Retroperitoneal mucinous cystadenoma.

Primary retroperitoneal mucinous cystadenoma is an uncommon tumor found exclusively in women. Herein, we describe a patient who had resection of a large retroperitoneal cystic mass. Histologic, immunohistochemical, and electron microscopic examination of the lining epithelial cells showed features of mesothelial cells in addition to ovarian mucinous cystadenoma. These findings suggest that these tumors arise from inclusions of mesothelial cells and subsequent mucinous metaplasia of the lining cells to form a cystadenoma. Estrogen receptors may be implicated in tumor promotion, explaining the occurrence exclusively in women.

Should central venous catheters be removed as soon as candidemia is detected in neonates?

BACKGROUND: Controversy exists regarding the most appropriate acute management of central venous catheters (CVCs) in neonates with candidemia, with up to two thirds of neonatologists preferring to attempt antifungal therapy without removing CVCs. OBJECTIVE: To determine whether CVCs should be removed as soon as candidemia is detected in neonates. Methods. A cohort study of candidemia and CVC was conducted in infants in a neonatal intensive care unit (NICU) over a 5-year period (1994-1998). RESULTS: Fifty infants had early-removal CVC (ER-CVC) within 3 days and 54 infants had late-removal CVC (LR-CVC) >3 days after the first positive blood culture for Candida species. All infants were treated with amphotericin B. There was no significant difference between infants in the ER-CVC and LR-CVC groups in terms of gender, ethnicity, birth weight, gestational age, age at candidemia, severity-of-illness scores, distribution of types of CVC, or in the distribution of Candida species causing candidemia. The ER-CVC group had significantly shorter duration of candidemia (median: 3 days; range: 1-14 days), compared with the LR-CVC group (median: 6 days; range: 1-24 days). The case fatality rate of Candida albicans candidemia was significantly affected by the timing of CVC removal: 0 of 21 (95% confidence interval [CI]: 0-14) infants died in the ER-CVC group in contrast to 9 of 23 (39%; 95% CI: 19-59) in the LR-CVC group. CONCLUSION: Failure to remove CVC as soon as candidemia was detected in neonates was associated with significantly increased mortality in C albicans candidemia and prolonged duration of candidemia regardless of Candida species.

Radial microbrain form of micrencephaly: possible association with carbamazepine.

A premature infant exposed to carbamazepine in utero had a markedly undersized brain on cranial ultrasonogram. Postmortem examination of the brain revealed no evidence of hypoxic-ischemic injury, hemorrhage, infarction, congenital infection, or calcification. The normal cortical gyral pattern, normal residual germinal matrix, and normal cortical lamination suggested the diagnosis of a radial microbrain form of micrencephaly.

Preoperative localization of insulinomas is not necessary.

BACKGROUND: Insulinomas are infrequent but are important to recognize and surgically remove. Several diagnostic tests have been used to increase the chances of operative success. The value of preoperative testing for insulinomas is the subject of this review. STUDY DESIGN: All patients treated at the Cleveland Clinic for insulinoma between 1985 and 1995 were retrospectively reviewed. All patients had biochemical evidence of primary hyperinsulinemia. RESULTS: There were 21 patients, 10 men and 11 women, with a median age of 58 years. Eighteen patients (85%) had a single insulinoma, two patients (10%) had multiple insulinomas, and one patient (5%) had nesidioblastosis. In addition, two patients (10%) had malignant insulinoma. A total of 13 patients (62%) had successful preoperative localization of their tumors, and all of these were found during exploration either by the surgeon (12 patients) or by intraoperative ultrasonography (1 patient). The remaining eight patients (38%) did not have their lesion localized by preoperative tests. In seven patients these tumors were found at operation, three by the surgeon and four by intraoperative ultrasonography. One patient failed preoperative and intraoperative localization and was later diagnosed with nesidioblastosis. Enucleation was performed in 13 patients and distal pancreatectomy in 7; the patient with nesidioblastosis had a negative laparotomy and a subsequent distal pancreatectomy. The mortality and morbidity rates were 0% and 14%, respectively. Only two patients, including the patient with nesidioblastosis, remained symptomatic after operation. CONCLUSIONS: The diagnosis of an insulinoma does not require extensive localization studies before operation. The combination of surgical exploration and intraoperative ultrasonography identified more than 90% of insulinomas. When technically feasible, enudeation is curative and can be accomplished with low morbidity.

Acute pancreatitis after aortic surgery.

Acute pancreatitis (AP) after aortic surgery has rarely been reported. A retrospective review of all abdominal and thoracoabdominal aortic operations complicated with AP from January 1982 to March 1992 was performed to study the presentation and outcome of this infrequently recognized complication. Thirteen cases of AP were found among 1965 abdominal aortic operations (0.7% incidence). The distribution of the original aortic operations was as follows: eight elective abdominal aortic aneurysm repairs, two aortoiliac grafts for aortoiliac occlusive disease, and three aortorenal bypasses. Two cases of pancreatitis complicated 170 thoracoabdominal aortic operations (1.2% incidence). Ten patients had mild pancreatitis, nine were discharged without any pancreatic complications after receiving supportive treatment. Five patients with severe AP died of multisystem organ failure despite aggressive surgical treatment; 4 had infected necrosis. The overall mortality was 40 per cent; severe AP resulted in a 100 per cent mortality. The diagnosis of severe AP was usually made in the second postoperative week, significantly later (P < 0.01) than for patients with mild disease. Typically, patients with mild AP presented with hyperamylasemia at a median of 5 postoperative days, and severe AP was found at reoperation or autopsy after a period of unexplained sepsis. Five patients with mild AP were found to have biliary tract stones, with one requiring endoscopic stone extraction. In conclusion, pancreatitis is an uncommon, although perhaps underreported complication. Underreporting may be due to a lack of hyperamylasemia when severe pancreatitis is diagnosed. The severe form is diagnosed late in patients with postoperative sepsis, associated with infected necrosis, and lethal. The complication may be reduced by incidental cholecystectomy for cholelithiasis.

Presentation and management of cystic neoplasms of the pancreas.

Pancreatic cystic neoplasms are uncommon, but it is important to differentiate them from pseudocysts and ductal adenocarcinoma. A retrospective review was performed to determine distinguishing characteristics and optimal treatment. In 51 patients operated on between 1981 and 1994 at a referral center, the following cystic neoplasms were found: 20 serous cystadenomas, 10 mucinous cystadenomas, 11 mucinous cystadenocarcinomas, five cases of mucinous ductal ectasia, and five papillary cystic neoplasms. Both mucinous ductal ectasia and papillary cystic neoplasms had distinguishing features when compared to other cystic neoplasms. Mucinous ductal ectasia was seen only in men, presented with typical symptoms, and had distinctive features on endoscopic retrograde cholangiopancreatography. Papillary cystic neoplasms occurred in young women (mean age 31 years) and were larger (mean 10.3 cm). Mucinous tumors were always symptomatic, whereas 55% of serous tumors were asymptomatic (P <0.001). The overall rate of resectability was 80%, and there was one operative death (2%). Intraoperative biopsy was diagnostic in 18 (78%) of 23 cases. An actuarial 5-year survival of 52% was found for resected mucinous cystadenocarcinomas. In conclusion, papillary cystic neoplasms and mucinous ductal ectasia have distinct characteristics that differentiate them from other types of pancreatic cystic tumors. Serous cystadenoma should be considered in asymptomatic patients and these patients should be closely observed. Symptomatic neoplasms should be resected with long-term survival expected for malignant forms. (J Gastrointest Surg 1998;2:504-508.)

Evidence of a non-MHC susceptibility locus in type I diabetes linked to HLA on chromosome 6.

Linkage studies have led to the identification of several chromosome regions that may contain susceptibility loci to type I diabetes (IDDM), in addition to the HLA and INS loci. These include two on chromosome 6q, denoted IDDM5 and IDDM8, that are not linked to HLA. In a previous study, we noticed that the evidence for linkage to IDDM susceptibility around the HLA locus extended over a total distance of 100 cM, which suggested to us that another susceptibility locus could reside near HLA. We developed a statistical method to test this hypothesis in a panel of 523 multiplex families from France, the United States, and Denmark (a total of 667 affected sib pairs, 536 with both parents genotyped), and here present evidence (P = .00003) of a susceptibility locus for IDDM located 32 cM from HLA in males but not linked to HLA in females and distinct from IDDM5 and IDDM8. A new statistical method to test for the presence of a second susceptibility locus linked to a known first susceptibility locus (here HLA) is presented. In addition, we analyzed our current family panel with markers for IDDM5 and IDDM8 on chromosome 6 and found suggestions of linkage for both of these loci (P = .002 and .004, respectively, on the complete family panel). When cumulated with previously published results, with overlapping families removed, the affected-sib-pair tests had a significance of P = .0001 for IDDM5 and P = .00004 for IDDM8.

Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12.

Crohn's disease (CD) and ulcerative colitis (UC), the chronic inflammatory bowel diseases (CIBD), are common causes of gastro-intestinal disease in the Western world, with a combined prevalence of 100-200/100,000 (ref. 1). Epidemiological studies, particularly concordance rates in twin pairs and siblings, strongly implicate genetic susceptibility in the pathogenesis of CIBD. In fact, the relative contribution of genetic factors to the pathogenesis of CD may be greater than in schizophrenia, asthma or hypertension, and at least equivalent to that in insulin-dependent diabetes. Systematic screening of the entire human genome now provides a strategy for the identification of susceptibility genes in complex polygenic disorders. We undertook a two-stage genome search for susceptibility genes in inflammatory bowel disease involving 186 affected sibling pairs from 160 nuclear families. We provide strong evidence for the presence of susceptibility loci for both CD and UC on chromosome 3, 7 and 12. We obtained the highest lod score (5.47; P = 2.66 x 10(-7) with the marker D12S83 and lod scores of 3.08 and 2.69 for D7S669 and D3S1573, respectively. Our data suggest that CD and UC are closely related, but distinct, polygenic disorders that share some, but not all, susceptibility genes.

Genetics of insulin-dependent diabetes mellitus.

Recent studies that have focused on the detection of non-MHC susceptibility loci in insulin-dependent diabetes mellitus are reviewed. It has been confirmed that the region on human chromosome 11p contains such a susceptibility locus and recent research has attempted to identify the causative DNA variants and their functional role in disease.

Pyogenic hepatic abscess: results of current management.

From 1980 to 1991, 56 cases of pyogenic liver abscess were treated at the Cleveland Clinic. The most frequently used treatment was percutaneous catheter drainage of the abscess under computed tomography (CT) guidance (39 patients), followed by CT-guided aspiration without catheter drainage (10 patients). Six patients were initially treated by open operative drainage; another five were operated upon after CT guided drainage had failed. One patient with advanced pancreatic cancer was treated with antibiotics only. The overall mortality rate was 12.5% (7/56). It is clear that the preferred method of treatment for pyogenic hepatic abscess is now CT guided catheter drainage. Operative drainage is reserved for patients who fail to respond to percutaneous drainage or in whom surgery is indicated for other purposes. Aspiration without catheter drainage is a modality that needs further evaluation to define its indications.

Recurrent small bowel obstruction secondary to a dilated Kock pouch: a case report.

We report a case of recurrent bowel obstruction caused by a hugely dilated Kock pouch. The approximate capacity of the pouch was at least 1300 ml. Frequent emptying of the pouch resulted in resolution of the obstructing symptoms.

Is sporadic MS caused by an infection of adolescence and early adulthood? A case-control study of birth order position.

Birth order position was examined in 164 cases with sporadic multiple sclerosis (MS), i.e. no other family members with MS, and spousal controls, matched for sibship size, socioeconomic status and opposite sex. The results did not find an association between birth order position and the subsequent development of MS and thus do not support the concept of an infectious cause for MS where "early exposure" is protective and exposure to the infection is a single event of short duration.

A study of birth order and multiple sclerosis in multiplex families.

Birth order position for affected siblings was examined for 88 sibships having 2 or more cases of multiple sclerosis (MS). The data show that MS patients are randomly ordered by birth within these multiplex sibships. The data therefore do not support the hypothesis that MS occurs in siblings because of a common environmental exposure as defined by proximity in birth order position.

Genetic mapping of a susceptibility locus for insulin-dependent diabetes mellitus on chromosome 11q.

Loci in the major histocompatibility complex (MHC) on chromosome 6 and the insulin (INS) region on chromosome 11 have been implicated in susceptibility to insulin-dependent diabetes mellitus (IDDM) through candidate gene investigations, but they may account for less than 50% of genetic risk for the disease. Genome-wide linkage studies have led to localization of more than 10 susceptibility loci for insulin-dependent diabetes in the non-obese diabetic (NOD) mouse and the BB rat. Similar studies are now possible in humans through the development of dense genetic maps of highly informative microsatellite loci obtained using polymerase chain reaction analysis. We have applied microsatellite markers from recent Généthon maps, and other highly informative markers, in a genome-wide linkage study in IDDM. Here we report evidence for the localization of a previously undetected susceptibility locus for IDDM in the region of the FGF3 gene on chromosome 11q. Our results shows the potential of genome-wide linkage studies to detect susceptibility loci in IDDM and other multifactorial disorders.

Immunoglobulin heavy chain variable region polymorphisms and multiple sclerosis susceptibility.

In addition to the major histocompatibility complex (MHC), genetic susceptibility in multiple sclerosis (MS) appears to be influenced by other loci. A recent study has identified a population association with an immunoglobulin heavy chain variable region polymorphism in the VH2-B5 family, with both familial and sporadic MS patients. We have repeated this association study in a second MS patient group and used two ethnically and geographically matched control groups and the MS patients' unaffected sibs for comparisons. The VH2-B5 polymorphism was found to be over-represented in MS patients when compared to all three control groups. This VH2-B5 association was stronger when the MS patient data were combined with data from our previous study. To further explore the implications of this population association, MS sibships were analyzed for haplotype sharing by identity by descent (IBD) for VH2 and VH3f gene segment polymorphisms. The distribution of haplotype sharing did not differ from that expected based upon random segregation. The data are consistent with the IGVH locus exerting a minor effect perhaps by interacting with other loci to influence MS susceptibility or with genetic heterogeneity and a role for this complex in a subgroup of patients.

A population-based study of multiple sclerosis in twins: update.

This study is a 7.5-year follow-up of a population-based series of twins with multiple sclerosis (MS) whose mean age now exceeds 50 years. The twin pairs were identified through the Canadian nationwide system of MS clinics and were drawn from a population of 5,463 patients. After 7.5 years, the monozygotic concordance rate increased from 25.9 to 30.8% and the dizygotic-like sex concordance rate from 2.4 to 4.7%. These results are very similar to those of other population-based studies and to our own modified replication twin data reported here. We interpret the data to mean that MS susceptibility is genetically influenced, and a single dominant or even a single recessive gene is unlikely to account for this effect. The difference in concordance rates suggests that at least two or more genes are operative. These data also have important implications for the nature of the environmental effect(s) in MS susceptibility. Most monozygotic twins are discordant even after a correction for age and magnetic resonance imaging findings. This unambiguously demonstrates the powerful effect of nonheritable factors.

Exclusion of linkage between hypokalemic periodic paralysis (HOKPP) and three candidate loci.

Hypokalemic periodic paralysis (HOKPP) is an autosomal dominant neuromuscular disorder characterized by flaccid paralysis accompanied by lowered serum potassium levels. We have tested polymorphic markers linked to the adult skeletal muscle sodium channel (SCN4A) locus at 17q23-q25, the T-cell receptor beta (TCRB) locus at 7q35, and the H-Ras cellular proton-cogene locus (HRAS) at 11p15.5 for linkage with the affected phenotype in a single multigenerational pedigree. No evidence for genetic linkage to HOKPP was found at any of the candidate loci.

Linkage of Thomsen disease to the T-cell-receptor beta (TCRB) locus on chromosome 7q35.

The chromosomal localization of the gene for Thomsen disease, an autosomal dominant form of myotonia congenita, is unknown. Electrophysiologic data in Thomsen disease point to defects in muscle-membrane ion-channel function. A mouse model of myotonia congenita appears to result from transposon inactivation of a muscle chloride-channel gene which maps to a region of mouse chromosome 6. The linkage group containing this gene includes several loci which have human homologues on human chromosome 7q31-35 (synteny), and this is a candidate region for the Thomsen disease locus. Linkage analysis of Thomsen disease to the T-cell-receptor beta (TCRB) locus at 7q35 was carried out in four pedigrees (25 affected and 23 unaffected individuals) by using a PCR-based dinucleotide repeat polymorphism in the TCRB gene. Two-point linkage analysis between Thomsen disease and TCRB showed a maximum cumulative lod score of 3.963 at a recombination fraction of .10 (1-lod support interval .048-.275). We conclude that the Thomsen disease locus is linked to the TCRB locus in these families.