Ki67 as a biologic marker of basal cell carcinoma: a retrospective study.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in humans. Several factors have been associated with the biological behavior of these tumors, including histopathologic type, depth of tumor invasion, perineural invasion, and the expression of several biological markers including Ki67, a proliferative marker. Previous studies assessing the relationship between the proliferative fraction, as expressed by Ki67, and the histological variants of BCC as well as its association with the tendency to recur, failed to illustrate significant statistical correlation. OBJECTIVES: To examine the proliferative index, as expressed by Ki67, in various subtypes of basal cell carcinoma, and to assess its relationship to various histological and clinical variables. METHODS: In this retrospective study 51 lesions of BCC were examined. In each case, the following data were gathered: demographic (age and gender), anatomic location, size of the lesion, and clinical follow-up. Each case was stained immunohistochemically with anti-Ki67 antigen (MIB-1), and the proliferative index was determined. Histological analysis was performed for the following data: presence of an ulcer, intensity of inflammatory infiltrate, histologic subtype, mitotic count, and the presence of perineural invasion. RESULTS: Basal cell carcinoma exhibited a wide variation of proliferative indices, ranging from 1% to 61%. A significant statistical correlation was observed between the proliferative index and the mitotic activity, tumor ulceration and brisk tumor-infiltrating lymphocytes. CONCLUSIONS: The wide variation in the degree of proliferation (from almost no activity to highly proliferative tumors) suggests that basal cell carcinoma exhibits a wide spectrum of biological characteristics. Ulcerated lesions were characterized by high proliferative index. No true correlation was demonstrated between the proliferative index and the aggressive histological subtypes, implying that other factors were more biologically significant. The degree of proliferation also showed significant statistical correlation with the degree of tumor infiltration by lymphocytes. The significance of this proliferation-associated increased immunogenicity needs to be further studied.

Clinical and genetic findings in eight Israeli patients with transthyretin-associated familial amyloid polyneuropathy.

BACKGROUND: Transthyretin (TTR)-associated familial amyloid polyneuropathy (FAP) is an autosomal dominant multisystem disease with neurological and extra-neurological manifestations. It is caused by various mutations in the TTR gene leading to the formation of insoluble amyloid. OBJECTIVES: To describe the clinical and genetic findings in patients with TTR-associated FAP in Israel. METHODS: We evaluated eight patients clinically and genetically during the years 2006 to 2011. RESULTS: At onset, all the patients exhibited sensory loss of the lower and upper limbs, five patients experienced muscle pain, and one patient had lower limb weakness. Five patients had autonomic nervous system manifestations, and four demonstrated evidence of amyloid cardiomyopathy. Nerve conduction studies showed sensorimotoraxonal neuropathy in all patients. Sural nerve biopsies were obtained in five patients; only three biopsies revealed amyloid deposit. In four patients of Yemenite descent, genetic analysis of the TTR gene demonstrated ser77tyr mutation. One patient of Tunisian descent and one Ashkenazi patient harbored the val30met mutation. One patient of Iranian descent showed val32ala mutation, and another Ashkenazi patient showed phe33leu mutation. CONCLUSIONS: TTR-associated FAP is a progressive and fatal disease that exists in the Israeli population and is unproportionally common among Yemenite Jews. This disease may be under-diagnosed and should be considered in the differential diagnosis of any patient with rapidly progressive neuropathy, especially with autonomic involvement or extra-neural features. The absence of amyloid in nerve biopsy should not rule out the diagnosis.

Clinical, electrophysiologic and pathologic findings in 10 patients with myotonic dystrophy 2.

BACKGROUND: Myotonic dystrophy type 2 (DM2) is an autosomal dominant, multisystem disorder caused by a CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene) on chromosome 3q 21.3. OBJECTIVES: To describe the clinical, electrophysiologic and pathologic findings in patients with myotonic dystrophy 2. METHODS: We evaluated 10 patients genetically, clinically and electrophysiologically during the years 2007 to 2008. RESULTS: All patients were of Jewish European ancestry. Among affected individuals, eight patients had symptoms of proximal muscle weakness, two had muscle pain, and two exhibited myotonia. On physical examination six patients had severe weakness of hip flexor muscles. Seven individuals underwent cataract surgery, and cardiac involvement was seen in one case. On the initial electromyographic (EMG) examination five patients demonstrated myotonic discharges; repeated studies showed these discharges in nine cases. Six muscle biopsies showed non-specific pathological changes. Seven patients had an affected first-degree relative with either a diagnosed or an undiagnosed muscular disorder consistent with an autosomal dominant trait. CONCLUSIONS: DM2 may often present with proximal muscle weakness without myotonia. EMG may initially fail to show myotonic discharges, but these discharges may eventually show in most cases on repeated EMG. Thus, DM2 may be underdiagnosed and should be included in the differential diagnosis of adult patients of Jewish European ancestry presenting with proximal lower limb weakness.

Acute heroin-related neuropathy.

Heroin-related peripheral nervous injury has scarcely been reported, mostly as compressive neuropathy. Rarely, other types of peripheral nervous system (PNS) injury have been recognized, such as plexopathy, polyradiculopathy, mononeuropathy, and rhabdomyolysis. These complications are usually not related to local trauma, but the nature of nerve injury remains unknown. Immunologic mechanisms have been proposed, although generally there is no laboratory evidence of inflammation and usually there is no improvement following steroid therapy. We describe six patients who developed acute PNS injury following intravenous or intranasal heroin self-administration with no evidence of compression injury or inflammation. Four patients had plexopathy (two lumbosacral and two brachial), and two had symmetric distal axonal sensorimotor neuropathy affecting the lower extremities. Of the six patients, five had concomitant rhabdomyolysis (creatine kinase, CK: 5,000-100,000 U/l) and one patient with brachial plexopathy had normal CK levels. The neurological deficit was noticed 3-36 h after heroin administration. Electromyography in five patients was consistent with sensorimotor axonal loss either confined to the affected plexus or with a diffuse distribution in the legs in the two patients with neuropathy. We propose that a toxic mechanism may be responsible for non-compression cases of acute neuropathy following heroin abuse.

Asymptomatic or minimally symptomatic hyperCKemia: histopathologic correlates.

BACKGROUND: Persistent creatine kinase elevation is occasionally encountered in subjects without any clinical manifestation of a neuromuscular disorder or any condition known to be associated with increased serum CK levels. It is still unresolved whether extensive investigations and specifically a muscle biopsy should be performed in clinically normal individuals with elevated CK levels. OBJECTIVE: To study the muscle pathology of patients with asymptomatic or minimally symptomatic hyperCKemia. METHODS: The clinical and laboratory data of patients with persistent hyperCKemia and normal neurologic examination were reviewed and their muscle biopsies evaluated. RESULTS: The study group included 40 patients aged 7-67 years; the male to female ratio was 3:1. Nineteen patients were completely asymptomatic, 20 had mild non-specific myalgia, and 1 had muscle cramps. Electromyography was performed in 27 patients and showed myopathic changes in 7 (26%). Abnormal muscle biopsy findings (e.g., increased variation in fiber size, increased number of central nuclei, and occasional degenerating fibers) were detected in 22 of the 40 patients (55%). No fat or glycogen accumulation was detected. Immunohistochemistry demonstrated abnormal dystrophin staining in 3 patients (8%), resembling the pathologic changes of Becker muscular dystrophy. No abnormal findings were detected on immunohistochemical staining for merosin, dysferlin, caveolin 3, or alpha and gamma sarcoglycans. The EMG findings did not correlate with the pathologic findings. CONCLUSIONS: Abnormal muscle biopsies were found in 55% of patients with asymptomatic or minimally symptomatic hyperCKemia. Specific diagnosis of muscular dystrophy, however, was possible in only 8% of the patients.

Nasal versus oral fiberoptic intubation via a cuffed oropharyngeal airway (COPA) during spontaneous ventilation.

STUDY OBJECTIVE: To compare the success rate of nasal versus oral fiberoptic intubation in anesthetized patients breathing spontaneously via the cuffed oropharyngeal airway (COPAtrade mark). DESIGN: Prospective, randomized, controlled study. SETTING: Two university-affiliated hospitals. PATIENTS: Patients scheduled for general or plastic surgery of the torso or extremities. INTERVENTIONS: Nasal (n=20) and oral (n=20) fiberoptic intubation were performed in patients while breathing spontaneously via the COPA during standardized anesthesia. MEASUREMENTS: Demographic data, mean arterial pressure, heart rate, end-tidal carbon dioxide (ETCO2), oxygen saturation (SpO2), COPA size, difficult airway predictors, rate of failed ventilation via COPA, and frequency of hypoxemia (SpO2 < 90%) during the procedure, and perioperative untoward events were recorded. MAIN RESULTS: The background, airway difficulty, vital signs and untoward effects were similar in the two groups. Nasal fiberoptic laryngeal view (scale 1-4) was better than the oral grading (3 [median] vs. 2, respectively; p <0.05). Eighty percent of the nasal intubations were successful compared with 40% of the oral intubations (p <0.05). Nasal intubations were accomplished within 153 +/- 15 SD seconds compared with 236 +/- 22 seconds (p <0.05) for the oral intubations, and less propofol was needed in the nasal intubations during the procedures (240 +/- 27 mg [nasal] vs. 277+/- 39 mg [oral]; p <0.05). CONCLUSIONS: Nasal fiberoptic laryngoscopy is more successful and easy than the oral approach in anesthetized patients who are breathing spontaneously through the COPA.

Two-stitch technique for distal shaft hypospadias repair.

The authors present a new technique for distal shaft hypospadias repair using a flip flap fashioned with only two stitches. In raising the flap, the tissues lateral and proximal to the flap are undermined but there is no undermining beneath the flap. The flap is sutured up to the glans with two 4-0 Vicryl sutures. No sutures are placed at the lateral edges of the flap to create the "tube" of the neo-urethra, and no postoperative urinary drainage is used. Thirty-three children with distal shaft hypospadias underwent the "two-stitch" flip flap operation. The complications were one fistula and one case of urinary retention. The technique is an easy method for reconstructing distal penile hypospadias with a very low rate of complications and is suitable for an outpatient surgical setting.