Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase.

Peutz-Jeghers (PJ) syndrome is an autosomal-dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer. The PJ gene was recently mapped to chromosome 19p13.3 by linkage analysis, with the highest lod score at marker D19S886. In a distance of 190 kb proximal to D19S886, we identified and characterized a novel human gene encoding the serine threonine kinase STK11. In a three-generation PJ family, we found an STK11 allele with a deletion of exons 4 and 5 and an inversion of exons 6 and 7 segregating with the disease. Sequence analysis of STK11 exons in four unrelated PJ patients has identified three nonsense and one acceptor splice site mutations. All five germline mutations are predicted to disrupt the function of the kinase domain. We conclude that germline mutations in STK11, probably in conjunction with acquired genetic defects of the second allele in somatic cells, cause the manifestations of PJ syndrome.

Vaginal evisceration.

Although vaginal laceration following sexual trauma is a well-reported entity, vaginal evisceration appears to be a rare occurrence. This paper presents 2 cases of vaginal evisceration recently managed at the Bronx Municipal Hospital Center and a review of the literature. Etiologic factors and management are discussed.

Chondrosarcoma of the larynx.

Cartilaginous tumors of the larynx are rare, and of those reported, most are chondromas. To date, approximately 157 cartilaginous tumors of the larynx have been reported, but only 37 have been chondrosarcomas. A review of the records of the past 25 years (1948-1974) of the Johns Hopkins University Hospital and the Greater Baltimore Medical Center was made and revealed only two previous cartilaginous tumors, both chondromas. A case of an exceptionally large chondrosarcoma of the larynx which appeared as a neck mass invading the thyroid cartilage in a patient with a six-month history of hoarseness is presented. A complete review of the literature was made which shows that most chondrosarcomas occur in middle-aged males originating most often from the posterior cricoid lamina, next from the thyroid cartilage. Misdiagnosis has been a problem with low-grade tumors, and although wide local excision has been stated as being the treatment of choice, the authors emphasize the need for more aggressive surgery because of the high recurrence rate discovered in the literature.

Ureteral dilation using a tapered dilator: a cost-effective approach.

BACKGROUND AND PURPOSE: The 6/12 AQ hydrophilically coated tapered dilator is a newly developed device for ureteral dilation prior to rigid and flexible ureteroscopy. PATIENTS AND METHODS: To evaluate the efficacy, safety, and cost-effectiveness of this device, it was used to gain ureteral access in 80 consecutive patients undergoing ureteroscopy for diagnostic purposes, stone treatment, or stricture dilation. RESULTS: In all 80 cases, the ureteral orifice and intramural ureter were dilated successfully. One complication occurred: an embedded stone was extruded through the ureteral wall. Each dilation procedure using the 6/12 AQ tapered dilator costs 20% of a balloon dilation, a saving of approximately $764 per dilation. CONCLUSION: Ureteral dilation with the 6/12 AQ tapered dilator is a safe, effective, and inexpensive alternative to traditional dilation techniques.

Retrolective, comparative, epidemiological cohort study with parallel groups design for evaluation of efficacy and safety of drugs with "well-established use".

UNLABELLED: The randomized controlled clinical trial (RCT) is accepted as the "golden standard" for the evaluation of efficacy and safety of new drugs. In contrast, to demonstrate efficacy and safety of drugs with "well-established use" that have been on the European Community market for long time, observational comparative epidemiological studies can be used according to the European drug regulation directive. However, because comparative epidemiological cohort studies can share some risk of bias with other nonrandomized observational study designs, there is a need for an approach that could effectively reduce the bias risk in this type of studies. STUDY OBJECTIVES: The purpose of the study was to evaluate the therapeutic efficacy and safety of a long-term complementary therapy of primary, non-metastatic breast carcinoma patients treated with standardized European mistletoe extract Iscador("mistletoe") in addition to the conventional adjuvant oncologic therapy, and compared to the control group treated with the conventional therapy alone. METHODS: The multicenter, comparative, retrolective, pharmaco-epidemiological cohort study with parallel groups design and randomly selected centers that routinely used both treatments was carried out according to Good Epidemiological Practice rules under a standard operating procedure control. The test group patients received the mistletoe extract treatment subcutaneously for at least 3 months, while the control group patients of the same cohort was exclusively treated with the conventional therapy. The patients were followed up for at least 3 years or until death. The primary endpoint of efficacy was the incidence of adverse reactions to the conventional oncologic therapy. Secondary endpoints were change from baseline of the symptoms associated with the disease and treatment as well as overall survival. All endpoints were adjusted to baseline imbalance and confounders. Safety was assessed descriptively by the number of patients with adverse drug reactions (ADRs) attributed to the test treatment. RESULTS: 1442 patients (710 tests and 732 controls) were eligible for the "per protocol" analysis of efficacy and safety. At baseline, the test group had a more advanced disease and worse prognostic factors profile. After a median follow-up of 66 vs. 60 months, and a median mistletoe therapy duration of 52 months, significantly fewer test group patients (16.2%) than control patients (54.0%) developed ADRs attributed to the conventional therapy [adjusted odds ratio, OR (95% confidence interval, CI), OR = 0.47 (0.32-0.67), p < 0.001]. In the test group, the majority of the symptoms disappeared more frequently, and overall mortality hazard was significantly lower [adjusted hazard ratio, HR (95% CI), HR = 0.46 (0.22-0.96), p = 0.038] than in the control group. Systemic ADRs attributed to the test treatment developed in 0.8%, and local ADRs in 17.3% of the patients. ADR severity was mild to intermediate. Tumor enhancement was not observed. CONCLUSIONS: Complementary therapy of patients with primary, non-metastatic breast carcinoma with the mistletoe extract Iscador was safe and in comparison to the control group within the same study cohort showed considerably fewer ADRs attributed to concurrent conventional therapy, reduced disease symptoms, and suggested a significant improvement of survival. Despite some methodical limitations that require careful study planning and conduction as well as critical interpretation, the applied study design seems suitable to evaluate the efficacy and safety of drugs with "well-established use", particularly in oncology.

Molecular mistletoe therapy: friend or foe in established anti-tumor protocols? A multicenter, controlled, retrospective pharmaco-epidemiological study in pancreas cancer.

Mistletoe is often used as complementary therapy in oncology. The anti-tumor effects of mistletoe (Iscador) are well documented in-vitro in respect to inhibition of cell proliferation, induction of apoptosis, segmental activation of immune competent cells and trapping of chemotherapeutic drugs within cancer cells by modulating the inhibitory potential of P-glycoprotein (P-gp)-mediated transport of cell toxifying substances (cytotoxic drugs). However, the clinical activity of mistletoe treatment remains still controversial. Implementation of mistletoe therapy as supportive care into anti-cancer programs should be based on the best evidence and must continually be evaluated to ensure safety, efficacy, collection of new data, and cost-effectiveness. Useful domains that can be evaluated include symptom control, adherence to conventional treatment protocols, quality of life, individual outcome and potential advantages of a whole-system health approach. Here we report the results of a multicenter, controlled, retrospective and observational pharmaco-epidemiological study in patients suffering from a pancreatic carcinoma. After surgery the patients were treated by adjuvant chemotherapy with gemcitabine supported by Iscador, or with gemcitabine alone, or any other best of care, but not including Iscador. Using a novel methodological pharmaco-epidemiological design and statistical approach it could be shown that Iscador offers benefits--symptom control, overall survival--as supportive care within gemcitabine protocols of patients with surgically resected pancreatic carcinoma.

Pseudosarcomas of the pharynx and larynx.

Pseudosarcoma of the pharynx and larynx has remained an enigma both to the pathologist and clinician since its original description by Lane in 1957. These lesions are usually polypoid growths that microscopically present very bizarre appearances beneath a squamous cell carcinoma. Eight cases of pseudosarcoma of the larynxand pharynx were observed. These occurred almost twice as often in males as females, with an average age of 56 years. Most were extralaryngeal lesions, and in all cases surgical excision was the primary therapeutic modality. A thorough review of the literature summarizes the clinical and pathologic characteristics of these lesions. There is strong clinical evidence against the traditional belief of the benign course of these lesions, and we recommend that they be treated aggresively like any other carcinoma of the head and neck.

Radical retropubic prostatectomy outcomes at a community hospital.

PURPOSE: We reviewed a 6-year experience performing radical retropubic prostatectomy at 2 community hospitals (for-profit and not-for-profit) to assess outcomes and to compare them to the published literature reflecting outcomes from major academic hospitals. MATERIALS AND METHODS: Charts of 116 patients who underwent radical retropubic prostatectomy (nerve sparing in select cases) between 1990 and 1996 were reviewed for clinical and pathological outcomes as well as hospital charges. Subjective patient reports of urinary continence, potency and satisfaction were evaluated postoperatively. RESULTS: Average patient age was 66.6 years and average preoperative prostate specific antigen level was 9.6 ng./ml. Of the patients 43% had T1c disease, 63% pT2 and 37% pT3. Positive margins were present in 17.2% of the specimens and 66% of the patients had Gleason scores of 5 and 6. No deaths occurred. Major complications occurred in 5.4% of patients and included deep venous thrombosis (1.8%), pulmonary embolism (1.8%), rectal injury requiring ileostomy (0.9%) and fascial dehiscence (0.9%). Mean blood loss was 872 cc and mean blood transfusion rate was 1.7 units (almost exclusively autologous blood). Hospital charges decreased at the not-for-profit hospital to $13,233 in 1996 from $17,743 in 1990 to 1995, whereas charges increased at the for-profit hospital to $25,979 in 1996 from $24,481 in 1990 to 1995. Mean length of stay decreased from 5 days in 1990 to 1995 to 3 days in 1996. Of the patients 80% were totally continent (pad-free), 12% wore a protective pad once per day for minimal incontinence and 8% wore 2 or more pads. Of the men who were potent preoperatively 18% retained potency and 46% remained sexually active postoperatively either spontaneously or with assistance. Of the patients 84% were satisfied with surgical outcomes, 11% were somewhat satisfied and 5% were dissatisfied. CONCLUSIONS: Radical retropubic prostatectomy can be performed safely and with acceptable clinical and pathological outcomes at a community hospital. Impotence continues to be one of the most bothersome morbidities, particularly in older men. Increasing cost awareness, coincident with the proliferation of managed care, has led to reductions in length of hospital stay and charges at certain hospitals.

False aneurysm of the facial artery.

A case of an unusual traumatic aneurysm of the facial artery secondary to blunt trauma is reported. The lesion was typical in that it was pulsatile, had a systolic bruit, and had a filling defect that was evident on carotid angiography. Although a traumatic aneurysm is a rare occurrence in the facial region, the inclusion of this lesion in the differential diagnosis of soft tissue lesions is important if the serious consequences of hemorrhage are to be avoided.