig, B. W.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS