F. Crucitti

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 entered 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.

The Italian registry for adrenal cortical carcinoma: Analysis of a multiinstitutional series of 129 patients

BACKGROUND Adrenal cortical carcinoma is an uncommon tumor with a poor prognosis. The low incidence of this tumor makes it difficult to achieve reliable data on clinical manifestations, natural history, and the impact of therapies. The purpose of this study was to evaluate such aspects in a large series. METHODS A retrospective series of 129 cases (55 men and 74 women, mean age of 49 years) was collected from 18 surgical institutions. At the time of diagnosis 45.7% of patients had endocrine symptoms. One hundred twenty-four patients underwent surgery, which was considered curative in 91 cases and palliative in 33. Sixty-three patients had local disease, 48 had regional disease, and 43 had distant metastases. RESULTS This study confirmed a higher incidence in the 40- to 50-year-old population with a female prevalence; hormonal hyperincretion was more common in women, but it was not caused by advanced disease. The overall 5-year survival rate was 35%. Tumor stage and curative resection affected prognosis significantly. The influence of gender, side, age, and hormonal function has not been confirmed. Adjuvant therapies were ineffective in prolonging survival. Reoperated patients experienced better survival (mean, 41.5 months) than nonreoperated cases (mean, 15.6 months). CONCLUSIONS The poor prognosis of adrenal cortical carcinoma may be improved by early diagnosis and complete resection. Radical surgery is the sole effective therapy, particularly in early stages. Surgical treatment of recurrence seems to improve survival and should be attempted systematically. Adjuvant therapies obtained contrasting results, and their role should be evaluated in prospective multicentric trials.

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 used 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 (37.5vs. 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=p.pr) 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 Collers and Tangs classifications confinrmed 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 downstage the tumor and exclude the patient from adjuvant therapies, with detrimental effects on the outcome of the case.

Role of reoperation in recurrence of adrenal cortical carcinoma: results from 188 cases collected in the Italian National Registry for Adrenal Cortical Carcinoma.

BACKGROUND Recurrence of adrenal cortical carcinoma (ACC) after radical surgery is a common finding. Although successful reoperations have been reported with encouraging results, most published experiences are anecdotal and based on few cases. We report the results of surgical treatment for recurrent ACC in a multiinstitutional series. METHODS One hundred eighty-eight cases of ACC were collected in a national registry. A complete follow-up was obtained in 179 cases. At initial diagnosis 92 patients had local disease (stage I or II). One hundred seventy patients underwent surgical treatment, considered radical in 140; in this group, recurrent disease was observed in 52 cases (37%) after a mean disease-free interval of 21.7 months. RESULTS Adjuvant chemotherapy was ineffective in ameliorating the prognosis. The mean survival in 20 patients who underwent reoperation was significantly higher (15.85 +/- 14.9 months) than in nonreoperated cases (3.2 +/- 2.9 months). Five-year actuarial survival in reoperated patients is significantly better than in nonreoperated patients (49.7% versus 8.3%, respectively). CONCLUSIONS Although the prognosis of this tumor is still poor, surgery is the only effective therapy; reoperation allows survival comparable to that observed in patients without recurrent disease. An aggressive strategy for recurrent ACC is advisable until prospective studies demonstrate a real effectiveness for chemotherapy.

Extracorporeal shock wave lithotripsy of pancreatic stones in chronic pancreatitis: immediate and medium-term results

BACKGROUND Obstruction of the main pancreatic duct with upstream hypertension and dilation is a cause of pain in patients with chronic pancreatitis. Pancreatic ductal drainage can be achieved endoscopically by intraductal stone removal after endoscopic pancreatic sphincterotomy and/or by insertion of a pancreatic stent. Extracorporeal shock wave lithotripsy may be needed whenever stones cannot be removed by endoscopic procedures. We present our results in 35 patients treated with a combined endoscopic-extracorporeal shock wave lithotripsy approach with at least 6 months of follow-up. METHODS Thirty-five patients with severe chronic pancreatitis were treated by extracorporeal shock wave lithotripsy for endoscopically unretrievable obstructive stones. Extracorporeal shock wave lithotripsy was performed with an electromagnetic lithotriptor in 29 patients and an electrohydraulic lithotriptor in 6. RESULTS The procedures were well tolerated by the majority of patients. Fragmentation of stones was obtained in all cases while complete clearance and decompression of pancreatic duct were obtained in 26 of 35 (74.3%) and in 30 of 35 (85.7%) cases, respectively. There was no mortality related to the procedure. Morbidity was observed in 8 of 35 patients (22.8%). CONCLUSIONS Extracorporeal shock wave lithotripsy is a safe and effective treatment for endoscopically unretrievable pancreatic stones in the main pancreatic duct. Extracorporeal shock wave lithotripsy should be considered complementary and not an alternative to endoscopic drainage. Combined with endoscopy, extracorporeal shock wave lithotripsy may increase the success rate of nonsurgical treatment of patients with chronic pancreatitis.

Epidermal growth factor receptor in human breast cancer: correlation with steroid hormone receptors and axillary lymph node involvement

Epidermal growth factor (EGF-R) estrogen (ER) and progesterone (PR) receptors were evaluated in 89 primary breast cancers and 23 axillary lymph node metastases. About 57% of primary and 72.2% of metastatic tumors were EGF-R positive and median EGF-R levels were higher in metastatic deposits than in primary breast tumors (P less than 0.05). An inverse distribution of EGF-R and steroid hormone receptor positive tumors was found (chi 2 = 10.87; P less than 0.001 for PR and chi 2 = 5.01; P less than 0.05 for ER) and an interesting correlation between EGF-R expression in primary tumor and axillary lymph node involvement was demonstrated (chi 2 = 21.4; P less than 0.001). Immunohistochemical studies with a monoclonal antibody against EGF-R revealed the presence of EGF-R only in malignant cells. Our data suggest that EGF-R could identify a class of more aggressive breast tumors endowed with a higher metastatic potential and may therefore represent an unfavorable prognostic parameter in breast cancer.

Adrenal cystic lesions: Report of 12 surgically treated cases and review of the literature

Adrenal cysts are rare (0, 064%–0, 18% in autopsy series) and less than 500 cases have been reported in the western literature. Incidental diagnosis of adrenal cysts, however, is reported with increasing rates. We observed 12 patients with adrenal cyst. Each of them had a careful laboratory and instrumental evaluation; all the patients were operated. In our series about 67% of the patients were symptomatic (6 patients with abdominal pain, 1 with palpable mass, 1 with hemorrhagic shock). No biochemical alteration was observed. Conversely we observed an unusual subclinically hyperfunctioning cystic adenoma, potentially progressive to a clinically recognizable endocrine syndrome. US, CT and MRI had a sensitivity of 66, 7%, 80% and 100% respectively. Adrenalectomy was performed in all patients. The pathological findings were: 1 epithelial cyst (cystic adenoma), 2 endothelial cysts (vascular cystic ectasia with adenomatous adrenocortical hyperplasia and 1 vascular cyst) and 9 pseudocysts. On the basis of these results, we conclude that a careful hormonal, morpho-functional and instrumental evaluation is indicated in all adrenal cysts, even if the available diagnostic procedures, even when combined, cannot always define their nature. Surgical excision, when possible by laparoscopic approach, is indicated in presence of symptoms, endocrine abnormalities (even when subclinic), complications, suspicion of malignancy and/or large size (>5 cm). Adrenal gland must be excised en bloc, also because of the possible presence of other adrenal lesions.

Diagnostic delay in breast cancer: correlation with disease stage and prognosis

Diagnostic delay in a group of 189 women with breast cancer was studied and correlated with first symptom, stage of disease, histologic grade and prognosis. Diagnostic delay was divided into patient delay (time from the patients discovery of a symptom to the first medical consultation) and system delay (time from medical diagnosis to treatment). Patients were divided into five groups by patient-delay time: 0 to 30 days; 31 to 90 days; 91 to 180 days; 181 to 365 days; and > 365 days. The median diagnostic delay was 60 days (range, 4-980) and was not influenced by patient age, marital status or nature of first symptom. A consistent and direct relationship was found between delay and tumor size, nodal involvement, presence of metastases, and histologic grade of disease at diagnosis. No correlation was found between diagnostic delay and histologic type distribution. The three-year survival rate after treatment was significantly lower for patients with a longer delay. Our data indicate that diagnostic delay appears to be an important determinant of stage at diagnosis in women with breast cancer and that it has an important influence on survival. In most cases, delay was mainly patient dependent (60 days); the median system-dependent delay was 15 days (range, 4-47). Since early treatment is generally accepted to be one of the most important determinants of prognosis in breast cancer patients, a reduction in diagnostic delay may lengthen survival time.

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-rascodons 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-rascodon 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-rascodons 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-rasalterations 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.

Surgery: Independent Prognostic Factor in Curable and Far Advanced Gastric Cancer

Abstract. The hospital records of 639 patients affected by primary gastric cancer who were consecutively admitted to our unit during the period 1981–1995 were reviewed. Overall 220 underwent total gastrectomy (38 palliative), 12 had resection of the gastric stump, 195 had distal subtotal gastrectomy (55 palliative), 78 had bypass procedures, 72 had explorative laparotomy, and 62 had no operation. Univariate and multivariate analyses were used to evaluate 5-year survival with respect to the main clinical, pathologic, and treatment variables after both curative and palliative treatments. Overall the 5-year survival after curative treatment (320 patients—operative mortality excluded) was 55.5%: 91.1% for stage IA, 71.5% IB, 62.4% II, 37.5% IIIA, 31.5% IIIB. Among patients who underwent palliative treatment 5-year survival was 13.1% after gastric resection (total or distal subtotal), 4.9% after the bypass procedures, 0 after explorative laparotomy, and 0 after no operation. Univariate and multivariate survival analyses showed that variables independently associated with poor survival were advanced stage, upper location and D1 lymphadenectomy after curative treatment, tumor spread to distant sites, and nonresectional surgery after palliative treatment. Multivariate analysis showed that even though survival with gastric cancer depends on predetermined factors, the type of surgery can have a significant effect on prognosis after both curative and palliative treatment.