Neoadjuvant chemoradiation for locally advanced resectable carcinoma of the esophagus: A single-center experience from India with a brief review of the literature.

BACKGROUND: The management of locally advanced carcinomas of the esophagus and esophagogastric junction has undergone a major evolution over the past two decades with the widespread use of combined modality therapy. Although many Indian centers practice the combined modality therapy with neoadjuvant chemoradiation (nCRT), published data are sparse. OBJECTIVES: The objective of this study was to study the safety and efficacy of nCRT in patients with locally advanced resectable carcinoma of the esophagus. MATERIALS AND METHODS: Prospective single-arm study of the first fifty patients enrolled over 3 years (2014-2016). RESULTS: The median age was 51 years (M:F = 3:2), 90% of the patients had squamous cell carcinomas, and 69% had lower-third lesions. All accrued patients completed the intended dose of radiation; however, approximately 20% had a treatment delay, which was duly gap corrected. Importantly, there were no treatment-related toxic deaths. Eleven patients could not undergo surgery following nCRT (two patients defaulted, two were deemed medically unfit, and seven (14%) patients had disease progression on imaging). Thirty-nine (78%) patients were planned for definitive surgery; however, a further 7 (14%) were found to be inoperable intraoperatively. Thirty-two patients successfully completed their definitive surgical procedures with R0 resections, of which 19 patients (38%) had a pathological complete response (pCR). There was no postoperative 90-day mortality in our study cohort. Analysis of prognostic factors that predicted a response showed that patients who had adenocarcinoma and with circumferential lesions responded poorly. CONCLUSION: nCRT appears to be a safe and a reasonably well-tolerated option in carefully selected patients with resectable locally advanced esophageal cancers. Although our data are not mature to analyze the survival outcomes with a pCR rate of 38%, it suggests nCRT to be a promising option in the management of locally advanced resectable esophageal cancers.

Corpora amylacea deposition in the hippocampus of patients with mesial temporal lobe epilepsy: A new role for an old gene?

BACKGROUND: Mesial temporal lobe epilepsy (MTLE) is the most common medically refractory epilepsy syndrome in adults, and hippocampal sclerosis (HS) is the most frequently encountered lesion in patients with MTLE. Premature accumulation of corpora amylacea (CoA), which plays an important role in the sequestration of toxic cellular metabolites, is found in the hippocampus of 50-60% of the patients who undergo surgery for medically refractory MTLE-HS. However, the etiopathogenesis and clinical importance of this phenomenon are still uncertain. The ABCB1 gene product P-glycoprotein (P-gp) plays a prominent role as an antiapoptotic factor in addition to its efflux transporter function. ABCB1 polymorphism has been found to be associated with downregulation of P-gp expression. We hypothesized that a similar polymorphism will be found in patients with CoA deposition, as the polymorphism predisposes the hippocampal neuronal and glial cells to seizure-induced excitotoxic damage and CoA formation ensues as a buffer response. MATERIALS AND METHODS: We compared five single nucleotide polymorphisms in the ABCB1 gene Ex06+139C/T (rs1202168), Ex 12 C1236T (rs1128503), Ex 17-76T/A (rs1922242), Ex 21 G2677T/A (rs2032582), Ex26 C3435T (rs1045642) among 46 MTLE-HS patients of south Indian ancestry with and without CoA accumulation. RESULTS: We found that subjects carrying the Ex-76T/A polymorphism (TA genotype) had a five-times higher risk of developing CoA accumulation than subjects without this genotype (Odds ratio 5.0, 95% confidence intervals 1.34-18.55; P = 0.016). CONCLUSION: We speculate that rs1922242 polymorphism results in the downregulation of P-gp function, which predisposes the hippocampal cells to seizure-induced apoptosis, and CoA gets accumulated as a buffer response.

Selection of ideal candidates for extratemporal resective epilepsy surgery in a country with limited resources.

AIM: To investigate how to select ideal candidates for extratemporal resective epilepsy surgery, without compromising efficacy and safety, in countries with limited pre-surgical diagnostic facilities. METHOD: From the prospective database maintained at an epilepsy surgery centre in southern India, we reviewed the attributes of consecutive patients who had completed at least two years of follow-up after resections involving frontal, parietal and occipital lobes for medically refractory focal seizures. RESULTS: Of 386 patients diagnosed with extratemporal refractory epilepsies during the study period, 61 (15.8%) were selected based on the presence of magnetic resonance imaging (MRI)-identified lesions (in all) and concordant scalp recorded electroencephalographic (EEG) data (in nearly two thirds). Seventeen (27.8%) required invasive investigations either to define the ictal onset zone, eloquent area, or both. During a median follow-up period of five years, 63% of our patients were seizure-free, excluding the presence of auras. Permanent disabling neurological sequelae occurred in three (4.9%) patients. According to univariate analysis, pre-operative secondary generalised seizures and interictal epileptiform discharges (IEDs), during a one-year post-operative EEG monitoring period, portended unfavourable seizure outcome. In multivariate analysis, frontal lobe resections and IEDs in post-operative EEGs were independent predictors of unfavourable outcome. CONCLUSIONS: Extratemporal resective epilepsy surgery can be undertaken in countries with limited resources with efficacy and safety, comparable to that in developed countries, when patients are selected based on the presence of MRI-identified lesions and scalp EEG concordance. In such patients, invasive EEG examinations, when necessary, can be undertaken by limited coverage of cortical areas at an affordable cost.

Corpora amylacea in mesial temporal lobe epilepsy: clinico-pathological correlations.

PURPOSE: To investigate the electro-clinical significance of premature accumulation of corpora amylacea (CoA) in the resected hippocampus of patients with medically refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). METHODS: We compared the clinical and EEG characteristics, and post-operative seizure outcome of 373 (mean age 29.4 years, range 7-55 years) surgically treated MTLE-HS patients with (MTLE-HS-CoA(+), n=129 [34.5%]) and without (MTLE-HS-CoA(-), n=244 [65.5%]) CoA. RESULTS: Age at surgery was significantly higher and duration of epilepsy before surgery was significantly longer for MTLE-HS-CoA(+) patients compared to MTLE-HS-CoA(-) patients. Although the distribution of interictal epileptiform EEG abnormalities did not differ, type 1 ictal EEG pattern was more frequent in MTLE-HS-CoA(+) patients. Among the 21 patients with major interictal psychosis detected prior to epilepsy surgery, 19 (90.5%) belonged to MTLE-HS-CoA(+) group. Schizophrenia-like psychosis was most prevalent. The post-operative seizure-free outcome was comparable, but significantly more MTLE-HS-CoA(-) patients were free of antiepileptic drugs. CONCLUSIONS: Overall, our observations support the hypothesis that the pathological process in MTLE-HS is progressive. MTLE-HS-CoA(+) patients are predisposed to increased psychiatric morbidity. In vivo detection of hippocampal CoA accumulation in the future will help us to understand the neurobiological significance of this phenomenon.

Medically refractory epilepsy associated with temporal lobe ganglioglioma: characteristics and postoperative outcome.

OBJECTIVES: To define the postoperative seizure outcome and its predictors in patients with ganglioglioma-related temporal lobe epilepsy (TLE). PATIENTS AND METHODS: We reviewed the pre- and post-surgical evaluation data of 23 patients with temporal lobe ganglioglioma, who had completed >or=1 year of postoperative follow-up. They comprised 4.9% of the patients with TLE and 67.6% of the tumoral TLE operated in a developing country epilepsy center during an 8-year period. RESULTS: Median age at surgery was 20 years; median duration of epilepsy prior to surgery was 9 years. Magnetic resonance imaging (MRI) revealed tumor in mesial temporal location in 18 patients (78.3%) and in the lateral location in 2; in the remaining 3, involved both mesial and lateral regions. EEG abnormalities were localized to the side of lesion in the majority. Mesial temporal lobe structures were included in the resection, if they were involved by the tumor; otherwise, lesionectomy alone was performed. During a median follow-up of 4 years, 19 (82.6%) patients were completely seizure-free. Epileptiform abnormalities persisting in the 1-year postoperative EEG predicted unfavorable seizure outcome. CONCLUSION: We emphasize that, in patients with temporal lobe ganglioglioma, when the seizures are medically refractory, surgery offers potential for cure of epilepsy in the majority.

Electro-clinical characteristics and postoperative outcome of medically refractory tumoral temporal lobe epilepsy.

BACKGROUND: Very few studies have specifically addressed surgical treatment and outcome of patients with tumor-related temporal lobe epilepsy (TLE). AIM: To define the postoperative seizure outcome and the factors that influenced the outcome of patients with tumor-related TLE. MATERIALS AND METHODS: We selected patients whose surgical pathology revealed a temporal lobe neoplasm and who had completed > 1 year of postoperative follow-up. We reviewed the clinical, EEG, radiological and pathological data, and the seizure outcome of these patients and assessed the factors that influenced the outcome. RESULTS: Out of the 409 patients who underwent surgery for refractory TLE during the 8-year study period, there were 34 (8.3%) patients with temporal lobe neoplasms. The median age at surgery was 20 years and the median duration of epilepsy prior to surgery was 9.0 years. MRI revealed tumor in the mesial location in 21 (61.8%) patients. Interictal and ictal epileptiform EEG abnormalities were localized to the side of th lesion in the majority. Mesial temporal lobe structures were included in the resection, if they were involved by the tumor; otherwise, lesionectomy alone was performed. During a median follow-up of 4 years, 27 (79%) patients were completely seizure-free. The only factor that predicted long-term seizure-free outcome was being seizure-free during the first two postoperative years. CONCLUSIONS: Our results emphasize the fact that in patients with tumoral TLE, when the seizures are medically refractory, surgery offers potential for cure of epilepsy in the majority.