Surgical nuances in the separation of craniopagus twins - Our experience and a follow up of 15 years.

Craniopagus twins are conjoined twins fused at the cranium. This is the rarest anomaly seen in conjoined twins and craniopagus twins account for 2- 6% of conjoined twins. Conjoined twins are also extremely rare, with the anomaly seen in about 10-20 subjects per billion births. A female preponderance has been noted. Craniopagus twins can be classified into complete or partial, depending on whether or not they have shared dural venous sinuses. They can be further classified into angular or total depending on the alignment of the inter-twin longitudinal axis. Surgical separation of these cases can be an elective procedure or an emergency, mandated by the death of one of the twins. Surgical separation of craniopagus twins is a complex exercise needing detailed evaluation and planning. For the successful management of these twins, a multi-disciplinary approach involving neurosurgeons, plastic surgeons, anesthetists, radiologists, pediatric critical care specialists and ancillary staff is mandatory. We present a case of partially successful elective separation of partial angular craniopagus twins performed in 2002.The surviving twin was managed conservatively for a cerebrospinal fluid leak. The patient subsequently developed a pseudomeningocele, necessitating re-exploration, excision of the gliotic tissue, and repair of the dura and the overlying scalp flap. The patient has a skull defect for which cranioplasty has been deferred. The child is neurologically intact. The post-operative evaluation and the detailed periodic neurological assessment till date (with a follow up of 15 years) have been presented in this study.

DTI correlates of cognition in conventional MRI of normal-appearing brain in patients with clinical features of subacute combined degeneration and biochemically proven vitamin B(12) deficiency.

BACKGROUND AND PURPOSE: Vitamin B12 deficiency may cause neural injury that results in cognitive deficits. The main purpose of our study was to evaluate morphometric and microstructural changes in the brain and relate them to cognition in subacute combined degeneration of the spinal cord and patients with biochemically deficient vitamin B12. MATERIALS AND METHODS: Fifty-one patients were recruited and underwent nerve-conduction velocity tests and routine hematologic examinations. Serum vitamin B12 and homocystine levels were also measured. All patients and 46 age- and sex-matched controls underwent cervical spine and brain MR imaging along with cognition tests. MR imaging included conventional scans and DTI. Voxel-based morphometry was performed for determining the WM and GM volumes, based on T1-weighted images. DTI measures that included fractional anisotropy, ADC, radial diffusivity, and axial diffusivity were determined by using tract-based statistics. RESULTS: None of the patients showed any abnormality on conventional MR imaging. No significant changes in GM and WM volumes were observed in patients compared with controls. Significant reductions in the fractional anisotropy and an increase in ADC and radial diffusivity values were observed in multiple brain regions in patients compared with controls. These changes were confirmed on the region-of-interest analysis. Neuropsychological scores were significantly different in patients compared with controls and showed significant correlation with fractional anisotropy and radial diffusivity in a few brain regions. CONCLUSIONS: Microstructural changes are seen in WM regions on DTI in patients with vitamin B12 deficiency and correlate with cognition scores. DTI can be used for objective assessment of microstructural changes in the brain in vitamin B12 deficiency.

Whole sentinel lymph node analysis by a molecular assay predicts axillary node status in breast cancer.

BACKGROUND: The one-step nucleic acid amplification (OSNA) assay is a rapid procedure for the detection of lymph node (LN) metastases using molecular biological techniques. The aim of this study was to assess the reliability of the whole sentinel lymph node (SLN) analysis by the OSNA assay as a predictor of non-SLN metastases. METHODS: Consecutive 742 patients with breast cancer were enroled in the study. The association of non-SLN or ≥4 LN metastases with clinicopathological variables was investigated using multivariate logistic analysis. RESULTS: In total, 130 patients with a positive SLN who underwent complete axillary LN dissection were investigated. The frequency of non-SLN metastases in patients who were OSNA+ and ++ was 19.3% and 53.4%, respectively, and that in patients with ≥4 LN metastases who were OSNA+ and ++ was 7.0% and 27.4%, respectively. The cytokeratin 19 (CK19) mRNA copy number (≥5.0 × 10(3); OSNA++) in the SLN was the most significant predictors of non-SLN metastases (P=0.003). The CK19 mRNA copy number (≥1.0 × 10(5)) in the SLN was the only independent predictor of ≥4 LN metastases (P=0.014). CONCLUSION: Whole SLN analysis using the OSNA assay could become a valuable method for predicting non-SLN and ≥4 LN metastases.

A phase II study of eribulin in Japanese patients with heavily pretreated metastatic breast cancer.

BACKGROUND: Eribulin mesylate is a non-taxane microtubule dynamics inhibitor that recently gained Food and Drug Administration approval for late-line metastatic breast cancer (MBC). PATIENTS AND METHODS: In this single-arm, multicentre open-label phase II trial Japanese patients pretreated with an anthracycline and a taxane received 1.4 mg/m(2) eribulin mesylate (2- to 5-min i.v. infusion on days 1 and 8 of a 21-day cycle). The primary efficacy end point was overall response rate (ORR) by independent review. RESULTS: Patients (N = 80) had received a median of three prior chemotherapy regimens (range 1-5). ORR was 21.3% [95% confidence interval (CI) 12.9-31.8; all partial responses (PRs)], stable disease (SD) occurred in 30 patients (37.5%) and the clinical benefit rate (complete response + PR + SD ≥6 months) was 27.5% (95% CI 18.1-38.6). Median duration of response was 3.9 months (95% CI 2.8-4.9), progression-free survival was 3.7 months (95% CI 2.0-4.4) and overall survival was 11.1 months (95% CI 7.9-15.8). The most frequent treatment-related grade 3/4 adverse events were neutropenia (95.1%), leukopenia (74.1%) and febrile neutropenia (13.6%). Grade 3 peripheral neuropathy occurred in 3.7% of patients (no grade 4). CONCLUSIONS: Eribulin exhibited efficacy and tolerability in Japanese patients with heavily pretreated MBC.

The versatility of the tongue flap in the closure of palatal fistula.

Aims Tongue flaps were introduced for intraoral reconstruction by Lexer in 1909. A retrospective study was performed in the Department of Oral and Maxillofacial Surgery, S.D.M. College of Dental Sciences (Dharwad, India), to assess the use of tongue flap in closure of palatal fistula. Material and Methods A total of 40 patients treated for palatal fistulas were included in this study from the period of January 1, 2000, to January 1, 2007; fistulas present in anterior and midpalate were considered. Patients' preoperative photographs, clinical records, and preoperative speech analysis were recorded. Following completion of fistula closure, patients were assessed over 6 months to check flap viability, fistula closure, residual tongue function, aesthetics, and speech impediment. Results A total of 40 (24 male and 16 female) patients with palatal fistulas were treated with tongue flap in our study. Six patients were 4 to 6 years old, three were 7 to 10 years old, and 22 were 11 to 20 years old, which accounts for 68% of study subjects. There were nine patients 21 to 30 years old. In the early postoperative period, we encountered bleeding in one patient and sloughing in one patient. There are three recurrences, and two flaps were detached; all remaining cases showed satisfactory healing, and donor site morbidity was minimal. No speech deficits were evident. Conclusion Tongue flaps are used in cleft palate surgery because of their excellent vascularity, and the large amount of tissue that they provide has made tongue flaps particularly appropriate for the repair of large fistulas in palates scarred by previous surgery.

Three dose regimens of fulvestrant in postmenopausal Japanese women with advanced breast cancer: results from a double-blind, phase II comparative study (FINDER1).

BACKGROUND: FINDER1 compared efficacy, tolerability and pharmacokinetics (PK) of three fulvestrant dose regimens in postmenopausal Japanese women with estrogen receptor (ER)-positive locally advanced/metastatic breast cancer recurring or progressing after prior endocrine therapy. PATIENTS AND METHODS: The primary end point of this randomised, multicentre, phase II study was objective response rate (ORR) and the secondary end points included time to progression (TTP), clinical benefit rate (CBR), PK profiles and tolerability. Postmenopausal women with ER-positive advanced breast cancer were randomised to 28-day cycles of fulvestrant approved dose (AD), loading dose (LD) or high dose (HD) until disease progression. RESULTS: Hundred and forty-three patients (median age 61 years) received fulvestrant AD (n = 45), LD (n = 51) or HD (n = 47). ORR was similar across dose regimens: 11.1%, 17.6% and 10.6% for AD, LD and HD, respectively, with overlapping confidence intervals. TTP and CBR were also similar between groups (median TTP: 6.0, 7.5 and 6.0 months, respectively; CBR: 42.2%, 54.9% and 46.8% for AD, LD and HD, respectively). C(max) and area under the plasma concentration-time curve were dose proportional and PK steady state was reached earlier with LD and HD than with AD. All three doses were well tolerated, with a similar adverse-event profile and no emerging safety concerns. CONCLUSION: Fulvestrant AD, LD and HD had similar efficacy and tolerability profiles in postmenopausal Japanese women with ER-positive advanced breast cancer.

Lapatinib monotherapy in patients with relapsed, advanced, or metastatic breast cancer: efficacy, safety, and biomarker results from Japanese patients phase II studies.

BACKGROUND: HER2-positive metastatic breast cancer (MBC) relapsing after trastuzumab-based therapy may require continued HER2 receptor inhibition to control the disease and preserve the patients' quality-of-life. Efficacy and safety of lapatinib monotherapy was evaluated in Japanese breast cancer patients after trastuzumab-based therapies. METHODS: In studies, EGF100642 and EGF104911 evaluated the efficacy and safety of oral lapatinib given 1500 mg once daily in patients with advanced or MBC. All patients progressed on anthracyclines and taxanes; HER2-positive patients had also progressed on trastuzumab. RESULTS: For HER2-positive tumours (n=100), objective response rate was 19.0% (95% confidence interval (CI): 11.8-28.1) and clinical benefit rate (CBR) was 25.0% (95% CI: 16.9-34.7). One out of 22 HER2-negative tumour was documented as complete response (n=22). The median time-to-progression (TTP) in the HER2-positive and HER2-negative groups was 13.0 and 8.0 weeks (P=0.007); median overall survival was 58.3 and 40.0 weeks, respectively. The most frequent adverse event was diarrhoea. TTP and CBR were significantly associated with HER2 expression. Patients with tumours harbouring an H1047R PIK3CA mutation or low expression of PTEN derived clinical benefit from lapatinib. CONCLUSION: Lapatinib monotherapy had shown anti-tumour activity in Japanese patients with HER2-positive MBC that relapsed after trastuzumab-based therapy, including those with brain metastases. Patients benefiting from lapatinib may have biomarker profiles differing from that reported for trastuzumab.

Effect of N-2-mercaptopropionylglycine in limiting myocardial reperfusion injury following 90 minutes of ischemia in dogs.

Present study was designed to examine the effectiveness of N-2-mercaptopropionyl glycine (MPG) on oxygen free radical (OFR) mediated reperfusion injury. Twenty dogs underwent 90 min of left anterior descending (LAD) coronary artery occlusion followed by 4 h of reperfusion. In control animals (n = 12), 115 ml of saline was infused through left atrium at the onset of reperfusion whereas treated animals (n = 8) received loading dose of MPG (40 mg/kg) infused through left atrium for 1 h followed by maintenance dose (25 mg/kg) for remaining 3 hours. Percentage area of necrosis vis-a-vis area at risk and percentage necrosis in left ventricular mass in MPG treated animals was significantly lower in comparison to control animals. Reperfusion in control group increased the lipid peroxidation and lowered glutathione (GSH) and superoxide dismutase (SOD) activity. MPG treatment significantly lowered the lipid peroxidation whereas GSH and SOD levels in necrotic zone were higher than in control. The above results suggest that MPG can offer a significant cardioprotection against oxidative stress in canine model.

RT-PCR detection of breast cancer cells in sentinel lymph modes.

Sentinel lymph node (SLN) biopsy is being evaluated in breast cancer patients to improve detection of metastases and to guide therapy with minimal morbidity. The aim of this study was to increase the sensitivity of tumor cell detection in SLNs using superior reverse transcription polymerase chain reaction (RT-PCR) for carcinoembryonic antigen (CEA) and mammaglobin (MMG) analysis rather than current methods which fail to identify clinically relevant disease in many patients. In seventy stage I and II breast cancer patients dye-guided lymph node mapping was performed and the SLNs were divided alternately for RT-PCR or hematoxylin and eosin staining (H&E). RT-PCR and H&E diagnosis of SLNs were compared. SLNs were identified in 66/70 (94.3%) patients. Seventeen patients (26. 2%) had histological metastasis in SLNs. CEA was expressed in 25.0% of 48 patients with H&E negative SLNs, and MMG was expressed in 20. 8%. SLNs could predict axillary lymph node status with 95.4% accuracy and 6.3% false negative rate by H&E. Moreover, RT-PCR improved these to 98.5% and 2.8%, respectively. SLN diagnosis using RT-PCR is a powerful and sensitive method, which increases the accuracy of clinical staging and may provide more informed choices for appropriate therapeutic management of breast cancer patients.

[A patient with hepatic metastasis of breast cancer successfully treated with combined chemoendocrine therapy using epirubicin, tegafur and tamoxifen].

A solitary 1 cm sized metastatic lesion was found in the S5 region of the liver on a postoperative ultrasound screening of a 52-year-old breast cancer patient. It was confirmed by CT, MRI and hepatic angiography. At first, she was successfully treated with trans-arterial pirarubicin and lipiodol infusion but a metastatic lesion of similar size was found 6 months later in the same region. We then administered a triple 20 mg dose of epirubicin intravenously, and 450 mg of UFT and 30 mg of tamoxifen daily. Six months later the lesion had disappeared on US and CT scans and a complete remission has persisted for 18 months.

Homoeopathic treatment of filariasis

A single-blind study was conducted to assess the effect of homoeopathic treatment on cases of bancroftian filariasis. Based on the predominant symptom, the filariasis cases were grouped as adenitis, genitalia involvement, lymphoedema and mastitis. Effect of treatment with homoeopathic drugs were assessed by comparing with groups tested with placebo. Filiariasis cases treated with homoeopathic medicines showed a better improved/not improved ratio (2.0) compared with cases treated with placebo (0.46). The results indicate that the improvements derived from homoeopathic medicines are statistically highly significant

Induction of N-acetyl-D-glucosamine catabolic enzymes and germinative response in Candida albicans.

The regulation of N-acetylglucosamine catabolic enzymes was studied in both yeast and germ tube forms of the dimorphic fungus Candida albicans. The induction pattern of these enzymes was the same for yeast cells incubated at 28 degrees C and in cells incubated at 37 degrees C which formed germ tubes. However, the level of activity of these enzymes in germ tube stage is lower as compared to yeast phase cells. A strain of C. albicans that did not form germ tubes was endowed with a pronounced ability for induction of N-acetylglucosamine catabolic enzymes. This result suggests that germ tube formation and N-acetylglucosamine metabolism are mutually exclusive events.

Purification and some properties of inducible N-acetylglucosamine kinase from Candida albicans.

N-Acetylglucosamine kinase (ATP:2-acetamido-2-deoxy-D-glucose 6-phosphotransferase, EC 2.7.1.59) catalyzes the first reaction in the inducible N-acetylglucosamine catabolic pathway of Candida albicans, an obligatory aerobic yeast. As a part of continuing biochemical studies concerning the regulation of gene expression in a simple eukaryote, N-acetylglucosamine kinase has been purified and characterized biochemically. The enzyme has been purified about 300-fold from the crude extract and its molecular weight of 75 000 has been determined by Sephadex G-100 gel filtration. Isolation and analysis procedures are described. The kinase reaction is optimal within a pH range of 7--8. The enzyme is strictly specific for GlcNAc as phosphate acceptor; ATP is the phosphoryl group donor for the kinase reaction and to a lesser extent dATP and CTP. Km values for GlcNAc and ATP are 1.33 mM and 1.82 mM, respectively. The enzyme required Mg2+, which may be replaced by other bivalent metal ions such as Mn2+, Ca2+, Ba2+ and Co2+ for a lesser degree of effectiveness. The purified enzyme is extremely sensitive to thermal denaturation and becomes completely inactive by heating at 65% C for 2 min. The enzyme is also inactivated by sulphydryl reagents such as p-chloromercuribenzene sulfonic acid and N-ethylmaleimide.