Luigi Roncoroni

Distinct molecular patterns based on proximal and distal sporadic colorectal cancer: arguments for different mechanisms in the tumorigenesis

Background and aimsColorectal cancer (CRC) ranks as the fourth most frequently diagnosed cancer worldwide. CRCs that arise proximally or distally to the splenic flexure show differences in epidemiologic incidence, morphology, and molecular alterations, suggesting the existence of two categories of CRC based on the site of origin. The aim of the present work is to investigate the histological and molecular differences between CRCs located proximally and distally to the splenic flexure, and their potential involvement in tumor prognosis and therapeutic strategies.MethodsWe evaluated 120 patients affected by sporadic CRC for clinicopathologic features, microsatellite instability (MSI), loss of heterozygosity (LOH) of chromosomes 18q, 8p, and 4p; they were also investigated for hMlh1, hMsh2, Fhit, p27, and Cox-2 immunostaining.ResultsThe mucinous histotype was more frequent in the proximal than in the distal CRCs (p<0.004). The frequency of MSI phenotype was higher in proximal than in distal tumors (p<0.001); moreover, reduced or absent hMlh1, Fhit, p27 immunohistochemical expressions were more frequent in proximal than in distal tumors (p<0.001 and 0.01 for p27). In contrast, the frequency of LOH in 18q was higher in distal than in proximal tumors (p=0.002). No significant differences were observed between proximal and distal tumors in the frequency of LOH in 8p and altered expression of hMsh2 and p53 protein.ConclusionThese different features may reflect different genetic pathways of carcinogenesis and support the hypothesis of a different mechanism of cancer development between the proximal and the distal colon, with potential implications in the therapeutic approach.

Preoperative endoscopic sphincterotomy and laparoscopic cholecystectomy for the management of cholecystocholedocholithiasis: 10-year experience

No procedure has yet been identified as the “gold standard” for the detection and treatment of common bile duct stones (CBDS) in patients undergoing laparoscopic cholecystectomy (LC). This prospective study involves 2137 patients undergoing elective laparoscopic cholecystectomy. The algorithm for diagnostic management in place until July 1997 involved routine intravenous cholangiography and selective endoscopic retrograde cholangiography (ERC). Subsequently, assessment of the bile duct was not routinely performed, but a scoring system was applied to single out those patients at risk of CBDS who should undergo intravenous cholangiography and/or ERC (see Fig. 2). Whenever bile duct stones were found, endoscopic sphincterotomy (ES) was performed, and LC was performed with a standardized four-cannula technique after endoscopic bile duct stone clearance. Common bile duct stones were suspected in 340 patients who were referred for preoperative ERC; 250 patients were referred for ES; 21 patients were referred for open surgery because of failure of ERC or sphincterotomy. Common bile duct stones, detected in 283 cases (13.2%), were removed before surgery in 250 cases (88.3%) and during surgery in 28 cases (9.9%). Self-limited pancreatitis occurred in 4.2% of the patients after sphincterotomy. Laparoscopic cholecystectomy was performed in 98.4% of the cases. The conversion rate was 8.3% if sphincterotomy had been performed previously and 3.4% after standard laparoscopic cholecystectomy (p < 0.001). The morbidity rate was 4.5%; mortality, 0.09%. During follow-up five patients (0.2%) had retained stones endoscopically treated. Future trials of novel strategies for detecting and treating CBDS should compare the results of novel strategies with those of the strategy employed in this study, which includes selective ERC, preoperative ES, and LC.

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.

Palliative resection of colorectal cancer: does it prolong survival?

BackgroundIt is still a matter of debate as to whether resective surgery of the primary tumor may prolong the survival of patients affected by incurable colorectal cancer (CRC). The main goal of this retrospective study, carried out on patients not undergoing any therapy other than surgery, was to quantify the benefit of primary tumor removal in patients with differently presenting incurable CRC.MethodsOne hundred and thirty consecutive patients were operated on for incurable CRC (83 undergoing resective and 47 non-resective procedures). With the purpose of comparing homogenous populations and of identifying patients who may benefit from primary tumor resection, the patients were classified according to classes of disease, based on the “metastatic pattern” and the “resectability of primary tumor.”ResultsIn patients with “resectable” primary tumors, resective procedures are associated with longer median survival than after non-resective ones (9 months vs 3). Only patients with distant spread without neoplastic ascites/carcinosis benefit from primary tumor removal (median survival: 9 months vs 3). Morbidity and mortality of resective procedures is not significantly different from that of non-resective surgery, either in the population studied or in any of the groups considered.ConclusionsPalliative resection of primary CRC should be pursued in patients with unresectable distant metastasis (without carcinomatosis), and, intraoperatively, whenever the primary tumor is technically resectable.

Subtotal colectomy with antiperistaltic cecorectal anastomosis in the treatment of slow-transit constipation: long-term impact on quality of life.

BackgroundThe aim of the study was to evaluate the effectiveness of subtotal colectomy with cecorectal anastomosis (SCCA) in the treatment of slow-transit constipation, not just in terms of symptom resolution but also the overall impact on patients’ quality of life.MethodsBetween 1991 and 2005, 43 patients underwent SCCA at our institution, 22 for slow-transit constipation (STC) and 21 for other types of colic diffuse disease (non-slow-transit constipation: NSTC), the latter being considered controls. A total of 29 patients (17 affected by STC) were administered a 50-item telephonic questionnaire, including the Gastrointestinal Quality of Life Index (GIQLI), the Wexner constipation and incontinence scale (WC, WI), and individual willingness to repeat the procedure. Questionnaire data and other parameters such as age, sex, length of follow-up, complications, and length of hospital stay were analyzed and compared, in order to evaluate possible correlations between the parameters and their related impact on quality of life, procedural effectiveness in terms of symptomatic regression, qualitative differences related to pathology (constipation versus non-constipation), and surgical approach (laparotomy versus video-laparo-assisted procedure).ResultsThere were no procedure-related deaths in this series (mortality: 0%); however, we found two complications in the STC group (9.1%), one requiring reoperation. The GIQLI mean score for the STC group was 115.5 ± 20.5 (mean score for healthy people 125.8 ± 13), and the WC mean score passed from a preoperative value of 20.3 to a postoperative value of 2.6. Regression analysis revealed a significant correlation between GIQLI and urgency and abdominal pain, and abdominal pain correlated significantly with pathology (STC). A high number of patients (88.2% in STC) expressed a willingness to repeat the procedure given the same preoperative conditions.ConclusionsComparing our results to those of the most homogeneous literature data, SCCA does not appear to be inferior to subtotal colectomy with ileorectal anastomosis (IRA) in terms of therapeutic effectiveness, postoperative mortality and morbidity, or overall impact on quality of life.

Scoring system to predict asymptomatic choledocholithiasis before laparoscopic cholecystectomy

Background: The purpose of this prospective study was to evaluate if a recently proposed score system based on six preoperative parameters [history of colic pain and/or jaundice, dyspepsia, cholecystitis, ultrasound (US), evidence of common bile duct stones (CBDS), number and size of gallbladder stones at US, level of serum glutamic oxalacetic transaminase and/or alkaline phosphatase is effective in the selection of patients undergoing laparoscopic cholecystectomy (LC) with asymptomatic CBDS and could allow a significant reduction of the total number of preoperative examinations. Methods: In the case group, 408 patients were categorized into low-, medium-, and high-risk classes and underwent, respectively, no further preoperative assessment of the bile duct, intravenous cholangiography (IVC), and endoscopic retrograde cholangiography (ERC). Intraoperative cholangiography (IOC) was performed whenever the surgeon was in doubt as to biliary anatomy or bile duct clearance. These patients were compared with 408 retrospectively matched patients (control group) undergoing routine preoperative IVC and/or ERC. Results: In the case group, significantly lower numbers of IVC (120 vs 392) and IOC (3 vs 16) were performed (p < 0.005), whereas no difference in the total number of ERCs was noted. One patient in the control group had retained CBDS detected during follow-up evaluation, whereas none occurred in the case group. Conclusion: The proposed scoring system allows selective use of IVC, ERC, and/or IOC in patients undergoing elective LC.

Pilot study of subtotal colectomy with antiperistaltic cecoproctostomy for the treatment of chronic slow-transit constipation.

PURPOSE: Functional results of total colectomy with ileorectal anastomosis for the treatment of chronic constipation caused by colonic inertia are often considered unsatisfactory because of the frequency of postoperative diarrhea and the high rate of postoperative small-bowel obstruction. Patients affected by severe colonic inertia underwent a subtotal colectomy with a novel antiperistaltic cecorectal anastomosis. The aim of the study was to assess the functional results after preservation of the cecorectal junction. METHODS: Eight females affected by isolated colonic inertia and two females with both paradoxical puborectalis contraction and colonic inertia, of a median age of 40 years, underwent subtotal colectomy with antiperistaltic cecorectal anastomosis. Before antiperistaltic cecorectal anastomosis all ten patients were laxative-dependant, with a mean bowel frequency of ten days; eight of them (80 percent) had distention, seven (70 percent) bloating, and three (30 percent) abdominal pain. RESULTS: There was no mortality or major postoperative morbidity. One month after antiperistaltic cecorectal anastomosis, bowel frequency was a mean of 2.2 (range, 1–4) per day, with a semiliquid stool consistency. After one year, bowel frequency was a mean of 1.3 (range, 0.5–3) per day, with a solid stool consistency; the same results were recorded at last follow-up. Although no patients used antidiarrheal medicine, laxatives continued to be used by both patients with paradoxical puborectalis contraction. All ten (100 percent) of the patients reported a good or improved quality of life. CONCLUSION: This preliminary experience seems to show that antiperistaltic cecorectal anastomosis is safe and effective for patients with colonic inertia. It results in prompt and prolonged relief from constipation for patients with isolated colonic inertia.

Computed tomography volumetric fat parameters versus body mass index for predicting short-term outcomes of colon surgery.

BackgroundAt present, the impact of obesity on short-term outcomes of general surgery remains controversial, especially in the field of laparoscopy. Most studies on the subject have used the body mass index (BMI) to define obesity without distinguishing between visceral and subcutaneous storage. Computed tomography (CT) volumetric analysis permits accurate evaluation of site-specific volume of adipose tissue. The purpose of this study was to compare CT volumetric fat parameters and the BMI for predicting short-term outcomes of colon surgery.MethodsA retrospective analysis was conducted of 231 consecutive patients undergoing elective colon resection, with open or laparoscopic technique, from January 2007 to April 2009. CT volumetric quantification of abdominal visceral and subcutaneous adipose tissue was performed. Intraoperative and perioperative data were collected.ResultsA total of 187 patients were enrolled. BMI showed a direct correlation with fat volumetric parameters but not with the visceral/subcutaneous fat ratio. Operating time was correlated with subcutaneous fat storage and BMI in the laparoscopic right colectomy subgroup. No associations were found with the conversion rate. Length of the hospital stay was correlated with the visceral/subcutaneous fat ratio in the laparoscopic left colectomy subgroup. Whereas the overall postoperative complication rate and mortality were not associated with fat parameters, the postoperative surgical complication rate was associated with visceral volumetric parameters in the laparoscopic left colectomy subgroup.ConclusionsShort-term outcomes of colon surgery are better predicted by fat volumetric parameters than by the BMI. This study has provided new elements for discussion on the impact of visceral and subcutaneous adiposity in laparoscopic and traditional colon surgery.

Routine laparoscopic cholecystectomy after endoscopic sphincterotomy for choledocholithiasis in octogenarians: is it worth the risk?

BackgroundNo unanimous consensus has been reached as to the need for routine laparoscopic cholecystectomy (LC) after endoscopic sphincterotomy (ES) for choledocholithiasis in very elderly patients, who are considered as high-risk subjects for surgery.MethodsFrom 1991 through 1997, 170 patients were referred to undergo preoperative ES and routine LC for common bile duct (CBD) stones. The results for 27 patients (age 80 years or older) were compared with those achieved for younger patients. Successively, in a retrospective case-control study, the results for the selected patients were compared with those for 27 very elderly patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), but did not receive LC. The mean follow-up period was 126 months.ResultsOctogenarians showed longer surgery time (79 vs 51 min) and postoperative hospital stay (2.8 vs 1.2 days), as well as more early low-grade complications (15% vs 3%), whereas there were no differences in conversion rate or serious complications. Recurrent symptoms or complications developed in 48% of octogenarians not undergoing routine LC, and 30% finally needed surgery. One patient in the control group died after emergency cholecystectomy for acute cholecystitis. The results of surgery were significantly poorer for the control group.ConclusionsAlthough a “wait-and-see” policy allowed two-thirds of LCs to be avoided in octogenarians, biliary-related events developed for every second patient, often requiring delayed surgery, with poorer results. Sequential treatment (ES followed by elective LC) is a safe procedure for octogenarians, and should be considered as a standard, definitive treatment for cholecystocholedocholithiasis even after the age of 80 years.

Ampullary Adenocarcinoma in Neurofibromatosis Type 1. Case Report and Literature Review

Periampullary tumors in patients affected by Neurofibromatosis Type 1 (NF-1) are usually carcinoids or stromal tumors and, rarely, adenocarcinomas. We report a case of an adenocarcinoma of the ampulla of Vater in a 54-year-old woman with NF-1 admitted to the hospital with jaundice and undergoing pancreato-duodenectomy. Histologically, the resected specimen showed an adenocarcinoma of the ampulla as being a part of a complex atypical epithelial proliferation extended from the papilla to the mucosa of the duodenum and distal choledochus, islet-cell adenomatosis of the pancreas and multiple gastric, duodenal, jejunal stromal tumors. The ampullary and periampullary adenocarcinomas in NF-1 patients have peculiar features, suggesting a widespread predisposition to cancer development in periampullary tissues and requiring widely demolitive surgery. Moreover, they occur at a younger age than those occurring in non-NF-1 patients, may be associated with additional periampullary epithelial tumors, are often operable and may present long survival.