Necrotizing fasciitis after Plastibell circumcision.

Necrotizing fasciitis is a potentially life-threatening infection of subcutaneous tissues and Scarpa's fascia that rarely affects neonates. We report the occurrence of this devastating infection in two neonates after routine Plastibell circumcision. These case reports highlight the presentation and management of this complication after a relatively routine and frequently performed operation. This report also emphasizes the differences between cellulitis and necrotizing fasciitis and suggests strategies for management.

Does posterior sagittal anorectoplasty in patients with high imperforate anus provide superior fecal continence?

The posterior sagittal anorectoplasty (PSARP) has become the primary surgical procedure for patients with high imperforate anus. Very few careful long-term follow-up studies have established the superiority of the PSARP procedure over other surgical repair techniques. The authors' goal was to evaluate the operation and to identify the factors associated with improved continence. The medical records, operative reports, and radiographs of 53 patients (46 male, 7 female) who underwent PSARP for high imperforate anus at Children's Hospital and Medical Center (CHMC) between 1982 and 1990 were reviewed retrospectively. Subjective follow-up data were collected by telephone questionnaire, assessing habits indicative of stool continence, and a "fecal continence score" (FCS) was calculated for each patient. A prospective, 7-day diary assessing similar patterns of fecal continence was completed by each patient's family. The mean age of the patients studied was 8.0 years, and the mean follow-up period was 6.8 years. The telephone questionnaire was completed for 48 patients (94%). Toilet training for bowel continence was successful in 20 patients (42%) and occasionally successful in another 20 patients (42%), but 8 patients (16%) had no awareness of impending stool. Forty-five (94%) were physically active, but 16 (33%) reported social problems related to offending odor. The mean fecal continence score for all patients was 3.0 +/- 1.4 (5=excellent, completely continent), which was nearly identical to published scores for the other types of surgical repair. The FCS did not improve with age. The parents' responses to the telephone questionnaire matched the results obtained from the prospectively collected continence diary data. The authors' results for PSARP in patients with high imperforate anus do not differ substantially from those achieved by other repair techniques. Previously cited prognostic factors such as fistula anatomy and sacral anomalies did not appear to alter the functional results in the authors' series. Aggressive postoperative bowel management should be anticipated in all patients who have high imperforate anus and may benefit those who otherwise would achieve less satisfactory continence.

Mesenteric cysts in children.

BACKGROUND: Mesenteric cysts are uncommon benign abdominal masses. Approximately one third of patients with these lesions are children. METHODS: We reviewed our clinical records for the past 14 years (corresponding to the period of time in which ultrasonography and computed tomography became reliable methods for imaging pediatric patients) and found 10 patients with mesenteric cysts. RESULTS: We were surprised to discover that abdominal pain was a presenting complaint in all but one patient. Five of the patients had the findings of an acute surgical abdomen and were thought to have appendicitis. Two patients operated on for appendicitis were transferred to our hospital with the diagnosis of an abdominal mass. In each case the mass was a mesenteric cyst. Cyst distribution included the small-bowel mesentery in seven patients, the transverse mesocolon in two patients, and the right mesocolon in one patient. Six cases required concomitant bowel resection for the cyst removal, and all were cystic lymphangiomas. The resected specimens were described as cystic lymphangiomas in eight of the 10 cases. CONCLUSIONS: Mesenteric cysts should be considered as an origin for abdominal pain in children, particularly after exclusion of more common diagnoses. We have found ultrasonographic imaging to be a reliable method for the diagnosis of appendicitis in children and advocate its use as an initial imaging study in patients with an acute surgical abdomen and presumed appendicitis. If appendicitis is indicated unlikely by ultrasonogram, the examination can be extended to the remainder of the abdomen, which can reveal mesenteric cysts or other pathologic conditions.

Calcitonin elevation in small cell lung cancer without ectopic production.

To determine the relative contribution of ectopic calcitonin (CT) production versus nonectopic secretion of CT in patients with small cell lung cancer (SCLC), serum and urine immunoreactive CT (iCT) levels of 86 different subjects were measured by radioimmunoassay (RIA) using two polyclonal antisera (Ab3b and Ab4). The subjects included 49 previously untreated patients with SCLC, 17 smokers, and 20 nonsmokers. Serum and urine iCT values were highest in the patients with SCLC, intermediate in the smokers, and lowest in the nonsmokers (p < 0.0003). Sixteen of the 49 patients with SCLC had tumor cell lines available for determination of CT mRNA expression by RNase protection assay (RPA) and iCT production by RIA. CT mRNA was detected in nine of 16 subjects and iCT in eight of 16. The tumor cell lines of seven patients had undetectable CT by both RPA and RIA, and of these, five had elevated urine or serum iCT values compared with those of nonsmokers, and two had levels above all values in the smoker group. Immunohistochemical staining of formalin-fixed, paraffin-embedded tumor samples detected iCT in two of four tumors from patients whose tumor cell lines had CT mRNA by RPA and iCT by RIA, but in none of six whose tumor cell lines had undetectable CT mRNA. Thus, increased iCT values in some patients with SCLC are likely due to sources other than CT production by tumor cells.

Fetus in fetu: molecular analysis of a fetiform mass.

Fetus-in-fetu is a rare condition presenting as a calcified intra-abdominal mass in the newborn infant. Over 50 cases of fetus-in-fetu have been reported since 1800. Karyotype analysis in 8 cases and protein polymorphisms in 4 documented identical findings in the host and fetiform mass. We report a case of fetus-in-fetu in a newborn female including cytogenetic and molecular studies of both the host and mass. Genotypic information from 7 polymerase chain reaction (PCR) assays representing 4 chromosomes demonstrates heterozygous and identical alleles in the infant and fetus-in-fetu at all loci studied. A review of the literature is provided including a discussion regarding the impact of molecular data on present hypotheses of fetus-in-fetu pathogenesis.

Molecular cloning and immunological characterization of the gamma polypeptide, a small protein associated with the Na,K-ATPase.

The gamma subunit of the Na,K-ATPase is a small membrane protein that copurifies with the alpha and beta subunits of the enzyme. Strong evidence that the gamma subunit is a component of the Na,K-ATPase comes from studies indicating that the subunit is involved in forming the site for cardiac glycoside binding. We have isolated and characterized the cDNAs coding the gamma subunit from several species. The gamma subunit is a highly conserved protein consisting of 58 amino acids with a molecular weight of 6500. Hydropathy analysis reveals the presence of a single hydrophobic domain that is sufficient to cross the membrane. There are no sites for N-linked glycosylation. Northern blot analysis revealed that the gamma subunit mRNA is expressed in a tissue-specific fashion and is present in all tissues characterized. gamma-specific antibodies have been used to verify that the sequenced protein is the same protein labeled by [3H]nitroazidobenzoyl-ouabain (NAB-ouabain), and that this protein, the gamma subunit of the Na,K-ATPase, has a distribution pattern along nephron segments that is identical with the alpha subunit. In addition, coimmunoprecipitation of the alpha, beta and gamma subunits demonstrate specific association of the subunits. These results are consistent with the notion that the gamma subunit is specifically associated with and may be an important component of the Na,K-ATPase.

Atrial natriuretic factor and arginine vasopressin production in tumor cell lines from patients with lung cancer and their relationship to serum sodium.

Patients with lung cancer (n = 263) were studied to determine the relationship among ectopic production of atrial natriuretic factors (ANF) and arginine vasopressin (AVP), serum sodium, and patient outcome. Of 133, 21 (16%) patients with small cell lung cancer (SCLC) had hyponatremia (serum sodium, < 130 mmol/liter), compared to none of 130 (0%) patients with non-small cell lung cancer (P < 0.0001). Patients with extensive-stage SCLC and hyponatremia had shorter survival than patients with extensive stage SCLC and normal serum sodium values (P = 0.012). Of the 11 hyponatremic patients with SCLC and tumor cell lines available for study, 9 produced ANF mRNA, 7 of 11 produced AVP mRNA, and 5 of 11 produced both ANF mRNA and AVP mRNA. All 11 cell lines produced either ANF mRNA and ANF peptide or AVP mRNA and AVP peptide, or both. The quantity of AVP peptide in the tumor cell lines was more closely associated with hyponatremia in the patients (P = 0.0026, r2 = 0.28) than was the production of ANF peptide (P = 0.066, r2 = 0.12), although neither association was strong. All tumor cell lines studied from SCLC patients with hyponatremia produce ANF and/or AVP mRNA and peptides.

Characteristics of cell lines established from human gastric carcinoma.

We report the establishment and characterization of four continuous cell lines derived from human primary and metastatic gastric carcinomas, and we compare their properties with a panel of colorectal carcinoma cell lines previously established and reported by us. Our success rate in culturing gastric carcinomas was relatively low, especially from primary tumors, compared to colorectal carcinoma. These observations may reflect the relatively modest number of gastric carcinoma cell lines established (mainly from Japan), compared to the abundance of colorectal carcinoma lines established worldwide. All four gastric lines expressed the surface glycoproteins carcinoembryonic antigen and TAG-72 and three lines expressed CA 19-9. Two of the lines expressed aromatic amino acid decarboxylase but lacked other markers for neuroendocrine differentiation. All four lines were positive for vasoactive intestinal peptide receptors but lacked gastrin receptors. In addition, two lines expressed receptors for muscarinic/cholinergic receptors but not beta-adrenergic receptors. Cytogenetic evidence for gene amplification was present in the cell lines. All four lines contained varying numbers of double-minute chromosomes. One line, SNU-16, was amplified for the c-myc proto-oncogene and contained four homogeneously staining regions. While c-myc and c-erb-B-2 RNA were expressed by all lines, there was no evidence of amplification or overexpression of several other proto-oncogenes and growth factors. The multiple properties we have described in our gastric carcinoma cell lines are remarkably similar to those found in the panel of colorectal carcinoma cell lines. These properties include morphology, growth characteristics, expression of surface glycoproteins, partial expression of neuroendocrine cell markers, frequent chromosomal evidence of gene amplification, and occasional amplification of the c-myc proto-oncogene. Our four well characterized cell lines should provide useful additions to the modest number currently available for in vitro studies of gastric carcinoma.

Expression of the atrial natriuretic factor gene in small cell lung cancer tumors and tumor cell lines.

Hyponatremia in patients with small cell lung cancer can be caused by tumor production of arginine vasopressin (AVP) and result in the syndrome of inappropriate antidiuretic hormone. In evaluating the expression of AVP mRNA from tumor and tumor cell line specimens from five patients with small cell lung cancer and hyponatremia (presumed to have the syndrome of inappropriate antidiuretic hormone), we found that the tumors and tumor cell lines from two of these five patients expressed AVP mRNA. The RNA samples from the three patients with undetectable AVP mRNA expressed abundant atrial natriuretic factor (ANF) mRNA. Analysis of specimens from three patients with small cell lung cancer and normal serum sodium levels revealed no detectable AVP mRNA expression, and samples from only one of these three patients' specimens expressed detectable ANF mRNA. The AVP and ANF peptide levels in lysate preparations of the tumor cell lines from four of these patients were tested by radioimmunoassay and confirmed the gene expression data. These studies demonstrate ectopic production of ANF mRNA in small cell lung cancer specimens from patients with this cancer and the syndrome of inappropriate antidiuretic hormone. These findings will be of particular interest if future studies demonstrate that ectopic ANF production can cause sodium abnormalities in patients with small cell lung cancer.

Carcinoma of the anal region.

Preservation of anorectal function makes chemoradiotherapy attractive as the primary treatment in patients with squamous cell carcinoma of the anal region. Despite variations in techniques of chemoradiotherapy administration, the accumulated experience of a number of institutions indicates substantial improvement over previous approaches, which included surgery or radiation therapy individually. Although no longer providing the definitive therapeutic role in this disease, the surgeon is frequently asked to evaluate lesions suspected of being anal malignancies. In addition, it is the surgeon who most often performs the diagnostic biopsy, consults on local complications of chemoradiotherapy, and manages complications of local recurrence. In this context, optimal care includes early organization of the medical oncologist, radiation therapist, and surgeon to participate in the initial diagnostic evaluations, examinations with the patient under anesthesia, and follow-up during therapy. A complete response is often not evident until 2 to 3 months after treatment. We recommend a follow-up schedule of monthly visits for the first 6 months, examinations every 3 months for the next 2 years, and assessment every 6 months thereafter. Evaluation during early routine visits includes manual and proctoscopic examination of the perineum and rectum and review of the hemogram and liver enzyme levels in the serum. CT, MRI, or lower endoscopy procedures are performed only if clinical examination or studies suggest the possibility of recurrence or a second primary tumor. Patients with an incomplete response to therapy after 3 months often undergo examination under anesthesia with biopsy of suspect areas. Chronic inflammatory changes in the area of previous carcinoma may be interpreted as persistent disease. Thus histologic proof of recurrent malignancy must be obtained before considering surgical or chemoradiotherapy salvage treatment.

Colon and rectal carcinoma.

In the United States the incidence of carcinoma of the colon or rectum appears to be increasing. Although certain dietary habits appear to be associated with disease incidence, the putative carcinogens in the lumen of the bowel remain unidentified. The use of clinical screening based on a combination of proctosigmoidoscopy and tests for occult fecal blood allows detection of colorectal carcinomas at an early stage; however, it is unclear whether such screening is cost-effective in persons over 40 years of age or if treatment undertaken on the basis of screening results truly alters the natural history of the disease. Surgical resection is the mainstay of curative therapy, and its effectiveness will probably be enhanced by adjuvant x-ray therapy and chemotherapy.