Five-year Prospective Audit of Routine Intravenous Cholangiography and Selective Endoscopic Retrograde Cholangiography with or without Intraoperative Cholangiography in Patients Undergoing Laparoscopic Cholecystectomy

Consensus has never been reached regarding the need or the imaging technique for evaluating the common bile duct (CBD) in patients considered for cholecystectomy. With the advent of laparoscopic cholecystectomy there has been a resurgence of interest in the role of preoperative intravenous cholangiography (IVC) as an alternative for evaluating the CBD. The purpose of this audit was to assess whether a diagnostic workup based on IVC, which permits selective use of intraoperative cholangiography (IOC) and endoscopic treatment of CBD stones before surgery, could be useful in patients undergoing laparoscopic cholecystectomy (LC). In patients without jaundice, gallstone pancreatitis, a prior diagnosis of CBD stones, a prior history of contrast allergy, or a risk of contrast-associated acute renal failure, IVC was performed routinely. Patients suspected to have CBD stones based on IVC results or with inconclusive IVC and patients with a strong clinical suspicion of CBD stones were referred for endoscopic retrograde cholangiography (ERC). IOC was carried out in patients who had a history of contrast allergy or risk of contrast-associated acute renal failure and whenever the surgeon was in doubt as to the biliary anatomy or CBD clearance. IVC was carried out in 1155 patients, ERC in 225, and IOC in 54. IVC was conclusive in 1132 patients, with a diagnostic accuracy of 99%. Our workup permitted the sequential endoscopic-laparoscopic treatment of cholecystocholedocholithiasis in 162 cases. During the follow-up period residual CBD stones were detected in four patients. Our diagnostic workup showed that routine IVC exposes the population to a large radiation burden, and the cost is high for the small number of patients who benefit. Moreover, it does not seem helpful in reducing the incidence of CBD injuries during LC.     

p53 mutations in human aggressive and nonaggressive basal and squamous cell carcinomas.

PURPOSE: The purpose is to investigate whether aggressive basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) differ from nonaggressive BCC and SCC with respect to the p53 mutation spectrum and whether specific mutations can serve as prognostic indicators of tumor aggressiveness. EXPERIMENTAL DESIGN: We analyzed 342 tissues from patients with aggressive and nonaggressive BCCs and SCCs for p53 mutations by single-strand conformation polymorphism and nucleotide sequencing. RESULTS: p53 mutations were detected in 33 of 50 aggressive BCCs (66%), 37 of 98 nonaggressive BCCs (38%), 28 of 80 aggressive SCCs (35%), 28 of 56 nonaggressive SCCs (50%), and 3 of 29 samples of sun-exposed skin (10%). About 71% of the p53 mutations detected in aggressive and nonaggressive BCCs and SCCs were UV signature mutations. The frequency of CC to TT mutations in aggressive (36%) and nonaggressive SCCs (39%) was 2-fold higher than in aggressive (18%) and nonaggressive (14%) BCCs. In contrast, aggressive BCCs had a higher frequency (24%) of transversions than nonaggressive BCCs (8%) and aggressive (14%) and nonaggressive (11%) SCCs did. CONCLUSIONS: Our results indicate that UV radiation is responsible for the induction of p53 mutations and perhaps for the initiation of both aggressive and nonaggressive BCCs and SCCs. Although some differences in p53 mutation frequency, types of mutation, and hot spots were seen between aggressive and nonaggressive BCCs and SCCs, these factors do not constitute as clear-cut diagnostic or prognostic indicators of tumor aggressiveness. Tumor aggressiveness may be attributable to other genetic changes or events that occur during tumor progression.     

Upper airway obstruction and pulmonary abnormalities due to lymphoproliferative disease following bone marrow transplantation in children

We report three patients who developed severe supraglottic airway obstruction due to Epstein-Barr virus lymphoproliferative disease following allogeneic bone marrow transplantation. In addition to enlarged pharyngeal lymphoid tissue seen in all three patients, two had supraglottic airway narrowing and two developed pulmonary lymphoproliferative disease. They were treated with unmanipulated T cells or EBV-specific cytotoxic T lymphocytes. Life-threatening upper airway obstruction is a radiologically detectable complication of allogeneic bone marrow transplantation in children. Received: 12 August 1997 Accepted: 11 December 1997     

Is there an incremental rise in the risk of obstetric intervention with increasing maternal age?

Objective To determine whether increasing maternal age increases the risk of operative delivery and to investigate whether such a trend is due to fetal or maternal factors.
Design Analysis of prospectively collected data on a maternity unit database.
Setting A postgraduate teaching hospital.
Population 6410 nulliparous women with singleton cephalic pregnancies delivering at term (37–42) weeks of gestation) between 1 January 92 and 31 December 95.
Main outcome measures Mode of delivery, rates of prelabour caesarean section, induction of labour and epidural usage.
Results There was a positive, highly significant association between increasing maternal age and obstetric intervention. Prelabour (  P < 0.001  ) and emergency (   P < 0.001  ) caesarean section, instrumental vaginal delivery (spontaneous labour   P < 0.001  ; induced labour   P = 0.001  ), induction of labour (   P < 0.001  ) and epidural usage in spontaneous labour (  P = 0.005  ) all increased with increasing age. In the second stage of labour fetal distress and failure to advance, requiring instrumental delivery, were both more likely with increasing maternal age (in both   P < 0.001  ). Epidural usage in induced labour and the incidence of small for gestational age newborns did not increase with increasing maternal age (P = 0.68 and  P = 0.50  , respectively).
Conclusions This study demonstrates that increasing maternal age is associated with an incremental increase in obstetric intervention. Previous studies have demonstrated a significant effect in women older than 35 years of age, but these data show changes on a continuum from teenage years. This finding may reflect a progressive, age-related deterioration in myometrial function.     

Atrazine and the hypothalamo-pituitary-gonadal axis in sexually maturing precocial birds: studies in male Japanese quail.

The herbicide atrazine is a putative endocrine disruptor. The present studies investigated the effects of atrazine in male Japanese quail during sexual maturation. Atrazine was administered for two weeks in the diet or systemically to birds under long photoperiods. Atrazine had no effect on mortality but depressed both feed intake and growth (average daily gain [ADG] in g/day) at dietary concentrations of 1000 ppm. Atrazine in the diet at 10 ppm, but at no other concentrations, increased testes weight and gonadal-somatic-index and decreased the seminiferous tubule diameter-to-testis weight ratio. However, there were no effects on absolute tubule diameter, relative stage of testicular development, or the presence of a lumen. Atrazine in the diet at 1000 ppm increased circulating concentrations of testosterone but this effect was not observed consistently in all studies. Dietary atrazine at 10 ppm increased circulating concentrations of estradiol. Moreover, in one study, atrazine at 1000 ppm in the diet decreased circulating concentrations of luteinizing hormone. Atrazine administered systemically exerted no effect on indices of growth or reproduction. Atrazine did not mimic the effects of either estradiol or tamoxifen in male quail; thus, atrazine did not exhibit overt estrogenic or anti-estrogenic activity. Conversely, atrazine augmented the effects of testosterone and estradiol on testis regression, presumably by increasing the negative-feedback effects of these sex-steroids on follicle stimulating hormone secretion. It is concluded that atrazine up to 1000 ppm in the diet may exert some effects on reproductive development in sexually maturing male birds, but these are inconsistent and modest.     

Cytological aspects of the nasal respiratory epithelium in reproductive-age women taking oral contraceptives.

OBJECTIVE: To determine the effects of monophasic oral contraceptives on the nasal respiratory epithelium in premenopausal women. DESIGN: Prospective open clinical trial. SETTING: Outpatient Family Planning Centre. PATIENT(S): Eighty-eight premenopausal women, with ovulatory cycle, who were planning to take oral contraceptives. INTERVENTION(S): Baseline endovaginal ultrasound examination and blood test to measure serum progesterone to confirm ovulatory cycle. Thirty-eight women on pill containing 30 microg ethinylestradiol (EE) plus 75 microg gestodene, and 35 women on pill containing 15 microg ethinylestradiol plus 60 microg gestodene. MAIN OUTCOMES/MEASURE(S): Cytological changes on the nasal respiratory epithelium evaluated with the maturation index performed during the follicular, periovular, and luteal phases of the menstrual cycle, and on the sixth cycle of pill intake. RESULT(S): Hematoxylin-eosin staining for the maturation index showed similar trophic cytological aspects between the nasal and vaginal epithelium during the menstrual cycle and pill usage. Both the nasal and vaginal cytological samples showed higher maturation indexes during both the follicular and the periovular phases than during the luteal phase. Women on pill containing 15 microg EE showed lower trophic aspects in the nasal cytological samples compared with those on pill with 30 microg EE. CONCLUSION(S): Along with the vaginal cells, the nasal respiratory epithelium is an ovarian steroid target. The maturation index of the nasal respiratory epithelium seems to depend on the variation of the ovarian steroids during the menstrual cycle and on the iatrogenic effects of oral contraceptives.     

Epididymal metastases as the first sign of a colon cancer recurrence

Metastastic tumours involving the epididymis are rare and most often found in patients with disseminated disease. It is even more unusual when the metastasis of the epididymis is the first sign of tumour recurrence. We report a case of an asymptomatic recurrent colon carcinoma presenting as metastasis in the epididymis. Although metastatic cancer presenting as an intra-scrotal mass is extremely rare, it should be considered as a possibility in patients who present with a mass involving the testicle or epididymis.     

Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials.

PURPOSE: Most cases of non-small-cell lung cancer (NSCLC) with dramatic responses to gefitinib have specific activating mutations in the epidermal growth factor receptor (EGFR), but the predictive value of these mutations has not been defined in large clinical trials. The goal of this study was to determine the contribution of molecular alterations in EGFR to response and survival within the phase II (IDEAL) and phase III (INTACT) trials of gefitinib. PATIENTS AND METHODS: We analyzed the frequency of EGFR mutations in lung cancer specimens from both the IDEAL and INTACT trials and compared it with EGFR gene amplification, another genetic abnormality in NSCLC. RESULTS: EGFR mutations correlated with previously identified clinical features of gefitinib response, including adenocarcinoma histology, absence of smoking history, female sex, and Asian ethnicity. No such association was seen in patients whose tumors had EGFR amplification, suggesting that these molecular markers identify different biologic subsets of NSCLC. In the IDEAL trials, responses to gefitinib were seen in six of 13 tumors (46%) with an EGFR mutation, two of seven tumors (29%) with amplification, and five of 56 tumors (9%) with neither mutation nor amplification (P = .001 for either EGFR mutation or amplification v neither abnormality). Analysis of the INTACT trials did not show a statistically significant difference in response to gefitinib plus chemotherapy according to EGFR genotype. CONCLUSION: EGFR mutations and, to a lesser extent, amplification appear to identify distinct subsets of NSCLC with an increased response to gefitinib. The combination of gefitinib with chemotherapy does not improve survival in patients with these molecular markers.