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Biomedical subjects

L Sofo

Publications and source records attributed to L Sofo.

At least 19 recordsLinked to original sources
PubMed2001

Preoperative chemoradiation with raltitrexed ('Tomudex') for T2/N+ and T3/N+ rectal cancers: a phase I study.

The use of raltitrexed ('Tomudex') as concomitant chemotherapy during preoperative radiotherapy in chemonaïve patients with stage II/III rectal cancer has been examined in this study and its recommended dose in conjunction with radiotherapy investigated. Forty-five Gray (Gy) of radiotherapy (1.8 Gy daily, 5 days per week) was delivered to the posterior pelvis, followed by a 5.4 Gy boost. Single doses of raltitrexed (2.0, 2.5 and 3.0 mg/m(2)) were administered on days 1, 19 and 38. Only 1 of the 15 patients entered experienced a dose limiting toxicity (DLT) (grade 3 leucopenia) at the 3.0 mg/m(2) dose level. The overall response rate was 80% (five complete responses, seven partial responses). These preliminary data suggest that raltitrexed is a well tolerated and effective treatment when combined with preoperative radiotherapy in patients with stage II/III rectal cancer. The recommended dose of raltitrexed for future phase II studies will be 3.0 mg/m(2).

Adenocarcinoma↗
PubMed2000

How can the assessment of fistula-inano be improved?

PURPOSE: Fistula-in-ano anatomy and its relationship with anal sphincters are important factors influencing the results of surgical management. Preoperative definition of fistulous track(s) and the internal opening play a primary role in minimizing iatrogenic damage to the sphincters and recurrence of the fistula. METHODS: Physical examination and endoanal ultrasound (performed with a 10 MHz endoprobe), either conventionally or with an injection of hydrogen peroxide, were performed in 26 consecutive patients. Results were matched with surgical features to establish their accuracy in preoperative fistula-in-ano assessment. RESULTS: Accuracy rates of clinical examination endoanal ultrasound, and hydrogen peroxide-enhanced ultrasound were 65.4, 50, and 76.9 percent for primary tracks, 73.1, 65.4, and 88.5 percent for secondary tracks, and 80.8, 80.8, and 92.3 percent for horseshoe extensions, respectively. Compared with physical examination and endoanal ultrasound, accuracy of hydrogen peroxide-enhanced ultrasound was higher for transsphincteric and intersphincteric primary tracks and horseshoe extensions. Both endoanal ultrasound and hydrogen peroxide-enhanced ultrasound displayed a significantly higher accuracy in detecting the internal openings (53.8 and 53.8 percent, respectively) compared with clinical evaluation (23.1 percent; P = 0.027). CONCLUSIONS: Our data suggest that hydrogen peroxide-enhanced ultrasound can be very reliable and useful in the definition of fistula anatomy, its relationship with anal sphincters, and, hence, surgical strategy. It also improves identification of secondary extensions, particularly horseshoe tracks. This method, besides being safe, economic and reputable, both preoperatively and postoperatively, could be helpful in checking operative results and recurrence.

Adult↗
PubMed1999

Accurate lymph-node detection in colorectal specimens resected for cancer is of prognostic significance.

PURPOSE: Lymph-node involvement is the most important prognostic factor in colorectal cancers. Many staging systems adopted node status as a parameter of tumor classification. However, the number of identified and positive glands varies across articles, depending on specimen examination. There is a consistent risk of substaging tumors and undertreating patients. Aim of this study was to investigate the prognostic significance of different pathologic methods. METHODS: Eight hundred one patients who underwent curative resection of colorectal cancer entered the study and were divided into two groups. In Group 1 the specimen was "en bloc" fixed, and nodes were identified by sight and palpation. In Group 2 the mesentery of the excised specimen was dissected away from the bowel, stretched, and pinned to cork board. The mesenteric segment surrounding the origin of principal vessels was divided from the segment surrounding the colic vessels. All specimen segments were fixed, node identification being performed by sight and palpation. Examined and positive nodes were recorded, and metastatic rate and incidence was calculated in the two groups. Patients were classified with use of different staging systems. Survival rates were calculated, related to tumor stage, and compared statistically. Pathologic procedures were included in a multivariate analysis. RESULTS: A significantly higher number of detected and positive nodes and metastatic rate (37.5 vs. 30.2 percent; P < 0.05) were observed in Group 2; 45.2 percent of Group 2 and 25.3 percent of Group 1 cases had more than three positive nodes (P < 0.05). In Group 2 several patients shifted from earlier to more advanced stages compared with Group 1 cases. Five-year and ten-year survival rates were significantly higher (P = 0.04) in Group 2 (81.5 and 77.2 percent) than in Group 1 (76.7 and 61.5 percent), mostly in patients with TNM Stage N0. Survival analysis related to Astler and Coller's and Tang's classifications confirmed such features. Higher rates of local recurrences and distant metastases were found in Group 1, particularly if related to node status (P < 0.05). Multivariate analysis demonstrated the pathologic method is an independent prognostic factor. CONCLUSIONS: This study demonstrates the prognostic impact of specimen examination. Inaccurate methods could down-stage the tumor and exclude the patient from adjuvant therapies, with detrimental effects on the outcome of the case.

Adult↗
PubMed1998

Prognostic factors in colorectal cancer. Literature review for clinical application.

PURPOSE: Identification of prognostic factors is a primary basis for planning the treatment and predicting the outcome of patients with colorectal cancer. Reviewing studies from the literature performed using univariate and multivariate analyses and their own study, the authors critically discuss the prognostic value of the clinicopathologic parameters of the tumor. METHODS: Among 853 patients with colorectal tumors seen at the Department of Clinical Surgery of the Catholic University of Rome, Italy, 690 cases that were curatively resected the study. Overall survival rate, related to the clinicopathologic variables, was calculated, and univariate and multivariate analyses were performed. RESULTS: Five-year and ten-year overall survival rates were 70 and 55 percent, respectively. Univariate and multivariate analyses showed that node involvement, distant metastases, bowel obstruction, and patient gender are factors independently related to outcome. CONCLUSIONS: Data from the literature and the present study suggest that only a few clinical parameters, particularly bowel obstruction, and some pathologic factors (tumor stage, vessels invasion, and tumor ploidy) are related to patient survival rate and are the most reliable prognostic criteria. In prospective clinical studies, any other new pathologic or molecular factors should be matched with these parameters to confirm their value in outcome prediction.

Adult↗
PubMed1997

[The anal canal: 2 cycles of radiochemotherapy and boost brachytherapy].

From 1988 to 1996, twenty-six patients with epidermoid anal cancer were examined at the Radiotherapy Department of Università Cattolica del S. Cuore, Rome. At diagnosis, 13 patients were stage II, 11 patients were stage III, 2 patients had a small recurrence after local excision. All the patients were treated with concomitant radiochemotherapy followed by a brachytherapy boost. Treatment was carried out in two cycles 4-5 weeks apart. Chemotherapy consisted of 5FU (1,000 mg/sqm, continuous infusion over the first 4 days) and Mitomycin C (10 mg/sqm on day 1, bolus administration). Radiotherapy was administered with two AP opposed coaxial beams of the same size. The target was T and inguinal, external, internal and common iliac lymph nodes. The total dose for each cycle was 23.4 Gy, administered with conventional fractionation and a daily dose of 180 cGy. Four-six weeks after the end of cycle 2, the patients received a boost of interstitial brachytherapy. During concomitant radiochemotherapy, grade 3-4 (RTOG-EORTC scale) acute hematologic and cutaneous toxicities were observed in 15% and 4% of patients, respectively; treatment was discontinued in 4 patients. Complete response was observed in 21 patients (81%) and partial response in 5 (19%). The later underwent surgery, namely local excision in 1 patient and abdominoperineal resection in 4 patients. The median observation period of our study population was 45 months. Five-year actuarial local control of the 26 patients was 88%. Five year actuarial survival was 75% and sphincter conservation 77%. Our results confirm the data reported by Cummings of Princess Margaret Hospital, who observed low toxicity when the two cycles of concomitant radiochemotherapy are split. Randomized phase-III studies should clarify the potential role of the new radiochemotherapy combinations which should be compared with reference treatments providing repeatable results and low toxicity. Our treatment may make a reference for more innovative combinations of radiochemotherapy.

Adult↗
PubMed1996

Intraoperative radiation therapy in integrated treatment of rectal cancers. Results of phase II study.

PURPOSE: Risk of local recurrence of rectal cancer remains high despite extensive therapeutic strategies, many of which have been tried to achieve better local control (i.e., external beam radiation therapy (EBRT)). Recently, intraoperative radiation therapy (IORT) has been introduced in clinical protocols to boost the areas at risk of local recurrence. METHODS: Between April 1990 and December 1995, 44 patients with "high risk" (T3,N0-2 primary tumors) extraperitoneal rectal tumors and 24 patients with "locally advanced" (2 T3,N3 and 11 T4,N0-3 primary tumors; 11 local recurrences) tumors entered a protocol that included preoperative EBRT (38 Gy), surgery plus IORT (10 Gy) in the high-risk group, and preoperative EBRT (45-48 Gy) and concomitant computerized tomography (5-fluorouracil plus mitomycin C), surgery plus IORT (10-15 Gy), and postoperative adjuvant computerized tomography (5-fluorouracil plus folinic acid) in the locally advanced group. RESULTS: In the high-risk group, acute Grade 3 (Radiation Therapy Oncology Group scale) skin toxicity, attributable to preoperative treatment, involved one patient (2.2 percent); among locally advanced cases, Grade 3 hematologic toxicity was observed in one patient (4.1 percent). Treatment was discontinued in no patients. On average, IORT prolonged surgery by 48 minutes. There was no mortality. Four anastomotic leakages, one pelvic infection, and five wound infections were observed. No chronic IORT-related toxicity occurred. After mean follow-up periods of 28.3 and 25.9 months, 41 and 15 patients in the high-risk and locally advanced groups, respectively, are alive and disease-free. In one high-risk patient, an anastomotic recurrence occurred. In four patients with locally advanced tumors (1 T4 primary, 3 local recurrences) an unresectable tumor relapse developed locally. Distant metastases occurred in two high-risk patients and in eight patients with a locally advanced tumor. Three-year actuarial survival was 100 percent in both high-risk and locally advanced primary tumors and 68.2 percent in local recurrences. CONCLUSIONS: Results of this study suggest that multimodal treatment (including IORT) in rectal cancer is safe, has no significant increase of mortality and morbidity, and also shows a trend for local improvement. A longer term follow-up and larger numbers of patients could demonstrate the therapeutic efficacy of IORT in rectal cancer.

Antimetabolites, Antineoplastic↗
PubMed1996

Detection of oncogene mutation from neoplastic colonic cells exfoliated in feces.

PURPOSE: Best chances of a cure from colorectal cancer are obtained before metastatic spread. Lack of specific tests allowing early diagnosis of the tumor accounts for investigation of gene alterations involved in carcinogenesis by a noninvasive method. In the present study, K-ras codons 12 and 13 mutations were studied in neoplastic cells shed from the bowel into the stool and those contained in the tumor and normal mucosa. Moreover, healthy patients and a few others with precancerous conditions were examined. METHODS: Stool, tumor, and mucosa samples were taken from 25 patients with colorectal adenocarcinoma. Stool and mucosa samples were obtained from 11 healthy patients, and stool, pathologic bowel tissue, and normal mucosa samples were obtained from 3 patients with adenoma (1) or ulcerative colitis (2). Polymerase chain reaction amplification and restriction enzyme analysis were performed. RESULTS: K-ras codon 12 mutations were detected in both tumor and stool samples of 10 cancer patients, and no gene alterations were observed in 14 patients. In one patient with a tumor, a mutation was shown in only the tumor tissue. The agreement rate in tumor and stool analysis was 96 percent. A normal pattern of K-ras codons 12 and 13 was observed in the bowel mucosa. All stool and mucosa samples from healthy patients were not altered in K-ras. Agreement was registered between samples taken from patients with preneoplastic lesions. CONCLUSIONS: These preliminary findings show a high rate of accuracy in the investigation of K-ras alterations in the colorectal cells shed into the feces, suggesting that such an approach could be used to study other gene alterations and, prospectively, to identify early colorectal cancers.

Aged↗
PubMed1996

Prognostic significance of cytoplasmic p53 overexpression in colorectal cancer. An immunohistochemical analysis.

p53 overexpression was studied by immunohistochemistry in 96 consecutive colorectal cancer patients, subdividing positive specimens according to two staining patterns: cytoplasmic or nuclear. Forty-seven per cent of the cases were p53 positive, a significant correlation being found with Dukes' stage (P = 0.0036). A prevalence of nuclear staining was observed in Dukes' B and cytoplasmic in Dukes' D stages. After 36 months, 23% of the patients had a recurrence, and 45% were p53 positive, all Dukes' C-D stage with cytoplasmic staining. The Kaplan-Meier curve showed a significant correlation between p53 cytoplasmic staining and disease-free survival period (P = 0.002). With respect to disease-free survival, the Cox proportional hazard regression test, comparing p53 positivity with Dukes' stage, showed the latter to be the most significant variable. In our series of patients, advanced Dukes' stage tumours were localised in the right colon, where a higher percentage of p53 positivity (67% versus 40% of the left side), as well as a higher frequency of cytoplasmic staining was observed. In conclusion, from the data obtained, a strong correlation between p53 cytoplasmic staining and patient prognosis is clearly indicated.

Adult↗
PubMed1992

Accurate specimen preparation and examination is mandatory to detect lymph nodes and avoid understaging in colorectal cancer.

Lymph node involvement in colorectal cancer, one of the most important prognostic factors, can be sometimes underestimated. In this study the authors report the results of two different techniques of specimen preparation and examination. In 240 patients (Group I), histologic examination was performed using a conventional procedure. In Group II (60 cases) the resected bowel and its mesentery were separately stretched, pinned on to a cork board, and fixed. The mesentery was divided according to node location (intermediate and principal) and evaluated by sight and palpation to identify lymph nodes. The bowel segment was divided from 5 cm proximally to 5 cm distally to the tumor every 10 mm in serial 3 mm slices. Three and 10 mm slices were then carefully examined by sight and palpation. Isolated lymph nodes embedded in groups (10-12 per paraffin block) were stained and investigated for neoplastic involvement. The specimen examination procedure used in Group II resulted in identification of a higher number of lymph nodes (mean = 41.1) and nodal metastases (mean = 10) compared to the standard technique used in Group I (mean = 11.3 and 2.4, respectively--P < .05). The percentage of N+ cases also was increased in Group II (48.3%) when compared to that in Group I (30.4%; P < .05). The new technique is simple, inexpensive, and efficacious for the detection of lymphatic metastases in colorectal cancer.

Colorectal Neoplasms↗
PubMed1992

Effect of omega-3 fatty acids on rectal mucosal cell proliferation in subjects at risk for colon cancer.

The effects of 12 weeks of omega-3 fatty acid supplementation on rectal mucosal proliferation were assessed with [3H]thymidine autoradiography in a double-blind, placebo-controlled study of 20 patients with sporadic adenomatous colorectal polyps. In the group of 10 that received fish oil containing eicosapentaenoic acid (4.1 g/day) and docosahexaenoic acid (3.6 g/day), the mean percentage of replicative "S"-phase cells in the upper part of colonic crypts (considered a reliable marker of colon cancer risk) significantly dropped from the baseline level after only 2 weeks of treatment and remained lower throughout the study period; no change in upper-crypt labeling was observed in the 10 placebo patients. Rectal mucosal eicosapentaenoic acid content increased in fish oil patients, whereas arachidonic acid levels decreased. The fish oil-induced kinetic changes represent contraction of the proliferative compartment to the levels of a low-risk population and may be related to omega-3 fatty acid effects on the arachidonic prostaglandin pathway. In this short-term trial, fish oil appeared to exert a rapid effect that may protect high-risk subjects from colon cancer.

Autoradiography↗
PubMed1991

Receptors for epidermal growth factor and steroid hormones in primary colorectal tumors.

The presence of epidermal growth factor, estrogen, and progesterone receptors (EGFR, ER, and PR) was investigated by a competitive binding assay in 43 colorectal adenocarcinomas and 32 normal colorectal mucosa specimens. EGFR were expressed in most of the tumor specimens analyzed at levels comparable with normal mucosa. There was no correlation between EGFR and tumor localization, tumor size, tumor stage, and grading. Among tumor specimens, 13.9% and 6.9% expressed very low but detectable ER and PR levels, respectively. No statistically significant difference was found between steroid hormone receptor levels in the tumor and normal mucosa specimens, and neither was there any correlation of ER and PR with the pathological findings. Our results suggest that the EGFR system may play a role in regulating the growth of colorectal tissues. Further studies should demonstrate whether, despite the lack of correlation with histopathological parameters, EGFR expression may have a biological significance in human colorectal cancer.

Adenocarcinoma↗
PubMed1991

Prognostic factors in colorectal cancer: current status and new trends.

The clinical, laboratory, and pathologic data of 361 patients who had curative resections for colorectal cancers were collected and analyzed in a multiple stepwise regression model. In univariate analysis, among clinical factors, bowel obstruction and emergency surgery showed the most significant prognostic value (P = 0.002, P = 0.004, respectively). Vegetating growth, Astler-Coller stage of tumor, intramural spread, lymph node involvement, and synchronous liver metastases resulted in the pathologic variable significantly affecting the prognosis (P = 0.006, P less than 0.001, P = 0.036, P less than 0.001, P less than 0.001, respectively). In the multivariate analysis, stage was the predictive factor with the highest hazard ratio in conjunction with bowel obstruction (P less than 0.0001 in both cases). Processing data excluding stage ("multiparametric factor" itself), hepatic metastases, lymph node involvement, bowel obstruction, and intramural spread appeared as independent predictors of survival (P less than 0.0001, P less than 0.0001, P = 0.0004, P = 0.0316, respectively). Other variables, as biologic and molecular factors, should be more widely tested in order to assess their impact on prognosis.

Actuarial Analysis↗
PubMed1991

5-Fluorouracil (FU) with folinic acid (FA) and mitomycin C (MMC) in the adjuvant treatment of colorectal carcinoma. Part I. Evaluation of toxicity.

Ninety-six patients with colorectal cancer (stage B2-C) were randomized to the control arm or to receive adjuvant chemotherapy with folinic acid, FU and MMC. Ninety-three patients are evaluable. The median follow up is 12 months. The average time between surgery and the start of therapy is 28 days. Toxicity is evaluable in 36 of 41 treated patients. Four patients (10%) failed to complete the projected treatment due to toxicity. Toxicity observed in 208 courses of therapy was mostly gastrointestinal and hematological. No cases of treatment related death or cancer-associated hemolytic uremic syndrome (C-HUS) were reported. The average relative dose intensity (rDI) of the projected treatment was 82.6%. Our study is ongoing and further patients are required to achieve statistically significant results.

Antineoplastic Combined Chemotherapy Protocols↗