Identification of postoperative adjuvant chemotherapy responders in non-small cell lung cancer by novel biomarker

Cisplatin-based (CDDP-based) adjuvant chemotherapy of non-small cell lung cancer (NSCLC) was reported to yield 5-15% improvement in 5-year survival compared to complete resection alone. The importance of information concerning preselection of good responders has become increasingly evident. The purpose of our study is the establishment of a preselection of good responders for CDDP-based adjuvant chemotherapy. We investigated protein expressions comparing intensity between parent strains (H69 and PC14 lung cancer cultured cells) and resistant strains against CDDP using 2-dimensional polyacrylamide gel electrophoresis (2-DE). Immunohistochemically, we evaluated the relationship between protein expression associated with CDDP-resistance and the clinical effects of platinum-based postoperative adjuvant chemotherapy using 126 surgically-resected NCLC materials. We detected 2 kinds of polypeptides that changed expression levels on 2-DE gels. The analyses of the amino acid sequence showed that these polypeptides were reticulocalbin (RCN) and glutathione-S-transferase-pi (GST-pi). The 2-DE analysis showed decreased expression in RCN and overexpression in GST-pi with the acquisition of CDDP-drug resistance. RCN-transfectant of H69 CDDP-resistant strain showed intermediate sensitivity between the parent strain and the CDDP-resistant strain. RCN-positive cases showed a statistically significant better disease-free survival only in the cases receiving postoperative platinum-based adjuvant chemotherapy after curative resection (p = 0.007). In addition, cases that were both RCN-positive and GST-pi-negative showed a statistically significantly better outcome (p = 0.0150). In the cases without postoperative adjuvant chemotherapy no relationship between the outcome and these expressions was seen. The evaluation of RCN and GST-pi might provide valuable information concerning postoperatively therapeutic strategy from the standpoint of individualized postoperative therapy.     

The C3435T polymorphism of MDR1 and susceptibility to adult glioma

INTRODUCTION: The multidrug resistance-1 (MDR1) gene encodes a pump that prevents potentially carcinogenic substances from crossing the blood-brain barrier. We compare adult glioma cases and controls for the C3435T polymorphism that has been associated with reduced MDR1 expression. METHODS: Adult glioma in the San Francisco Bay area and population-based controls were identified between 1991-1994 and 1997-1999. Genotyped cases (n = 458) and controls (n = 528) were compared using logistic regression controlling for age, gender and ethnicity, with later stratification by ethnicity, gender and histology. RESULTS: With CC as the referent, the TT genotype was nonsignificantly less frequent among cases compared to controls (OR, 0.87; 95% CI: 0.6, 1.2). After stratification, only male glioblastoma was associated with TT genotype (OR, 0.51; 95% CI: 0.3, 1.0). CONCLUSIONS: Although the C3435T polymorphism does not appear to be associated with other types of glioma, we cannot rule out that this MDR1 polymorphism may be associated with glioblastoma among men.     

Color doppler ultrasound criteria to diagnose varicoceles: correlation of a new scoring system with physical examination

Objectives

Color Doppler ultrasound (CDU) diagnostic criteria for varicoceles are poorly defined, and the role of CDU in diagnosing varicoceles is controversial. The purpose of this study is to assess the diagnostic accuracy of CDU for varicoceles compared to physical examination.

Methods

We prospectively studied 64 patients with CDU and collected the following data: maximum diameter of scrotal veins, the presence of a venous plexus, sum of the diameter of up to six veins of the plexus, and the duration and amplitude of flow change on Valsalva maneuver. To avoid interphysician variation, all patients were examined by one designated senior urologist with the sonographer remaining unaware of the findings.

Results

CDU parameters of 127 testis units in 64 patients were analyzed and compared to the physical findings. Fifty-nine testis units were positive and 57 units were negative for varicocele on physical examination. In 11 testis units, results of physical examination were inconclusive regarding the presence of varicocele. The commonly accepted CDU criterion for varicocele (maximal vein diameter of 3 mm or greater) had a sensitivity of 53% and specificity of 91% compared to physical examination. We developed a new scoring system incorporating the maximal venous diameter (score 0 to 3), the presence of a venous plexus and the sum of the diameters of veins in the plexus (score 0 to 3), and the change of flow on Valsalva maneuver (score 0 to 3). Using a total score of 4 or more to define the presence of CDU-positive varicocele, we observed a sensitivity of 93% and a specificity of 85% when compared to physical examination. All moderate to large varicoceles found on physical examination were positive by CDU diagnosis using the scoring system, but the same group had only a 68% positive rate by traditional CDU diagnostic criteria.

Conclusions

Using the proposed new scoring system, CDU has been shown to be a reliable and accurate method of diagnosis for varicoceles compared to the current reference standard physical examination. CDU has the advantages of being able to objectively examine venous plexus and measure blood flow parameters and to be less observer-dependent than physical examination. UROLOGY 50: 953-956, 1997.     

Percutaneous burrhole trephination of the skull: a study of 519 cases

We want to report on our experiences with the percutaneous trephination using a 2.35 mm round dental drill with serrated saws around it, a Rosenbohrer. It is a methodically similar activity as described by J. Zentner [11].From 1981 to 1992 519 patients were treated and 546 trephinations were performed.At the beginning this treatment was only used in connection with intracerebral bleedings and biopsies.In a considerable short time the indication could be extended to the subdural hematoma, tumor cyst, obstructive hydrocephalus as well as to the abscess and the subdural epyema.The rate of infection was 1.28% and the risk of bleeding 0.36%.In our opinion the advantages of this small electrical trephination are the easy handling, the universal use and mobility and the avoidable risk of anesthesia as well as the sterilisation at the same time and the stopping of blood, caused by the contact surface friction.     

Safety and usefulness of emergency maternal transport using helicopter

AIM: Japan has a shortage of tertiary medical care facilities for maternal and fetal medicine. Establishment of efficient medical transport systems is needed for pregnant women and fetuses with severe complications. Maternal transport by helicopters is expected to shorten transportation time to advanced facilities, although its feasibility has not yet been evaluated. The aim of the present study was to investigate the status of maternal helicopter transport, and conditions of the pregnant patients and children transferred by helicopter to Kameda Medical Center (KMC). METHODS: Between August 2005 and July 2006, 26 pregnant women were transported by helicopters to KMC. RESULTS: The median net flight time was 24 min (range 15-29 min), and the median of estimation of ground transportation time was 125 min (range 90-180 min). The causes for transfers were preterm labor in eight, preterm premature rupture of the membrane in five, cervical incompetence in five, pre-eclampsia in three and other medical reasons in five. Five of the 26 patients were discharged with restored stability of pregnancy. The remaining 21 patients underwent delivery at KMC. The median gestational age was 26 weeks (range 22-33 weeks) at the time of transfer and 31 weeks (range 22-37 weeks) at delivery. Four of 26 neonates who were born at KMC died after birth due to severe premature or congenital anomaly. Seventeen of the remaining 22 neonates, including 10 twins, received treatment in the neonatal intensive care unit. All of the 22 neonates and all the mothers were discharged in good condition. No patients developed any complications requiring treatment during flights. CONCLUSION: Helicopter transfer is feasible for pregnant patients with severe complications.     

Predicting outcome of one-step total hysteroscopic resection of sessile submucous myoma

STUDY OBJECTIVE: To analyze variables for successful 1-step hysteroscopic myomectomies of sessile submucous myomas. DESIGN: Retrospective case-control study. (Canadian Task Force classification II-2). SETTING: Single operator's practice in a university hospital and its related hospitals. PATIENTS: Twenty-eight patients with sessile submucous myomas and menorrhagia, infertility, or both. INTERVENTIONS: Our strategy for hysteroscopic myomectomy is as follows. First, we scraped and/or vaporized intrauterine dome of myoma until top of myoma was even with level of wall of cavity. Next, the remnant intramural node was squeezed by uterine contractions induced by prostaglandin F2alpha injection. Finally, the newly raised myoma dome was sectioned or vaporized electrosurgically only within the space of the intrauterine cavity and/or was separated mechanically from healthy myometrium without electrosurgery. MEASUREMENTS AND MAIN RESULTS: Submucous myomas in 16 (57.1%) patients were completely removed after 1 surgery. By logistic regression analysis, thickness of outer myometrial layer of myoma node (OR 3.06, p = .02), myoma size (OR 0.86, p = .04), and intramural extension degree (OR 0.91, p = .03) were significantly associated with outcome of complete resection. CONCLUSION: Thickness of outer myometrial layer of myoma node, myoma size, and intramural extension degree predicted outcome of 1-step hysteroscopic myomectomy. The chance of performing successful surgery increased with increased thickness of outer myometrial layer of myoma, and decreased with larger myomas and greater degrees of intramural extension.     

Annuloplasty ring removal from patients with hemolysis after mitral valve repair

We present a case of severe hemolysis following a mitral valve repair, which was successfully treated by removing the annuloplasty ring. The etiology of the hemolysis appeared to be a small regurgitant jet at the level of the annuloplasty ring.     

Serum IgE, tumor epidermal growth factor receptor expression, and inherited polymorphisms associated with glioma survival

In population-based glioma patients, we examined survival in relation to potentially pertinent constitutive polymorphisms, serologic factors, and tumor genetic and protein alterations in epidermal growth factor receptor (EGFR), MDM2, and TP53. Subjects were newly diagnosed adults residing in the San Francisco Bay Surveillance Epidemiology and End Results Area during 1991 to 1994 and 1997 to 1999 with central neuropathology review (n = 873). Subjects provided blood for serologic studies of IgE and IgG to four herpes viruses and constitutive specimens for genotyping 22 polymorphisms in 13 genes (n = 471). We obtained 595 of 697 astrocytic tumors for marker studies. We determined treatments, vital status, and other factors using registry, interview, medical record, and active follow-up data. Cox regressions for survival were adjusted for age, gender, ethnicity, study series, resection versus biopsy only, radiation, and chemotherapy. Using a stringent P < 0.001, glioma survival was associated with ERCC1 C8092A [hazard ratio (HR), 0.72; 95% confidence limits (95% CL), 0.60-0.86; P = 0.0004] and GSTT1 deletion (HR, 1.64; 95% CL, 1.25-2.16; P = 0.0004); glioblastoma patients with elevated IgE had 9 months longer survival than those with normal or borderline IgE levels (HR, 0.62; 95% CL, 0.47-0.82; P = 0.0007), and EGFR expression in anaplastic astrocytoma was associated with nearly 3-fold poorer survival (HR, 2.97; 95% CL, 1.70-5.19; P = 0.0001). Based on our and others' findings, we recommend further studies to (a) understand relationships of elevated IgE levels and other immunologic factors with improved glioblastoma survival potentially relevant to immunologic therapies and (b) determine which inherited ERCC1 variants or other variants in the 19q13.3 region influence survival. We also suggest that tumor EGFR expression be incorporated into clinical evaluation of anaplastic astrocytoma patients.