Only strongly enhanced residual FDG uptake in early response PET (Deauville 5 or qPET ≥ 2) is prognostic in pediatric Hodgkin lymphoma: Results of the GPOH-HD2002 trial.

PURPOSE: In 2014, we published the qPET method to quantify fluorodeoxyglucose positron emission tomography (FDG-PET) responses. Analysis of the distribution of the quantified signals suggested that a clearly abnormal FDG-PET response corresponds to a visual Deauville score (vDS) of 5 and high qPET values ≥ 2. Evaluation in long-term outcome data is still pending. Therefore, we analyzed progression-free survival (PFS) by early FDG-PET response in a subset of the GPOH-HD2002 trial for pediatric Hodgkin lymphoma (PHL). PATIENTS/METHODS: Pairwise FDG-PET scans for initial staging and early response assessment after two cycles of chemotherapy were available in 93 PHL patients. vDS and qPET measurement were performed and related to PFS. RESULTS: Patients with a qPET value ≥ 2.0 or vDS of 5 had 5-year PFS rates of 44%, respectively 50%. Those with qPET values < 2.0 or vDS 1 to 4 had 5-year PFS rates of 90%, respectively 80%. The positive predictive value of FDG-PET response assessment increased from 18% (9%; 33%) using a qPET threshold of 0.95 (vDS ≤ 3) to 30% (13%; 54%) for a qPET threshold of 1.3 (vDS ≤ 4) and to 56% (23%; 85%) when the qPET threshold was ≥ 2.0 (vDS 5). The negative predictive values remained stable at ≥92% (CI: 82%; 98%). CONCLUSION: Only strongly enhanced residual FDG uptake in early response PET (vDS 5 or qPET ≥ 2, respectively) seems to be markedly prognostic in PHL when treatment according to the GPOH-HD-2002 protocol is given.

Bloodstream infection in paediatric cancer centres--leukaemia and relapsed malignancies are independent risk factors.

UNLABELLED: In a prospective multicentre study of bloodstream infection (BSI) from November 01, 2007 to July 31, 2010, seven paediatric cancer centres (PCC) from Germany and one from Switzerland included 770 paediatric cancer patients (58% males; median age 8.3 years, interquartile range (IQR) 3.8-14.8 years) comprising 153,193 individual days of surveillance (in- and outpatient days during intensive treatment). Broviac catheters were used in 63% of all patients and Ports in 20%. One hundred forty-two patients (18%; 95% CI 16 to 21%) experienced at least one BSI (179 BSIs in total; bacteraemia 70%, bacterial sepsis 27%, candidaemia 2%). In 57%, the BSI occurred in inpatients, in 79% after conventional chemotherapy. Only 56 % of the patients showed neutropenia at BSI onset. Eventually, patients with acute lymphoblastic leukaemia (ALL) or acute myeloblastic leukaemia (AML), relapsed malignancy and patients with a Broviac faced an increased risk of BSI in the multivariate analysis. Relapsed malignancy (16%) was an independent risk factor for all BSI and for Gram-positive BSI. CONCLUSION: This study confirms relapsed malignancy as an independent risk factor for BSIs in paediatric cancer patients. On a unit level, data on BSIs in this high-risk population derived from prospective surveillance are not only mandatory to decide on empiric antimicrobial treatment but also beneficial in planning and evaluating preventive bundles. WHAT IS KNOWN: • Paediatric cancer patients face an increased risk of nosocomial bloodstream infections (BSIs). • In most cases, these BSIs are associated with the use of a long-term central venous catheter (Broviac, Port), severe and prolonged immunosuppression (e.g. neutropenia) and other chemotherapy-induced alterations of host defence mechanisms (e.g. mucositis). What is New: • This study is the first multicentre study confirming relapsed malignancy as an independent risk factor for BSIs in paediatric cancer patients. • It describes the epidemiology of nosocomial BSI in paediatric cancer patients mainly outside the stem cell transplantation setting during conventional intensive therapy and argues for prospective surveillance programmes to target and evaluate preventive bundle interventions.

Life partnerships in childhood cancer survivors, their siblings, and the general population.

BACKGROUND: Life partnerships other than marriage are rarely studied in childhood cancer survivors (CCS). We aimed (1) to describe life partnership and marriage in CCS and compare them to life partnerships in siblings and the general population; and (2) to identify socio-demographic and cancer-related factors associated with life partnership and marriage. METHODS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS), a questionnaire was sent to all CCS (aged 20-40 years) registered in the Swiss Childhood Cancer Registry (SCCR), aged <16 years at diagnosis, who had survived ≥ 5 years. The proportion with life partner or married was compared between CSS and siblings and participants in the Swiss Health Survey (SHS). Multivariable logistic regression was used to identify factors associated with life partnership or marriage. RESULTS: We included 1,096 CCS of the SCCSS, 500 siblings and 5,593 participants of the SHS. Fewer CCS (47%) than siblings (61%, P < 0.001) had life partners, and fewer CCS were married (16%) than among the SHS population (26%, P > 0.001). Older (OR = 1.14, P < 0.001) and female CCS (OR = 1.85, <0.001) were more likely to have life partners. CCS who had undergone radiotherapy, bone marrow transplants (global P Treatment = 0.018) or who had a CNS diagnosis (global P Diagnosis < 0.001) were less likely to have life partners. CONCLUSION: CCS are less likely to have life partners than their peers. Most CCS with a life partner were not married. Future research should focus on the effect of these disparities on the quality of life of CCS.

A composite score combining waist circumference and body mass index more accurately predicts body fat percentage in 6- to 13-year-old children.

PURPOSE: Body mass index (BMI) and waist circumference (WC) are widely used to predict % body fat (BF) and classify degrees of pediatric adiposity. However, both measures have limitations. The aim of this study was to evaluate whether a combination of WC and BMI would more accurately predict %BF than either alone. METHODS: In a nationally representative sample of 2,303 6- to 13-year-old Swiss children, weight, height, and WC were measured, and %BF was determined from multiple skinfold thicknesses. Regression and receiver operating characteristic (ROC) curves were used to evaluate the combination of WC and BMI in predicting %BF against WC or BMI alone. An optimized composite score (CS) was generated. RESULTS: A quadratic polynomial combination of WC and BMI led to a better prediction of %BF (r (2) = 0.68) compared with the two measures alone (r (2) = 0.58-0.62). The areas under the ROC curve for the CS [0.6 * WC-SDS + 0.4 * BMI-SDS] ranged from 0.962 ± 0.0053 (overweight girls) to 0.982 ± 0.0046 (obese boys) and were somewhat greater than the AUCs for either BMI or WC alone. At a given specificity, the sensitivity of the prediction of overweight and obesity based on the CS was higher than that based on either WC or BMI alone, although the improvement was small. CONCLUSION: Both BMI and WC are good predictors of %BF in primary school children. However, a composite score incorporating both measures increased sensitivity at a constant specificity as compared to the individual measures. It may therefore be a useful tool for clinical and epidemiological studies of pediatric adiposity.

Clustering of health behaviours in adult survivors of childhood cancer and the general population.

BACKGROUND: Little is known about engagement in multiple health behaviours in childhood cancer survivors. METHODS: Using latent class analysis, we identified health behaviour patterns in 835 adult survivors of childhood cancer (age 20-35 years) and 1670 age- and sex-matched controls from the general population. Behaviour groups were determined from replies to questions on smoking, drinking, cannabis use, sporting activities, diet, sun protection and skin examination. RESULTS: The model identified four health behaviour patterns: 'risk-avoidance', with a generally healthy behaviour; 'moderate drinking', with higher levels of sporting activities, but moderate alcohol-consumption; 'risk-taking', engaging in several risk behaviours; and 'smoking', smoking but not drinking. Similar proportions of survivors and controls fell into the 'risk-avoiding' (42% vs 44%) and the 'risk-taking' cluster (14% vs 12%), but more survivors were in the 'moderate drinking' (39% vs 28%) and fewer in the 'smoking' cluster (5% vs 16%). Determinants of health behaviour clusters were gender, migration background, income and therapy. CONCLUSION: A comparable proportion of childhood cancer survivors as in the general population engage in multiple health-compromising behaviours. Because of increased vulnerability of survivors, multiple risk behaviours should be addressed in targeted health interventions.

Use of linezolid in neonatal and pediatric inpatient facilities--results of a retrospective multicenter survey.

The purpose of this investigation was to describe the use of linezolid in pediatric inpatient facilities. A retrospective multicenter survey including data from nine participating tertiary care pediatric inpatient facilities in Germany and Austria was undertaken. Data on 126 off-label linezolid treatment courses administered to 108 patients were documented. The survey comprises linezolid treatment in a broad spectrum of clinical indications to children of all age groups; the median age was 6.8 years (interquartile range 0.6-15.5 years; range 0.1-21.2 years; ten patients were older than 18 years of age but were treated in pediatric inpatient units). Of the 126 treatment courses, 27 (21%) were administered to preterm infants, 64 (51%) to pediatric oncology patients, and 5% to patients soon after liver transplantation. In 25%, the infection was related to a medical device. Linezolid iv treatment was started after intensive pre-treatment (up to 11 other antibiotics for a median duration of 14 days) and changed to enteral administration in only 4% of all iv courses. In 39 (53%) of 74 courses administered to children older than 1 week and younger than 12 years of age, the dose was not adjusted to age-related pharmacokinetic parameters. In only 17 courses (13%) was a pediatric infectious disease consultant involved in the clinical decision algorithm. Linezolid seemed to have contributed to a favorable outcome in 70% of all treatment courses in this survey. Although retrospective, this survey generates interesting data on the off-label use of linezolid and highlights several important clinical aspects in which the use of this rescue antibiotic in children might be improved.

H-ficolin serum concentration and susceptibility to fever and neutropenia in paediatric cancer patients.

H-ficolin (Hakata antigen, ficolin-3) activates the lectin pathway of complement similar to mannose-binding lectin. However, its impact on susceptibility to infection is currently unknown. This study investigated whether the serum concentration of H-ficolin at diagnosis is associated with fever and neutropenia (FN) in paediatric cancer patients. H-ficolin was measured by time-resolved immunofluorometric assay in serum taken at cancer diagnosis from 94 children treated with chemotherapy. The association of FN episodes with H-ficolin serum concentration was analysed by multivariate Poisson regression. Median concentration of H-ficolin in serum was 26 mg/l (range 6-83). Seven (7%) children had low H-ficolin (< 14 mg/l). During a cumulative chemotherapy exposure time of 82 years, 177 FN episodes were recorded, 35 (20%) of them with bacteraemia. Children with low H-ficolin had a significantly increased risk to develop FN [relative risk (RR) 2.24; 95% confidence interval (CI) 1.38-3.65; P = 0.004], resulting in prolonged duration of hospitalization and of intravenous anti-microbial therapy. Bacteraemia occurred more frequently in children with low H-ficolin (RR 2.82; CI 1.02-7.76; P = 0.045). In conclusion, low concentration of H-ficolin was associated with an increased risk of FN, particularly FN with bacteraemia, in children treated with chemotherapy for cancer. Low H-ficolin thus represents a novel risk factor for chemotherapy-related infections.

Fulminant Essential Thrombocythemia Associated with Acquired Von Willebrand Syndrome and Bleeding Episodes in a 14-year-old Girl.

BACKGROUND: Essential thrombocythemia is a chronic myeloproliferative neoplasm. It is extremely rare in children below 15 years of age with an estimated annual incidence of only 0.09 per million. Usually, clinical symptoms associated with essential thrombocythemia are mild or absent. CASE: Here, we present the case of a 14-year-old female patient fulminantly presenting with acute symptoms comprising visual impairment, palmar and plantar stabbing pain. Blood count revealed massive thrombocytosis of 2373 × 109/L. Bone marrow morphology showed elevated numbers of mature megakaryocytes. Von Willebrand factor activity/antigen ratio was significantly reduced compatible with an acquired Von Willebrand syndrome associated with high platelet counts. Molecular analyses for driver mutations of myeloproliferative neoplasms including JAK2V617F, CALR and MPL were negative. Acute therapy comprising hyperhydration and oxygen supply complemented by acetylsalicylic acid led to amelioration of symptoms. Medication with hydroxycarbamide maintained a significant reduction of platelet counts but had to be reduced or withheld several times due to neutropenia. Repeated bleeding episodes observed in the course were clearly associated with increases in platelet counts above 1200 × 109/L explained by acquired von Willebrand syndrome. Sixteen months after diagnosis, therapy was switched to pegylated interferon and platelet counts could be stabilized without significant side effects.

Obesity in long-term survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) with current cure rates reaching 80% emphasizes the necessity to determine treatment related long-term effects. The present study examines the prevalence of and the risk factors for overweight and obesity in a cohort of ALL survivors treated and living in the French speaking part of Switzerland. METHODS: In this retrospective two-center study, height and weight of 54 patients diagnosed with ALL in first complete remission and treated with chemotherapy only were recorded at specified time points during treatment and off-therapy. Body mass index (BMI) and its age- and gender-adjusted standard deviation score (BMI-SDS) were calculated for the patients and their parents separately. Overweight and obesity were defined by a threshold of BMI-SDS >1.645 and BMI-SDS >1.96, respectively. RESULTS: At last follow-up, 16 (30%) of the 54 survivors were overweight and 10 (18%) were obese. The off-treatment period was most at risk with 11 of the 16 becoming overweight and 9 of the 10 becoming obese during that period. Overweight/obesity at diagnosis and abnormal maternal BMI were significantly associated with abnormal weight at follow-up, while age at diagnosis, gender, cumulative dose of steroids and paternal BMI showed no association. CONCLUSIONS: Consistent with published evidence from other regions of the developed and developing world, there is a significant prevalence of obesity in young ALL survivors in the French speaking part of Switzerland. Factors significantly associated with this late effect were mostly related to the familial background rather than to the treatment components.

Alveolar echinococcosis of the liver: sequelae of chronic inferior vena cava obstructions in the hepatic segment.

BACKGROUND: The clinical pattern and long-term course of chronic inferior vena cava (IVC) obstructions are variable and depend on the underlying cause, the segment involved, and the extension of secondary thrombosis. Pertinent data on IVC obstructions in well-defined series of patients are lacking. We report the sequelae of chronic IVC obstructions in the hepatic segment in 11 consecutive patients derived from a cohort of 104 patients with alveolar echinococcosis of the liver. METHODS: Based on the results of computed tomography scans, 11 patients (7 men, 4 women; mean age, 53.4 years) with IVC obstructions were selected from an ongoing prospective long-term chemotherapy trial comprising 104 patients with alveolar echinococcosis studied at yearly intervals according to a protocol. Obstruction of the IVC in the 11 patients existed for a mean duration of 8.6 years. In these patients, magnetic resonance imaging was performed to assess the morphologic features and extension of the IVC obstruction, as well as the collateral venous pathways. Patency and valvular function of the femoropopliteal veins were analyzed by color-coded duplex ultrasonography. RESULTS: Total occlusions of the IVC were evident in 8 patients (73%) and subtotal stenoses in 3 patients (27%). Only 4 patients (36%) exhibited signs and symptoms of chronic venous insufficiency of the lower extremities; 2 (18%) of the 4 had a history of swelling in the lower extremity. Seven patients (64%) had no lower extremity symptoms. One patient had a history of pulmonary embolism. Abdominal collateral veins were documented in 5 patients (45%) by using magnetic resonance imaging; however, they were clinically evident in only 3 patients (27%). In the 8 patients with IVC occlusion, thrombosis ended at the confluence of the hepatic veins. Obstruction of the IVC was limited to the hepatic segment in 2 patients (18%) and extended to the distal IVC or the iliofemoral veins in 6 patients (54%). Chronic venous insufficiency was present only if the femoropopliteal veins had been involved in the thrombotic process, showing residual venous obstruction, valvular incompetence, or both. Bilateral renal vein thrombosis with moderate proteinuria was observed in 2 patients (18%). The main collateral drainage was achieved through the ascending lumbar, azygos, and hemiazygos veins. CONCLUSIONS: In patients with alveolar echinococcosis, obstruction of the IVC in the hepatic segment often develops asymptomatically and rarely leads to the impairment of renal function. The collateral circulation fully compensates for obstruction of the IVC. Thrombotic involvement and valvular incompetence of the femoropopliteal veins seems to determine the development of chronic venous insufficiency of the lower extremities.

Mutational analysis of the first 14 exons of the adenomatous polyposis coli (APC) gene.

In the present study, the polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) technique has been applied to the mutation analysis of the adenomatous polyposis coli (APC) gene. We examined the first 14 exons of the APC gene in 46 polyposis coli patients. Five germline mutations were observed, including a single-nucleotide substitution and small (1-4 bp) deletions leading, in 4 cases, to a stop codon. A missense mutation in exon 3 and a 1 bp deletion in exon 4 of the APC gene were observed in patients presenting with the attenuated form of FAP.

5'-Cytosine DNA-methyltransferase mRNA levels in hereditary colon carcinoma.

DNA methylation plays an important part in the regulation of gene expression. Alterations in DNA methylation in tumours have been reported and have been used to generate hypotheses about mutagenesis and silencing of tumour suppressor genes. However, the underlying mechanism is still poorly understood, and conflicting data on the levels of overexpression of 5'-cytosine DNA methyltransferase in sporadic colon carcinoma have been published. We used a competitive RT-PCR assay for quantification of mRNA of 5'-cytosine DNA methyltransferase in colon biopsies obtained from patients with hereditary colon carcinoma syndromes and compared the results with those obtained in a control group. No significant difference was found between the flat mucosa of FAP patients and the mucosa of the control group. In FAP and HNPCC patients, the 5'-cytosine DNA methyltransferase mRNA levels of adenomas were significantly higher (P<0.05) than of flat mucosa in the same group, but both showed great variability from patient to patient. Our findings suggest that the mRNA levels of methyltransferase cannot be used as predictive marker for screening in families affected by hereditary colon carcinoma.

Recurrence rate after discontinuation of long-term mebendazole therapy in alveolar echinococcosis (preliminary results).

The recurrence rate was investigated in 19 patients with non-resectable alveolar echinococcosis after discontinuation of a long-term therapy with mebendazole (average treatment 4.3 years). A control group consisted of 14 patients who underwent radical surgery and finished a course of prophylactic postoperative mebendazole treatment of 2 years. In the controls, no recurrence was observed after a post-therapy period averaging 3.5 years. In contrast, recurrence occurred in 7/19 patients (37%) with non-resectable alveolar echinococcosis an average of 1.6 years after discontinuation of the long-term mebendazole therapy. The absence of clinically detectable recurrence in the remaining 12 patients seems to be due either to spontaneous inactivation of alveolar echinococcosis preceding chemotherapy or too short post-therapy surveillance. The patients with recurrence responded favorably to reintroduction of chemotherapy. The data indicate that mebendazole therapy is parasitostatic rather than parasiticidal.

Specific cellular and humoral immune responses in patients with different long-term courses of alveolar echinococcosis (infection with Echinococcus multilocularis).

Alveolar echinococcosis is a serious and often fatal disease of humans that in most cases can be efficiently cured only by complete surgical resection of the Echinococcus multilocularis lesion. In a few patients, however, a spontaneous cure of the disease has been observed by demonstrating the presence of lesions with dead metacestodes. The present study shows a comparative analysis of the cellular (lymphoproliferative assay) and humoral (antibody activity in an Em2 enzyme-linked immunosorbent assay [ELISA] and immunoblotting) immune response in 1) patients who were cured by a radical surgical resection of the E. multilocularis parasite lesion, 2) patients who had a partial surgical resection of the parasite lesion, 3) patients who had a non-resectable alveolar echinococcosis, and 4) patients who were shown to be spontaneously cured and had lesions with dead parasites. The in vitro lymphoproliferative response to E. multilocularis antigen stimulation was very high in cured patients who had radical surgery or in patients with lesions containing dead parasites, but it was significantly lower in patients who had partial surgical or no resection. Antibody concentrations in the Em2-ELISA were high in patients who had incomplete or no surgery, and low or negative in cured patients who had radical surgery or in patients with lesions containing dead parasites. Immunoblot analysis of patient sera revealed a consistent antibody banding pattern among cured patients with radical surgery and patients with incomplete or no surgery, whereas cured patients with lesions containing dead parasites showed a very faint antibody pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of plasma mebendazole concentrations in the treatment of human echinococcosis.

High oral doses of mebendazole were given for a mean period of 23 months to 22 patients with inoperable alveolar or cystic echinococcosis (Echinococcus multilocularis n = 18, E. granulosus n = 4). Clinical, morphological, biochemical and serological findings and plasma mebendazole levels were monitored. Clinical and biochemical improvement or stabilization was observed in 17 patients but the parasitic lesions did not decrease in size in most instances. One patient died shortly after onset of therapy with hemorrhage of esophageal varices. Three patients with alveolar and one with cystic echinococcosis had evidence of progressive disease such as increase of cholestasis, destruction of lumbar vertebrae and growth of an intraperitoneal cyst. The plasma mebendazole levels (4 hr after the morning dose) of the latter 4 patients were 0.09 +/- SD 0.02 mumol/l, while in those with clinical stabilization or improvement it was 0.30 +/- SD 0.14 mumol/l (P less than 0.001). These preliminary data indicate 1) a good clinical response to chemotherapy in most patients despite unchanged size of the parasitic lesions, and 2) a direct correlation of clinical response with plasma mebendazole levels.

Does acute pancreatitis progress to chronic pancreatitis? A microvascular pancreatitis model in the rat.

Ischemia as a causative factor for acute pancreatitis has been discussed for decades but has only recently gained wider acceptance. Chronic pancreatitis, however, has rarely been attributed to ischemic injury. While experimental evidence is available for the ischemic pathogenesis of acute pancreatitis, no studies have been reported about pancreatic ischemia as a single cause of chronic pancreatitis. Also, the progression from acute to chronic pancreatitis has been a very controversial issue. To address both questions we have injected polystyrene microspheres of 20-microns diameter into the pancreatic branches of the splenic artery of 36 rats. Thirteen more rats were sham operated and injected with saline. The animals were killed at 1, 2, 3, and 9 weeks after operation and macroscopically and histologically examined, and serum alpha-amylase and weight gain were determined. For the pancreas the following parameters were assessed using a score from 0 (no change) to 4 (severe change): atrophy, hemorrhage, edema, fat necrosis, acinar necrosis, polymorphonuclear infiltration, mononuclear infiltration, interstitial fibrosis, and ductal changes. While no difference between control and experiment was observed for serum alpha-amylase, weight gain, edema, and hemorrhage, persistent differences were evident for the parameters characteristic of chronic pancreatitis, most significantly for interstitial fibrosis, ductal changes, mononuclear infiltration, acinar necrosis, and atrophy. No spontaneous deaths occurred. The severity of the lesions remained stationary after the first week. Our work shows for the first time that pancreatic ischemia by microvascular hypoperfusion can cause histopathologic changes characteristic of chronic pancreatitis and that these changes follow acute necrotizing pancreatitis.

Lipasuria in acute pancreatitis: result of tubular dysfunction?

Lipase, in contrast to amylase, is completely reabsorbed by the proximal tubules after glomerular filtration. Therefore, no lipase is detectable in the unconcentrated urine according to the current opinion. The handling of lipase (detected with an enzyme-immunoassay) by the kidney was investigated in comparison with creatinine, amylase, and beta-2-microglobulin by clearance studies in acute pancreatitis (n = 10), burn injury (n = 4), glomerular proteinuria (n = 8), and controls without evidence of pancreatic or renal diseases (n = 5). In initial stages of acute pancreatitis a measurable clearance of lipase (mean: 49.6 microliters/min, range: 0.5-234) was found in association with corresponding increased clearances of beta-2-microglobulin (mean: 10.5 ml/min, range: 0.02-58.9) and of amylase (mean: 8.9 ml/min, range: 2.4-22.6) in nine of ten patients. This finding is consistent with a defect of tubular function. However, regression analysis failed to show a significant correlation between lipase and beta-2-microglobulin clearance. Repeated measurements during the course of pancreatitis in seven patients showed reversibility of tubular dysfunction. In patients with burn injury a similar elevation of clearances of beta-2-microglobulin and of amylase was found, but tubular dysfunction in this condition was not associated with lipasuria. In glomerular proteinuria a lipase clearance was found in two of five cases with moderate, and in the other three cases with severe impairment of creatinine clearance. beta-2-microglobulin clearance was normal in the former and only slightly elevated in the latter group. In conclusion lipase is measurable in the urine of most patients with acute pancreatitis as a result of a reversible tubular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholic nonprogressive chronic pancreatitis: prospective long-term study of a large cohort with alcoholic acute pancreatitis (1976-1992).

140 patients with alcoholic acute (recurrent) pancreatitis were enrolled in a prospective long-term study over the last 16 years. Regular control studies regarding progression to advanced chronic pancreatitis were performed. Based on long-term outcome the patients were classified into two groups: group A (n = 109; 77.8%) with progression to advanced chronic pancreatitis (84% with calcification, 95% with exocrine insufficiency) and group B (n = 31; 22.2%) without progression (no calcification, no exocrine insufficiency). The two groups were comparable in age, sex, and mean duration of disease from onset (13.1 +/- 5.2 vs. 13.8 +/- 4.9 years). Surgery for pseudocysts was performed in 47% of group A and in 29% of group B. In group B, no pancreatic duct dilatation occurred (in 86% > 8 years from onset). However, 4 of 7 patients with adequate histology showed unequivocal chronic pancreatitis. Surprisingly, all patients of group B except two got spontaneous lasting pain relief irrespective of alcohol intake or normal pancreatic function. Our findings indicate that a subgroup of alcoholic acute pancreatitis does not progress to advanced chronic pancreatitis. This subgroup may be identical with "small duct" chronic pancreatitis. The factors responsible for progression (group A) or nonprogression (group B) remain to be elucidated.

Element distribution in organelles of pancreatic acinar cells of rat, mouse, and pig investigated by energy-dispersive X-ray microanalysis.

The exocrine pancreas was long thought to be composed of identical subunits, the acinar cells that store the inactive forms of the digestive enzymes in zymogen granules (ZGs). These were generally seen as a homogeneous population of vesicles. This homogeneity was recently questioned: Digestive demands are answered by the release of specific enzymes and immunocytochemical labeling showed distinctive nonidentical populations of ZGs. We have aimed at finding concomitant differences in element contents. We analyzed by energy-dispersive x-ray microanalysis (EDX) the subcellular distribution of elements in acinar cells of resting and stimulated rat, resting mouse, and resting pig pancreas and compared the results with values from the literature. We found large variances in the concentrations of Na, Mg, P, S, Cl, K, and Ca in cytoplasm rich in endoplasmic reticulum (C/E), whereas the concentrations of P, Cl, K, and Ca in mitochondria and ZGs had surprisingly small variations. Na and Mg were detected in measurable amounts only in C/E and mitochondria and Ca was detectable only in ZGs. We could not find any other elements. We have not found clearly distinguishable populations of ZGs. We critically discuss our findings in comparison with the literature. Many discrepancies can be explained by the different preparation procedures. We show that it is questionable to present absolute values of concentration in biological specimens on the basis of EDX. The technique should, in our opinion, be used only for the study of relative concentrations.

Injection of microspheres into pancreatic arteries causes acute hemorrhagic pancreatitis in the rat: a new animal model.

Alterations in the vascular bed of the pancreas or disturbances of the blood coagulation system are mostly considered to be sequelae of acute pancreatitis, but it seems that impairment of the pancreatic blood supply can per se lead to acute hemorrhagic pancreatitis. To test this hypothesis with a new animal model, we injected 20 microns polystyrene microspheres retrogradely into the distal splenic artery of rats, thus incompletely blocking blood perfusion in the splenic portion of the pancreas. Eight of eight rats (100%) subjected to microsphere injection developed acute hemorrhagic pancreatitis by 27 h after surgery, when they were killed, but none of the six sham-operated control animals (0%) showed macroscopic signs of pancreatitis. Blood amylase levels at death were 3,087 +/- 650 I.U./L (mean +/- SEM) and the histologic severity score for pancreatitis was 10.8 +/- 1.0 (mean +/- SEM), whereas in the six control rats amylase levels were 1,375 +/- 158 I.U./L and the histology score was only 1.7 +/- 1.0. The result is, with p less than 0.0005, highly significant (chi 2 analysis) and shows that acute experimental pancreatitis can indeed be induced by partially blocking the arterial blood supply within the organ.