Pedro Luna-Pérez

Specific c-K-ras Gene Mutations as a Tumor-Response Marker in Locally Advanced Rectal Cancer Treated With Preoperative Chemoradiotherapy

Background: Forty percent of patients with colorectal cancer develop mutations in the K-ras gene.Objective: Our objective was to evaluate whether the presence of c-K-ras gene mutations is a useful tumor-response marker in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy.Material and Methods: Thirty seven patients with locally advanced rectal cancer were treated with preoperative chemoradiotherapy. Four to six weeks later, surgery was performed. Specimens were classified according to the UICC-AJC classification. A segment of the tumor was obtained to analyze specific c-K-ras gene mutations. Restriction fragment length polymorphism (RFLP) and single strand confirmation polymorphism (SSCP) techniques were used with a set of probes to detect specific c-K-ras mutations in codons 12, 13, and 61. The 37 patients were divided into Group A (with mutations) and Group B (without mutations).Results: All 37 patients completed the scheduled treatment. Group A consisted of 12 patients, whose tumors were classified and specific c-K-ras mutations were located as follows: eight in codon 12, two in codon 13, and one in codon 61. Group B consisted of 25 patients. The tumors were classified and there were more early-stage tumors in Group A, whereas in Group B there were more advanced-stage tumors (P 5 .05, respectively). The mean follow-up was 36.2 6 18.3 months. All Group A patients survived, whereas 8 of the 25 patients in Group B died due to progressive metastatic disease. Survival in Group A was 100%, whereas in Group B it was 59% (P 5 .03).Conclusions: The presence of specific c-K-ras mutations is an indicator of tumor response in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy and surgery. Therefore, responding patients may be more amenable to less radical surgical procedures based on c-K-ras mutations.

Prognostic significance of retrieved lymph nodes per specimenin resected rectal adenocarcinoma after preoperative chemoradiation therapy

BACKGROUND Histologic examination of a regional lymphadenectomy specimen ordinarily should include 12 or more lymph nodes. However, in specimens from patients who received preoperative chemoradiotherapy this number has not yet been established. METHODS From January 1990 to December 2000, 210 patients with rectal adenocarcinoma located between 0 and 10 cm from anal verge with invasion into perirectal fat, tethered or fixed to the pelvis, diagnosed by computed tomography (CT) scan and/or rectal ultrasound were included. All patients received 45 Gy+bolus infusion of 5-FU (450 mg/m2/days 1-5, 28-33 of RT) 4-8 weeks after surgery was performed. Specimens were mapped and sliced. Lymph nodes were studied under clearing or manual techniques. Five-year survival was calculated by Kaplan-Meier method and comparison of groups with log-rank test. Multivariate Cox regression analysis was performed to find risk factors affecting local control and survival. RESULTS There were 126 males and 84 females; mean age was 55.2 years. Low anterior resection was performed in 112 patients, abdominoperineal resection in 85, and pelvic exenteration in 13. Total retrieved lymph nodes numbered 2,554, of which 252 contained metastasis. The group was divided into patients with 1-10 retrieved lymph nodes (n=119) and patients with > or = 11 retrieved lymph nodes (n=91). Median follow-up was 49 months. Local recurrence was as follows: 15% in patients with specimens containing 1-10 lymph nodes and conversely 7.4% in those with > or = 11 (p=0.01). Five-year survival of patients with 1-10 lymph nodes was 48%, whereas for those with > or = 11 lymph nodes it was 69% (p=0.02). CONCLUSIONS Retrieval of at least 11 lymph nodes in the surgical specimen is not only a powerful tool to properly stage patients with rectal adenocarcinoma treated with preoperative chemoradiotherapy and surgery, but it is also of prognostic relevance in that 5-year survival and local recurrence were better in this group of patients.

p53 protein overexpression and response to induction chemoradiation therapy in patients with locally advanced rectal adenocarcinoma

AbstractBackground: The association between mutations in the p53 gene and prognosis in colorectal cancer remains controversial. This report evaluates the role of p53 protein to predict the response of neoadjuvant chemoradiation therapy in patients with primary locally advanced rectal adenocarcinoma. Methods: Between January 1993 and December 1994, 26 patients were seen with locally advanced primary rectal adenocarcinoma, located between 0 and 10 cm from the anal verge, demonstrated clinically and by CT scan. Each received 45 Gy of preoperative radiation therapy (RT) concomitantly with bolus infusion of 5-fluorouracil (5-Fu) (450/mg/m2 on days 1 to 5 and 28 to 33 of RT). Surgery was performed between 4 and 8 weeks later. All the primary tumors were mapped and sliced. The response rate was divided according to the percentage of malignant cells in the rectal wall and perirectal fat. Lymph nodes were studied with the manual or modified clearing technique. p53 mutant status was assessed immunohistochemically from sections of the formalin-fixed, paraffin-embedded pretreatment biopsy and the resected specimen. Results: There were 14 females and 12 males, with a mean age of 54 years. All received the scheduled treatment. An abdominoperineal resection (n=10), low anterior resection (n=10), and pelvic exenteration (n=6) were performed. The stages of tumors were as follows: no residual tumor (n=4); T2 (n=6); T3–4 (N=9); and T3–4, N1,2 (n=7). Fourteen specimens (54%) had mutated p53, and 10 (71%) had >50% of residual tumor, whereas only two (17%) of the specimens with normal p53 had >50% of residual tumor (P=.018). Eight of the 10 low anterior resections were performed in patients whose specimens expressed normal p53. Conclusion: Our results suggest that the determination of p53 is a factor in predicting tumor response in patients who undergo preoperative chemoradiation therapy for rectal adenocarcinoma.

Composite pelvic exenteration: Is it worthwhile?

BackgroundIn locally advanced pelvic cancer, tumor fixation to the bony pelvis is regarded as unresectable and often inoperable. Few data exist regarding the futility or utility of pelvic exenteration with en bloc resection of involved portions of the bony pelvis.MethodsThirty-four of 625 patients undergoing radical pelvic procedures had an en bloc resection of pelvic organs with portions of the bony pelvis. There were 19 female and 15 male patients, and the median age was 59 years. Primary neoplasms included 19 rectal, 6 cervicouterine, 4 anal, 3 vaginal, 1 sarcoma, and 1 penile. All but three patients underwent preoperative pelvic irradiation. Pelvic exenterations were posterior in 7 patients, anterior in 3, supralevator in 3, and total in 21 patients. Pelvic bony resections included portions of the sacrum-coccyx in 18 patients, ischium in 5, pubic symphysis in 4, and ischial pubic rami in 4, and hemipelvectomy was performed in 3.ResultsSurgical morbidity occurred in 67.6% (23) of 24 patients. Median follow-up was 37 months. Pelvic or perineal tumor recurrence was concurrent with distant metastases in 9 patients (26.4%); 6 (17.6%) had only distant relapse, and 2 (5.8%) died with local recurrence alone. Overall cancer-related mortality rate was 50%. Five-year overall and cancer-specific survival rates were 44% and 52%, respectively.ConclusionsSubstantial survival can be accomplished for patients whose tumors are fixed to limited portions of the bony pelvis. These procedures are still associated with substantial morbidity, but operative mortality is infrequent.

Preoperative Chemoradiation Therapy and Anal Sphincter Preservation with Locally Advanced Rectal Adenocarcinoma

Preoperative irradiation has been used to produce tumor regression and allow complete resection of rectal cancer with a sphincter-saving procedure. To evaluate the associated toxicity, the response in the primary tumor, and the postsurgical morbidity in a group of patients with locally advanced rectal cancer treated with preoperative chemoradiation therapy and low anterior resection, 120 patients were treated with 45 Gy of preoperative radiotherapy and a bolus infusion of 5-fluorouracil 450 mg/m2 on days 1 to 5 and 28 to 32 of radiotherapy. Four to six weeks later, 16 lesions were found unresectable; 36 patients underwent abdominoperineal resection or pelvic exenteration, and in the remaining 68 a low anterior resection was performed. For the purpose of this study only the latter group was included. There were 38 men and 30 women, with a mean age of 54.7 ± 13.1 years. Gastrointestinal and hematologic acute toxicity grade 3 to 4 occurred in 12 and 7 patients, respectively. The mean distance of the tumor above the anal verge was 8.2 ± 2.6 cm. In 10 patients the surgical resection included neighboring pelvic organs; 16 patients (23.5%) required a temporary diverting colostomy. The main causes of surgical morbidity were clinical anastomotic leakage in seven (10%), abdominal wall infection in five (7.4%), anastomotic stenosis in three (4.5%), and intraabdominal abscess in one (1.5%). No operative deaths occurred. The postsurgical stages were as follows: no tumor in the specimen, 17 (25%); T1, 4 (6%); T2, 12 (17%); T3, 17 (25%); T4, 5 (7%); any T with N+, 9 (13%); and any T, N with M+, 4 (6%). The median and mean follow-ups were 30.0 months and 37.4 ± 25.0 months, respectively. The local recurrence rate was 2.9%, and the distant recurrence rate was 17%. The administration of preoperative chemoradiation therapy for locally advanced rectal cancer is associated with tolerable toxicity, a high rate of response in the primary tumor that allowed anal sphincter preservation, and a low rate of local recurrence.

Patterns of recurrence following pelvic exenteration and external radiotherapy for locally advanced primary rectal adenocarcinoma

AbstractBackground: Local recurrence remains the main site of failure after pelvic exenteration for locally advanced primary rectal adenocarcinoma. This is a report on the patterns of recurrence in a group of such patients treated with pelvic exenteration and radiotherapy. Methods: Between 1980 and 1992, we treated 49 patients. Thirty-one received preoperative radiotherapy (pre-RT), 4,500 cGy. Six weeks later, we performed posterior pelvic exenteration (PPE) in 21 patients, and total pelvic exenteration (TPE) in 10. Nine patients received postoperative radiotherapy (post-RT), 5,000 cGy after a PPE. Nine patients had surgery only, PPE (n=7) and TPE (n=2). Results: Surgical mortality occurred in 16% of those patients who received pre-RT. The median follow-up was 52 months. Recurrences occurred in 23% of those patients who received pre-RT (local, one; local/distant, one; distant, four); in 88% of those patients treated with surgery only (local/distant, four; distant, four); and in 11% of those treated with post-RT (distant, one). The 5-year survival for patients who received radiotherapy was 66 versus 44% for those treated with surgery only. Conclusion: Local control of locally advanced primary rectal adenocarcinoma requiring a pelvic exenteration is improved by the addition of radiotherapy. When recurrences do occur they are predominantly at extrapelvic sites.

Thrombocytosis as a predictor of distant recurrence in patients with rectal cancer.

BACKGROUND AND AIMS Thrombocytosis is frequently observed in patients with malignancy. We undertook this study to determine the prognostic value of thrombocytosis in patients with rectal cancer. METHODS We performed a retrospective study of patients undergoing low anterior resection for rectal cancer between January 2000 and March 2007. Preoperative platelet count was measured before surgery. Postoperative platelets were determined 1 month after surgery. Two-tailed p values <0.05 were considered statistically significant. RESULTS One hundred sixty three patients with rectal cancer were included in the study. Preoperative platelet count >350,000 was found in 8% of patients. Postoperative platelet count >350,000 was found in 6% of patients. Distant metastases were found in 17 patients (10.4%). Significant variables in the multivariate analyses were preoperative platelets >350,000 (p = 0.001), postoperative platelets >350,000 (p = 0.002), carcinoembryonic antigen >13 ng/dL (p = 0.003). Patients with preoperative platelet count <350,000 showed a 5-year survival rate of 81%, whereas patients with platelet count >350,000 had a 25-month survival [95% confidence interval (CI): 20-26]; p <0.001. Patients with postoperative platelets <350,000 showed a 5-year survival rate of 80%, whereas patients with platelets >350,000 showed a 3-year survival rate of 37.5% (p <0.05). CONCLUSIONS Pre- or postoperative platelet count >350,000 is associated with poor survival in patients with rectal cancer. The measurement of platelets is a clinical marker useful to define the prognosis for patients with rectal cancer.

Inguinal lymph node metastases from rectal adenocarcinoma.

The prognosis of patients with inguinal lymph node metastases from rectal adenocarcinoma is poor. The purpose of this study is to analyze the clinical behavior and response to different therapies in a group of these patients.

Anorectal malignant melanoma

BACKGROUND Great controversy exists with regard to the best surgical therapy for anorectal malignant melanoma. MATERIALS AND METHODS Between 1980 and 1996, 15 patients with anorectal malignant melanoma were treated. The recurrence pattern after therapeutic intervention and their survival were evaluated. RESULTS There were nine females and six males, their mean age was 66.3 years. At diagnosis their disease stages were: I (n=7), 11 (n=3) and III (n=5). Patients with stage I disease were treated with abdominoperineal resection (APR) (n=6) and local excision (n=1); their average tumour size and thickness were: 4.7 cm and 6.4 mm respectively; their median follow-up and disease-free survival were 11 months and 7 months respectively; their recurrence pattern was: local (n=6), inguinal (n=4) and distant (n=6). Those patients with stage II and III disease were treated with transverse colostomy (n=6); two of them received 50 Gy of radiotherapy and local excision plus interferon alpha-2b (n=2), all had progressive distant disease. Patients with stage I disease had a median survival of 12 months compared with 5 months for those with stages II and III (P=0.10). The overall 5-year survival was 0%. CONCLUSION The recurrence pattern in anorectal malignant melanoma is mainly at distant sites. The role of APR in maintaining local control over tumours larger than 4 cm or thicker than 5 mm remains elusive.

Medial thigh myocutaneous flap for covering extended hemipelvectomy

When a large tumour involves the buttock and anterolateral upper thigh, modifications to the classical hemipelvectomy may be required for its removal. Herein, we report the use of a medial myocutaneous flap for coverage of soft tissue defects produced by such procedures.