Sphincter-Sparing Treatment for Distal Rectal Adenocarcinoma

Background: Studies suggest that the anal sphincter can be preserved in some patients with distal rectal adenocarcinoma (DRA), but this has not been validated in any prospective multi-institutional trial.Methods: To test the hypothesis that the anal sphincter can be preserved in some patients with DRA, the Cancer and Leukemia Group B and collaborators reviewed 177 patients who had T1/T2 adenocarcinomas 4 cm in diameter, which encompassed 40% of bowel wall circumference, and were 10 cm from the dentate line. Of the 177 patients, 59 patients who were eligible for the study had T1 adenocarcinomas and received no further treatment; 51 eligible T2 patients received external beam irradiation (5400 cGY/30 fractions 5 days/week) and 5-fluorouracil (500 mg/m² IV d1–3, d29–31) after local excision.Results: At 48 months median follow-up, 6-year survival and failure-free survival rates of the eligible patients are 85% and 78% respectively. Three patients died of unrelated disease. Two patients were treated for second primary colorectal tumors; both remain disease free (NED). Another eight patients died of disease, four with distant recurrence only. One T1 patient is alive with distant disease. Two T1 and seven T2 patients experienced isolated local recurrences; all underwent salvage abdominoperineal resection (APR). After APR, one T1 and four of seven T2 patients were NED at the time of last visit (2–7 years). One T1 patient died of local and distant disease. Three of seven T2 patients died with distant disease.Conclusions: We conclude that sphincter preservation can be achieved with excellent cancer control without initial sacrifice of anal function in most patients. After local recurrence, salvage resection appears effective, but longer follow-up time of local and distant disease-free survival is advised before extrapolation to patients with T3 primaries.Presented at the 1999 Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Adequacy of 1-cm Distal Margin After Restorative Rectal Cancer Resection With Sharp Mesorectal Excision and Preoperative Combined-Modality Therapy

Background: Preoperative combined-modality therapy (CMT) for rectal cancer allows a sphincter-sparing procedure in some individuals who would otherwise require an abdominoperineal resection. To further define the subset of rectal cancer patients suitable for this approach, we determined the adequacy of a distal margin of 1 cm in patients with locally advanced rectal cancer requiring preoperative CMT.Methods: Ninety-four consecutive patients, status post curative low anterior resection for rectal cancer after preoperative CMT, were identified from the prospective Colorectal Service Database. Distal margin length, tumor grade, tumor-node-metastasis stage, presence of lymphovascular and perineural invasion, and tumor distance from the anal verge were examined for their effect on recurrence and survival. Median follow-up was 44 months.Results: Distal margin length ranged from .1 to 9.5 cm (median, 2.0 cm) and did not correlate with local recurrence (hazard ratio, 1.1; P = .34) or recurrence-free survival (hazard ratio, 1.1; P = .29) by univariate analysis. Kaplan-Meier estimates of recurrence-free survival and local recurrence at 3 years for the 1 cm versus >1 cm and the 2 cm versus >2 cm groups were not significantly different. Groups were well matched for other clinicopathologic variables.Conclusions: Our data suggest that for patients with locally advanced rectal cancer undergoing resection and preoperative CMT, distal margins 1 cm do not seem to compromise oncological outcome.     

Distal Intramural Spread Is an Independent Prognostic Factor for Distant Metastasis and Poor Outcome in Patients With Rectal Cancer: A Multivariate Analysis

Background:The aim of this study was to clarify the prognostic value of distal intramural spread of tumor for survival and recurrence in patients with rectal cancer.Methods:Microscopic distal intramural spread was examined in 134 consecutive specimens of resected rectal cancer. Correlations among distal intramural spread, established clinicopathologic factors, and patients prognoses were examined by univariate and multivariate analyses. American Joint Committee on Cancer classification and stage groupings were used for tumor assessment.Results:Thirty-three patients (24.6%) had distal intramural spread. Multivariate logistical regression analysis revealed that T3/T4 and M1 were independent predictive variables for the presence of distal intramural spread. Patients with distal intramural spread had a shorter disease-specific or disease-free survival time after curative surgery than those without distal intramural spread (P = .0003 and P = .0006, respectively). Most patients with distal intramural spread developed distant recurrence. Coxs regression with multiple covariates showed that distal intramural spread is an independent factor in predicting distant recurrence and worse outcomes after curative surgery in patients with rectal cancer.Conclusions:Distal intramural spread is an independent risk factor for distant metastasis and poor prognosis in patients with rectal cancer.Deceased     

Complete Response to Neoadjuvant Chemoradiation for Rectal Cancer Does Not Influence Survival

Background: Up to 30% of patients with locally advanced rectal cancer have a complete clinical or pathologic response to neoadjuvant chemoradiation. This study analyzes complete clinical and pathologic responders among a large group of rectal cancer patients treated with neoadjuvant chemoradiation.Methods: From 1987 to 2000, 141 consecutive patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative 5-fluorouracil-based chemotherapy and radiation. Clinical restaging after treatment consisted of proctoscopic examination and often computed tomography scan. One hundred forty patients then underwent operative resection, with results tracked in a database. Standard statistical methods were used to examine the outcomes of those patients with complete clinical or pathologic responses.Results: No demographic differences were detected between either clinical complete and clinical partial responders or pathologic complete and pathologic partial responders. The positive predictive value of clinical restaging was 60%, and accuracy was 82%. By use of the Kaplan-Meier life table analysis, clinical complete responders had no advantage in local recurrence, disease-free survival, or overall survival rates when compared with clinical partial responders. Pathologic complete responders also had no recurrence or survival advantage when compared with pathologic partial responders. Of the 34 pathologic T0 tumors, 4 (13%) had lymph node metastases.Conclusions: Clinical assessment of complete response to neoadjuvant chemoradiation is unreliable. Micrometastatic disease persists in a proportion of patients despite pathologic complete response. Observation or local excision for patients thought to be complete responders should be undertaken with caution.Presented in part at the 54th Annual Cancer Symposium of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.     

Preoperative Combined Radiotherapy and Chemotherapy for Middle and Lower Rectal Cancer: Preliminary Results

Background: Adjuvant treatment for rectal cancer is still controversial. This study reports on overall survival and disease-free survival, toxicity, downstaging, and surgical morbidity in rectal cancer patients who received combined chemoradiation therapy followed by curative surgery.Methods: Between 1993 and 1998, 51 patients (31 males and 20 females; median age, 60 years; range, 33–73 years) underwent chemoradiation therapy followed by radical surgery for middle and lower rectal adenocarcinoma. Criteria for giving preoperative radiotherapy (total 45 Gy in 25 fractions of 1.8 Gy/day for 5 weeks) and chemotherapy (5-fluorouracil 350 mg/m2/day and leucovorin 10 mg/m2/day, bolus on days 1–5 and 29–33) were an age younger than 75 years; an Eastern Cooperative Oncology Group performance status score of 0 to 2; and clinical preoperative stage II–III. Forty-three low anterior and eight abdominoperineal resections were performed. Median follow-up time was 29 (range, 3–63) months.Results: Although grade 3 to 4 toxicity occurred in 14 cases (27.4%), all patients completed the planned adjuvant therapy. At pathology, a complete response was found in eight (15.7%) cases. Of the remaining 43 cases, 22 were stage I, 12 were stage II, and 9 were stage III. Five-year actuarial disease-free survival and overall survival rates were 86.4% and 85.5%, respectively. Whereas no local recurrences were found, 4 patients had distant metastases. Three patients died (1 of cancerrelated causes), 45 are alive and disease free, and 3 are alive with disease.Conclusions: The combined preoperative chemoradiation approach used by us seems to improve the disease-free survival and overall survival of selected patients with rectal cancer. However, a longer follow-up time is required to confirm these preliminary results.Presented at the 52nd Annual Meeting of Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Preoperative Prediction of Tumor Heterogeneity and Recurrence After Radical Prostatectomy for Localized Prostatic Carcinoma with Digital Rectal Examination, Prostate Specific Antigen and the Results of 6 Systematic Biopsies

Purpose

Digital rectal examination, preoperative serum prostate specific antigen (PSA) concentration and results of 6 ultrasound guided systematic sextant biopsies in 257 consecutive patients with clinical stages T2 and T1c prostatic carcinoma were evaluated for their use in predicting pathological stage and tumor recurrence.

Materials and Methods

Each of the 257 consecutive specimens was examined using the 3 mm. step section technique. Results of preoperative digital rectal examination, PSA and 6 systematic sextant biopsies were correlated with pathological stage, margin status and postoperative PSA during a mean followup of 2 years. Patients were considered to have disease progression based on an elevated PSA level by a supersensitive assay.

Results

Digital rectal examination could not predict pathological stage and tumor recurrence. Preoperative PSA concentration, number of positive biopsies and tumor grade in the biopsy specimens correlated well with pathological stage. The best predictor of tumor recurrence was the biopsy result. However, a precise prediction of outcome (87 percent probability of being PSA negative versus 0 percent) was possible only in a third of the patients if the biopsy results were used. Use of preoperative PSA concentration did not improve this probability.

Conclusions

Preoperative PSA concentration and/or biopsy results correlate significantly with pathological stage and margin status. Precise prediction of tumor recurrence is possible in only approximately a third of the patients with clinical stage T2 prostatic carcinoma.     

Adenocarcinoma of the lower third of the rectum surgically treated with a <10-MM distal clearance: preliminary results in 35 N0 patients

Background: Recent reports suggest that a distal clearance (DC) of 10 mm at the lower surgical margin may be considered adequate in the surgical treatment of rectal cancer, but there are no data on the possible adequacy of a <10-mm DC in N0 patients in whom a good prognosis can otherwise be expected, that is, those with negative surgical margins and negative lymph nodes.Methods: Between November 1991 and December 1998, 154 consecutive patients with adenocarcinoma of the lower third of the rectum had a total rectal resection with total mesorectal excision and coloendoanal anastomosis. Among 76 N0 patients, there were 35 with <10-mm DC and 41 with 10-mm DC. Each group was divided into two subgroups depending on whether the surgical margins were involved or not, and the rate of local recurrence in the various categories was compared. All B2 Astler-Coller stage patients in the series received postsurgical chemoradiotherapy.Results: The local recurrence rate in the 35 patients with DC <10 mm was 11.4% and that of the 41 patients with DC 10 mm was 7.3%. When only patients with negative surgical margins were considered, the local recurrence rate was 3.4% for those with <10-mm DC and 5.1% for those with 10-mm DC.Conclusions: Our results suggest that a radical surgery with <10-mm DC followed by chemoradiotherapy may be adequate in N0 patients, provided that a careful pathologic examination of the surgical specimen excludes the presence of lymph node metastases and that the distal rectal and mesorectal resection margins fall in healthy tissue.     

Urinary Diversion After Total Pelvic Exenteration for Rectal Cancer

Background: Total cystectomy is indicated for the treatment of bulky primary rectal cancers as well as previously treated, locally recurrent tumors that invade the bladder, prostate, seminal vesicle, or urethra. We review a 10-year Memorial Sloan-Kettering Cancer Center experience with urinary diversion in this setting.Methods: Between April 1988 and June 1998, 47 patients underwent urinary diversion during a total pelvic exenteration for rectal cancer. Charts and operative records were reviewed to determine pathological findings, short-term and long-term urological complications, and survival.Results: Forty-seven patients (25 males and 22 females; median age, 62 years; age range, 27–79 years) were included. Sixteen (34%) patients underwent cystectomy for a primary rectal tumor (including 1 for rectal sarcoma and 1 for synchronous invasive bladder cancer), and 31 (66%) patients underwent surgery for a locally recurrent rectal cancer. Thirty (64%) patients underwent preoperative, 18 (38%) underwent intraoperative, and 11 (23%) underwent postoperative radiotherapy. Twenty-six (55%) patients received preoperative and 16 (34%) underwent postoperative chemotherapy. Two patients had continent ileal cecal reservoirs, 1 a colonic conduit, and the remaining 45 had ileal conduits. The tumor invaded the bladder in 24 (51%) patients, the prostate in 5 (11%) patients, and the seminal vesicle in 5 (11%) patients. Complete resection was achieved in 42 (89%) patients. There were a total of eight complications in eight (17%) patients. There were three early complications, two of which were ileoureteral anastomotic leaks, one managed by reoperation, the second by percutaneous drainage, and one moderate hydronephrosis managed expectantly. There were five late complications; three patients had ureteral stricture/stenosis, leading to nephrectomy in one patient and percutaneous stenting in two patients. Two patients developed late hydronephrosis, so far managed expectantly. There was one perioperative death. After a median follow-up of 16.83 months, 20 patients were dead of the disease, 6 were alive with disease recurrence, 2 were dead of other causes, and 19 had no evidence of disease. Three-year actuarial disease-specific survival was 34%.Conclusions: Complete resection of bulky primary or locally recurrent rectal cancer can be performed with acceptable urological morbidity. Complete resection was obtained in 89% of patients, with 72% having urological organ invasion. Overall urological complications of 17% are acceptably low despite intensive perioperative radiation and chemotherapy. Disease-specific survival in these patients remains limited.Presented at the 52nd Annual Meeting of Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

A Prospective Randomized Trial Comparing Intravenous 5- Fluorouracil and Oral Doxifluridine As Postoperative Adjuvant Treatment for Advanced Rectal Cancer

Background: Postoperative adjuvant chemoradiation treatment after curative resection for rectal cancer was needed to reduce recurrence and improve a survival rate. Intravenous 5-fluorouracil (5-FU) and leucovorin has been a mainstay of chemotherapy, but oral 5-FU derivatives have been shown a comparable antitumor activity. Intravenous 5-FU and oral doxifluridine were compared with respect to therapeutic efficacy, drug toxicity, and quality of life.Methods: A total of 166 patients were randomized to receive intravenous 5-FU (450 mg/m²/day) or oral doxifluridine (900 mg/m²/day) in combination with leucovorin (20 mg/m²/day) for depth of invasion, nodal status, metastasis (TNM) stage II and III patients between October 1997 and February 1999. Consecutive daily intravenous infusion for 5 days per every month for a total of 12 cycles (IV arm, n = 74) and oral doxifluridine daily for 3 weeks and 1 week rest for a total of 12 cycles (oral arm, n = 92). Drug toxicity and quality of life were observed. Quality of life was scored according to 22 daily activity items (good, 71; fair, < 70; poor, < 52).Results: There was no difference of sex between two groups (IV arm: male/female = 45/29, oral arm: male/female = 59/33). The mean age was 52.3 vs. 59.5, respectively. There was also no difference of TNM stage distribution and type of operation between groups (P = .05). Mean numbers of chemotherapy cycles were 6.5 ± 3.7 (IV arm) vs. 7.2 ± 4.3 (oral arm), respectively. The rate of recurrence was 9/74 (12.1%) in the IV arm and 6/92 (6.5%) in the oral arm, respectively (P = .937). Local recurrence was 2/74 (stage III; 2.7%) in the IV arm and 1/92 (stage II;1.1%) in the oral arm, respectively. Systemic recurrence was 7/74 (stage III; 9.4%) in the IV arm and 5/92 (stage III; 5.4%) in the oral arm, respectively. The most common site of systemic recurrence was the liver. Toxicity profile was as follows: leukopenia (30/74 vs. 17/92) and alopecia (21/74 vs. 13/92) were statistically more common in the IV arm. Diarrhea was more common in the oral arm. Poor quality of life score between two groups was observed at 1 month (23.9% vs. 13%) and 2 months (15.8% vs. 3.7%) after chemotherapy. Good quality of life score was observed at 1 month (19.5% vs. 49%) and 2 months (47% vs. 72%), respectively (P < .05).Conclusions: Oral doxifluridine with leucovorin shows a comparable therapeutic efficacy to intravenous 5-FU regimen with high quality of life as postoperative adjuvant therapy. The oral regimen also can be safely given with appropriate toxicity and tolerability.Presented at the 53rd Annual Meeting of the Society of Surgical Oncology, March 16–19, 2000, New Orleans.     

Institutional Commitment to Rectal Cancer Screening Results in Earlier-Stage Cancers on Diagnosis

Background: The Veterans Administration hospitals underwent an institutional directive in 1998 to meet a colorectal cancer screening (CRCS) standard. This intervention should result in an increase in the hospitals screening rate and percentage of early-stage rectal cancers diagnosed.Methods: A retrospective review, from 1991 to 2002, of our institutions pathology and cancer registry databases for rectal cancers. CRCS data were obtained from the Veterans Administration Prevention Disease Index. Cancer stage at diagnosis was compared before and after the directive and was compared with the National Cancer Data Base and the Surveillance, Epidemiology, and End Results data.Results: The rate of CRCS was 55% in 1998 and increased to 75% in 2003. During the 11 years studied, a total of 147 rectal cancers were diagnosed. After the Veterans Administration directive, there was a significant increase in stage 0 cancers (P < .02) and an overall migration to earlier-stage cancers. Our Veterans Administration hospital had a significantly greater percentage of stage 0 cancers both before (P < .007) and after the directive (P < .00) and had fewer stage 3 cancers after the directive (P < .03) compared with National Cancer Data Base data. Compared with Surveillance, Epidemiology, and End Results data, the Palo Alto Veterans Affairs Health Care System had more local disease (P < .03) and less regional disease (P < .006).Conclusions: These data suggest that a monitored institutional directive may significantly increase early detection of rectal cancers. This should result in a greater survival rate and lower local recurrence rate, because survival is predicated on stage at presentation. This may serve as a model for other health-care systems.     

Results After Rectal Cancer Resection With In-Continuity Partial Vaginectomy and Total Mesorectal Excision

Background: Although sharp mesorectal excision reduces circumferential margin involvement and local recurrence, a concomitant partial vaginectomy may be required in women with locally advanced rectal cancer.Methods: Sixty-four patients requiring a partial vaginectomy during resection of primary rectal cancer were identified. Survival was determined by the Kaplan-Meier method, and distributions were compared by the log-rank test.Results: Locally advanced disease was reflected by presentation with malignant rectovaginal fistulae (n = 6) or cancers described as bulky or adherent/tethered to the rectovaginal septum (n = 32). Thirty-five patients received adjuvant radiation with or without chemotherapy. At a median follow-up of 22 months, 27 (42%) patients developed recurrent disease, with most of these occurring at distant sites. The 5-year overall survival was 46%, with a median survival of 44 months. The 2-year local recurrence–free survival was 84%. The crude local failure rate was 16% (10 of 64), and local recurrence was more common in patients with a positive as opposed to a negative microscopic margin (2 [50%] of 4 vs. 8 [13%] of 60, respectively). Positive nodal status had a significant effect on overall survival (P < .001).Conclusions: Partial vaginectomy is indicated for locally advanced rectal cancers involving the vagina. The results are most favorable in patients with negative surgical margins and node-negative disease.Presented in part at the 54th Annual Cancer Symposium of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.     

Long-term Outcome of Local Excision after Complete Pathological Response to Neoadjuvant Chemoradiation Therapy for Rectal Cancer

Background

Neoadjuvant chemoradiotion therapy (CRT) for advanced rectal cancer has improved local disease. Complete rectal wall tumor regression may be associated with the absence of viable cancer cells in the mesorectum, and thus local excision (LE) of such lesions as an alternative to radical surgery has recently gained interest. We report the long-term outcome of LE in patients with a mural pathological complete response (ypT0) after CRT.

Methods

A retrospective review of patients with rectal cancer treated by CRT and followed by LE with pathological complete response in the specimen between 1998 and 2009 was performed.

Results

A total of 174 patients had neoadjuvant CRT, and 68 (39?%) showed complete clinical response (cCR). Thirty-one of the cCR patients underwent LE; 23 of them resulted in ypT0 and 8 had residual disease. The ypT0 group included 12 men and 11 women with a median age of 66. The pretreatment stage was T3N1 in 4 (17?%) patients, T3N0 in 11 (48?%), T2N1 in 3 (13?%), and T2N0 in 5 (22?%). The median tumor distance from the anal verge was 6?cm. Sixteen patients (70?%) underwent transanal excision, and 7 (30?%) were treated by transanal-endoscopic microsurgery. Three patients died: one of pneumonia, one of melanoma of the rectum, and one of lung carcinoma. No local or distant recurrences were detected in the remaining 20 patients. The median follow-up was 87?months.

Conclusions

Although radical rectal resection is the treatment of choice, LE of complete rectal tumor regression could be a safe alternative with an acceptable result in selected patients.     

Transanal endoscopic microsurgery and radical surgery for T1 and T2 rectal cancer

Background: Transanal endoscopic microsurgery (TEM) has gained increasing acceptance as a local treatment of early rectal cancer. The purpose of this study was to compare the results of TEM and radical surgery in patients with T1 and T2 rectal cancer. Methods: From October 1994 to December 2000, 74 patients with T1 and T2 rectal adenocarcinoma treated with TEM were compared with 100 patients with T1N0M0 and T2N0M0 rectal adenocarcinoma treated with radical surgery. Retrospective analysis was performed regarding to recurrence and survival rate. Neither group received adjuvant chemoradiation. There was no significant difference in age, gender, tumor location, or follow-up period between the two groups. The only difference was in tumor size. Results: Of the 74 patients in TEM group, 52 were T1 (70.3%) and 22 were T2 (29.7%). Of the 100 patients in radical surgery group, 17 were T1 (17%) and 83 patients were T2 (83%). The 5-year local recurrence rates were 4.1% for T1, 19.5% for T2 after TEM, 0% for T1, and 9.4% for T2 after radical surgery. There was no statistical difference between the TEM and radical surgery groups for T1 rectal cancer (p = 0.95), but for T2 rectal cancer, the 5-year local recurrence rate was higher after TEM than after radical surgery (p = 0.04). There were no significant statistical difference between the two groups in terms of the 5-year disease-free survival rate and the survival rate. Conclusions: For T1 rectal cancer, there was no difference in recurrence or 5-year survival rate between the TEM and the radical surgery groups. For T2 rectal cancer, there was no statistical difference in the 5-year survival rate between the two groups, but TEM carried higher risk of local recurrence. Therefore, careful selection of the patients is required for TEM, and when proper muscle invasion is proven, the TEM procedure should be supplemented by further treatment, or radical surgery should be performed. Presented at the Society of American Gastrointestinal Endoscopic Surgeons (SAGES) meeting and the 8th World Congress of Endoscopic Surgery, New York, New York, USA, 13–16 March 2002     

Platelet-to-Lymphocyte Ratio and Neutrophil-to-Lymphocyte Ratio Are Not Prognostic Biomarkers in Rectal Cancer Patients with Curative Resection

Background

Actual predictors of survival and recurrence for rectal cancer patients undergoing curative resection mostly come from pathological data of surgical specimen. Recently, novel blood biomarkers have been proposed as useful tools in cancer patient management, but few and conflicting data have been reported in rectal cancer. We evaluated the prognostic relevance of preoperative platelet-to-lymphocyte (P/L) ratio and neutrophil-to-lymphocyte (N/L) ratio on survival and recurrence in patients undergoing laparoscopic curative resection for rectal cancer.

Methods

All consecutive patients who referred for primary rectal disease to the Department of General Surgery in Cittadella (Italy) from June 2005 to September 2015 were retrospectively evaluated. Patients with metastatic disease at surgery were excluded. P/L and N/L ratios were calculated. For patients undergoing neoadjuvant chemo-radiotherapy, pre-treatment data were considered. Follow-up data were updated at December 2016.

Results

One hundred fifty-two patients were included in the study, 49 (32%) received neoadjuvant chemo-radiotherapy. Both P/L and N/L ratios showed poor discriminative performance on 5-year OS and DFS. Time-dependent ROC curves showed no improvements in discriminative performance of P/L and N/L ratios when considering different time endpoints. Multivariable analysis identified CEA—rather than P/L or N/L ratios—as independent predictor of OS and DFS, adjusting for age, tumor stage, and postoperative morbidity.

Conclusion

Neither P/L nor N/L ratios were associated with survival after rectal cancer surgery. Further studies on large series might provide insights on the role of these inexpensive blood biomarkers in rectal cancer.

     

Paradigm-Shifting New Evidence for Treatment of Rectal Cancer

Background

Treatment of rectal cancer has dramatically evolved during the last three decades shifting toward a tailored approach based on preoperative staging and response to neoadjuvant combined modality therapy (CMT).

Methods

A literature search was performed using PubMed/Medline electronic databases.

Results

Selected patients with T1 N0 rectal cancer are best treated with local excision by transanal endoscopic microsurgery (TEM). Satisfactory results have been reported after CMT and TEM for the treatment of highly selected T2 N0 rectal cancers. CMT followed by rectal resection and total mesorectal excision is considered the standard of care for the treatment of locally advanced rectal cancer. However, a subset of stage II and III patients may not require neoadjuvant radiation treatment. Finally, there are mounting data supporting a “watch and wait” approach or local excision in patients with complete clinical response after neoadjuvant CMT.

Conclusions

Current evidence shows that selected T1 N0 rectal cancers can be managed by TEM alone, while locally advanced cancers should be treated by CMT followed by radical surgery. Studies are underway to identify patients that do not benefit from neoadjuvant radiation therapy. A non-operative approach in case of complete clinical response must be validated by large prospective studies.     

Patterns of Recurrence After Sentinel Lymph Node Biopsy for Breast Cancer

Background: Sentinel lymph node biopsy (SLNB) is gaining acceptance as an alternative to axillary lymph node dissection. The purpose of this study was to determine the frequency and pattern of disease recurrence after SLNB.Methods: Two-hundred twenty-two consecutive patients undergoing SLNB from April 6, 1998, to October 27, 1999, and who were 24 months out from their procedure were identified from a prospectively maintained database. Retrospective chart review and data analysis were performed to identify variables predictive of recurrence.Results: The median patient follow-up was 32 months (range, 24–43 months). A total of 159 patients (72%) were sentinel lymph node (SLN) negative and had no further axillary treatment. Five of these patients (3.1%) developed a recurrence (one local and four distant), with no isolated regional (axillary) recurrences. Sixty-three patients (28%) were SLN positive and underwent a subsequent axillary lymph node dissection. Six of these patients (9.5%) developed a recurrence (three local, one regional, and two distant). Pathologic tumor size (P < .001), lymphovascular invasion (P = .018), and a positive SLN (P = .048) were all statistically significantly associated with disease recurrence.Conclusions:With a minimum follow-up of 24 months, patients with a negative SLN and no subsequent axillary treatment demonstrate a low frequency of disease recurrence. This supports the use of SLNB as the sole axillary staging procedure in SLN-negative patients.     

Expression of p27 in Residual Rectal Cancer after Preoperative Chemoradiation Predicts Long-term Outcome

Background: Compared with surgery alone, preoperative radiotherapy and 5-fluorouracil–based chemotherapy (combined-modality therapy; CMT) improves outcomes in patients with locally advanced rectal cancer. Although numerous studies have focused on identifying molecular markers of prognosis in the primary rectal cancer before CMT, our aim was to identify markers of prognosis in residual rectal cancer after preoperative CMT.Methods: Sixty-seven patients with locally advanced (T3–4 and/or N1) rectal cancer were treated with preoperative radiotherapy (median, 5040 cGy) with or without 5-fluorouracil–based chemotherapy. Residual tumor in the resected specimen, available for 52 patients, was analyzed for tumor-node-metastasis stage, lymphovascular and/or perineural invasion, and immunohistochemical expression of p27, p21, p53, Ki-67, retinoblastoma gene, cyclin D1, and bcl-2. Recurrence-free survival (RFS) was determined by the Kaplan-Meier method and compared by the log-rank test.Results: With a median follow-up of 69 months, the overall 5-year RFS was 74%. RFS was significantly worse for patients with positive p27 expression (P = .005), T3–4 tumors (P = .02), and positive lymph nodes (P = .04) in the irradiated specimen. On multivariate analysis, positive p27 expression remained an independent negative prognostic factor for RFS (P = .04). None of the other proteins was significantly associated with RFS.Conclusions: Our results indicate that positive p27 expression in rectal cancer after preoperative chemoradiation is an independent negative predictor of RFS. Expression of p27 in the residual rectal cancer may therefore identify patients with disease likely to be refractory to standard therapy and for whom investigational approaches should be strongly considered.the 56th Annual Cancer Symposium, Society of Surgical Oncology, Los Angeles, California, March 5–9, 2003.     

Comparative Outcomes of Preoperative Chemoradiotherapy and Selective Postoperative Chemoradiotherapy in Clinical Stage T3N0 Low and Mid Rectal Cancer

Abstract

Purpose/aim: Preoperative chemoradiotherapy (pre-CRT) and total mesorectal excision (TME) have become the standard of care for patients with locally advanced rectal cancer (LARC). Nevertheless, it is a controversial issue whether pre-CRT in cT3N0M0 patients would result in potential overtreatment. Materials and methods: In total, 183 clinical stage IIA rectal cancer patients treated with and without pre-CRT between 2011 and 2014 were retrospectively analyzed. Capecitabine/FOLFOX/CAPOX chemotherapy was co-administered with preoperative radiotherapy. Surgical resection with laparoscopic or open TME was conducted 8–12?weeks after completion of the pre-CRT. Postoperative radiotherapy was routinely given to patients with pT4 lesion or circumferential margin (CRM) and/or distal resection margin (DRM) involvement. Results: In total, 108 (59%) patients received pre-CRT and 75 (41%) underwent surgery first. The pre-CRT patients presented with less-advanced pathological T stage tumors compared with the surgery-first patients (p?<?0.001). However, the pathological N stage was not significantly different between the two groups (p?=?0.065). The 3-year overall survival (OS), disease-free survival (DFS), and 2-year local recurrence (LR) rate were similar in the pre-CRT and surgery-first patients (88.4 versus 88.7%, p?=?0.552; 79.6 versus 83.3%, p?=?0.797; 2.8 versus 2.7%, p?=?0.960, respectively). Cox regression analysis showed that pN stage and CRM/DRM involvement were independently correlated with an unfavorable DFS. Conclusions: In this study, the omission of pre-CRT in cT3N0M0 patients did not translate into a worse oncological outcome. Postoperative radiotherapy should remain a standard option for patients with CRM/DRM involvement and pathological T4 tumors. A generalized indication for pre-CRT in cT3N0 patients is likely to result in overtreatment.     

Symptom Control in Patients With Locally Recurrent Rectal Cancer

Background: Although resection of locally recurrent rectal cancer has been associated with improved survival, clinical outcomes after such repeat surgery have been incompletely characterized.Methods: From 1997 to 1999, 105 consecutive patients requiring repeat surgery for locally recurrent rectal cancer were identified. Patients were observed for a minimum of 2 years or until death.Results: An operation was performed with palliative intent in 23% of patients. Before repeat surgery, 79% of the palliative-intent patients had symptoms: 21% bleeding, 42% obstruction, and 21% pain. After repeat surgery with palliative intent, improvement was noted in 40% with bleeding, 70% with obstruction, and 20% with pain. Additional or recurrent symptoms were noted in 87% during follow-up. Seventy-seven percent of patients had an operation with nonpalliative intent. Before repeat surgery, 57% of nonpalliative patients had symptoms, with 32% experiencing bleeding, 11% obstruction, and 19% pain. After repeat surgery with nonpalliative intent, initial improvement was noted in 88% with bleeding, 78% with obstruction, and 40% with pain. During follow-up, symptoms arose in 37% of the initially asymptomatic patients, and additional or recurrent symptoms were seen in 63% of those previously symptomatic.Conclusions: Although symptomatic relief is associated with repeat surgery, the recurrence or development of alternate symptoms makes a completely asymptomatic clinical course uncommon.     

Transanal Endoscopic Microsurgery: A Viable Operative Alternative in Selected Patients With Rectal Lesions

Background: Local excision of rectal lesions is being increasingly undertaken, especially in those unfit for major surgery. The traditional transanal approach is often cumbersome and limited to low and mid rectal lesions. Transanal endoscopic microsurgery (TEMS) is being used to excise both benign and malignant rectal lesions, including those in the upper rectum.Methods: Prospective analysis of all patients undergoing a TEMS excision between January 1997 and December 2000 in a specialized colorectal unit.Results: Forty patients underwent a TEMS resection, with a mean age of 72 years (SD, 10 years). The mean distance of the lesions from the anal verge was 9.8 cm (SD, 3.1 cm). In 24 patients, the lesion was located 10 cm from the anal verge, making them unsuitable for traditional transanal resection. The mean operative time was 91 minutes (SD, 34 minutes), and the mean postoperative stay was 3 days (SD, 1.5 days). No mortality was associated with the procedure, and there was minimal morbidity in 15%. There has been no recurrence in the 18 patients who had a malignant lesion excised.Conclusions: The TEMS operating system provides the surgeon with a suitable alternative for the resection of benign and malignant rectal neoplasms in selected patients. It has the advantage of providing visual clarity of the operative field, allowing more precise dissection and a minimally invasive approach to mid and upper rectal lesions. There has been no mortality and minimal morbidity. We advocate its inclusion as part of a colorectal surgeons operative armamentarium for these selected cases.