Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer.

A population-based series of 649 unselected incident cases of ovarian cancer diagnosed in Ontario, Canada, during 1995-96 was screened for germline mutations in BRCA1 and BRCA2. We specifically tested for 11 of the most commonly reported mutations in the two genes. Then, cases were assessed with the protein-truncation test (PTT) for exon 11 of BRCA1, with denaturing gradient gel electrophoresis for the remainder of BRCA1, and with PTT for exons 10 and 11 of BRCA2. No mutations were found in all 134 women with tumors of borderline histology. Among the 515 women with invasive cancers, we identified 60 mutations, 39 in BRCA1 and 21 in BRCA2. The total mutation frequency among women with invasive cancers, 11.7% (95% confidence interval [95%CI] 9.2%-14.8%), is higher than previous estimates. Hereditary ovarian cancers diagnosed at age <50 years were mostly (83%) due to BRCA1, whereas the majority (60%) of those diagnosed at age >60 years were due to BRCA2. Mutations were found in 19% of women reporting first-degree relatives with breast or ovarian cancer and in 6.5% of women with no affected first-degree relatives. Risks of ovarian, breast, and stomach cancers and leukemias/lymphomas were increased nine-, five-, six- and threefold, respectively, among first-degree relatives of cases carrying BRCA1 mutations, compared with relatives of noncarriers, and risk of colorectal cancer was increased threefold for relatives of cases carrying BRCA2 mutations. For carriers of BRCA1 mutations, the estimated penetrance by age 80 years was 36% for ovarian cancer and 68% for breast cancer. In breast-cancer risk for first-degree relatives, there was a strong trend according to mutation location along the coding sequence of BRCA1, with little evidence of increased risk for mutations in the 5' fifth, but 8.8-fold increased risk for mutations in the 3' fifth (95%CI 3.6-22.0), corresponding to a carrier penetrance of essentially 100%. Ovarian, colorectal, stomach, pancreatic, and prostate cancer occurred among first-degree relatives of carriers of BRCA2 mutations only when mutations were in the ovarian cancer-cluster region (OCCR) of exon 11, whereas an excess of breast cancer was seen when mutations were outside the OCCR. For cancers of all sites combined, the estimated penetrance of BRCA2 mutations was greater for males than for females, 53% versus 38%. Past studies may have underestimated the contribution of BRCA2 to ovarian cancer, because mutations in this gene cause predominantly late-onset cancer, and previous work has focused more on early-onset disease. If confirmed in future studies, the trend in breast-cancer penetrance, according to mutation location along the BRCA1 coding sequence, may have significant impact on treatment decisions for carriers of BRCA1-mutations. As well, BRCA2 mutations may prove to be a greater cause of cancer in male carriers than previously has been thought.

Characterization of the in vitro and in vivo activity of monoclonal antibodies to human IL-18.

IL-18 is a cytokine with potent IFN-gamma inducing activities as well as an important mediator of Th1 polarized immune responses. In this study we demonstrated that IL-18 induces the concentration-dependent production of the proinflammatory mediators IFN-gamma, IL-6, and GM-CSF, but not the anti-inflammatory cytokine, IL-10 from peripheral blood lymphocytes in the presence of mitogen. Three neutralizing IL-18 monoclonal antibodies (MAbs) were investigated, one of which (2C10) inhibited IL-18 bioactivity with an IC50 of 0.1 nM and had a K(D) of 3.9 x 10(-11) M. A NOD/SCID mouse model engrafted with human peripheral blood lymphocytes was developed to test the in vivo efficacy of this MAb. The IFN-gamma production induced by LPS administration was inhibited approximately 90% by prior dosing of MAb 2C10. The therapeutic utility of a high-affinity IL-18 MAb may be of benefit in Th1-driven autoimmune diseases such as rheumatoid arthritis and Crohn's Disease, where elevated levels of IL-18 have been observed.

Laparoscopic cholecystectomy for acute cholecystitis: can the need for conversion and the probability of complications be predicted? A prospective study.

BACKGROUND: Laparoscopic cholecystectomy (LC) in acute cholecystitis is associated with a relatively high rate of conversion to an open procedure as well as a high rate of complications. The aim of this study was to analyze prospectively whether the need to convert and the probability of complications is predictable. METHODS: A total of 215 patients undergoing LC for acute cholecystitis were studied prospectively by analyzing the data accumulated in the process of investigation and treatment. Factors associated with conversion and complications were assessed to determine their predictive power. RESULTS: Conversion was indicated in 44 patients (20.5%), and complications occurred in 36 patients (17%). Male gender and age >60 years were associated with conversion, but these factors had no sensitivity and no positive predictive value. The same factors, together with a disease duration of >96 h, a nonpalpable gallbladder, a white blood count (WBC) of >18,000/cc(3), and advanced cholecystitis, predicted conversion with a sensitivity of 74%, a specificity of 86%, a positive predictive value of approximately 40%, and a negative predictive value of 96%. However, these data became available only when LC was underway. Male gender and a temperature of >38 degrees C were associated with complications, but these factors had no sensitivity and no positive predictive value. Progression along the stages of admission and therapy did not add predictive factors or improve the predictive characteristics. Male gender, abdominal scar, bilirubin >1 mg%, advanced cholecystitis, and conversion to open cholecystectomy were associated with infectious complications. Their sensitivity and positive predictive value remained 0 despite progression along the stages of admission and therapy. CONCLUSION: Although certain preoperative factors are associated with the need to convert a LC for acute cholecystitis, they have limited predictive power. Factors with higher predictive power are obtained only during LC. The need to convert can only be established during an attempt at LC. Preoperative and operative factors associated with total and infectious complications have no predictive power.

Identification of SAF-2, a novel siglec expressed on eosinophils, mast cells, and basophils.

BACKGROUND: Eosinophils, basophils, and mast cells are believed to be the central tenet cells in allergic conditions including allergic rhinitis, asthma, and eczema. The molecular mechanisms underlying the recruitment of these cells to sites of allergic inflammation are poorly understood. OBJECTIVES: Our aim was to identify a common adhesion molecule that could potentially be responsible for mediating the recruitment of the allergic cell types to the lungs and other sites of allergy. METHODS: We have cloned a sialoadhesin molecule from a human eosinophil library with the use of expressed sequence tag technology and characterized its expression on allergic cells by the use of flow cytometry and specific mAbs. RESULTS: With the use of expressed sequence tag sequencing, we have identified a novel siglec molecule, SAF-2. SAF-2 has homology with other sialoadhesin family members (CD33 and siglec-5) and belongs to a subgroup of the Ig superfamily. SAF-2 is a 431-amino acid protein composed of 3 Ig domains with a 358-amino acid extracellular domain and a 47-amino acid tail. SAF-2 is highly restricted to eosinophils, basophils, and mast cells. Antibodies to SAF-2 do not modulate Ca(++) mobilization or chemotaxis of human eosinophils induced by eotaxin. CONCLUSION: SAF-2 is a highly restricted sialoadhesin molecule, which may be useful in the detection and/or modulation of allergic cells.

Laparoscopic cholecystectomy for acute cholecystitis: how do fever and leucocytosis relate to conversion and complications?

OBJECTIVE: To find out whether fever and raised white cell count (WCC) are associated with conversion and complications of laparoscopic cholecystectomy in acute cholecystitis, and whether their presence could help in deciding the place of laparoscopic procedures. DESIGN: Prospective study. SETTING: Teaching hospital, Israel. SUBJECTS: 256 patients who were treated for clinical acute cholecystitis between January 1994 and November 1997. INTERVENTIONS: Emergency laparoscopic cholecystectomy. MAIN OUTCOME MEASURES: Raised temperature and WCC; incidence of conversion and complications. RESULTS: Raised temperature (>38 degrees C) was independently associated with advanced cholecystitis (p = 0.002, odds ratio [OR] 2.7) and a palpable gallbladder preoperatively (p = 0.02, OR 2.1). Total complications correlated with a temperature of >38 degrees C. Raised WCC (>15 x 10(9)/L) was independently associated with age >45 years (p = 0.02, OR 2.4), a palpable gallbladder preoperatively (p = 0.001, OR 2.9), and a raised temperature (>38 degrees C) (p < 0.0001, OR 6.2). Conversion was associated with a WCC >18 x 10(9)/L (p = 0.0, OR 3.2). CONCLUSION: A WCC of >18 x 10(9)/L may assist in predicting conversion, and fever of >38 degrees C may assist in predicting the development of complications.

Ball lightning caused by oxidation of nanoparticle networks from normal lightning strikes on soil

Observations of ball lightning have been reported for centuries, but the origin of this phenomenon remains an enigma. The 'average' ball lightning appears as a sphere with a diameter of 300 mm, a lifetime of about 10 s, and a luminosity similar to a 100-W lamp. It floats freely in the air, and ends either in an explosion, or by simply fading from view. It almost invariably occurs during stormy weather. Several energy sources have been proposed to explain the light, but none of these models has succeeded in explaining all of the observed characteristics. Here we report a model that potentially accounts for all of those properties, and which has some experimental support. When normal lightning strikes soil, chemical energy is stored in nanoparticles of Si, SiO or SiC, which are ejected into the air as a filamentary network. As the particles are slowly oxidized in air, the stored energy is released as heat and light. We investigated this basic process by exposing soil samples to a lightning-like discharge, which produced chain aggregates of nanoparticles: these particles oxidize at a rate appropriate for explaining the lifetime of ball lightning.

The impact of patient delay and physician delay on the outcome of laparoscopic cholecystectomy for acute cholecystitis.

BACKGROUND: Laparoscopic cholecystectomy is now used in the management of acute cholecystitis. Under these circumstances unfavorable conditions may result in conversion and complications. Information about these conditions may help in planning the laparoscopic approach or in proceeding directly to open cholecystectomy. This study was initiated to evaluate perioperative factors associated with conversion and complications of laparoscopic cholecystectomy in acute cholecystitis. Special attention was paid to the duration of complaints until surgery, to the delay on the part of the patient, and to the delay on the part of the physician. METHODS: Between January 1994 and December 1997, we attempted to perform laparoscopic cholecystectomy on 348 patients with acute cholecystitis. All perioperative data were collected on standardized forms. RESULTS: There were 182 cases (52%) of acute uncomplicated cholecystitis, 90 (26%) of gangrenous cholecystitis, 33 of hydrops (9.5%), and 43 of empyema of the gallbladder (12.5%). Seventy six patients (22%) needed conversion to open cholecystectomy and complications occurred in 57 cases. Advanced cholecystitis was associated with significant patient delay (P = 0.01), and it had a significantly higher conversion rate (39%) compared with early cholecystitis (14.5%); (P <0.00001). Conversion rates were also associated with male gender (P = 0.0017), a history of biliary disease (P = 0.0085), and a patient delay of >48 hours (P = 0.028). The total and infectious complication rates were associated with an age older than 60 years (P = 0.023 and 0.007, respectively) and male gender (P = 0.026 and 0.014, respectively). CONCLUSIONS: In acute cholecystitis, patient delay is associated with a high conversion rate. Early timing of laparoscopic cholecystectomy tends to reduce the conversion rate, as well as the total and the infectious complication rates. Male gender, a history of biliary disease, and advanced cholecystitis are associated with conversion. Male and older patients are associated with a high total and infectious complication rates.

Intron variants of the p53 gene are associated with increased risk for ovarian cancer but not in carriers of BRCA1 or BRCA2 germline mutations.

Two biallelic polymorphisms in introns 3 and 6 of the p53 gene were analysed for a possible risk-modifying effect for ovarian cancer. Germline DNA was genotyped from 310 German Caucasian ovarian cancer patients and 364 healthy controls. We also typed 124 affected and 276 unaffected female carriers with known deleterious BRCA1 or BRCA2 germline mutation from high-risk breast-ovarian cancer families. Genotyping was based on PCR and high-resolution gel electrophoresis. German ovarian cancer patients who carried the rare allele of the MspI restriction fragment length polymorphism (RELP) in intron 6 were found to have an overall 1.93-fold increased risk (95% confidence internal (CI) 1.27-2.91) which further increased with the age at diagnosis of 41-60 years (odds ratio (OR) 2.71, 95% CI 1.10-6.71 for 41-50 and OR 2.44, 95% CI 1.12-5.28 for 51-60). The 16 bp duplication polymorphism in intron 3 was in a strong linkage to the MspI RFLP. In BRCA1 or BRCA2 mutation carriers, no difference in allele frequency was observed for carriers affected or unaffected with ovarian cancer. Our data suggest that intronic polymorphisms of the p53 gene modify the risk for ovarian cancer patients but not in carriers with BRCA1 or BRCA2 mutations.

The value of histomorphometric nuclear parameters in the diagnosis of well differentiated follicular carcinomas and follicular adenomas of the thyroid gland.

AIMS: To explore the potential of histomorphometric analysis in distinction between follicular adenomas and well differentiated follicular carcinomas of the thyroid gland. Their differentiation on routine histological study may be a challenging exercise, being contingent upon the absence or presence of vascular invasion and penetration of neoplastic follicles through the capsule of the tumour. METHODS AND RESULTS: Computer-assisted image analysis was performed to gauge the nuclear area, nuclear Ferret diameter, nuclear regularity factor, nuclear elongation factor, number of nuclear vesicles and total area of all nuclear vesicles in the follicles of 37 adenomas and 36 well differentiated carcinomas. By univariate analysis, these nuclear descriptors (with the exception of the elongation factor) were found to correlate with the benign or malignant nature of the tumours. By multivariate analysis, only the nuclear area, Ferret diameter and regularity factor were ascertained to be significant predictors of malignancy. A fitted logit model correctly predicted 91% of the cancers and 87% of the adenomas. CONCLUSIONS: Histomorphometrically gauged nuclear parameters of the tumour cells may reinforce pathologists' decision-making by adding objective and unbiased criteria to their subjective assessment of follicular neoplasms in cases in which vascular or capsular invasion are not detected.

p53 regulates a G2 checkpoint through cyclin B1.

The p53 tumor suppressor controls multiple cell cycle checkpoints regulating the mammalian response to DNA damage. To identify the mechanism by which p53 regulates G2, we have derived a human ovarian cell that undergoes p53-dependent G2 arrest at 32 degrees C. We have found that p53 prevents G2/M transition by decreasing intracellular levels of cyclin B1 protein and attenuating the activity of the cyclin B1 promoter. Cyclin B1 is the regulatory subunit of the cdc2 kinase and is a protein required for mitotic initiation. The ability of p53 to control mitotic initiation by regulating intracellular cyclin B1 levels suggests that the cyclin B-dependent G2 checkpoint has a role in preventing neoplastic transformation.

Laparoscopic cholecystectomy for acute cholecystitis and the consequences of gallbladder perforation, bile spillage, and "loss" of stones.

OBJECTIVE: To study the factors associated with accidental perforation of the gallbladder and spillage of bile and stones and to assess the consequences of these mishaps. DESIGN: Prospective study with retrospective bacteriological evaluation. SETTING: Teaching hospital, Israel. SUBJECTS: 189 Patients who were treated for clinical acute cholecystitis between January 1994 and August 1996. INTERVENTIONS: Emergency laparoscopic cholecystectomy. MAIN OUTCOME MEASURES: Incidence of accidental perforation of gallbladder and spillage of bile and stones and of conversion and complications in relation to preoperative and operative findings. RESULTS: Bile was spilt in 65 (34%) and gall-stones were "lost" in 27 (14%), 44 (23%) required conversion to an open approach and 36 (19%) developed complications. Preoperative duration of symptoms >96 hours and a palpable gallbladder were associated with accidental perforation of the gallbladder and spillage of bile. A palpable gallbladder, gangrenous cholecystitis, and WBC > 15 x 10(9)/L were associated with stones "lost" in the peritoneum. A history of biliary disease was inversely related to "lost" stones. Conversion of laparoscopic to open cholecystectomy was associated with male sex, age >60 years, a non-palpable gallbladder, WBC > 15 x 10(9)/L, and a gangrenous gallbladder. Complications of surgery were more common among men and associated with fever of >38 degrees C. Neither the conversion nor the complications were associated with perforation of the gallbladder or "lost" stones. CONCLUSION: Perforation of the gallbladder and intraperitoneal spillage of bile or stones during laparoscopic cholecystectomy for acute cholecystitis are not associated with undesirable events, are not indications for conversion, and are not associated with further complications. When patients are given appropriate antibiotics perioperatively and the spilt bile is properly aspirated and the peritoneum irrigated, the operative and postoperative courses are similar to those of patients with unperforated gallbladder.

No association of the I1307K APC allele with ovarian cancer risk in Ashkenazi Jews.

Familial adenomatous polyposis is a dominantly inherited colon cancer syndrome associated with germ-line mutations in the APC tumor suppressor gene. An APC gene sequence alteration, the I1307K allele, occurs in 6% of the Ashkenazi Jewish population and is reported to double the risk for colorectal cancer. We screened a population of 190 Ashkenazi women who were diagnosed with epithelial ovarian carcinoma for the I1307K variant and measured the effect of this allele on the risk for cancer development in their first-degree relatives. We identified the I1307K allele in 7.9% (15 of 190) of our ovarian cancer cases. The average age of ovarian cancer diagnosis in carriers of the I1307K allele (57.5 years) was not statistically different than the age for noncarriers (56.4 years; P = 0.70). Among the 1087 first-degree relatives, there were 23 cases of colorectal cancer; 3 of 100 relatives of probands with the I1307K allele (3.0%) had a history of colorectal cancer versus 20 of 987 relatives of probands without the I1307K allele (2.1%; relative risk, 1.48; 95% confidence interval, 0.45-4.88; P = 0.462). Relatives of the I1307K carriers had a risk of 38.0% for developing any cancer to age 80, similar to the risk for relatives of noncarriers of the I1307K allele (42.1%; P = 0.86). The average age of diagnosis of cancer of any type was not different between relatives of carriers (59.0 years) and noncarriers (60.4 years). In the Ashkenazi Jewish population, the I1307K allele is unlikely to increase the risk of ovarian cancer or of cancer in general.

Laparoscopic cholecystectomy for the various types of gallbladder inflammation: a prospective trial.

Laparoscopic cholecystectomy (LC), the procedure of choice for elective cholelithiasis, is now also used in the management of acute cholecystitis. In the various types of gallbladder disease, favorable and unfavorable conditions may influence the conversion and complication rates. Information about these conditions may help elucidate the optimal circumstances for LC or indicate when the procedure is best avoided. We attempted to perform emergency LC on 215 patients with acute cholecystitis. The procedure was successful in 171 patients (79.5%), and conversion to open cholecystectomy (OC) was needed in 44 (20.5%). Complications occurred in 37 patients (17%). Uncomplicated acute cholecystitis was associated with age <50 years, duration of complaint <48 h, temperature <38.5 degrees C, a nonpalpable gallbladder, and an alkaline phosphatase >100 U/L. Acute gangrenous cholecystitis was associated with a negative gallbladder history, other associated diseases, temperature >38.5 degrees C, a palpable gallbladder, and serum bilirubin levels <1 mg/dl. Hydrops was associated with a temperature <38 degrees C and a leukocyte count of >12,000/cc3, and empyema of the gallbladder was associated with duration of complaint >48 h and a palpable gallbladder. The conversion rate of acute gangrenous cholecystitis (40%) was significantly higher than that of uncomplicated acute cholecystitis (8%) (p < 0.00001, odds ratio=7.7), as well as that of empyema of the gallbladder (12.5%) (p=0.005, odds ratio=4.7). The conversion from LC to OC in uncomplicated acute cholecystitis was associated with male sex and with duration of complaint >24 h, and in gangrenous cholecystitis with age >60 years, a nonpalpable gallbladder, and a leukocyte count of >15,000/cc3. The complication rates of acute cholecystitis, hydrops, empyema of the gallbladder, and gangrenous cholecystitis were 16%, 7%, 22%, and 21%, respectively (p = NS). The total complication rate in acute cholecystitis tended to be associated with a duration of complaint >48 h and in gangrenous cholecystitis with male sex, age >60 years, other associated disease, larger bile stones, and elevated serum bilirubin levels. Generally, LC is safe in all forms of cholecystitis, with acceptably low conversion and complication rates, excluding gangrenous cholecystitis. In gangrenous cholecystitis, a conversion rate of approximately 40% is expected. Predictors of conversion and complications may be particularly helpful in planning the laparoscopic approach to acute gangrenous cholecystitis. Patients >60 years of age, with a nonpalpable gallbladder and with a leukocyte count >15,000/cc3, frequently need conversion. In men >60 years old, with other associated disease, with larger bile stones, and with elevated serum bilirubin levels, complications are frequently expected. Under these conditions, laparoscopic approach should be undertaken by especially experienced teams, or OC should be considered.

Effect of smoking on breast cancer in carriers of mutant BRCA1 or BRCA2 genes.

BACKGROUND: Smoking has carcinogenic effects, and possibly antiestrogenic effects as well, but it has not been found to be a risk factor for breast cancer in women in the general population. However, hereditary breast cancer is primarily a disease of premenopausal women, and interactions between genes and hormonal and environmental risk factors may be particularly important in this subgroup. METHODS: We conducted a matched case-control study of breast cancer among women who have been identified to be carriers of a deleterious mutation in either the BRCA1 or the BRCA2 gene. These women were assessed for genetic risk at one of several genetic counseling programs for cancer in North America. Information about lifetime smoking history was derived from a questionnaire routinely administered to women who were found to carry a mutation in either gene. Smoking histories of case subjects with breast cancer and age-matched healthy control subjects were compared. Odds ratios for developing breast cancer were determined for smokers versus nonsmokers by use of conditional logistic regression for matched sets after adjustment for other known risk factors. RESULTS: Subjects with BRCA1 or BRCA2 gene mutations and breast cancer were significantly more likely to have been nonsmokers than were subjects with mutations and without breast cancer (two-sided P = .007). In a multivariate analysis, subjects with BRCA1 or BRCA2 mutations who had smoked cigarettes for more than 4 pack-years (i.e., number of packs per day multiplied by the number of years of smoking) were found to have a lower breast cancer risk (odds ratio = 0.46, 95% confidence interval = 0.27-0.80; two-sided P = .006) than subjects with mutations who never smoked. CONCLUSIONS: This study raises the possibility that smoking reduces the risk of breast cancer in carriers of BRCA1 or BRCA2 gene mutations.

Etiology and pathophysiology of primary and recurrent groin hernia formation.

The cause of primary groin hernia is multifactorial with evolutionary, hereditary, congenital, environmental aspects, and the general state of health all playing their part. Besides maintaining general body fitness and not smoking tobacco, there is little one can do to avoid this common affliction. On the other hand, recurrent groin hernia is largely due to easily controllable human factors and can be avoided by choosing an experienced surgeon with a particular interest and understanding of the subject, preferably one who specializes in and confines himself to the surgery of groin hernias, working in a unit dedicated to herniology he will select the best operation for the particular type of hernia and execute it to conform to the highest acceptable standards, using the best materials and techniques. The patient will rapidly, within a matter of days, return to his full, normal activities and can look forward to a success rate of over 99%.

Does the index operation influence the course and outcome of adhesive intestinal obstruction?

OBJECTIVE: To ascertain the incidence of obstruction after various operations and find out if the index operation influenced the course and outcome of adhesive small bowel obstruction. DESIGN: Retrospective study. SETTING: Teaching hospital, Israel. SUBJECTS: 190 of 248 patients who presented with small bowel obstruction between January 1980 and December 1994. INTERVENTIONS: All patients were treated conservatively and operated on only if they did not improve or deteriorated. MAIN OUTCOME MEASURES: Incidence of obstruction depending on site of index operation, and response to treatment. RESULTS: 46 Patients (24%) had undergone upper abdominal operations, 26 (14%) small bowel resection, 47 (25%) appendicectomy, 27 (14%) gynaecological operations, and 44 (23%) colonic resections. The annual incidence of obstructive complications among the 190 patients in the groups studied was highest after appendicectomy (3.1/year) and colonic resections (2.9/year) and lowest after operations on the gallbladder and pancreas (1.1/year). Postoperative adhesive obstruction presented earlier after operations on the small bowel (median 1 year, range 5.4-20) and colon (median 1 year, range 2.2-40) than after the other operations. 60 (32%) of patients with acute small bowel obstruction had a history of abdominal malignancy, and obstruction was more likely to be complete after small bowel resection (20/26, 77%) compared with 39/74 (53%) after appendicectomy or gynaecological surgery, 17/46 (37%) after upper abdominal surgery, and 15/44 (34%) after colonic resection. Patients who developed obstruction after colonic resection had the longest period of conservative treatment (median 60 hours, range 24-216) and had the highest morbidity (8/44, 18%) although only 2 required bowel resection. Two patients died, both after obstruction following upper abdominal operations. CONCLUSIONS: Patients who present with obstruction after small bowel resection are extremely likely to be completely obstructed. Perhaps the morbidity associated with obstruction after colonic resection could be reduced if patients were operated on earlier.

Laparoscopic cholecystectomy for acute cholecystitis: prospective trial.

This prospective study determines the indications for and the optimal timing of laparoscopic cholecystectomy (LC) following the onset of acute cholecystitis. It also evaluates preoperative and operative factors associated with conversion from laparoscopic cholecystectomy to open cholecystectomy in the presence of acute cholecystitis. Having been established as the procedure of choice for elective cholelithiasis, LC is now also used for management of acute cholecystitis. Under these circumstances the procedure may be difficult and challenging. Certain favorable and unfavorable conditions may be present that influence the conversion and complication rates. Information about these conditions may be helpful for elucidating the optimal circumstances for LC or when the procedure is best avoided. We performed LC on an emergency basis as soon as the diagnosis was made on all patients presenting with acute cholecystitis from January 1994 to December 1995. All preoperative, operative, and postoperative data were collected on standardized forms. Of the 137 patients registered, 130 were eligible for the audit. Seven patients found by laparoscopic intraoperative cholangiography to have choledocholithiasis were converted for common bile duct exploration and were excluded from the study. Altogether 83 patients (72%) underwent successful LC and 37 (28%) needed conversion to open cholecystectomy. The conversion rate of acute gangrenous cholecystitis (49%) was significantly higher than that for uncomplicated acute cholecystitis (4.5%) (p < 0.00001) and for hydrops (28.5%) and empyema of the gallbladder (28.5%) (p = 0.004). The difference in conversion between the group with acute necrotizing (gangrenous) cholecystitis and the two groups with hydrops and empyema of the gallbladder was not statistically significant (p = 0.07). The complication rates of acute cholecystitis, hydrops, empyema of the gallbladder, and gangrenous cholecystitis were 9.0%, 9.5%, 14.0%, and 20.0%, respectively (p = NS). Patients with an operative delay of 96 hours or less from the onset of acute cholecystitis had a conversion rate of 23%, whereas a delay of more than 96 hours was associated with a conversion rate of 47% (p = 0.022). The complication rate was 8.5% in the laparoscopic group and 27% in the converted group (p = 0.013). Patients over 65 years of age, with a history of biliary disease, a nonpalpable gallbladder, WBC count over 13,000/cc, and acute gangrenous cholecystitis were independently associated with a high LC conversion rate; male patients, finding large bile stones, serum bilirubin over 0.8 mg/dl, and WBC count over 13,000/cc were independently associated with a high complication rate following laparoscopic surgery with or without conversion. Generally, LC can be performed safely for acute cholecystitis, with acceptably low conversion and complication rates. Different forms of cholecystitis carry various conversion and complication rates in selected cases. LC for acute cholecystitis should be performed within 96 hours of the onset of disease. Predictors of conversion and complications may be helpful when planning the laparoscopic approach to acute cholecystitis.

Delay of surgery in acute appendicitis.

BACKGROUND AND OBJECTIVES: It is generally assumed that delayed diagnosis of acute appendicitis results in higher morbidity but this assumption is not strongly supported in the literature. We attempt to define the effect of patient and physician delay on the outcome of patients with acute appendicitis. PATIENTS AND METHODS: We studied 486 patients admitted between 1980 and 1992. Patient delay in presenting to a physician and surgeon delay from hospital admission to operation were studied in relation to stage of disease at operation as well as to postoperative complications. RESULTS: Postoperative complications occurred in 10% of cases with simple acute appendicitis versus about 20% of cases with gangrenous or perforated appendicitis (P <0.001). The mean patient delay from onset of symptoms to presentation to a physician was 1.7 days in simple acute appendicitis versus 2.3 days in gangrenous or perforated appendicitis (P <0.001). Mean surgeon delay was 13.6 hours in simple acute appendicitis versus 14.5 hours in advanced appendicitis (P = NS). CONCLUSION: Delay in patient presentation adversely affects the stage of disease in acute appendicitis and leads to increased incidence of infectious complications and to prolonged hospital stay. Conversely, physician delay does not affect the stage of disease. A surgeon's decision to observe patients in hospital in order to clarify the diagnosis is justified, as it does not adversely affect outcome.