Nicola Pietra

Role of follow-up in management of local recurrences of colorectal cancer

PURPOSE: This prospective, randomized, single-center study was designed to evaluate the influence of follow-up on detection and resectability of local recurrences and on survival after radical surgery for colorectal cancer. METHODS: Between 1987 and 1990, 207 consecutive patients who underwent curative resections for primary untreated large-bowel carcinoma were randomly assigned to a conventional follow-up group (Group A; n=103) and to an intense follow-up group (Group B; n=104). All the patients were followed up prospectively, and the outcome was known for all of them at five years. Patients in Group A were seen at six-month intervals for one year, and once a year thereafter. Patients in Group B were checked every three months during the first two years, at six-month intervals for the next three years, and once a year thereafter. RESULTS: Of the 103 patients in Group A, local recurrence was detected in 20; 9 (13 percent) of these patients had colon cancer, and 11 (29 percent) had rectal cancer. Of the 104 patients in Group B, local recurrence was detected in 26; 12 (16 percent) of these patients had colon cancer, and 14 (45 percent) had rectal cancer. Twelve cases (60 percent) of local recurrence in Group A and 24 cases (92 percent) in Group B were detected at scheduled visits (P<0.05). Local recurrences were detected earlier in patients of Group B (10.3±2.7vs. 20.2±6.1 months;P<0.0003). Curative re-resection was possible in 2 patients (10 percent) in Group A, 1 with colon cancer and 1 with rectal cancer, and in 17 patients (65 percent) in Group B, 6 with colon cancer and 11 with rectal cancer (P<0.01). Of the Group B patients who had curative re-resections of local recurrence, 8 (47 percent) were disease-free and long-term survivors as of the last follow-up, and 2 (11.7 percent) were alive, but with a new recurrence. The 2 patients in Group A who had curative re-resections died as a result of cancer. The five-year survival rate in Group A was 58.3 percent and in Group B was 73.1 percent. The difference is statistically significant (P < 0.02). CONCLUSIONS: Our data support use of an intense follow-up plan after primary resection of large-bowel cancer, at least in patients with rectal cancer.

Gallbladder perforation during laparoscopic cholecystectomy.

Abstract. A matched-cohort analytic study was performed to assess the influence on postoperative morbidity and on long-term outcome of gallbladder perforation (GP) during laparoscopic cholecystectomy (LC) and to determine the existence of risk factors of GP. A total of 1127 consecutive patients who underwent successful LC were included. All patients received a preoperative dose of intravenous antibiotic. If GP occurred, free bile was aspirated, the abdominal cavity was irrigated, spilled stones were retrieved whenever possible, and antibiotic treatment was prolonged. Intraoperative GP occurred in 131 cases (11.6%). The Cox multivariate proportional hazards model showed that the surgeons experience was the only factor associated with a higher risk of GP (p < 0.0001). Patients who had GP were retrospectively matched with 131 patients who did not have perforation. Statistical differences between the two matched groups were found for the median length of surgery: 74 minutes in the GP group versus 61 minutes, p < 0.01). No differences were found for (1) postoperative complications and reoperations (3.8% in GP group vs. 6.1%, and 0% in GP group vs. 0.8%, respectively); or (2) mean postoperative hospital stay (2.9 ± 2.3 days in GP group vs. 2.6 ± 1.6 days). No late consequences occurred that could be attributed to intraoperative GP. The results suggest that the frequency of GP during LC tends to diminish as the surgeon gains experience with this type of surgery. This event does not cause complications if adequate prophylactic antibiotic therapy is administered; spilled stones are retrieved whenever possible, and the abdominal cavity is abundantly irrigated.

Curative surgery for colorectal cancer: Long-term results and life expectancy in the elderly

PURPOSE: The long-term prognosis after curative surgery for colorectal cancer was evaluated in relation to age and life expectancy as a possible basis for assessing the risk to benefit ratios in the elderly. METHODS: Data relating to 1,256 patients operated on from 1976 to 1994 were stored in a computer database prospectively from 1987. Patients were subdivided into four age groups (A=<60 years; B=60–69; C=70–79; D=≥80). Distribution of general contraindications to curative surgery was examined. In the 869 patients who underwent curative treatment (A=206; B=256; C=289; D=118), distribution of tumor stage and elective/emergency surgery and the operative mortality rate were evaluated. Crude and age-corrected survival curves were calculated in 794 patients. The median crude survival of each group was related by gender and tumor stage to demographic life expectancy, assuming as “relative median survival index” the ratio between the two values. RESULTS: General contraindications to curative surgery increased significantly with age. The operative mortality rate was higher in Group D than in Groups A, B, plus C over the total series (P<0.001) and in both elective (P<0.001) and emergency surgery (P<0.05). Intergroup analysis of long-term survival rates showed significant differences between “crude” (P=0.0057) but not age-corrected (P=0.66) curves. The relative median survival index increased with age, up to approximately 1 in the local stages of Groups C and D. CONCLUSIONS: To evaluate long-term results, elderly patients should be compared with unaffected, same-age subjects. Because the risks may be very high, the surgical policy in the elderly should be carefully weighed and related to life expectancy and actual results.

Routine intravenous cholangiography, selective ERCP, and endoscopic treatment of bile duct stones before laparoscopic cholecystectomy

BACKGROUND No procedure has yet been identified as the standard for the detection and management of choledocholithiasis in patients undergoing laparoscopic cholecystectomy. METHODS A prospective study involved 1305 patients undergoing elective laparoscopic cholecystectomy. Intravenous cholangiography was performed on all patients except those with jaundice or cholangitis, acute pancreatitis, or allergy to contrast material. Patients underwent endoscopic retrograde cholangiography (ERC) and endoscopic sphincterotomy when there was a strong suspicion of choledocholithiasis, positive or inconclusive findings on intravenous cholangiography or allergy to contrast material with signs of possible choledocholithiasis. Intraoperative cholangiography was performed when patients did not undergo ERC or intravenous cholangiography and whenever the surgeon was in doubt about biliary anatomy or biliary clearance. RESULTS Two hundred thirty-one patients (17.7%) were referred for preoperative ERC; 14 of them were referred for open surgery because of failure of ERC or sphincterotomy. Only 54 patients underwent intraoperative cholangiography. Bile duct stones, detected in 186 cases (14.2%) (68 of which were asymptomatic), were removed before surgery in 162 cases (87.1%) and during surgery in 20 (10.7%). Self-limited pancreatitis occurred in 3.6% of the patients after sphincterotomy. Laparoscopic cholecystectomy was performed in 98.7% of the cases. The conversion rate was 8% if sphincterotomy had been performed previously, and 3% after standard laparoscopic cholecystectomy (p < 0.001). The morbidity rate was 5% and the mortality rate 0.08%. During the follow-up period 4 patients had retained stones that were treated endoscopically. CONCLUSIONS Preoperative ERC followed by laparoscopy is the best approach to treatment of patients with cholecystolithiasis and suspected choledocholithiasis.

Is Tumour Angiogenesis a Prognostic Factor in Patients with Colorectal Cancer and No Involved Nodes

OBJECTIVE To examine a possible association between tumour angiogenesis and conventional prognostic variables and to assess the prognostic value of the variables examined in patients with colorectal cancer, with no involved nodes. DESIGN Retrospective study. SETTING University hospital, Italy. SUBJECTS 119 patients who had had colorectal cancers resected for cure with no involved nodes between 1985-1990. INTERVENTIONS The three microscopic fields with the most microvessels were identified by immunohistochemical techniques. 10 high-power fields in each area were used for the microvessel count and the mean values indicated the microvessel density. MAIN OUTCOME MEASURES Correlation of microvessel density with conventional prognostic factors, recurrence rates, and survival. RESULTS There was a significant correlation between microvessel density and sex, women having a higher density than men (p < 0.05), but no significant correlations between density and recurrence rates or survival. Multivariate analysis did not indicate that microvessel density had a prognostic role. CONCLUSION Microvessel density in colorectal cancer without involved nodes does not correlate with conventional prognostic factors and provides no prognostic information.

Gallstone Ileus: Laparoscopic-Assisted Enterolithotomy

Although longevity in Western countries has probably increased the prevalence of gallstone ileus,1 this disorder remains a rare, often unrecognized, cause of gastrointestinal mechanical obstruction, accountable for no more than 4% of cases.1-3 The advanced age of the patients, the frequent concomitant presence of severe medical diseases, and the delay before surgical treatment contribute to high morbidity and mortality rates, ranging from 11 to 75% and from 8 to 20%, respectively.2,4 Although consensus has not been reached as to the emergency surgical procedure for gallstone ileus, especially regarding the timeliness and timing of biliary surgery,5 a simple enterolithotomy is considered to be the procedure of choice by most authors.1,2,6 To optimize results, the operation should be expeditious and surgical trauma kept to a minimum. We use the videolaparoscopic approach, described here, in the treatment of three cases of gallstone ileus.

Five-year Prospective Audit of Routine Intravenous Cholangiography and Selective Endoscopic Retrograde Cholangiography with or without Intraoperative Cholangiography in Patients Undergoing Laparoscopic Cholecystectomy

Consensus has never been reached regarding the need or the imaging technique for evaluating the common bile duct (CBD) in patients considered for cholecystectomy. With the advent of laparoscopic cholecystectomy there has been a resurgence of interest in the role of preoperative intravenous cholangiography (IVC) as an alternative for evaluating the CBD. The purpose of this audit was to assess whether a diagnostic workup based on IVC, which permits selective use of intraoperative cholangiography (IOC) and endoscopic treatment of CBD stones before surgery, could be useful in patients undergoing laparoscopic cholecystectomy (LC). In patients without jaundice, gallstone pancreatitis, a prior diagnosis of CBD stones, a prior history of contrast allergy, or a risk of contrast-associated acute renal failure, IVC was performed routinely. Patients suspected to have CBD stones based on IVC results or with inconclusive IVC and patients with a strong clinical suspicion of CBD stones were referred for endoscopic retrograde cholangiography (ERC). IOC was carried out in patients who had a history of contrast allergy or risk of contrast-associated acute renal failure and whenever the surgeon was in doubt as to the biliary anatomy or CBD clearance. IVC was carried out in 1155 patients, ERC in 225, and IOC in 54. IVC was conclusive in 1132 patients, with a diagnostic accuracy of 99%. Our workup permitted the sequential endoscopic-laparoscopic treatment of cholecystocholedocholithiasis in 162 cases. During the follow-up period residual CBD stones were detected in four patients. Our diagnostic workup showed that routine IVC exposes the population to a large radiation burden, and the cost is high for the small number of patients who benefit. Moreover, it does not seem helpful in reducing the incidence of CBD injuries during LC.

Reduced Postoperative Morbidity after Elective Laparoscopic Cholecystectomy: Stratified Matched Case-Control Study

Abstract. To answer the question whether laparoscopic cholecystectomy (LC) or open cholecystectomy (OC) is safer in terms of complications and to what extent the “learning curve” influences the frequency of complications after LC, we conducted a matched case–control study. First, 200 patients undergoing LC (LC group A), and two groups of 200 patients undergoing LC at two different periods of the learning curve (LC groups B and C) were matched, taking into account sex, age, anesthesiologic risk, and surgical difficulties. We evaluated the frequency and grade of postoperative complications of these patients and of the last 200 patients undergoing OC before the introduction of LC, retrospectively matched with the LC groups. The total rate of complications in the OC group was 16.0% compared with 5.5% in the LC groups (p < 0.003); the difference was particularly significant for complications classified as grade I, in female patients, those younger than 70, those with low anesthesiologic risk (ASA), and those after cholecystectomy without surgical difficulties. Matched case–control analysis revealed that the complication rate in the LC group significantly decreases with experience (p < 0.01). We conclude that LC is today the treatment of choice for symptomatic cholelithiasis and is replacing OC as the gold standard against which new therapies should be compared.

Prognostic value of ploidy, cell proliferation kinetics, and conventional clinicopathologic criteria in patients with colorectal carcinoma: A prospective study

PURPOSE: The aim of this study was to obtain additional biologic determinants that may be of use in segregating into subgroups with different prognosis patients with similarly staged colorectal cancers. METHODS: Between 1989 and 1991, a prospective study of prognostic factors has been performed in a group of 98 consecutive, unselected patients who underwent curative resections for primary untreated large bowel carcinoma. The fate of all patients is known at three years after operation. Clinical and pathologic data were recorded at the time of presentation and operation, and patients have been the subjects of regular follow-up. Tumor DNA content was determined by flow cytometry, and cell proliferative activity was determined by autoradiography with tritiated thymidine labeling index (LI). RESULTS: Univariate analysis revealed that the most important predictors of survival (P<0.001) were the presence of positive lymph nodes, the presence of preoperative complications, Dukes stage, and LI. The multivariate analysis showed that Dukes stage (P<0.002) and LI(P<0.0001) were the only factors significantly related to survival. Disease-free survival was influenced significantly by Dukes stage (P<0.001), LI, according to the classification in the two groups of high and low proliferative activity, respectively, (P<0.0001), LI, calculated as a continuous variable (P<0.0002), and the presence of lymph node metastases (P<0.003). Outcome (favorable/unfavorable) was influenced significantly by Dukes stage (P<0.0001) and LI (P<0.0001). Concordance for each patient between Dukes stage and outcome was 73.1 percent and between LI, calculated as a continuous variable, and outcome was 74.1 percent. If, on the other hand, Dukes stage and LI are used together, concordance with outcome reaches 89.2 percent. CONCLUSION: We can conclude that, from a practical point of view, LI is an essential factor that must be combined with pathologic variables for a better prediction of patient outcome.

DNA content in human colon cancer and non-neoplastic adjacent mucosa.

DNA content was determined by flow cytometry in a series of 51 paired fresh tissue samples of primary colorectal carcinomas and the respective non-neoplastic adjacent mucosa in order to assess the relationship between DNA ploidy and the most commonly used prognostic factors. Aneuploidy was observed in 70.6% of the tumors and more than one aneuploid peak was present in 3.9%. Aneuploid tumor frequency was higher in left (93.3%) and right colon (64.7%) cancers than in rectal carcinomas (60.0%), and multiple aneuploid clones were detected more frequently in men than in women and in patients with advanced disease (Dukes stage D). Non-neoplastic mucosa adjacent to aneuploid tumors showed aneuploidy in 4 out of 51 samples (7.8%). The mucosa adjacent to diploid cancers had only diploid characteristics. Polidy did not correlate with histological abnormalities. These findings suggest that DNA content as determined by flow cytometry needs further study with adequate follow-up to evaluate possible correlations with relapse-free and overall survival. Furthermore the aneuploidy of non-neoplastic mucosa provides evidence for a field defect in mucosa adjacent to colorectal cancer and supports the concept that this alteration may be of influence on carcinogenesis.