Multiple Endocrine Neoplasia 2B Syndrome due to Codon 918 Mutation: Clinical Manifestation and Course in Early and Late Onset Disease

More than 50% of patients with typical MEN-2B have a de novo M918T germline mutation of the RET protooncogene. However, even in typical MEN-2B, extrathyroidal manifestations of MEN-2B can be found to be differently expressed. We analyzed the clinical manifestation and course in 21 patients harboring a de novo RET M918T mutation. Mean age at MEN-2B diagnosis was 14.2 years (range: 1–31 years). All patients had medullary thyroid carcinoma (MTC). At the time of syndrome diagnosis, oral manifestations (bumpy lips, ganglioneuroma), ocular manifestations (corneal fibers, conjunctivitis sicca), intestinal dysfunctions, musculoskeletal manifestations, and pheochromocytoma were found in 86%, 90%, 74%, 79%, and 19% of the patients, respectively. At the time of follow-up examination, the symptoms were found at higher frequency. Severe intestinal manifestation was predominantly found in patients with prepubertal onset ( 12 years) of MTC (n = 4/10) compared with patients with late onset (> 12 years) of MTC (n = 0/11) (40% versus 0%; p = 0.019). Although biochemical cure was found only in four patients with early onset of MTC, the long-term prognosis for patients with early onset of MTC was poorer than for patients presenting with late onset of MTC (p = 0.005). During mean follow-up of 55.8 months (range: 3–161 months), seven patients (33%) died from MTC. In conclusion, whereas most typical MEN-2B symptoms were found to be age-related, severe intestinal manifestation was found to be predominantly expressed in patients with early onset of MTC. Furthermore, in patients with early onset of MTC who could not be biochemically cured, the long-term prognosis was found to be worse than that of non-cured patients with late onset of MTC, suggesting an additional pathological process in the younger subgroup reinforcing the very high transforming in vitro activity of the M918T RET mutation.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14–17, 2004.     

Current status of minimally invasive esophagectomy

Minimally invasive esophagectomy is emerging as an option in the management of benign and malignant esophageal diseases. With minimally invasive esophagectomy, the conventional laparotomy is substituted with laparoscopy and the open thoracotomy with thoracoscopy. This article discusses the surgical techniques and outcomes for a variety of minimally invasive esophagectomy options.     

Reduced pH and chloride levels in exhaled breath condensate of patients with chronic cough

BACKGROUND: Increased hydrogen and reduced chloride ionic environments of the airways are conducive to the stimulation of cough. However, the constituents of the local milieu of the airways of patients with chronic cough are unknown. METHODS: The pH and chloride levels in exhaled breath condensate and capsaicin cough threshold (C5) were measured in 50 patients with chronic cough and in 16 healthy controls. pH and chloride measurements were repeated after capsaicin challenge in those with cough. The cause of cough was asthma (n = 13), postnasal drip/rhinitis (n = 7), gastro-oesophageal reflux (n = 5), bronchiectasis (n = 5), but remained unidentified in 20. RESULTS: Compared with controls, patients with chronic cough had lower pH (mean 7.9 v 8.3, 95% CI of difference -0.5 to -0.2, p<0.0001), chloride levels (median 4 v 6 mmol/l, 95% CI -3.1 to -0.2, p = 0.007), and C5 (median 3.9 v 125 micro M, 95% CI -270.0 to -17.6, p = 0.002). The pH levels were different in the six subgroups including controls, and were reduced in all diagnostic subgroups of patients with cough compared with controls but did not differ between them. Chloride levels were significantly different in the six subgroups but were lower than controls in only the gastro-oesophageal reflux subgroup. There was a weak but significant correlation between chloride levels and C5 when all participants were analysed together, but not between pH and C5 or chloride levels. pH and chloride levels did not change after capsaicin challenge. CONCLUSIONS: The epithelial lining fluid of patients with chronic cough has a reduced pH and reduced chloride levels which could contribute to the enhanced cough reflex.     

A cost-utility and cost-effectiveness analysis of an acute pain service

STUDY OBJECTIVE: To analyze, from a societal perspective, the cost-effectiveness and cost-utility of acute pain management after inception of a nurse-based Acute Pain Service (APS) in a general hospital. DESIGN: Open, observational, interventional study. SETTING: Postanesthesia care unit and surgical wards of a university hospital center. PATIENTS: 1975 surgical inpatients who had undergone various types of surgery. INTERVENTIONS: Visual analog scale (VAS) pain scores and all systemic analgesics prescribed by anesthesiologists and administered by ward nurses were recorded before and after APS inception. All costs (drugs, disposal, and working time of nurses) related to the APS were identified. Pain measurements were performed by VAS every 4 hours over 3 consecutive days post-surgery and transformed into a health state scale, with 0 being equivalent to absence of pain and 10 to the worst imaginable pain.Using these data, analgesic effectiveness (cost-utility analysis) was expressed as postoperative pain days averted (PPDA) in the two surveys. To perform the cost-effectiveness analysis, we focused on postoperative complications, duration of hospital stay, and postoperative mortality rate. (Note: At the time of the study, 1 EURO = 0.85 US dollars.) MAIN RESULTS: VAS pain scores decreased in the post-APS phase (p < 0.001). One the first day, PPDA was 0.075, on the second day PPDA was 0.05, and the third day PPDA was 0.0375. Cost of analgesic drugs and disposal, as well as nursing hours, increased. The incremental cost of pain management after APS inception amounted to 19 EURO per patient per day, resulting in an incremental cost-effectiveness ratio of 350.77 EURO per PPDA gained. The cost-effectiveness analysis showed minor improvement (reduction of postoperative complication rate in some surgical specialties). Duration of hospital stay and postoperative mortality rate did not change. CONCLUSIONS: A hospital-wide, comprehensive, postoperative pain management program provides an overall positive result for the health care system by improving postoperative pain and morbidity. This service is cost-effective, costing 19 EURO per patient per day. A cost-utility analysis for short-term assessment of quality of life showed no benefit in determining usefulness of such a pain management program.     

Comparison of conventional bacteriology with nucleic acid amplification (amplified mycobacterium direct test) for diagnosis of tuberculous meningitis before and after inception of antituberculosis chemotherapy

The role of nucleic acid amplification techniques in the rapid diagnosis of tuberculous meningitis remains uncertain. We compared the performance of Ziehl-Neelsen (ZN) staining, the Gen-Probe amplified Mycobacterium tuberculosis direct test (MTD), and culture with 341 cerebrospinal fluid specimens from 152 adults (73 with and 79 without tuberculous meningitis) before and after inception of antituberculosis chemotherapy. The sensitivity, specificity, and positive and negative predictive values of ZN staining before treatment were 34/66 (52%), 79/79 (100%), 34/34 (100%), and 79/111 (71%), compared with 25/66 (38%), 78/79 (99%), 25/26 (96%), and 79/120 (66%) for MTD. The sensitivity of combined ZN staining and MTD (either positive) was 45/66 (68%). The sensitivity of staining and culture fell more rapidly than that of MTD after the start of treatment: after 5 to 15 days of treatment, MTD was more sensitive than ZN staining (12/43 [28%] versus 2/43 [2%]; P = 0.013). Slower bacterial clearance was observed if M. tuberculosis was resistant to isoniazid and/or streptomycin: resistant organisms were more likely to be cultured from cerebrospinal fluid after 2 to 5 days of treatment than fully sensitive organisms (P < 0.001). The sensitivities of ZN staining, MTD, and the two tests combined were improved by repeated sampling to 38/59 (64%), 35/59 (59%), and 49/59 (83%), respectively. In conclusion, ZN staining of the cerebrospinal fluid is at least as good as MTD for the rapid diagnosis of tuberculosis and is much faster and less expensive. However, the combination of these methods on serial samples detects more cases. Alternative tests are still urgently required.     

Delayed facial palsy after vestibular schwannoma resection: the role of viral reactivation. Our experience in 8 cases

OBJECTIVE: To study the role of herpes virus reactivation in the onset of more than three days-delayed facial paralysis (FP) following vestibular schwannoma (VS) surgery and advocate a specific medical management. MATERIAL AND METHODS: Retrospective study on 8 cases from a series of 348 patients operated on of a VS between 1996 and 2002. Seven of the eight patients were given intravenously acyclovir (30 mg x kg(-1) x d(-1) for 5 days) and methyl-prednisolone (2 mg x kg(-1) x d(-1) for 7 days). A serologic testing looking for specific anti-herpes simplex viruses type 1 and 2 (HSV-2) and varicella-zoster virus (VZV) antibodies at the onset of the FP and 2 weeks later could be done in only 3 cases. RESULTS: Mean delay of FP onset was 8.75 days. Mean time for recovery with intravenous treatment was 90 days. All treated patients had a House and Brackmann grade 1 recovery. The last one had only a grade 3 after 400 days of evolution: he could not be treated because of postoperative transient psychiatric problems. Serologic testing revealed in those patients in whom it could be done either a high level of anti-HSV or -VZV antibodies at the time of onset or a dramatic increase in anti-HSV or anti-VZV antibodies between the two samples, strongly suggesting a HSV or VZV reactivation. CONCLUSION: HSV or VZV reactivation can be evocated in most cases of delayed FPs arising in the postoperative course of VSs, suggesting usefulness of emergency-given steroid and acyclovir intravenous regimen to block virus replication and fight secondary oedema and inflammation causative of nerve lesions. Evoked reactivation mechanism is comparable to that already suspected in delayed FP arising with the same delay in middle ear surgical procedures.