Claudio Soravia

Randomized clinical trial of mechanical bowel preparation versus no preparation before elective left-sided colorectal surgery

Mechanical bowel preparation (MBP) is performed routinely before colorectal surgery to reduce the risk of postoperative infectious complications. The aim of this randomized clinical trial was to compare the outcome of patients who underwent elective left‐sided colorectal surgery with or without MBP.

long-term Follow-up After First Acute Episode of Sigmoid Diverticulitis: Is Surgery Mandatory? : a Prospective Study of 118 Patients

AbstractPURPOSE: This study was designed to evaluate the long-term natural history of sigmoid diverticulitis in patients treated nonoperatively after a first acute episode and to assess the role of elective colectomy. METHODS: Between 1986 and 1991, 144 patients were admitted for acute diverticulitis diagnosed by abdominal computed tomography and had a successful nonoperative treatment. Remote complications (persisting or recurring diverticulitis) were also diagnosed by computed tomography. Patients had a poor outcome if they had one of these complications. Diverticulitis was graded mild or severe on computed tomography according to Ambrosetti’s criteria. We determined statistically whether young age (≤50 years old) and severe diverticulitis were risk factors for a poor outcome. RESULTS: One hundred eighteen patients with a contributive computed tomographic scan at admission were followed up. Median age was 63 (range, 23–93) years, with a median follow-up of 9.5 (range, 0.2–13.8) years. Eighty patients had no complications, and 38 had remote complications. The incidence of remote complications was the highest (54 percent at 5 years) for young patients with severe diverticulitis on computed tomography and the lowest (19 percent at 5 years) for older patients with mild disease. Young age and severe diverticulitis taken separately were both statistically significant factors of poor outcome (P = 0.007 and P = 0.003, respectively), although age was no longer significant after stratification for disease severity on computed tomography (P = 0.07). Twenty-four patients died. The cause of death was unrelated to diverticulitis in 21 cases and unknown in the remaining 3. CONCLUSIONS: We propose that after a first acute episode of diverticulitis treated nonoperatively, elective colectomy should be offered to young patients (≤50 years old) with severe diverticulitis on computed tomography.

Long-Term Outcome of Mesocolic and Pelvic Diverticular Abscesses of the Left Colon: A Prospective Study of 73 Cases

PURPOSEThe aim of of this study was to evaluate prospectively the long-term outcome of mesocolic and pelvic diverticular abscesses of the left colon.METHODSBetween October 1986 and October 1997, a total of 465 patients urgently admitted to our hospital with a suspected diagnosis of acute left-sided colonic diverticulitis had a CT scan. Of 76 patients (17 percent) who had an associated mesocolic or pelvic abscess, 3 were lost to follow-up. The remaining 73 patients (45 with a mesocolic abscess and 28 with a pelvic abscess) were followed for a median of 43 months.RESULTSof the 45 patients with a mesocolic abscess, 7 (15 percent) required surgery during their first hospitalization versus 11 (39 percent) of the 28 patients with a pelvic abscess (P = 0.04). At the end of follow-up, 22 (58 percent) of the 38 patients with a mesocolic abscess who had successful conservative treatment during their first hospitalization did not need surgical treatment vs. 8 (47 percent) of the 17 who had a pelvic abscess. Altogether, 51 percent of the patients with a mesocolic abscess had surgical treatment versus 71 percent of those with a pelvic abscess (P = 0.09).CONCLUSIONSConsidering the poor outcome of pelvic abscess associated with acute left-sided colonic diverticulitis, percutaneous drainage followed by secondary colectomy seems justified. Mesocolic abscess by itself is not an absolute indication for colectomy.

Familial Adenomatous Polyposis-Associated Thyroid Cancer : A Clinical, Pathological, and Molecular Genetics Study

We report two familial adenomatous polyposis (FAP) kindreds with thyroid cancer, harboring two apparently novel germlineAPC mutations. The clinical phenotype in the first kindred was typical of classical adenomatous polyposis, whereas the second kindred exhibited an attenuated adenomatous polyposis phenotype. There was a female predominance with a mean age of 34 years (range, 23-49) at cancer diagnosis. Multiple sections of four thyroid tumors from three FAP patients were analyzed in detail. Histological examination of thyroid tumors showed a range of morphological features. Some tumors exhibited typical papillary architecture and were associated with multifocal carcinoma; in others, there were unusual areas of cribriform morphology, and spindle-cell components with whorled architecture. Immunoreactivity for thyroglobulin and high molecular weight keratins was strong. Somatic APC mutation analysis revealed an insertion of a novel long interspersed nuclear element-1-like sequence in one tumor sample, suggesting disruption of APC. In three FAP patients, ret/PTC-1 and ret/PTC-3 were expressed in thyroid cancers. No positivity was observed for ret/ PTC-2. p53 immunohistochemistry was positive in only one section of a recurrent thyroid tumor sample. Our data suggest that genetic alterations in FAP-associated thyroid cancer involve loss of function of APC along with the gain of function of ret/PTC, while alterations of p53 do not appear to be an early event in thyroid tumorigenesis.

Family history characteristics, tumor microsatellite instability and germline MSH2 and MLH1 mutations in hereditary colorectal cancer.

Recent characterization of the molecular genetic basis of hereditary nonpolyposis colorectal cancer provides an important opportunity for identification of individuals and their families with germline mutations in mismatch repair genes. Cancer family history criteria that accurately define hereditary colorectal cancer are necessary for cost-effective testing for germline mutations in mismatch repair genes. The present report describes the results of analysis of 33 colorectal cancer cases/families that satisfy our modified family history criteria (Mount Sinai criteria) for colorectal cancer. Fourteen of these families met the more stringent Amsterdam criteria. Germline MSH2 and MLH1 mutations were identified by the reverse transcription-polymerase chain reaction and the protein truncation test, and confirmed by sequencing. Microsatellite instability analysis was performed on available tumors from affected patients. MSH2 or MLH1 mutations were detected in 8 of 14 Amsterdam criteria families and in 5 of the remaining 19 cases/families that only satisfied the Mount Sinai criteria. Three of the latter families had features of the Muir-Torre syndrome. A high level of microsatellite instability (MSI-H) was detected in almost all (16/18) colorectal cancers from individuals with MSH2 and MLH1 mutations, and infrequently (1/21) in colorectal cancer specimens from cases without detectable mutations. Families with germline MSH2 and MLH1 mutations tended to have individuals affected at younger ages and with multiple tumors. The Amsterdam criteria are useful, but not sufficient, for detecting hereditary colorectal cancer families with germline MSH2 and MLH1 mutations, since a proportion of cases and families with mutations in mismatch repair genes will be missed. Further development of cancer family history criteria are needed, using unbiased prospectively collected cases, to define more accurately those who will benefit from MSH2 and MLH1 mutation analysis.

Morphologic Alterations Associated With Mechanical Bowel Preparation Before Elective Colorectal Surgery: A Randomized Trial

PurposeThe feasibility and safety of left-sided colorectal procedures with avoidance of mechanical bowel preparation has recently been demonstrated. Moreover, mechanical preparation has been associated with an increased risk for abdominal septic complications, including anastomotic leakage. This study was designed to determine whether mechanical bowel preparation is associated with histologic alterations in the colon.MethodsFifty patients (mean age, 61 (range, 45–78) years) scheduled to undergo elective colorectal surgery were prospectively randomized to receive mechanical preparation (polyethylene glycol; Group 1) or no preparation (Group 2) preoperatively. A macroscopically healthy segment of the bowel was excised at the proximal margin of the colectomy piece. A pathologist, blinded to the patients group allocation, assessed various morphologic parameters.ResultsIndications for colectomy (cancer and complicated diverticulosis) did not differ between groups. Bowel wall alterations were more frequent in patients who received a preparation. The most striking alterations associated with mechanical preparation were loss of superficial mucus (moderate-to-severe in 96 and 52 percent in Groups 1 and 2, respectively; P < 0.001) and epithelial cells (moderate-to-severe in 88 and 40 percent in Groups 1 and 2, respectively; P < 0.01). In addition, inflammatory changes, i.e., lymphocytes (severe in 48 and 12 percent in Groups 1 and 2, respectively; P < 0.02) and polymorphonuclear cells infiltration (severe in 52 and 8 percent in Groups 1 and 2, respectively; P < 0.02), were more prevalent after mechanical preparation.ConclusionsMechanical bowel preparation is associated with structural alteration and inflammatory changes in the large bowel wall. Although bowel wall inflammation is a known risk factor for anastomotic leak, it remains to be elucidated whether these changes have a direct relation to the deleterious effect of mechanical bowel preparation in terms of abdominal morbidity.

Comparison of ileal pouch-anal anastomosis and ileorectal anastomosis in patients with familial adenomatous polyposis

PURPOSE: The aim of this study was to evaluate the surgical complications and long-term outcome and assess the functional results and quality of life after ileorectal anastomosis and ileal pouch-anal anastomosis in patients with familial adenomatous polyposis. METHODS: From 1980 to 1997, 131 patients with familial adenomatous polyposis were operated on or were followed up or both at the Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital. Demographic and operative data were prospectively collected in the ileal pouch-anal anastomosis group, and retrospectively in the ileorectal anastomosis group. A questionnaire or telephone interview or both were undertaken to evaluate functional outcome and quality of life. RESULTS: The ileorectal anastomosis group consisted of 60 patients (mean age, 31 years; mean follow-up, 7.7 years). In the ileal pouch-anal anastomosis group there were 50 patients (mean age, 35 years; mean follow-up, 6 years). There were no statistically significant differences with respect to anastomotic leak rate in ileal pouch-anal anastomosisvs. ileorectal anastomosis (12vs. 3 percent;P=0.21), risk of small-bowel obstruction (24vs. 15 percent;P=0.58), and risk of intra-abdominal sepsis (3vs. 2 percent;P=0.86). Reoperation rate was similar in the two groups (14vs. 16 percent;P=0.94). Twenty-one patients (37 percent) with ileorectal anastomosis were converted to ileal pouch-anal anastomosis (12 patients) or proctocolectomy (9 patients), because of rectal cancer (5 patients), dysplasia (1 patient), or uncontrollable rectal polyps (15 patients). Two pelvic pouches were excised, and another one was defunctioned. Information regarding functional results and quality of life was obtained in 40 patients (66.6 percent) in the ileorectal anastomosis group and in 43 patients (86 percent) in the ileal pouch-anal anastomosis group. Patients with ileorectal anastomosis had a significantly better functional outcome with regard to nighttime continence and perineal skin irritation. But otherwise, functional results and quality of life were similar. CONCLUSIONS: Although ileorectal anastomosis has a better functional outcome, ileal pouch-anal anastomosis may be preferable because of the lower long-term failure rate. Ileorectal anastomosis is still an option in patients with familial adenomatous polyposis with rectal polyp sparing and good compliance for follow-up.

Early prediction of acute pancreatitis: Prospective study comparing computed tomography scans, Ranson, Glasgow, acute physiology and chronic health evaluation II scores, and various serum markers

The aim of this study was to assess the predictability of the outcome of acute pancreatitis using the Ranson, Glasgow, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores, the computed tomography (CT) scan, and several serum markers. Altogether, 137 consecutive patients with acute pancreatitis confirmed by CT scan were prospectively included. Blood samples were obtained daily for 6 days. The predictive value of each parameter was studied by univariate and multivariate analyses comparing mild and severe pancreatitis. A total of 111 attacks were graded as mild (81%) and 26 as severe (19%). Ranson (p=0.3) and APACHE II (p=0.049) scores appeared insufficiently predictive in the univariate analysis. Pancreatic imaging by CT scan was insufficiently predictive (p>0.05), whereas the presence of extrapancreatic fluid collections was more indicative of outcome (p<0.05). With the univariate analysis, the four most reliable serum markers were pancreatic amylase (p<0.001), neutrophil elastase (p<0.05), albumin (p<0.002), and C-reactive protein (p<0.001). Results became homogeneous when the CT results were added; serum albumin plus extrapancreatic fluid collections (negative predictive value 92%–96% and positive predictive value 67%–100%) comprised the best indicator of severity. None of the parameters tested achieved sufficient predictability when used alone. Serum albumin plus extrapancreatic fluid collections comprise the best indicator of severity at the time of admission.RésuméLe but de cette étude a été d’évaluer dans la pancréatite aiguë la valeur prédictive des scores de Ranson, de Glasgow et d’APACHE II, la tomodensitométrie (TDM) et plusieurs marqueurs sériques. On a inclus dans cette étude de façon prospective 137 patients consécutifs ayant une pancréatite aiguë confirmée par TDM. On a prélevé du sang tous les jours pendant six jours. La valeur prédictive de tous les paramètres a été comparée par analyse uni- et multivariée. En ce qui concerne la gravité de la pancréatite, 111 crises ont été classées «modérées» (81%) et 26, «évères» (19%). La prédiction de gravité par des scores de Ranson (p=0.3) et d’APACHE II (p=0.049) n’étaient pas significativement discriminative en analyse univariée. L’imagerie du pancréas par TDM n’était pas prédictive de façon significative (p τ; 0.05) alors que la présence de collections liquidiennes extra pancréatiques était plus prédictive en ce qui concerne l’évolution (p<0.05). En analyse univariée, les quatre marqueurs les plus fiables étaient ï’amylase d’origine pancréatique (p<0.001), l’élastase neutrophile (p<0.05), l’albumine (p<0.002) et la CRP (p<0.001). Les résultats étaient plus homogènes lorsqu’on a ajouté des données supplémentaires provenant de la TDM: la combinaison d’albumine dans le sérum + collections liquidiennes extrapancréatiques (valeur predictive negative allant de 92 à 96% et valeur predictive positive, de 67 à 100%) était le meilleur indicateur de sévérité. Utilisé seul, aucun des paramètres testés n’était suffisamment prédictif. La combinaison d’albumine dans le sérum + collections liquidiennes extra pancréatiques est le meilleur indicateur de sévérité au moment de l’admission.ResumenEl objetivo de este trabajo fue averiguar el valor diagnóstico en pancreatitis agudas de: las punctuaciones de Ranson, Glasgow y APACHE II, la tomografía axial computarizada (CT) y de diversos marcadores séricos. Se estudiaron prospectivamente 137 pacientes con pancreatitis aguda cuyo diagnóstico fue confirmado mediante CT. El valor diagnóstico de todos los parámetros estudiados se comparó entre pacientes con una pancreatitis leve o grave, mediante análisis uni y multivariante. Se registraron 111 casos de pancreatitis leves (81%) y 26 graves (19%). Las puntuaciones de Ranson (p=0.3) y del APACHE II (p=0.049) no tienen suficiente valor diagnóstico en un análisis uni-variante. La imagen del páncreas obtenida con CT tampoco tuvo valor diagnóstico suficiente (p<0.05) mientras que la existencia de colecciones líquidas extrapancreáticas tuvieron más valor por lo que al pronóstico se refiere (p<0.05). En un análisis univariante los marcadores séricos más fiables fueron la amilasa pancreática (p<0.001) la elastasa de los neutrófilos (p<0.05) la albúmina (p<0.002) y la proteína C reactiva (CRP) (p<0.001). Los resultados se homogeneizaron al añadirse a estos parámetros séricos las imágenes obtenidos por CT. Así, la albúmina sérica + colecciones líquidas extrapancreáticas (valor diagnóstico negativo entre el 92–96% y positivo en el 67–100% de los casos) constituyeron el mejor indicador por lo que a la gravedad se refiere. Ninguno de los parámetros estudiados tienen, por sí solos, valor diagnóstico o pronóstico alguno. La albúmina sérica + colecciones líquidas extrapancreáticas constituyen, al ingreso, el mejor indicador de la gravedad del cuadro pancreático.

Prostate cancer is part of the hereditary non‐polyposis colorectal cancer (HNPCC) tumor spectrum

The recognized urologic tumor spectrum in hereditary non‐polyposis colon cancer includes ureteral and renal pelvis malignancies. Here, we report a family in which the proband, who had three metachronous adenocarcinomas of the colon and rectum (at ages 54, 57, and 60), presented with an adenocarcinoma of the prostate at age 61. Immunohistochemical (IHC) staining of colonic, rectal, and prostatic tumor tissues demonstrated lack of expression of both MSH2 and MSH6. Accordingly, microsatellite instability (MSI) was found in the rectal, colonic, and prostatic tumors. The kindred complies with the Amsterdam criteria for HNPCC, as five members over three generations had colorectal cancer. Molecular investigations were initiated when the probands son presented with an adenocarcinoma of the colon at age 35. Southern blotting analysis of genomic DNA led to identification of a novel genomic deletion encompassing exon 5 of the MSH2 gene. Although prostate cancer has occasionally been described in HNPCC families, to the best of our knowledge, this is the first report where the MSI and IHC analysis of the prostatic adenomcarcinoma clearly link its aetiology to the germline mismatch repair mutation. Hence, prostate cancer should be included in the HNPCC tumor spectrum.

Surgery for adult polycystic liver disease

BACKGROUND Occasionally patients with adult polycystic liver disease (APLD) have symptoms. For these patients surgery may represent a valuable therapeutic option to relieve symptoms. METHODS From September 1977 to August 1993 at our institution, 10 women with APLD were examined and surgically treated. They underwent a partial hepatic resection together with cyst fenestration. The surgical outcome and long-term follow-up were retrospectively analyzed. RESULTS Postoperative morbidity consisted of one case of pneumonia, and one case of acute pancreatitis with deep vein leg thrombosis. One patient died after acute Budd-Chiari syndrome developed as a result of liver collapse after fenestration of a posterior cyst. In the long term six of nine patients were symptom free. Late surgical complications included acute cholecystitis (one patient), small bowel obstruction (one), and incisional hernia (two). CONCLUSIONS A combined surgical approach of hepatic resection and cyst fenestration has proved feasible for patients with highly symptomatic APLD. Extensive fenestration of posterior cysts should be avoided; transverse hepatic resection (frontal hepatectomy) up to the costal margin is proposed. This therapy provides good results at long-term follow-up.