Desidério Roberto Kiss

Operative Versus Nonoperative Treatment for Stage 0 Distal Rectal Cancer Following Chemoradiation Therapy Long-term Results

Objective:Report overall long-term results of stage 0 rectal cancer following neoadjuvant chemoradiation and compare long-term results between operative and nonoperative treatment. Methods:Two-hundred sixty-five patients with distal rectal adenocarcinoma considered resectable were treated by neoadjuvant chemoradiation (CRT) with 5-FU, Leucovorin and 5040 cGy. Patients with incomplete clinical response were referred to radical surgical resection. Patients with incomplete clinical response treated by surgery resulting in stage p0 were compared to patients with complete clinical response treated by nonoperative treatment. Statistical analysis was performed using χ2, Student t test and Kaplan-Meier curves. Results:Overall and disease-free 10-year survival rates were 97.7% and 84%. In 71 patients (26.8%) complete clinical response was observed following CRT (Observation group). Twenty-two patients (8.3%) showed incomplete clinical response and pT0N0M0 resected specimens (Resection group). There were no differences between patients demographics and tumors characteristics between groups. In the Resection group, 9 definitive colostomies and 7 diverting temporary ileostomies were performed. Mean follow-up was 57.3 months in Observation Group and 48 months in Resection Group. There were 3 systemic recurrences in each group and 2 endorectal recurrences in Observation Group. Two patients in the Resection group died of the disease. Five-year overall and disease-free survival rates were 88% and 83%, respectively, in Resection Group and 100% and 92% in Observation Group. Conclusions:Stage 0 rectal cancer disease is associated with excellent long-term results irrespective of treatment strategy. Surgical resection may not lead to improved outcome in this situation and may be associated with high rates of temporary or definitive stoma construction and unnecessary morbidity and mortality rates.

Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy.

Neoadjuvant chemoradiation therapy (CRT) is the preferred treatment option for distal rectal cancer. Complete pathological response after CRT has led to the proposal of nonoperative approach as an alternative treatment for highly selected patients with complete clinical response. However, patterns of failure following this strategy remains undetermined. Three hundred sixty-one patients with distal rectal cancer were managed by neoadjuvant CRT including 5-FU, leucovorin, and 5040 cGy. Tumor response assessment was performed at 8 weeks following CRT. Patients with complete clinical response were not immediately operated on and were closely followed. One hundred twenty-two patients were considered to have complete clinical response after the first tumor response assessment. Of these, only 99 patients sustained complete clinical response for at least 12 months and were considered stage c0 (27.4%) and managed nonoperatively. Mean follow-up was 59.9 months. There were 13 (13.1%) recurrences: 5 (5%) endorectal, 7 (7.1%) systemic, and 1 (1%) combined recurrence. All 5 isolated endorectal recurrences were salvaged. Mean recurrence interval was 52 months for local failure and 29.5 months for systemic failure. There were five cancer-related deaths after systemic recurrences. Overall and disease-free 5-year survivals were 93% and 85%. Even though surgery remains the standard treatment for rectal cancer, nonoperative treatment after complete clinical response following neoadjuvant CRT may be safe and associated with good survival rates in a highly selected group of patients. Survival in these patients is significantly affected by systemic failure. Exclusive local failure occurs late after CRT completion and is frequently amenable to salvage therapy.

Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival

Neoadjuvant chemoradiation treatment (CRT) has resulted in significant tumor downstaging and improved local disease control for distal rectal cancer. The purpose of the present study was to determine the correlation between final stage and survival in these patients regardless of initial disease stage. Two hundred sixty patients with distal (0-7 cm from anal verge) rectal adenocarcinoma considered resectable were treated by neoadjuvant CRT with 5-FU and leucovorin plus 5040 cGy. Patients with incomplete clinical response 8 weeks after CRT completion were treated by radical surgical resection. Patients with complete clinical response were managed by observation alone. Overall survival and diseasefree survival were compared according to Kaplan-Meier curves and log-rank tests according to final stage. Seventy-one patients (28%) showed complete clinical response (clinical stage 0). One hundred sixtynine patients showed incomplete clinical response and were treated with surgery. In 22 of these patients (9%), pathologic examination revealed pT0 N0 M0 (stage p0), 59 patients (22%) had stage I, 68 patients (26%) had stage II, and 40 patients (15%) had stage III disease. Overall survival rates were significantly higher in stage c0 (P = 0.01) compared with stage p0. Disease-free survival rate showed better results in stage c0, but the results were not significant. Five-year overall and disease-free survival rates were 97.7% and 84% (stage 0); 94% and 74% (stage I); 83% and 50% (stage II); and 56% and 28% (stage III), respectively. Cancer-related overall and disease-free survival may be correlated to final pathologic staging following neoadjuvant CRT for distal rectal cancer. Also, stage 0 is significantly associated with improved outcome.

Interval Between Surgery and Neoadjuvant Chemoradiation Therapy for Distal Rectal Cancer: Does Delayed Surgery Have an Impact on Outcome?

BACKGROUND The optimal interval between neoadjuvant chemoradiation therapy (CRT) and surgery in the treatment of patients with distal rectal cancer is controversial. The purpose of this study is to evaluate whether this interval has an impact on survival. METHODS AND MATERIALS Patients who underwent surgery after CRT were retrospectively reviewed. Patients with a sustained complete clinical response (cCR) 1 year after CRT were excluded from this study. Clinical and pathologic characteristics and overall and disease-free survival were compared between patients undergoing surgery 12 weeks or less from CRT and patients undergoing surgery longer than 12 weeks from CRT completion and between patients with a surgery delay caused by a suspected cCR and those with a delay for other reasons. RESULTS Two hundred fifty patients underwent surgery, and 48.4% had CRT-to-surgery intervals of 12 weeks or less. There were no statistical differences in overall survival (86% vs. 81.6%) or disease-free survival rates (56.5% and 58.9%) between patients according to interval (< or =12 vs. >12 weeks). Patients with intervals of 12 weeks or less had significantly higher rates of Stage III disease (34% vs. 20%; p = 0.009). The delay in surgery was caused by a suspected cCR in 23 patients (interval, 48 +/- 10.3 weeks). Five-year overall and disease-free survival rates for this subset were 84.9% and 51.6%, not significantly different compared with the remaining group (84%; p = 0.96 and 57.8%; p = 0.76, respectively). CONCLUSIONS Delay in surgery for the evaluation of tumor response after neoadjuvant CRT is safe and does not negatively affect survival. These results support the hypothesis that shorter intervals may interrupt ongoing tumor necrosis.

Conventional approach x laparoscopic abdominoperineal resection for rectal cancer treatment after neoadjuvant chemoradiation: results of a prospective randomized trial

OBJECTIVE The aims of this study were to evaluate the safety and efficacy of laparoscopic abdominoperineal resection compared to conventional approach for surgical treatment of patients with distal rectal cancer presenting with incomplete response after chemoradiation. METHOD Twenty eight patients with distal rectal adenocarcinoma were randomized to undergo surgical treatment by laparoscopic abdominoperineal resection or conventional approach and evaluated prospectively. Thirteen underwent laparoscopic abdominoperineal resection and 15 conventional approach. RESULTS There was no significant difference (p<0,05) between the two studied groups regarding: gender, age, body mass index, patients with previous abdominal surgeries, intra and post operative complications, need for blood transfusion, hospital stay after surgery, length of resected segment and pathological staging. Mean operation time was 228 minutes for the laparoscopic abdominoperineal resection versus 284 minutes for the conventional approach (p=0.04). Mean anesthesia duration was shorter (p=0.03) for laparoscopic abdominoperineal resection when compared to conventional approach : 304 and 362 minutes, respectively. There was no need for conversion to open approach in this series. After a mean follow-up of 47.2 months and with the exclusion of two patients in the conventional abdominoperineal resection who presented with unsuspected synchronic metastasis during surgery, local recurrence was observed in two patients in the conventional group and in none in the laparoscopic group. CONCLUSIONS We conclude that laparoscopic abdominoperineal resection is feasible, similar to conventional approach concerning surgery duration, intra operative morbidity, blood requirements and post operative morbidity. Larger number of cases and an extended follow-up are required to adequate evaluation of oncological results for patients undergoing laparoscopic abdominoperineal resection after chemoradiation for radical treatment of distal rectal cancer.

Absence of Lymph Nodes in the Resected Specimen After Radical Surgery for Distal Rectal Cancer and Neoadjuvant Chemoradiation Therapy: What does it Mean?

PurposeThe number of retrieved lymph nodes during radical surgery has been considered of great importance to ensure adequate staging and radical resection. However, this finding may not be applicable after neoadjuvant therapy in which, not only is there a decrease in lymph nodes recovered, but also a subgroup of patients with absence of lymph nodes in the resected specimen.MethodsPatients with absence of lymph nodes were compared with patients with ypN0 disease and patients with ypN+ disease.ResultsThirty-two patients (11 percent) had absence of lymph nodes, 171 patients (61 percent) had ypN0 disease, and 78 patients (28 percent) had ypN+ disease. Patients with absence of lymph nodes had significantly lower ypT status (ypT0-1, 40 vs. 13 percent; P < 0.001) and decreased risk of perineural invasion (6 vs. 21 percent; P = 0.04) compared with ypN0 patients. Five-year disease-free survival (74 percent) was similar to patients with ypN0 (59 percent; P = 0.2), and both were significantly better than patients with ypN+ disease (30 percent; P < 0.001).ConclusionsAbsence of lymph nodes retrieved from the resected specimen is associated with favorable pathologic features (ypT and perineural invasion status) and good disease-free survival rates. In this setting, absence of retrieved lymph nodes may reflect improved response to neoadjuvant chemoradiation therapy rather than inappropriate or suboptimal oncologic radicality.

The role of carcinoembriogenic antigen in predicting response and survival to neoadjuvant chemoradiotherapy for distal rectal cancer.

PURPOSE: Carcinoembriogenic antigen (CEA) is the most frequently used tumor marker in rectal cancer. A decrease in carcinoembriogenic antigen after radical surgery is associated with survival in these patients. Neoadjuvant chemoradiotherapy may lead to significant primary tumor downstaging, including complete tumor regression in selected patients. Therefore, we hypothesized that a decrease in CEA after neoadjuvant chemoradiotherapy could reflect tumor response to chemoradiotherapy, affecting final disease stage and ultimately survival. METHODS: Patients with distal rectal cancer managed by neoadjuvant chemoradiotherapy and available pretreatment and postchemoradiotherapy levels of CEA were eligible for the study. Outcomes studied included final disease stage, relapse, and survival, and these were compared according to initial CEA level, post-chemoradiotherapy CEA level, and the reduction in CEA. RESULTS: Overall 170 patients were included. Post-chemoradiotherapy CEA levels <5 ng/ml were associated with increased rates of complete clinical response and pathologic response. Additionally, postchemoradiotherapy CEA levels <5 ng/ml were associated with increased overall and disease-free survival (P = 0.01 and P = 0.03). There was no correlation between initial CEA level or reduction in CEA and complete response or survival. CONCLUSION: A postchemoradiotherapy CEA level <5 ng/ml is a favorable prognostic factor for rectal cancer and is associated with increased rates of earlier disease staging and complete tumor regression. Postchemoradiotherapy CEA levels may be useful in decision making for patients who may be candidates for alterative treatment strategies.

Lymph node size in rectal cancer following neoadjuvant chemoradiation--can we rely on radiologic nodal staging after chemoradiation?

OBJECTIVES: Local excision is currently being considered as an alternative strategy for ypT0-2 rectal cancer. However, patient selection is crucial to rule out nodal disease and is performed by radiologic studies that consider size as a surrogate marker for positive nodes. The purpose of this study was to determine the difference in size between metastatic and nonmetastatic nodes and the critical lymph node size after neoadjuvant chemoradiation therapy. METHODS: The 201 lymph nodes available from 31 patients with ypT0-2 rectal cancer were reviewed and measured. Lymph nodes were compared according to the presence of metastases and size. RESULTS: There was a mean of 6.5 lymph nodes per patient and 12 positive nodes of the 201 recovered (6%). Ninety-five percent of all lymph nodes were <5 mm, whereas 50% of positive lymph nodes were <3 mm. Metastatic lymph nodes were significantly greater in size (5.0 vs. 2.5mm; P = 0.02). Lymph nodes >4.5 mm had a greater risk of harboring metastases (P = 0.009). CONCLUSIONS: Patients with ypT0-2 rectal cancer following neoadjuvant chemoradiation have very small perirectal nodes. Individual metastatic lymph nodes are significantly larger. However, a significant number of lymph nodes after neoadjuvant chemoradiation (negative and positive) are <3 mm. Individual lymph node size is not a good predictor of nodal metastases and may lead to inaccurate radiologic staging.

Mucinous colorectal adenocarcinoma : influence of mucin expression (Muc1, 2 and 5) on clinico-pathological features and prognosis

BackgroundMucinous component is associated with distinct clinical and pathological features and poor survival in colorectal cancer. The purpose of this study was to determine differences in outcomes of patients with mucinous colorectal adenocarcinoma according to the type of mucin expressed.Materials and MethodsImmunohistochemistry was performed in all tumors of patients who underwent radical surgery between 1998 and 2003 with mucinous colorectal cancer using antibodies against MUC1, 2, and 5. Correlation between immunoexpression and clinical, pathological features and survival was performed.ResultsOf the 418 patients treated in this period, only 35 had a mucinous adenocarcinoma. Of these, 25 were positive for 1 or more mucin expression. MUC2 expression correlated with tumor site and depth of penetration, while MUC5 expression correlated to tumor site. Overall survival was significantly worse for patients with MUC2 expression, and disease-free survival was significantly worse for patients with MUC1 expression.ConclusionsMucin expression may have significant correlation to specific clinical-pathological features and survival of patients with mucinous-type colorectal adenocarcinoma. These differences may reflect distinct molecular mechanisms involved in carcinogenesis of mucinous colorectal adenocarcinoma.

Gluteal and Perianal Hidradenitis Suppurativa

AbstractPURPOSE: Hidradenitis suppurativa is a chronic inflammatory disease of the skin and subcutaneous tissue. Extensive gluteal and perianal disease represents a challenge presentation. The aim of this study was to present results of management of extensive hidradenitis suppurativa in gluteal, perineal, and inguinal areas. METHODS: From January 1980 to May 2000, 56 patients underwent treatment of hidradenitis suppurativa in gluteal, perineal, and inguinal areas through wide excision; 52 (93 percent) were male and 36 (64 percent) were white. Mean age was 40 years. We evaluated distribution of disease, associated conditions, use of diverting colostomy, management of operative wounds, time to complete healing, complications, and recurrence. RESULTS: Twenty-one (37.6 percent) and 17 (30.6 percent) patients had gluteal and perineal disease, respectively. Squamous-cell carcinoma and Crohn’s disease were observed in one patient each. Wide surgical excision was performed in all. Healing by second intention was the choice in 32 (57.1 percent) patients, and 24 (42.9 percent) patients underwent delayed skin-grafting. Diverting colostomy was used in 23 (41 percent) patients. Mean time for complete healing in the nongrafted group was 10 (range, 7–17) weeks and in the skin graft group was 6 (range, 3–9) weeks. New resection was performed in five (8.9 percent) patients. Partial graft loss rate was 37.5 percent and recurrence was observed in only one (1.8 percent) patient. CONCLUSION: Significant morbidity derives from extensive gluteal and perineal hidradenitis suppurativa caused by the disease extension and large wounds that result from surgical treatment. Wide surgical excision is the treatment of choice and leads to cure. Skin-grafting and healing by second intention lead to effective wound healing.