To present and discuss a high-performance negative depletion method for the isolation of circulating tumor cells (CTCs) in the blood of patients with head and neck cancer and to determine the correlation between the presence of CTCs and early clinical outcome in these patients.
Prospective clinical follow-up study of patients with squamous cell carcinoma of the head and neck (SCCHN) undergoing surgical intervention, who had peripheral blood examined for the presence of CTCs.
The study population comprised 48 patients diagnosed as having SCCHN and undergoing surgical intervention.
A negative depletion process to isolate and quantify CTCs from the blood of patients with SCCHN using immunomagnetic separation was developed and validated. Immunostaining for cytokeratin was performed on the enriched samples to determine the number of CTCs extracted from each patient’s blood sample. Correlation of the presence of CTCs, tumor stage, nodal status, clinical characteristics, and outcome was made.
Main Outcome Measure
Our initial data, that have a mean follow-up of 19.0 months, suggest that patients with no detectable CTCs per milliliter of blood had a significantly higher probability of disease-free survival (P=.01). There was no correlation between the presence of CTCs with regard to age, sex, tumor site, stage, or nodal involvement.
Our enrichment technology, based on the removal of normal cells, has been used on the peripheral blood of patients with head and neck cancer for which follow-up data were collected. If no CTCs were present, a statistically significant improved disease-free survival was observed in SCCHN. A blood test with such a prognostic capability could have important implications in the treatment of patients with head and neck cancer.
Background and Aims
Status asthmaticus is a common cause of morbidity and mortality. The addition of ketamine to the standard treatment regimen of severe asthma has shown to improve outcome and alleviate the need for mechanical ventilation. The purpose of this review is to determine the pulmonary effects of ketamine and to determine whether sufficient evidence exists to support its use for refractory status asthmaticus.
MEDLINE, EMBASE, Google Scholar, and Cochrane data bases (from their inception to Jan 2012) using key words “ketamine”, “asthma”, “bronchospasm”, “bronchodilator”, and “mechanical ventilation” were searched to identify the reports on the use of ketamine as a bronchodilator in acute severe asthma or status asthmaticus, and manual review of article bibliographies was done. Relevant databases were searched for the ongoing trials on use of ketamine as a bronchodilator. Outcome measures were analyzed using following clinical questions: Indication, dose and duration of ketamine use, main effects on respiratory mechanics, adverse effects, and mortality.
Twenty reports illustrating the use of ketamine as a bronchodilator were identified. In total, 244 patients aged 5 months to 70 years received ketamine for bronchospasm. Twelve case reports, 3 double-blind randomized placebo-controlled trials, 2 prospective observational studies, 2 clinical evaluation study, and 1 retrospective chart review were retrieved. Most of the studies showed improved outcome with use of ketamine in acute severe asthma unresponsive to conventional treatment. Patients who received ketamine improved clinically, had lower oxygen requirements, and obviated the need for invasive ventilation. Mechanically-ventilated patients for severe bronchospasm showed reduction in peak inspiratory pressures, improved gas exchange, dynamic compliance and minute ventilation, and could be weaned off successfully following introduction of ketamine.
In various studies, ketamine has been found to be a potential bronchodilator in severe asthma. However, a large prospective clinical trial is warranted before laying down any definitive recommendations on its use in status asthmaticus.
Bronchodilator; emergency department; intensive care unit; ketamine; status asthmaticus
The comprehensive characterization of a large number of cancer genomes will eventually lead to a compendium of genetic alterations in specific cancers. Unfortunately, the number and complexity of identified alterations complicate endeavors to identify biologically relevant mutations critical for tumor maintenance, because many of these targets are not amenable to manipulation by small molecules or antibodies. RNAi provides a direct way to study putative cancer targets; however, specific delivery of therapeutics to the tumor parenchyma remains an intractable problem. We describe a platform for the discovery and initial validation of cancer targets, composed of a systematic effort to identify amplified and essential genes in human cancer cell lines and tumors partnered with a novel modular delivery technology. We developed a tumor-penetrating nanocomplex (TPN) comprised of siRNA complexed with a tandem tumor-penetrating and membrane-translocating peptide, which enabled the specific delivery of siRNA deep into the tumor parenchyma. We employed TPN in vivo to evaluate inhibitor of DNA binding 4 (ID4) as a novel oncogene. Treatment of ovarian tumor-bearing mice with ID4-specific TPN suppressed growth of established tumors and significantly improved survival. These observations not only credential ID4 as an oncogene in 32% of high-grade ovarian cancers, but also provide a framework for the identification, validation, and understanding of potential therapeutic cancer targets.
Member A3 of the ATP-Binding Cassette family of transporters (ABCA3) is essential for surfactant metabolism. Nonsense, missense, frameshift and splice-site mutations in the ABCA3 gene (ABCA3) have been reported as causes of neonatal respiratory failure (NRF) and interstitial lung disease. We tested the hypothesis that mutations in non-coding regions of ABCA3 may cause lung disease.
ABCA3 specific cDNA was generated and sequenced from frozen lung tissue from a child with fatal lung disease with only one identified ABCA3 mutation. ABCA3 was sequenced from genomic DNA prepared from blood samples obtained from the proband, parents and other children with NRF.
ABCA3 cDNA from the proband contained an sequences derived from intron 25 that would be predicted to alter the structure and function of the ABCA3 protein. Genomic DNA sequencing revealed a heterozygous C>T transition in intron 25 trans to the known mutation, creating a new donor splice site. Seven additional infants with an ABCA3 deficient phenotype and inconclusive genetic findings had this same variant, which was not found on 2132 control chromosomes.
These findings support that this variant is a disease-causing mutation, which may account for additional cases of ABCA3 deficiency with negative genetic studies.
Lobular carcinoma in accessory breast tissue is a rare occurrence. We present such a case in a 61-year-old woman.
A skin nodule in the axillary skin on excision biopsy revealed invasive lobular carcinoma.
Carcinoma in accessory breast tissue is uncommon especially invasive lobular type. A high index of suspicion may avoid late diagnosis.
Lateral meningocoele is a very rare disorder characterized by extensions of the dura and arachnoid through an enlarged neural foramen. We report a case of a 23-year-old female with deformity of spine who presented with low back pain and no neurological deficits. A whole spine magnetic resonance imaging showed multiple well-defined cystic masses involving dorsal, lumbar, and sacral spinal levels bilaterally, with dural ectasia and neural foraminal widening suggestive of bilateral multiple level lateral meningocoele. The patient is being managed conservatively and is on regular follow-up.
Lateral meningocele; multiple menigocoele; spinal dysraphism
Blood transfusions form a crucial and irreplaceable part in the medical management of many diseases. The collection of blood from voluntary, non-remunerated blood donors from low risk populations is an important measure for ensuring the availability and safety of blood transfusion. In a state like Uttarakhand which is visited by lakhs of visitors during pilgrimage season and where natural calamities and accidents are very common, the availability of blood is of utmost importance.
To find out knowledge, attitude and practices of people towards voluntary blood donation to comprehend the situation and find ways to enhance voluntary blood donation in the state of Uttarakhand.
Materials and Methods:
Multi stage methodology was designed to target population including general population, influencers (doctors) and supporting organizations (camp organizers, State AIDS Control Society Officials) who were subjected to in-depth interview using pre-structured questionnaires to assess knowledge/awareness about voluntary blood donation, factors preventing and source of knowledge about voluntary blood donation.
The sample population consisted of mostly men (67%) in the age-group of 26-35 years. Requirement of blood and the measures to promote voluntary blood donation have a direct relationship with the total population and literacy level of the population. Awareness about blood donation, source of knowledge about blood donation, reasons for not donating blood are particularly stressed. With increase in educational level, the awareness level was also found to increase. While among illiterates 81 percent of the respondents knew about blood donation, among the post graduates the same ratio was found to be almost cent-percent. Among various reasons cited for not donating blood, lack of awareness being the most common reason. People gathered information about blood donation from several different sources with electronic media being the most prominent.
This study illustrates how increasing awareness and marketing ‘Voluntary blood donation’ can enhance adequacy of blood needs of a state or for that matter the entire country. This study also underlines how different media, especially electronic media, can be used to propagate altruistic blood donation.
Blood transfusion services; electronic media; voluntary blood donation
Post-operative course after complex pediatric cardiac surgery is unpredictable. Although, change in arterial lactate levels has been used as a surrogate marker for many years, scientific evidence correlating the early perioperative lactate levels with outcome is still lacking.
To evaluate the trends in lactate levels from intraoperative period to an extended post-operative period in pediatric intensive care unit (PICU) and to assess its usefulness as a prognostic marker.
Prospective observational study.
Tertiary pediatric cardiac surgical unit.
Thirty-five non-consecutive children aged 1-140 months who underwent surgery for congenital heart diseases (CHD) on cardiopulmonary bypass (CPB).
Materials and Methods:
Arterial blood lactate levels were obtained at the following time points: After induction of anesthesia, 15 and 45 min after institution of CPB, at the start of rewarming, after sternotomy closure, then at 1, 6, 24, and 48 h in PICU. Other hemodynamic and clinical variables, CPB variables, blood gas values, and laboratory variables were also recorded.
Four patients died out of 35 patients (11.4%). Non-survivors showed significant persistent elevation in lactates (>4.0 mmol/l). Peak lactates correlate significantly with longer aortic cross clamp time, CPB duration, ventilation hours and PICU stay.
Early point of care lactate can be a useful prognostic marker in post-cardiac surgery patients in adjunct with other parameters measured in PICU. This reiterates the importance of measuring lactates and timely recognition of at-risk patients, which on early intervention can help in reducing post-operative morbidity and mortality.
Children; pediatric cardiac surgery; plasma lactate
Cavernous angiomas or hemangiomas or cavernomas are benign, vascular malformations of the central nervous system and classified as occult vascular brain lesions, usually present in adulthood. With the advent of computed tomography and magnetic resonance imaging, these lesions are increasingly recognized in children. We report two cases of pediatric brain cavernomas where the children presented with recurrent seizures. Imaging findings were suggestive of giant cavernous hemangioma. The lesions were excised completely and the patients recovered well without deficits with good control of seizures.
Cavernous hemangioma; epilepsy; giant; magnetic resonance imaging
Though some studies have described traumatic brain injuries in tertiary care, urban hospitals in India, very limited information is available from rural settings.
To evaluate and describe the epidemiological and clinical characteristics of patients with traumatic brain injury and their clinical outcomes following admission to a rural, tertiary care teaching hospital in India.
Settings and Design:
Retrospective, cross-sectional, hospital-based study from January 2007 to December 2009.
Materials and Methods:
Epidemiological and clinical data from all patients with traumatic brain injury (TBI) admitted to the neurosurgery service of a rural hospital in district Wardha, Maharashtra, India, from 2007 to 2009 were analyzed. The medical records of all eligible patients were reviewed and data collected on age, sex, place of residence, Glasgow Coma Scale (GCS) score, mechanism of injury, severity of injury, concurrent injuries, length of hospital stay, computed tomography (CT) scan results, type of management, indication and type of surgical intervention, and outcome.
Data analysis was performed using STATA version 11.0.
The medical records of 1,926 eligible patients with TBI were analyzed. The median age of the study population was 31 years (range <1 year to 98 years). The majority of TBI cases occurred in persons aged 21 - 30 years (535 or 27.7%), and in males (1,363 or 70.76%). Most patients resided in nearby rural areas and the most frequent external cause of injury was motor vehicle crash (56.3%). The overall TBI-related mortality during the study period was 6.4%. From 2007 to 2009, TBI-related mortality significantly decreased (P < 0.01) during each year (2007: 8.9%, 2008: 8.5%, and 2009: 4.9%). This decrease in mortality could be due to access and availability of better health care facilities.
Road traffic crashes are the leading cause of TBI in rural Maharashtra ffecting mainly young adult males. At least 10% of survivors had moderate or more severe TBI-related disabilities. Future research should include prospective, population based studies to better elucidate the incidence, prevalence, and economic impact of TBI in rural India.
Head injury; India; rural; traumatic brain injury
Cerebrospinal fluid (CSF) otorrhoea is an uncommon condition arising from defects in the tegmen and middle cranial fossa. 33 year gentleman presented with post-mastoidectomy CSF otorrhoea of 5 year duration. Imaging finding were suggestive of fracture in the tegmen region. A combined middle cranial fossa/transmastoid was used to repair the defect. Defect was identified in the tegmen plate and it was closed with pedicled pericranial graft, laterally based pedicled temporalis muscle graft reinforced by bone dust and supported with intact mucosal flap. The leak stopped completely following surgery. The patient is doing well at follow up. Repair of these defects need careful analysis of imaging findings to understand pathological anatomy, and a well planned surgical approach to achieve meticulous repair.
Temporal bone; Fracture; Otorrhoea; Cerebrospinal fluid; Mastoidectomy
Peroral extrusion of the distal end of a ventriculo-peritoneal shunt tube is the potentially hazardous end result of a bowel perforation with only few case reports in the literature. The distal end of the peritoneal catheter got fractured in a 4-year-old child and it protruded out through the mouth. The cranial incision was opened and the shunt divided below the chamber. The ventricular end and the chamber and distal end were removed through this incision. In the present successfully managed case we review the current strategies in the management of such a rare complication and discuss the possible pathogenesis of this entity.
Bowel perforation; Hydrocephalus; Oral extrusion; Ventriculo-perioneal shunt
Rapidly proliferating epithelial crypt cells of the small intestine are susceptible to radiation-induced oxidative stress, yet there is a dearth of data linking this stress to expression of antioxidant enzymes and to alterations of intestinal nutrient absorption. We previously showed that 5 – 14 d after acute γ-irradiation, intestinal sugar absorption decreased without change in antioxidant enzyme expression. In the present study, we measured antioxidant mRNA and protein expression in mouse intestines taken at early times postirradiation. Observed changes in antioxidant expression are characterized by a rapid decrease within 1 h postirradiation, followed by dramatic upregulation within 4 h, and then downregulation a few days later. The cell type and location expressing the greatest changes in levels of the oxidative stress marker 4HNE and in antioxidant enzymes are, respectively, epithelial cells responsible for nutrient absorption and the crypt region comprised mainly of undifferentiated cells. Consumption of a cocktail of antioxidant vitamins A, C and E, before irradiation, prevents reductions in transport of intestinal sugars, amino acids, bile acids and peptides. Ingestion of antioxidants may blunt radiation-induced decreases in nutrient transport, perhaps by reducing acute oxidative stress in crypt cells, thereby allowing the small intestine to retain its absorptive function when those cells migrate to the villus days after the insult.
SOD; catalase; glutathione peroxidase; oxidation; enzyme; sugars
Spontaneous intracerebral haemorrhage (SICH) is a rare occurrence in children, with different aetiological factors, clinical characteristics and prognosis. A 14 year male child had sudden onset of headache associated with multiple vomiting. Magnetic resonance imaging showed deep seated intracerebral haematoma. Haematoma was evacuated successfully and child recovered without deficits. A high index of suspicion is necessary for the diagnosis of spontaneous intracerebral haemorrhage in children.
Spontaneous intracerebral haemorrhage; Intracerebral haematoma
Aggressive osteoblastoma is a rare primary bone neoplasm with the potential for local invasion and recurrence. While the vertebrae or long bones are most commonly affected, few well-documented cases have been reported in the jaws. A 25-year-old man presented with a palatal mass of several months’ duration. He reported the lesion had undergone gradual enlargement and, while generally asymptomatic, had recently become increasingly painful. An incisional biopsy was interpreted as “osteoblastic neoplasm” most suggestive of osteoblastoma. However, final diagnosis was deferred until the resection specimen could be evaluated. Following partial maxillectomy, histopathologic examination revealed a proliferation of large epithelioid cells with eccentric nuclei and prominent nucleoli associated with broad, irregular deposits of osteoid and trabeculae of bone. The lesional cells exhibited minimal pleomorphism with infrequent, normal-appearing mitotic figures and numerous osteoclast-like giant cells were observed within an associated loose fibrovascular stroma. Transformation of “blue bone” to more organized eosinophilic trabeculae of woven bone was noted at the periphery of the lesion and there was no evidence of invasion. A diagnosis of aggressive osteoblastoma was made. Previous reports of gnathic aggressive osteoblastoma are reviewed and the features that distinguish this process from conventional osteoblastoma or osteoblastoma-like osteosarcoma are presented.
Aggressive osteoblastoma; Gnathic; Maxilla; Osteoblastoma-like osteosarcoma
Warkany syndrome 2 or Trisomy 8 mosaicism (T8M) is a well-described, but very rare, chromosomal abnormality. The phenotype is extremely variable ranging from normal individual to severe malformation syndrome and because of this variability, this condition often goes undiagnosed. We report trisomy 8 mosaicism (T8M) in a 3-year-old boy evaluated for facial dysmorphism and delayed development.
It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy".
Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1) estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years), locally advanced or metastatic breast cancer; (2) disease deemed suitable for treatment by hormonal manipulation; (3) disease assessable by UICC criteria; (4) received "withdrawal" from a prior endocrine agent as a form of therapy; (5) on "withdrawal therapy" for ≥ 6 months unless they progressed prior.
Seventeen patients with median age of 84.3 (53.7-92.5) had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10), an aromatase inhibitor (n = 5), megestrol acetate (n = 1) or fulvestrant (n = 1). Ten patients (58.8%) had clinical benefit (CB) (complete response/partial response/stable disease ≥ 6 months) with a median duration of Clinical Benefit (DoCB) of 10+ (7-27) months. Two patients remain on "withdrawal therapy" at the time of analysis.
"Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.
Traumatic brain injuries (TBI) are steadily increasing and are a major cause of mortality and morbidity, particularly in the young population, leading to the loss of life and productivity in the developing countries. Providing critical care to these patients with TBI is a challenge even in well-advanced centers in major cities of India. In the present study, we describe our experience of resource utilization in the management of TBI in a critical care unit (CCU) from a rural setup.
Materials and Methods:
All consecutive patients who were admitted from January 2007 to December 2009 in the CCU for the management of traumatic brain injury were included in the study. The case records of the patients were reviewed retrospectively, and data were collected on age, gender, severity of head injury, associated injuries, total CCU stay, total hospital stay, and outcome.
The total duration (days) of hospital stay was 8.96±6.16 days and a median of 8 days, and CCU stay was 3.77±6.34 days with a median of 2 days. No deaths occurred with mild head injury. A total of 73 (19.16%) deaths occurred in 381 admitted subjects in CCU. The risk of death among both the sexes is not significantly different, that is, odds ratio (OR) 1.032 [95% confidence interval (CI) 0.351–3.03], so also the risk of death among the different age groups is also not significant having OR, 0.978 (95% CI, 0.954–1.00). The severity of head injury (mild, moderate, and severe) and CCU stay parameters had significant difference with risk of death [OR, 3.22 (95% CI, 2.49–4.16) and OR, 2.50 (95% CI, 1.9–3.2)].
Apparently it seems possible to use the existing health care structures in rural areas to improve trauma care. It becomes particularly relevant in poor resource, developing countries, where health care facilities and access to specialized care units are still far below the acceptable standard, there is a need to compare with the reference group to further support the evidence.
Critical care; head injury; intensive care unit; rural; traumatic brain injury
We report an unusual case of pituitary hyperplasia secondary to primary hypothyroidism clinically masquerading pituitary apoplexy. A 22-year-old female presented with intermittent headache, easy fatigability, facial puffiness, coarseness of facial features, and hoarseness of voice for six months duration. Diplopia and diminution of vision was also observed for the last 15 days. Brain imaging findings showed pituitary enlargement, the thyroid function test were suggestive of primary hypothyroidism. Patient did well with thyroid hormone replacement therapy.
Endocrine; hypothyroidism; pituitary adenoma; pituitary tumor; thyroiditis
The ideal reconstructive material for cranioplasty is autogenous bone, however if it is not available the use of alloplastic materials is recommended. We present a case of 26-year-male patient who sustained compound depressed fracture of the frontal bone and associated anterior cranial fossa fracture following a road traffic accident. He was managed at hospital where the fractured bone fragments were removed but recently presented with watery discharge from nose (CSF rhinorrhoea) and cosmetic deformity of forehead. We describe the utilization of autogenous local frontal bone split calvarial graft for the reconstruction of the defect.
Frontal fracture; CSF rhinorrhea; Calvaria; Graft
Gastrointestinal stromal tumours (GIST) are histologically heterogenous group of mesenchymal tumours arising in gastrointestinal tract (GIT), though they represent only 0.2% of all GI tumours. The advent of effective chemotherapy for GIST has altered but not diminished the role of surgery which remains the standard therapy for all resectable non-metastatic tumours.
To present our experience of management of GIST which are most common sarcomas of the GIT, commonly seen in stomach and small bowel.
All cases of GIST managed at our centre from April 2006 to June 2008 were included in the study.
Thirteen cases of GIST were operated in the study period. Commonest presenting symptoms were, lump abdomen and dull abdominal pain. After initial USG, CECT was done in all cases. Tumour was seen to arise from small bowel (7/13), stomach (4/13) and one each from oesophagus and omentum. Resection and anastomosis was done in (12/13) cases, one case was inoperable at surgery. Histopathological examination confirmed GIST in all. Immunohistochemistry studies were done in 4/13 cases. 2/13 patients required postoperative chemotherapy.
GIST has varied presentation as shown by our study. All patients require accurate delineation by CECT scan and individualised management. Immunohistochemistry should be done in all, and those who are in high risk group, metastatic or unresectable require imatinib mesylate. Patients who are CD117 positive show good response to imatinib mesylate. Six monthly follow up is recommended with USG/CECT.
GIST; CD117; Imatinib; Mesylate