Giuliano Sansebastiano

Relationships between serum IGF-1, IGFBP-2, interleukin-1beta and interleukin-6 in inflammatory bowel disease.

Aims: To study the relationships between serum IGF-1, IGFBP-3 and IGFBP-2 and interleukin (IL)-1β and IL-6 in inflammatory bowel disease (IBD). Methods: Thirty-seven patients (18 males, 19 females, aged 8.8–26.1 years) with IBD (Crohn’s disease, CD, n = 17, and ulcerative colitis, UC, n = 20) were studied. Patients were in relapse or remission according to established criteria. Serum IGF-1, IGFBP-3, IGFBP-2, IL-1β and IL-6 levels were determined in patients and 15 healthy controls (aged 8.2–19.0 years). Results: IGF-1 levels were lower in patients with CD in relapse compared with controls (p < 0.05). IGFBP-2 levels were higher in CD in relapse compared with other groups (all p < 0.05). In CD and UC patients (n = 37), IGF-1 levels were inversely correlated with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). IGFBP-2 levels correlated positively with ESR and IL-1β. IL-6 levels correlated positively with ESR and CRP. IL-1β levels were elevated in CD in relapse compared to controls (p < 0.05) and were higher in UC in relapse than in other groups (all p < 0.05). In combined CD/UC patients in relapse (n = 20), IL-1β levels were higher (p < 0.05) in patients with recto-sigmoiditis (n = 5) than in other patients. Conclusions: IGF-1, IGFBP-2 levels were related to IL levels, disease activity and anatomical distribution, consistent with active inflammation modifying the IGF-IGFBP system, possibly relevant to disturbance of growth.

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.

Simultaneous repair of bilateral inguinal hernias: a prospective, randomized study of open, tension-free versus laparoscopic approach.

No randomized trial exists that specifically addresses the issue of laparoscopic bilateral inguinal hernia repair. The purpose of the present prospective, randomized, controlled, clinical study was to assess short-and long-term results when comparing simultaneous bilateral hernia repair by an open, tension-free anterior approach with laparoscopic “bikini mesh” posterior repair. Forty-three low-risk male patients with bilateral primary inguinal hernia were randomly assigned to undergo either laparoscopic preperitoneal “bikini mesh” hernia repair (TAPP) or open Lichtenstein hernioplasty. There was no difference in operating time between the two groups. The mean cost of laparoscopic hernioplasty was higher (P < 0.001). The intensity of postoperative pain was greater in the open hernia repair group at 24 hours, 48 hours, and 7 days after surgery (P < 0.001), with a greater consumption of pain medication among these patients (P < 0.05). The median time to return to work was 30 days for the open hernia repair group and 16 days for the laparoscopic “bikini mesh” repair group (P < 0.05). Only 1 asymptomatic recurrence (4.3%) was discovered in the open group. The laparoscopic approach to bilateral hernia with “bikini mesh” appears to be preferable to the open Lichtenstein tension-free hernioplasty in terms of the postoperative quality of life and interruption of occupational activity.

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.

Exposure to active and passive smoking during pregnancy and severe small for gestational age at term

Objective. The objective of this study was to assess the relationship between active smoking as well as environmental tobacco smoke (ETS) exposure and severe small for gestational age (SGA) at term in a sample of pregnant Italian women. Methods. A case–control study was conducted in nine cities in Italy between October 1999 and September 2000. Cases of severe SGA were singleton, live born, at term children with a birth weight ≤ 5th percentile for gestational age. Controls (10:1 to cases) were enrolled from among singleton at term births that occurred in the same hospitals one or two days after delivery of the case, with a birth weight > 10th percentile for gestational age. A total of 84 cases of severe SGA and 858 controls were analyzed. A self-administered questionnaire was used to assess active smoking and ETS exposure, as well as potential confounders. Results. Multivariate logistic regression analysis showed a relationship between active smoking during pregnancy and severe SGA (adjusted odds ratio (OR) 2.10, 95% confidence interval (CI) 1.13–3.68). ETS exposure was associated with severe SGA (adjusted OR 2.51, 95% CI 1.59–3.95) with a dose–response relationship to the number of smokers in the home.

Asymptomatic bile duct stones: selection criteria for intravenous cholangiography and/or endoscopic retrograde cholangiography prior to laparoscopic cholecystectomy

Objective Routine use of endoscopic retrograde cholangiography (ERC) and/or intravenous cholangiography (IVC) or magnetic resonance cholangiopancreatography (MRCP) before laparoscopic cholecystectomy (LC) is not cost‐effective. The objective of this study was to determine precise and easily applicable criteria to select patients who should undergo IVC, MRCP and/or ERC before LC. Design and methods Prospectively collected data from 74 consecutive patients who were diagnosed with asymptomatic common bile duct stones (CBDS) before undergoing LC, were compared with data from 74 matched controls without CBDS. Using the X2 test, those variables were identified which were significantly related to the presence of CBDS. These were inserted into a logistic multiple regression model and, by means of conditional regression analysis, each variable was assigned a score from −2 to +4 proportional to the odds ratio. By adding up the scores obtained, a classification was made as to high, medium and low CBDS risk. Results As a result, 51 patients were found to be low‐risk cases, 53 medium‐risk and 44 high‐risk. Assuming no further assessment of the bile duct needed to be carried out in low‐risk patients, an IVC or MRCP in those at medium risk and an ERC in those at high risk, a calculation was made of the positive predictive value and the sensitivity of the system proposed. The positive predictive value and the sensitivity of the procedure were calculated as being greater than 90%. Conclusions This predictive system for the risk of CBDS allows the selective use of ERC, IVC and MRCP to ensure a high yield and improve cost‐effectiveness. A controlled prospective study will verify these results.

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.

Prospective Comparison of Laparoscopic Left Hemicolectomy for Colon Cancer with Laparoscopic Left Hemicolectomy for Benign Colorectal Disease

BackgroundShort-term outcome and anorectal function results after laparoscopic hemicolectomy for colon cancer were compared with results after laparoscopic hemicolectomy for benign diseases.MethodsA total of 108 patients who underwent laparoscopic left colectomy (60 for colon cancer, 48 for diverticulitis or polyposis) were enrolled in the study. Left hemicolectomy in patients affected by cancer was performed by high ligation of the inferior mesenteric artery. A questionnaire concerning anorectal function was mailed to patients 6 months after surgery.ResultsComplications were more frequent in the cancer group than in the benign disease group: overall morbidity rate (29.6% versus 8.7%; P = 0.009), diarrhea during the first 6 postoperative months (58.7% versus 34.1%; P = 0.022), and anorectal function problems (fecal incontinence and/or the inability to discriminate between gas and stool, and/or urgency, and/or tenesmus) (65.2% versus 31.7%; P = 0.002).DiscussionThe level of ligation of the lower mesenteric artery and damage at the lower mesenteric ganglion could explain the poorer anorectal function outcome in the colon cancer group.

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.