Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients.

Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p = 0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p < 0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34-0.72; p < 0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13-0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients.

Single-nucleotide polymorphisms in pigment genes and nonmelanoma skin cancer predisposition: a systematic review.

Nonmelanoma skin cancer (NMSC) is the most common cancer in the U.S.A. The two most common NMSCs are basal cell carcinoma and squamous cell carcinoma. The associations of single-nucleotide polymorphisms (SNPs) in pigmentation pathway genes with NMSC are not well characterized. There is a series of epidemiological studies that have tested these relationships, but there is no recent summary of these findings. To explain overarching trends, we undertook a systematic review of published studies. The summarized data support the concept that specific SNPs in the pigmentation pathway are of importance for the pathogenesis of NMSC. The SNPs with the most promising evidence include MC1R rs1805007(T) (Arg151Cys) and rs1805008(T) (Arg160Trp), and ASIP AH haplotype [rs4911414(T) and rs1015362(G)]. There are a few other SNPs found in TYR, OCA2 and SLC45A2 that may show additional correlation after future research. With additional research there is potential for the translation of future findings to the clinic in the form of SNP screenings, where patients at high risk for NMSC can be identified beyond their phenotype by genotypically screening for predisposing SNPs.

Cervical and vaginal cytologic smears suggestive of adenocarcinoma.

OBJECTIVE: To determine the appropriate evaluation of women with cervical cytologic smears suggestive of adenocareinoma. STUDY DESIGN: Of 1,192,972 smears obtained between July 1989 and March 1992, 57 (0.005%) were interpreted as adenocarcinoma, adenocarcinoma in situ or "rule out" adenocarcinoma. Review of medical records allowed the determination of pathologic diagnoses in 46 of 57 women. Thirty of the 46 cytologic smears were reviewed. RESULTS: Fifteen of the 46 women were premenopausal and < 50 years of age. Twenty-three were asymptomatic, 22 had abnormal vaginal bleeding, and 1 had increasing abdominal girth. Twenty-nine (63%) of the 46 women had cancer, 12 (26%) had cervical intraepithelial neoplasia 2 (CIN 2) or 3, and 5 (11%) had CIN 1, condyloma or no pathology. Of the 29 women with cancer, 11 had cervical cancer, 1 had vaginal cancer, 13 had uterine cancer, and 4 had extrauterine cancer. Nineteen of 22 women (86%) with abnormal vaginal bleeding had cancer; 9 of 23 asymptomatic women had cancer (39%) (chi 2 = 9.84, P < .01). DISCUSSION: Women with smears suggestive of adenocarcinoma require biopsy of cervical or vaginal masses, colposcopy with directed biopsy, endocervical curettage and endometrial biopsy. If cancer is not diagnosed, cervical conization with dilatation and curettage (D&C) is indicated. If conization with D&C is negative, laparoscopy is indicated to exclude extrauterine cancer.

Alternative prenatal care. Impact of reduced visit frequency, focused visits and continuity of care.

OBJECTIVE: To investigate the impact of an alternative prenatal care program for low-risk patients. STUDY DESIGN: Five hundred forty-nine low-risk pregnant women were allocated to the study and control groups. The study group received, on average, eight visits, all of them with one of nine study providers. Each study visit had specific objectives and accompanying targeted patient education handouts. The control group received the usual prenatal care (on average, 13 visits) with different providers, according to the customary schedule. RESULTS: There were no significant pregnancy outcome differences between the groups. The study vs. control group differed significantly (P < .0001) in patient satisfaction regarding the number of prenatal visits. There was a higher level of satisfaction in the study group concerning continuity of care (P < .0001). The alternative prenatal care program reduced the number of prenatal visits by 27% and was not associated with any change in maternal or perinatal outcomes. Patient satisfaction parameters were either maintained or improved with alternative prenatal care. CONCLUSION: An alternative prenatal care program for low-risk patients reduced resource utilization without adversely affecting prenatal care process variables, pregnancy outcome or patient satisfaction.

Combined vesicovaginal-ureterovaginal fistulas associated with a vaginal foreign body.

A case is presented of vesicovaginal-ureterovaginal fistulas associated with a neglected vaginal foreign body. The patient complained of a foul-smelling vaginal discharge and was found to have a 4-cm hard vaginal mass on examination. Urinary incontinence developed subsequently. Examination under anesthesia was performed, and an aerosol deodorant cap was operatively removed from her posterior vagina/perirectal space. Subsequent work-up demonstrated the presence of both a vesicovaginal fistula and a right ureterovaginal fistula. The patient underwent a combined vaginal repair of the vesicovaginal fistula and abdominal ureteroneocystostomy. The frequency, types, etiology, and treatment of genitourinary fistulas are reviewed with particular attention to those associated with a vaginal foreign body.

A comparison of compliance techniques on the control of high blood pressure.

Four compliance strategies were compared with education alone to investigate their impact on the control of high blood pressure. One hundred twelve subjects with documented high blood pressure were randomly assigned to receive education alone, home blood pressure monitoring, contracts, pill packs, or a combination of techniques. Groups were similar in terms of age, sex, race, initial blood pressure, and medications. At the end of the year, there was no significant change in blood pressure for the group that received education alone (-3/-1 mm Hg). There was a statistically significant change in both systolic and diastolic blood pressure for all compliance groups (-17/-10 mm Hg). Information from compliance questionnaires adds further support to the observation that education alone does not influence compliance while the specific techniques studied did improve compliance. The study was too small to show any difference among techniques.

The clinical implications of retroperitoneal endometriosis.

Over the past 10 years five patients with endometriosis involving only retroperitoneal structures in the pelvis without intraperitoneal involvement have been managed at the University of California-Los Angeles Hospital. These patients have presented difficult diagnostic and therapeutic problems. Moreover, this interesting but uncommon distribution of the disease has led to speculation concerning its pathogenesis. The substantial threat to the urinary tract and rectosigmoid colon is noted. Although a concurrent study at this hospital indicates a low incidence of endometriosis involving pelvic lymph nodes, it is quite apparent from the distribution of these instances of retroperitoneal involvement that its spread from the endometrium very likely takes place through pelvic lymphatics.

Adenocarcinoma in a choledochal cyst during pregnancy: a case report and guidelines for management.

Choledochal cysts, although more common in females than males, have only rarely been encountered in association with pregnancy. We report a patient with a large choledochal cyst that was excised at the time of cesarean section. Pathologically, the cyst wall was found to contain a focus of adenocarcinoma. The development of carcinoma is a recognized risk in patients with choledochal cysts that mandates cyst excision, rather than bypass, whenever possible. The literature regarding choledochal cysts in pregnancy is reviewed. Pregnant patients with choledochal cysts require careful management so as to avoid cyst rupture; and cesarean section is preferable to normal vaginal delivery in most cases. Although the preferred management of a choledochal cyst is excision and Roux-en-Y reconstruction, this may have to be deferred until after delivery, depending on gestation age, because of the risk of fetal mortality and maternal morbidity that is associated with this procedure.

Coffee and pancreatic cancer: an analysis of international mortality data.

This study assessed the relationship of per capita coffee imports and consumption, total dietary fat, saturated fat, cholesterol, tobacco, cigarettes, and national income for 1957-1965 to age-adjusted pancreatic cancer death rates of men and women from 22 countries in 1971-1974. With simple correlation analysis, coffee, total dietary fat, saturated fat, and national income were each significantly correlated with both male and female pancreatic cancer mortality. Bivariate partial correlation coefficients of coffee with pancreatic cancer mortality were significant (one-tailed) in 11 of 12 analyses and borderline significant in two-way analyses of variance (ANOVA) (two-tailed) controlling for each of the other variables. Saturated fat and pancreatic cancer were also significantly related in univariate analyses, and in 11 of 12 bivariate partial correlation analyses; in ANOVA, significance was borderline in 10 of 12 analyses. Total fat and pancreatic mortality were also significantly associated in most of the univariate and bivariate correlation analyses, but not in the two-way analyses of variance. The findings of this study are consistent with the hypothesis that coffee and dietary lipid are involved in the etiology of pancreatic cancer.

Pseudotumor cerebri in an obese woman with Turner syndrome.

Extraovarian estrogen production was studied in an obese young woman with pathologically confirmed mosaic Turner syndrome and pseudotumor cerebri. Diet plus enough dexamethasone to suppress adrenal steroidogenesis promptly lowered cerebrospinal fluid testosterone. Estrone was detected in cerebrospinal fluid before and after but not during dexamethasone treatment. Extraovarian estrogen probably produces the menstrual irregularities of obese young women with pseudotumor cerebri and may be involved in the pathogenesis of that syndrome.

Effect of calcitonin and glutocorticoids in combination on the hypercalcemia of malignancy.

The effects of the combination of glucocorticoids and calcitonin on serum calcium levels were compared with the responses to calcitonin alone in 14 patients with malignant disease and hypercalcemia. The serum calcium concentrations of those patients treated with calcitonin alone returned to pretreatment concentrations within 48 hours, whereas those treated with the combination of calcitonin and glucocorticoids maintained the lower serum calcium concentrations for more than 4 days. These results suggest that the combination of calcitonin and glucocorticoids is a rapidly effective form of medical treatment for hypercalcemia and that glucocorticoids help to maintain the acute response to calcitonin in patients with hypercalcemia.