Vulvar carcinoma associated with lichen sclerosus. Experience at the Florence,Italy, Vulvar Clinic

OBJECTIVE: To compare demographic and clinical characteristics of patients with lichen sclerosus (LS)-associated squamous cell carcinoma (SCC) of the vulva with those of patients with tumors not histologically associated with LS in a series of patients with vulvar SCC not HPV correlated. STUDY DESIGN: We retrospectively reviewed histologic specimens and clinical files of all vulvar SCCs referred to the Vulvar Clinic, University of Florence, Florence, Italy, since 1990. RESULTS: Twenty-five out of the 72 cases in this study (34.7%) were LS associated. Among these cases, 8 (32%) were diagnosed with LS before occurrence of the cancer and received treatment for the disease. In 17 cases the diagnosis of LS was simultaneous with that of SCC; in 13 cases the diagnosis was achieved by clinical examination and confirmed afterwards histologically. In 4 cases this was confirmed only by means of histologic examination. The shared profile of patients with LS-associated vulvar SCC was a subject (mean age, 72 years) seldom with a past medical history of vitiligo (16% of cases), with invasive cancer (92% of cases), clinically characterized by an exophitic tumor (73%), seldom ulcerated (18%) or showing hyperkeratosis (9%). Labia majora (32%), labia minora (27%) and vestibule (23%) were the most frequently involved sites. In most cases (80%) the cancer was limited to 1/3 of the vulvar region. An itch was the most frequent symptom. However, for all of these variables, no overall statistically significant difference was found with patients who had SCCs not associated with LS. CONCLUSION: The experience of the Vulvar Clinic, University of Florence, confirms the suggested role of LS as a possible precursor of vulvar carcinoma since 32% of our cases not HPV related were LS associated. We demonstrated that the profile of patients with LS-associated cancer does not differ from that of patients with cancer not associated with LS, excluding HPV-related cases. The existence of accessory conditions, probably needed to promote the progression from LS to cancer in a minority of subjects remains to be established.     

Female reproductive health after ileal pouch anal anastomosis for ulcerative colitis

Ileal pouch anal anastomosis is the surgical treatment of choice for ulcerative colitis, offering intestinal continuity and fecal continence. IPAA does not seem to affect menstrual function or gynecologic symptoms. Overall sexual satisfaction may be improved with surgery, although ability to experience orgasm and coital frequency remain essentially unchanged. However, dyspareunia seems to increase postoperatively. Fertility is also adversely affected by IPAA, possibly a result of pelvic adhesions. Pregnancy is characterized by a transient increase in day and night stool frequency and incontinence that resolves after delivery. The ideal route of delivery has not been determined, but vaginal delivery seems safe and does not directly cause pouch dysfunction. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the procedure ileal pouch anal anastomosis, to summarize the effects of IPAA on menstrual function and sexual health, and to outline the association of IPAA and infertility.     

Fetal lung maturity indices-a plea for gestational age-specific interpretation: a case report and discussion

A fetus with mature amniotic fluid lung indices was delivered with subsequent respiratory distress syndrome, demonstrating that fetal pulmonary maturity needs to be viewed as a probability. We calculated the probability of respiratory distress as a function of gestational age and fetal lung maturity. The percent risks are displayed in an easily readable table format.     

Human immunodeficiency virus-induced apoptosis of human hepatocytes via CXCR4

Human immunodeficiency virus (HIV) infection is commonly associated with liver dysfunction. The X4 HIV glycoprotein 120 envelope (env) induces apoptosis in T cells and neurons via the HIV coreceptor CXCR4. Therefore, we investigated whether hepatocyte death could result from the HIV env signaling through CXCR4 on the hepatocyte. We demonstrated that hepatocytes in humans express CXCR4 on the cell surface. Furthermore, we established that the X4 HIV env and the entire HIV virion signal hepatocyte apoptosis through CXCR4. The apoptotic process is dependent on G(ialpha) protein signaling, yet it is independent of caspase cascade activation. Thus, HIV can directly cause hepatocyte death in humans by signaling through CXCR4, without infecting the cell.     

Enlarged fetal bladder: Differential diagnosis and outcomes

The sonographic finding of an enlarged fetal bladder may simply be a transitory normal variant, but it may also be secondary to reflux or to obstructive, neurogenic, or myopathic causes. In this report, we describe the cases of 3 fetuses with an enlarged bladder, each of which had a different cause. The first fetus had posterior urethral valve obstruction, the second, a ruptured neurogenic bladder, and the third, megacystic-microcolon-intestinal hypoperistalsis syndrome. When sonographic examination reveals an enlarged fetal bladder, the ureter, kidneys, genitalia, and spine should be evaluated carefully. Although sonography is good at identifying urinary tract abnormalities, it often cannot provide the specific diagnosis or cause. We recommend frequent sonographic monitoring to evaluate such fetuses for persistence of or changes in bladder enlargement and for changes in the volume of amniotic fluid because these signs may be indicators of abnormalities of renal function and risk factors for a poor prognosis. Analysis of fetal electrolyte levels can also aid in determining the prognosis and whether the condition is amenable to therapeutic intervention.     

Adverse effects from inappropriate medication administration via a jejunostomy feeding tube.

Numerous complications can arise when administering medications to patients receiving continuous enteral feeding. We report a case of a patient who could not be fed by mouth and was receiving continuous jejunal enteral feeding who had an adverse event associated with inappropriate administration of a medication via his jejunostomy tube. He had taken an extended-release niacin product before hospitalization for type IIb hyperlipidemia. The patient was inappropriately given a single dose of 750 mg of niacin as the short-acting tablets that were crushed and administered via the jejunostomy tube. He experienced severe cutaneous flushing, a feeling of warmth, itching, nausea, and emesis. He was noted to have "prickly heat" to the forehead, according to the nursing notes. A discussion of problems and guidelines for medication administration in adult patients receiving continuous tube feeding is provided.     

Di-alkyl phosphate biomonitoring data: assessing cumulative exposure to organophosphate pesticides

The 1996 Food Quality Protection Act (FQPA) requires the evaluation of both aggregate and cumulative health risks from pesticides (FFDCA 408(b)(2)(D)(v) and (vi).) Organophosphate (OP) pesticides are the first class of chemicals to undergo FQPA mandated aggregate and cumulative assessments. In this report, summary data on biomonitoring for urinary levels of six alkyl phosphate (AP) metabolites of OPs, as reported in the initial, March 2001, U.S. Centers for Disease Control and Prevention's (CDC) "National Report on Human Exposure to Environmental Chemicals," are compared to EPA modeled estimates of OP exposure reported in Registration Eligibility Decision documents (REDs), Interim REDs and to currently reported cumulative exposure estimates in the EPA's Cumulative Risk Assessment of the Organophosphate Pesticides. This comparison indicates that EPA's aggregate exposure estimates (dietary, drinking water, and non-dietary residential exposures) for many individual OPs were greater than the cumulative estimate for all OPs combined based on the CDC AP biomonitoring data. The results also suggest that EPA's screening level assessments of OPs, while being qualitative indicators of the relative importance of various exposure sources, are not good quantitative indicators of actual exposures. However, the mean biomonitoring estimate of cumulative OP exposure appears to exceed the EPA's subsequent preliminary estimate of cumulative OP exposure by as much as the REDs appear to overestimate the biomonitoring results. While the conservatism, tendency to overestimate exposure, in the individual REDs is readily acknowledged, the conservatism and limitations of applying currently available CDC AP biomonitoring data to evaluate human exposure to OPs are not as readily apparent. We postulate that oral absorption of non-anti cholinergic, pre-hydrolyzed OPs, sources of APs other than pesticides, and the conservative result of summing exposure from each AP at the geometric mean contribute to non-quantified overestimates of absorbed dosage from the CDC biomonitoring data reported in March 2001. CDC AP biomonitoring data may serve a useful purpose in providing an upper bound estimate of absorbed dosage for "ground truthing" aggregate exposure estimated from first tier models used in REDs, but at best may provide only a credible "target" for the complex cumulative exposure assessment models currently under development. The reliability of quantitative estimates of OP exposure levels will improve as cumulative risk exposure models are validated over time and under use conditions prevalent at the time the AP biomonitoring samples are collected. Analyses contained herein should be revisited and compared to the CDC Second National Report on Human Exposure to Environmental Chemicals ( http://www.cdc.gov/exposurereport), released to the public on January 31, 2003, and the final EPA OP Cumulative Risk Assessment.     

Transitions and transversions in Ki-ras gene in colorectal cancers in Mexican patients

AIMS & BACKGROUND: An important increase in the incidence of colorectal cancers has been detected in the last 15 years in Mexico. This fact has been attributed to several causes, including the change in diet acquired from industrialized countries. Various groups have studied the mutational pattern of oncogenes, including Ki-ras gene, in colorectal cancers from different human populations. The aim of this work was to study the prevalence of mutations at codons 12, 13 and 61 of the Ki-ras gene in 37 colorectal tumors from Mexican patients and to correlate them with clinical data. METHODS: Point mutations were studied in 37 colorectal cancers at codons 12 and 13 of the Ki-ras gene, using PCR followed by RFLP. We also performed PCR-SSCP to identify mutations at codon 61. We confirmed mutations by sequence analysis in all the altered codons. RESULTS: Our results indicated that 24.3% of the tumors presented mutations at codon 12, 5.4% at codon 13, and 2.7% at codon 61 of the Ki-ras gene. We found that 75% of these mutations were transitions and 25% transversions. The overall results indicated that the frequency of Ki-ras mutations in colorectal cancers in a sample of a Mexican population (Mexico City) was 32.4%, which is similar to that reported in other populations. We did not find a correlation between the Ki-ras mutations and gender, location of the tumor, or Dukes' stage, but survival of the patient without recurrence was statistically significant. CONCLUSIONS: The study of colorectal cancer indicated that in a Mexican population Ki-ras mutations were present in tumors of patients who survived without tumor recurrence. Most of them were transitions in the first and second base of codon 12.     

Recovery of stromal stem cells in bone sarcoma patients after chemotherapy: implication for cell-based therapy in bone defect reconstruction

Bone sarcomas, such as osteosarcoma (OS) or Ewing sarcoma (ES), frequently arise in the intramedullary region of long bones. Patients affected by bone sarcomas are treated with preoperative aggressive chemotherapy immediately after diagnosis. After chemotherapy, patients undergo surgery that frequently entails the excision of wide bone segments. If a large segment of the bone is lost (defined as a critical defect) the patient undergoes bone reconstruction. Because bone marrow derived stromal stem cells (SSC) offer great promise for cell-based regenerative medicine in bone reconstruction, we investigated whether SSC could be isolated from chemotherapy-treated bone sarcoma patients. We also investigated whether chemotherapy modified SSC differentiation capability. We studied 9 SSC derived from OS and ES patients that had undergone chemotherapy and 5 SSC derived from bone sarcoma patients that had not undergone chemotherapy. SSC could be obtained from all the patients analyzed regardless of whether the patients received chemotherapy or not. Our results also showed that post-chemotherapy SSC can be cultured and expanded ex vivo, these cells retained the ability to differentiate toward the osteogenic lineage in vitro. In conclusion, our results support that SSC cells can be obtained from bone sarcoma patients that undergo chemotherapy and suggest that SSC can be used for cell-based bone reconstruction techniques in bone sarcoma patients treated with preoperative chemotherapy.