Sonia Labastida

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.

Risk of nodal metastases from malignant salivary gland tumors related to tumor size and grade of malignancy

Indications for elective treatment of the neck are not well defined in salivary gland tumors. We retrospectively reviewed 153 cases of malignant salivary gland tumors treated from 1965 to 1985 at the Hospital de Oncología, Mexico City. There were 106 parotid cancers, 26 in the submandibular gland and 21 in minor salivary glands. Median follow-up was 48 months. In T1-2 tumors there was a 12% incidence of nodal metastases as compared with 27% in T3-4 cancers (P = 0.01). Thirty-six elective neck dissections were performed. Patients with high-grade tumors had an increased risk (50%) of occult node metastases, while no cases were found in low-grade carcinomas (P < 0.05). The risk of neck recurrence was higher in N+ (23.5%) than in NO patients (3.2%). The 5-year actuarial survival was significantly better in lowgrade tumors (78%), T1-2 tumors (85%) and negative nodes (63%) than in high-grade neoplasms (49%), T3-4 tumors (35%) and positive nodes (36%) (P = 0.001, P = 0.001 and P = 0.04, respectively).

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.

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.

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.

Oral feeding after total laryngectomy for endolaryngeal cancer

There is still no agreement about the beginning of oral feedings after total laryngectomy. Some authors begin routine feedings on the 3rd postoperative day, while others delay oral feedings until 12–14 days after surgery. The present study was devised as a prospective randomized clinical trial concerning beginning oral feedings on the 7th or 14th postoperative day in 35 patients following total laryngectomy as treatment for endolaryngeal cancer. There were no differences in risk factors present in either group. Only two pharyngocutaneous fistulae occurred in the overall series (5.7%), with both appearing in the 7-day group and developing on the 18th and 20th postoperative days respectively. There were no statistically significant differences in fistula formation between the two groups (P = 0.49). We conclude that it is not necessary to delay oral feedings more than 7 days in patients without suture line tension.

Colorectal sarcoma: analysis of failure patterns.

Background and Objectives: Colorectal sarcomas (CRS) are rare and their treatment remains controversial, especially for those located in the rectum. The aim of this paper is to evaluate our experience, with special emphasis on the failure pattern after surgical therapy alone or combined with postoperative radiotherapy.

Quality control in planning and technique of radiotherapy with cobalt-60 for T1 glottic cancer increase local control and organ preservation

BACKGROUND In order to evaluate whether individualized technique and dosimetry of radiotherapy increase local control, organ preservation, and survival of patients with T1 glottic cancer, we reviewed 76 cases treated from 1979 to 1993. METHODS Group A included 32 patients treated from 1979 to 1989 with different techniques, based on clinical aspects. Group B included 44 patients treated from 1990 to 1993 with individualized technique according to tumor extension and patients anatomy. RESULTS Five-year local control with radiotherapy alone was achieved in 53% of group A versus 91% of group B (P > 0.005). Survival was similar in both groups with rescue surgery (90% versus 96%). Five-year survival with larynx preservation was 65% in group A versus 88% in group B (P = 0.02). Most recurrences (78%) appeared within 24 months of follow-up. CONCLUSION Adequate staging, individualized technique, computing planning using simulation and use of immobilization devices during cobalt-60 radiotherapy significantly increase local control and organ preservation in T1 glottic cancer.