AIM Recent clinical experience suggests that minimal access portoenterostomy (the Kasai procedure) for biliary atresia leads to transplantation sooner, compared to the traditional open approach. It should be emphasized that elevated intra-abdominal pressure (IAP) may reduce hepatic and portal blood flow and thus may cause histologic liver damage. The aim of the present study was to evaluate the effects of IAP on blood flow in the portal vein (PV), compared to the superior mesenteric artery (SMA), and on the systemic mean arterial blood pressure (MABP). MATERIALS AND METHODS Male Sprague-Dawley rats were anesthetized with intraperitoneal ketamine (90 mg per kg) and xylasine (13 mg per kg). Polyethylene catheters (PE-50) were introduced into the right carotid artery for the measurement of MABP. After a midline laparotomy, the SMA and PV were isolated. Ultrasonic blood-flow probes were placed on the vessels for the continuous measurement of regional blood flow. Two large-caliber percutaneous peripheral intravenous catheters were introduced into the peritoneal cavity for inflation of air and for the measurement of IAP. The time course of MABP and SMA and PV flow as well as the relationship between IAP and SMA and PV flow were determined. RESULTS Although all three hemodynamic parameters decreased with the increase in the IAP, the most significant changes were observed in PV blood flow. IAP at 3 mm Hg resulted in a 26% decrease in PV flow (P < 0.05), a 19% decrease in SMA flow (P < 0.05), and an 11% decrease in MABP (P < 0.05). IAP at 6 mm Hg caused a two-fold decrease in PV flow (P < 0.05), a 30% decrease in SMA flow (P < 0.05), and a 19% decrease in MABP (P < 0.05). There were no changes in the time course of MABP and PV and SMA flow. PV and SMA flow returned to normal values immediately after abdominal deflation. CONCLUSIONS Persistent IAP decreased MABP, SMA, and, especially, PV flow by 50%. We speculate that in biliary atresia patients with already present liver dysfunction, decrease in SMA flow and even a greater decrease in PV flow from increased IAP, which occurs during a laparoscopic Kasai procedure, may further compromise liver function. This may be one of the explanations for the progression to earlier transplantation in infants undergoing a laparoscopic Kasai procedure.

BACKGROUND/PURPOSE:Indications for a laparoscopic approach for the management of biliary atresia in children are not clearly defined. We have recently shown that persistent intra-abdominal pressure (IAP) significantly decreased portal vein (PV) flow. Ventilation with a high concentration of oxygen after abdomen deflation raises concerns of increased oxidative stress but has also been shown to exert beneficial effects on splanchnic ischemia/reperfusion. The purpose of the present study was to evaluate the effects of IAP and hyperoxia on liver histology, hepatocyte proliferation and apoptosis in a rat model of abdominal compartment syndrome (ACS).METHODS:Male Sprague-Dawley rats were anesthetized with intraperitoneal ketamine and xylasine. After a midline laparotomy, the PV was isolated. Ultrasonic blood flow probes were placed on the vessel for continuous measurement of regional blood flow. Mean arterial blood pressure (MABP) was continuously measured. Two large-caliber percutaneous peripheral intravenous catheters were introduced into the peritoneal cavity for inflation of air and measurement of IAP. Rats were divided into three experimental groups: 1) Sham rats were subjected to IAP of 0 mmHg; 2) ACS rats were subjected to IAP of 6 mmHg for 2 hours and were ventilated with air; and 3) ACS-O (2) rats were subjected to IAP of 6 mmHg for 2 hours and were ventilated with 100 % O (2) during the operation and ventilation was continued for 6 hours after operation. Liver structural changes, hepatocyte proliferation (using BrdU assay) and apoptosis (using Tunel assay) were determined 24 hours following operation.RESULTS:IAP at 6 mmHg caused a twofold decrease in PV flow compared to sham animals. Hyperoxia resulted in a less significant decrease in PV flow compared to air-ventilated animals. Despite a significant decrease in PV blood flow, 24 hours after abdominal deflation only a few animals demonstrated histological signs of liver damage. The small histological changes were accompanied by increased hepatocyte apoptosis and enhanced hepatocyte proliferation in 25 % of animals, suggesting a liver repair response.CONCLUSIONS:Despite a significant decrease in PV blood flow, persistent IAP for 2 hours results in few changes in liver histology, and stimulates hepatocyte proliferation and apoptosis in only a few animals, supporting the presence of a recovering mechanism. Treatment with hyperoxia did not significantly change hepatocyte proliferation and apoptosis.

Although bactibilia is an important condition of acute cholecystitis, its effect on the course and outcome of the infectious gallbladder disease has rarely been studied, particularly in relation to the laparoscopic procedure. The current study attempts to learn more about the inter-relationship between bactibilia and laparoscopic cholecystectomy during acute cholecystitis. Demographic, preoperative, operative, and postoperative data were prospectively collected in every patient with acute cholecystitis treated in the department of surgery at the Bnai Zion Medical Center, Israel. Intraoperative biliary samples were collected under aseptic conditions at the time of operation for bacteriologic examination and were routinely cultured in aerobic and anaerobic media for 3 days. The study population was divided into culture-positive and culture-negative groups, and the collected parameters were compared between the groups. Age over 60 years, a palpable gallbladder, temperature over 37.5 degrees C, a white blood cell (WBC) count of more than 12,000/cc(3), and serum alkaline phosphatase higher than 100 U/dL were all found to be factors capable of predicting bactibilia. Bactibilia was a significant factor associated with total, as well as infectious, operative complications. Bactibilia is considered to indicate an advanced stage of acute cholecystitis. In cases of laparoscopic cholecystectomy for infectious gallbladder disease, bactibilia is strongly associated with total, as well as local, infectious complications. Preoperative conditions such as older age, elevated temperature, a palpable gallbladder, elevated WBC count, and elevated serum levels of alkaline phosphatase can serve as predictors of bactibilia and its consequent complications. Although the sensitivity and specificity of the predictive factors for bactibilia are limited to 63% and 67%, respectively, in their presence during acute cholecystitis, conservative wide-spectrum antibiotics as the first-line therapy is appropriate, and, upon regimen failure, laparoscopic surgery by an experienced surgeon is indicated as the adjusted therapy.

Recent evidence suggests that neutrophil recruitment may initiate germ cell apoptosis in the ischemic testis. The purpose of the present study was to examine the relationship between germ cell apoptosis and neutrophil recruitment in the contralateral testis following testicular ischemia-reperfusion (IR) injury in a rat. Adult male Sprague-Dawley rats were divided randomly into two experimental groups: Group A: Sham operated animals; Group B: IR rats underwent 90 min of unilateral testicular ischemia following by 96 h of reperfusion. The rats were sacrificed and testes were harvested. Johnsen's criteria and the number of germinal cell layers were measured to categorize the spermatogenesis. TUNEL assay was used to determine germ cell apoptosis in both the ischemic and contralateral testis. The recruitment of neutrophils was calculated per 100 venules. Expression of E-selectin was determined using immunohistochemical analysis. Statistical analysis was performed using Student's t test, with P less than 0.05 considered statistically significant. Germ cell apoptosis in both the ischemic and the contralateral testis increased significantly after IR. E-selectin expression was significantly greater in ischemic testis from IR rats compared to sham animals. The small increase in E-selectin expression and the concomitant increase in neutrophil recruitment in the contralateral testis of the IR rats (vs. sham animals) were not statistically significant. In conclusion, testicular ischemia causes an increase in germ cell apoptosis in the contralateral testis. Mechanisms other than neutrophil recruitment apparently initiate this process.

In this study, we investigated the sensitivity, specificity, and predictive values of morphometric parameters of thyroideal follicular neoplasms based on concepts of fractal geometry. Thirty-seven follicular adenomas and 36 well-differentiated follicular carcinomas were assessed morphometrically. The nuclear area, nuclear area fraction, nuclear regularity factor, nuclear elongation factor, and slope setting (representing the ratio between the nuclear perimeter and nuclear regularity factor) were subjected to fractal dimensions analysis. By univariate analysis, the nuclear area, nuclear area fraction, nuclear regularity factor and slope values discriminate between adenomas and carcinomas. By multivariate analysis, the nuclear area, nuclear area fraction and slope values possess significant discriminatory powers in distinguishing between adenomas and carcinomas. Incorporating the nuclear area, nuclear area fraction, and slope values leads to a discriminatory power with 92% specificity and 83% sensitivity. The reciprocal relationships between the nuclear area, nuclear perimeter, and nuclear regularity factor of the cells of thyroideal adenomas and carcinomas may be expressed by fractal dimensions. Analysis limited to one parameter provides incomplete data. Expressing variations of the nuclear perimeter as a function of the nuclear regularity factor, the slope values constitute an independent attribute that significantly differentiates thyroideal adenomas from carcinomas.

When acute cholecystitis follows orthopaedic operations, the disease is frequently obscure and fulminating, with rapid progress to gangrene and perforation of the gallbladder, which may be fatal. Three cases are reported and the literature is reviewed. Various aspects of the disorder are discussed. It is important that orthopaedic surgeons should be aware of the condition in order to be able to make an early diagnosis and so prevent a lethal outcome.

Primary leiomyosarcoma of the inferior vena cava (IVC) is a rare disease with fewer than 220 cases reported in the literature. Symptoms usually develop late in the course of the disease delaying the diagnosis and worsening the prognosis. Curative treatment consists of total surgical resection of the tumour with interposition grafting for the missing portion of the IVC. The reported 5 year survival rate ranges from 37 to 53%.

OBJECTIVE In studying patients with chronic fatigue syndrome (CFS) we developed a method that confers numerical expression to the degree of blood pressure and heart rate lability, ie, the 'hemodynamic instability score' (HIS). The HIS in CFS patients differed significantly from healthy subjects. The present investigation compares the HIS in CFS, non-CFS chronic fatigue and patients with recurrent syncope. METHODS Patients with CFS (n = 21), non-CFS chronic fatigue (n = 24), syncope of unknown cause (n = 44), and their age and sex-matched healthy controls (n = 21) were evaluated with a standardized head-up tilt test (HUTT). Abnormal reactions (endpoints) on HUTT were classified 'clinical outcomes' (cardioinhibitory or vasodepressor reaction, orthostatic hypotension, postural tachycardia syndrome) and 'HIS endpoint', i.e. HIS >-0.98. RESULTS The highest incidence of endpoints was noted in patients with CFS (79%), followed by patients with syncope of unknown cause (46%), non-CFS chronic fatigue (35%), and healthy subjects (14%). Presyncope or syncope during tilt occurred in 38% of CFS patients, 21% of patients with non-CFS chronic fatigue, and 43% of patients with recurrent syncope. The average HIS values were: CFS = +2.02 (SD 4.07), non-CFS chronic fatigue = -2.89 (SD 3.64), syncope = -3.2 (SD 3.0), healthy = -2.48 (4.07). The odds ratios for CFS patients to have HIS >-0.98 was 8.8 compared with non-CFS chronic fatigue patients, 14.6 compared with recurrent syncope patients, and 34.8 compared with healthy subjects. CONCLUSION The cardiovascular reactivity in patients with CFS has certain features in common with the reactivity in patients with recurrent syncope or non-CFS chronic fatigue, such as the frequent occurrence of vasodepressor reaction, cardioinhibitory reaction, and postural tachycardia syndrome. Apart from to these shared responses, the large majority of CFS patients exhibit a particular abnormality which is characterized by HIS values >-0.98. Thus, HIS >-0.98 lends objective criteria to the assessment of CFS.

Response of breast carcinomas to tamoxifen treatment depends, among others, on the estrogen receptor status. The estrogen receptor content was semiquantitatively determined in immunostained sections of stage 1 and 2 cancers of patients who had undergone tumor excision, tamoxifen treatment, adjuvant chemotherapy and radiotherapy. Weighted scores of the estrogen receptor content of the tumors were established by calculating the arithmetic means of the intensity of stained nuclei and the number of positively stained nuclei. Statistically, a cut-off value of > or = 2.1 signified a good prognosis; all patients whose tumors disclosed a weighted score of > or = 2.1 were alive and free of disease at the 10-year postoperative follow-up examination. On the other hand, one third of the patients whose carcinomas had a weighted score of < 2.1 presented with locally recurrent cancer, distant metastases, or both during the follow-up observation period. The statistically significant association between the patients' 10-year event-free survival and carcinomas with a weighted score of > or = 2.1 may serve oncologists in their decision making with respect to hormonal treatment.

Laparoscopic cholecystectomy is now also performed for acute cholecystitis. In the presence of inflammatory conditions, technical difficulties leading to conversion to open cholecystectomy may occur and overshadow the advantages of the laparoscopic approach. Factors associated with these undue events combined with techniques capable of learning from them may help in determining when to completely avoid the laparoscopic procedure. In this study we determined predictors of conversion in acute cholecystitis and tested their predictive ability by means of statistical multivariate analysis and artificial neural networks. Between January 1994 and February 1997, 225 patients underwent laparoscopic cholecystectomy for acute cholecystitis. Preoperative and operative data were prospectively collected on standardized forms. The first 180 laparoscopically approached cases entered the training set, which was learned by both the statistical and the artificial neural networks methods. Conversion was first studied in relation to a set of preoperative data. Prediction models were then fitted by both of these methods. The last 45 operated cases, which remained unknown to the learning systems, served for testing the fitted models. The forward stepwise logistic regression technique, the forward stepwise linear discriminant analysis, and the artificial neural networks method enabled positive prediction of conversion in 0%, 27%, and 100% of the cases, and a negative prediction in 80%, 85.5%, and 97% respectively, in the training set. A positive prediction of conversion in 0%, 25%, and 67% of the cases, and a negative prediction in 82%, 88%, and 94%, respectively, in the untrained, validation set of patients. An artificial neural networks based model provides a practical tool for the prediction of successful laparoscopic cholecystectomies and their conversion. The high degree of certainty of prediction in untrained cases reveals its potential, and justifies, under appropriate conditions, the complete avoidance of laparoscopy and turning directly to open cholecystectomy.

The normal response to postural challenge is characterised by maintenance of relatively stable blood pressure (BP) and heart rate (HR) after 30 sec to 30 min of head-up tilt. The objective of the present study was to determine the degree of instability of cardiovascular responses to postural challenge in normotensive and hypertensive subjects. In the initial phase of the study, two groups of age and sex-matched subjects were assessed: essential hypertension (n = 20) and healthy (n = 37). The BP and HR were recorded at 5-min intervals during the course of the 10-min supine-30-min head-up tilt test (HUTT). We categorised ‘BP-change’ as the difference between individual BP measurements during HUTT and the last recumbent BP value, divided by latter value. The average and standard deviation (SD) of the recorded BP changes were calculated, and BP changes were plotted along a time curve. A computerised image analyser then calculated the outline ratio (OR) and fractal dimension (FD) values for each of the curves. An identical process evaluated measurements for HR-changes. BP- and HR-changes were then converted into absolute numbers, and the average, SD, OR, and FD were calculated. A multivariate analysis was conducted, evaluating independent predictors of hypertension. Finally, an equation for the calculation of ‘haemodynamic instability score’ (HIS) was deduced and a cut-off between HIS of hypertensive and normotensive subjects was established. Independent predictors of the cardiovascular response to postural challenge of hypertensives (Group I) vs healthy (Group II) were: a.DIAST-FD, a.HR-AVG, a.HR-SD, a.HR-FD, DIAS-SD and HR-SD and HR-SD. Based on these five predictors, a linear discriminant score was computed and called the Haemodynamic Instability Score (HIS): HIS = 59.4 + (−16.6*a.DIAST-FD) + (−29.0*a.HR-AVG) + (−82.4*a.HR-SD) + (−30.1*a.HR-FD) + (−57.9*DIAS-SD) + (73.4*HR-SD) The HIS values in Group I (hyper- tensives) were: avg = 3.348, SD = 2.863, and 95% CI for mean = 2.008, 4.688. The HIS values in Group II (healthy) were: avg = −3.394, SD = 2.435, 95% CI for mean = −4.206, −2.582. Values of the HIS >−2.09 were generally observed in hypertensives (sensitivity 95%) and values ⩽−2.09 were usually seen in the healthy (specificity 81.1%). The HIS was cross-validated in an additional group of hypertensive patients (n = 73). In the latter group, the HIS values were: avg = −0.456, SD = 4.403, 95% CI for mean = −1.506, 0.593 and 71.4% sensitivity at the proposed cut-off point. In conclusion, the HIS confers numerical expression to the degree of lability of BP and HR during postural challenge. Based on this score, a distinction between the cardiovascular reactivity of hypertensives vs normotensives is drawn. Possible applications of HIS are discussed.

OBJECTIVES:To evaluate the cardiovascular response to postural challenge in patients with chronic fatigue syndrome (CFS) and to determine whether the degree of instability of the cardiovascular response may aid in diagnosing CFS.METHODS:Patients with CFS (n = 25) and their age- and gender-matched healthy controls (n = 37), patients with fibromyalgia (n = 30), generalized anxiety disorder (n = 15), and essential hypertension (n = 20) were evaluated with the aid of a standardized tilt test. The blood pressure (BP) and heart rate (HR) were recorded during 10 minutes of recumbence and 30 minutes of head-up tilt. We designated BP changes as the differences between successive BP values and the last recumbent BP. The average and standard deviation (SD) were calculated. Time curves of BP differences were loaded into a computerized image analyzer, and their outline ratios and fractal dimensions were measured. HR changes were determined similarly. The average and SD of the parameters were calculated, and intergroup comparisons were performed.RESULTS:On multivariate analysis, the independent predictors of CFS patients versus healthy controls were the fractal dimension of absolute values of the systolic BP changes (SYST-FD.abs), the standard deviation of the current values of the systolic BP changes (SYST-SD.cur), and the standard deviation of the current values of the heart rate changes (HR-SD.cur). The following equation was deduced to calculate the hemodynamic instability score (HIS) in the individual patient: HIS = 64.3303 + (SYST-FD.abs x -68.0135) + (SYST-SD.cur x 111.3726) + (HR-SD.cur x 60.4164). The best cutoff differentiating CFS from the healthy controls was -0.98. HIS values >-0.98 were associated with CFS (sensitivity 97%, specificity 97%). The HIS differed significantly between CFS and other groups (P <.0001) except for generalized anxiety disorder. Group averages (SD) of HIS were CFS = +3.72 (5.02), healthy = -4.62 (2.26), fibromyalgia = -3.27 (2.63), hypertension = -5.53 (2.24), and generalized anxiety disorder = +1.08 (5.2).CONCLUSION:The HIS adds objective criteria confirming the diagnosis of CFS.

Neuropilin-2 (np-2) is a receptor for semaphorin-3F (sema-3F) and semaphorin-3C (sema-3C). These semaphorins repel tips of growing axons that express np-2. In addition, np-2 functions as a receptor for heparin binding forms of the angiogenic factor vascular endothelial growth factor (VEGF) such as VEGF145 and VEGF165. We report that np-2 is strongly expressed in neuroendocrine cells located all along the human digestive tract. Confocal fluorescent microscopy revealed that np-2 is concentrated in vesicle-like structures located near the nucleus at the basolateral side of these cells. In the colon, the np-2-expressing subpopulation of neuroendocrine cell is almost identical with the serotonin-producing subpopulation of neuroendocrine cells. Gastrointestinal carcinoid tumors are digestive tract tumors that develop from neuroendocrine cells. Interestingly, most of the carcinoid tumors derived from the colon and the appendix did not contain np-2-producing cells. However, some carcinoid tumors derived from the small intestine and stomach did express low levels of np-2 in isolated foci of cells. By contrast, strong serotonin and chromogranin-A expression was observed in all of the carcinoid tumors that were examined. These results suggest that loss of np-2 expression may accompany tumor progression in carcinoid tumors.

Purpose: The aim of this work was to detect nuclear parameters related to the prognosis of patients with stage III, IV or DS neuroblastomas. Methods: Histological sections of 25 operation specimens obtained from children with advanced-stage neuroblastomas were subjected to computer-assisted image analysis. Statistical relationships between nuclear descriptors of the tumor cells and patients' clinical outcome were determined. Results: The coefficient of variability of the mean nuclear area the mean nuclear elongation factor, and the mean nuclear averaged Feret diameter of the neuroblastoma cells were ascertained to be discriminators separating high-grade from low-grade tumors. Conclusions: The histomorphometrically gauged nuclear parameters may help oncologists to assess the prognosis of patients with advanced-stage neuroblastoma.

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.

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.

We performed 75 laparoscopic cholecystectomies during July and September 1996. In 3 men and 4 women, aged 32-87 years, there was obstructive jaundice caused by choledocholithiasis. During laparoscopy in the jaundiced patients, calculi were identified by cholangioscopy and intra-operative cholangiography. They were washed into the duodenum (confirmed cholangiographically) after intravenous glucagon injections and dilation of the papilla of Vater. Serum bilirubin and liver enzyme levels returned to normal within a few days. There was no operative or postoperative morbidity, nor any biliary-related systemic complications. Average postoperative hospitalization was 3 days.

The authors studied the effect of ligation of the femoral and saphenous veins on the evolution of lipase injection-induced subcutaneous fibrosis and inflammation in the rats' hindlimbs. The superficial muscular fascia was thickened and the number of veins was increased 3 days and 3 weeks after vein ligation; both abnormalities disappeared 6 weeks postoperatively. Vein ligation did not quantitatively affect fascial thickening or fibrosing panniculitis in hindlimbs injected with lipase 6 weeks prior to sacrifice. The results contradict the proposition that lipase-induced injury of rats' subcutaneous tissues compromised by venous stasis may lead to a persistent chronic inflammation and fibrosis of the subcutaneous-fascial complex duplicating lipodermatosclerosis in man.