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Biomedical subjects

Chandrakanth Are

Publications and source records attributed to Chandrakanth Are.

7 recordsLinked to original sources

Anaplastic thyroid carcinoma: biology, pathogenesis, prognostic factors, and treatment approaches.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors known to affect humans and carries a dismal prognosis. Our primary aim was to review its epidemiology, biology, risk factors, and prognostic indicators. We also reviewed the individual and combined roles of surgery, radiotherapy, chemotherapy, and newer therapeutic options in the management of ATC. METHODS: An extensive literature review was conducted to include all published reports on ATC. The changing trends in the management of anaplastic thyroid cancer were analyzed to summarize the current practice of management of ATC. RESULTS: Although ATC is rare, there has been a decline in its incidence worldwide. ATC accounts for more than half of the 1200 deaths per year attributed to thyroid cancer. Long-term survivors are rare, with >75% and 50% of patients harboring cervical nodal disease and metastatic disease, respectively, at presentation. ATC can arise de novo or from preexisting well-differentiated thyroid cancer. Surgical management has shifted from tracheostomy only for palliation to curative resection when possible. Tracheostomy is performed for impending obstruction rather than for prophylaxis. Radiotherapy has evolved from postoperative administration only to preoperative treatment, combining preoperative and postoperative treatment and using higher doses, along with hyperfractionating and accelerating dose schedules. Chemotherapy has changed from monotherapy to combination therapy, and newer drugs such as paclitaxel show promise. Similarly, novel angiogenesis-inhibiting agents are currently being used, with early reports of some benefit. CONCLUSIONS: Despite multimodality approaches, ATC still carries a dismal prognosis. This should provoke innovative strategies beyond conventional methods to tackle this uniformly lethal disease.

Carcinoma↗

Laparoscopy and malignancy.

BACKGROUND: The advantages of pneumoperitoneum-based surgery are well documented. Laparoscopy is the gold standard of treatment in certain benign conditions such as cholelithiasis and gastroesophageal disease. This success has led to the application of laparoscopy in the management algorithm of malignant conditions. There is currently no universally accepted consensus of the role of pneumoperitoneum-based surgery in the treatment of cancer. This is due to the early reports of port site metastasis, initial lack of randomized controlled trials and the concern of performing oncologically adequate operations. The aim of this section is to review the current literature and attempt to obtain a consensus of the role of laparoscopy in the treatment of cancer. MATERIALS AND METHODS: A literature search was conducted through Pubmed with key words laparoscopy, pneumoperitoneum, carbon dioxide, malignancy, cancer, and port site metastasis. The obtained results were divided into various sections such as non-randomized reports, randomized reports, animal studies, human studies, etc. A comparison was made between laparoscopic and open resections when possible. RESULTS: There are several published reports of studies in animal models and in humans relating to pneumoperitoneum-based surgery in the setting of malignancy. There are also a few randomized controlled trials that compared open versus laparoscopic surgery for malignancies of various organ systems. In addition, the early reports of alarmingly high rate of port site metastasis have been scaled down to rates comparable to wound recurrences after open resections. SUMMARY: Laparoscopy has added another dimension to the management of patients with cancer. Advanced training, superior instrumentation, and a better understanding of the pathophysiology of carbon dioxide pneumoperitoneum has led to the successful application of laparoscopy. The improved results are obtained in centers with high volume of patients and with experience in both fields of oncology and minimally invasive surgery. Laparoscopy is now an integral tool in the management algorithm of malignancies of some organ systems and its role will be further expanded in the future.

Animals↗

Decreased cardiac output in humans during laparoscopic antireflux surgery: direct measurements.

OBJECTIVE: In a porcine model, we demonstrated that laparoscopic Nissen fundoplication causes a significant drop in cardiac output (30%) because it exposes both the peritoneal cavity and the mediastinum to CO(2) under pressure. To determine if this occurs in humans, we examined cardiovascular physiology during laparoscopic Nissen fundoplication. Because of invasiveness required in this pilot trial, only six patients were studied. METHODS: The arterial blood pressure (via radial arterial catheter) and the pulmonary artery diastolic pressure and cardiac index (via pulmonary artery thermodilution catheter) were measured at seven points in time during each laparoscopic Nissen fundoplication. RESULTS: The systolic blood pressure decreased in all patients, and the cardiac index decreased in all but one patient. The exception was a patient with Huntington disease, in whom the cardiac output did not decrease. In four of the five patients, the cardiac output was lowest during hiatal dissection, and in the fifth, it was lowest after reverse Trendelenburg positioning. No significant change in the pulmonary artery diastolic pressure was noted. All patients received adequate intravenous fluid replacement (average, 58 +/- 16 mL/kg) to support blood pressure. In one patient, with a particularly large paraesophageal hernia, profound hypotension (40/25 mm Hg) developed during the mediastinal phase of the procedure, and this patient required alpha-adrenergic support followed by laparotomy to eliminate a surgical cause (none found). CONCLUSIONS: Although it is a tremendous advance for patients, laparoscopic Nissen fundoplication can be associated with a significant reduction in cardiac output and blood pressure. Surgeons and anesthesiologists must be alert to changes reflecting these decreases during procedures, which violate both the peritoneal cavity and the mediastinum. We propose careful hemodynamic monitoring during these procedures, especially in patients with coronary artery disease or significant left ventricular dysfunction.

Aged↗

Vessel injury and capillary leak.

OBJECTIVE: To understand the mechanism of pathologic capillary leak in the critically ill patient. DESIGN: Review of normal and altered physiology of the microvasculature. Review of recent literature describing pathogenesis, mediators, and interventions influencing capillary leak and microvascular repair. SETTING: In vitro and in vivo studies, the latter including animal and human subjects. MEASUREMENTS AND MAIN RESULTS: Capillary leak with resultant edema develops in the critical care setting on the basis of perturbations in Starling's equation, primarily as a result of increased capillary permeability to larger molecules. This process is most likely fueled by inflammatory mediators or mechanical stress. Attempts to prevent or treat this process remain largely unsuccessful; resuscitation is more often symptomatic than therapeutic. Models of microvascular repair focus on discrete injury and may not be applicable to the recovery of capillary damage secondary to a systemic leak CONCLUSIONS: Our understanding of capillary leak syndrome remains fragmented and weighted toward specific mediators contributing to the leak. The implications of extensive edema and the mechanism by which it resolves continue to be the subject of speculation rather than study.

Capillary Leak Syndrome↗

Effect of laparoscopic antireflux surgery upon renal blood flow.

BACKGROUND: Hypercapnia and local pressure effects unique to CO(2) base minimally invasive surgery alter renal blood flow. We have demonstrated laparoscopic antireflux surgery to have an additional impact upon hemodynamics (decreased cardiac output), potentially extending known effects upon renal blood flow. METHODS: We measured renal blood flow with radioactive microspheres during laparoscopic antireflux surgery in a porcine model. Six pigs were anesthetized, monitoring lines were placed, and microspheres injected five time points associated with a laparoscopic antireflux operation. After euthanasia kidneys were retrieved and fixed, and representative samples counted for radioactivity specific for each of the five time points. RESULTS: The greatest reduction in renal blood flow was 36% below baseline (p<0.05). Concurrently, cardiac output had a maximum reduction of 39%. CONCLUSIONS: Laparoscopic Nissen fundoplication in this pig model is associated with a significant reduction in renal blood flow, probably related to reduction in cardiac output. Caution is warranted when considering laparoscopic antireflux surgery in patients with a compromised renal blood flow.

Animals↗

Polypoid esophageal adenocarcinoma--a clinicopathological variant of esophageal cancer?

PURPOSE: Neoplastic polyps are common in the colon, but not elsewhere in the gastrointestinal tract. They are rare at the gastroesophageal junction, especially associated with Barrett's dysplasia or adenocarcinoma. We identify a subset of early esophageal adenocarcinomas that present as symptomatic polyps with gastrointestinal bleeding, reflux, and even dysphagia. Because little is known about polypoid esophageal adenocarcinomas, we examine the clinical presentation, pathological features, and postoperative outcomes of these lesions. METHODS: We defined esophageal polyps as macroscopic, well-demarcated projections above the mucosa that project the greater percentage of their mass into the lumen without central ulceration. From a consecutive series of 400 patients who underwent esophagectomies for adenocarcinoma (1988 to 2000), 14 (4%) had polyps on presentation. Clinical records, pathology reports, photographs, and original slides of these resected specimens were reviewed. RESULTS: All patients with polyps had early staged esophageal adenocarcinomas. Lymph node involvement was found in only 4 patients, and no patients with distant metastases were found. All but 1 patient (13 of 14; 93%) were symptomatic at diagnosis. Most presented either with gastrointestinal bleeding or gastroesophageal reflux (11 of 14; 79%). Only 2 patients complained of mild dysphagia, and mean weight loss of the series was minimal at 1.3 +/- 4.0 kg (range, 0 to 15 kg). Barrett's was present in 10 patients (71%), and in 80% of these cases, high-grade dysplasia was found. The polyps were small 3.4 +/- 1.1 cm, and most contained poorly differentiated adenocarcinomas. No postoperative mortalities occurred, and follow-up was complete at 100%. Actuarial 2-year survival was 88%, with a mean survival of 61.3 months. Recurrent disease was identified in 4 patients. CONCLUSIONS: Polypoid adenocarcinomas of the distal esophagus are a subset of esophageal cancer that produce clear symptoms at an early tumor stage, which allows prompt detection and favorable prognosis. Their pathological features and demographics suggest an origin via the Barrett's esophagus-dysplasia-carcinoma sequence.

Journal Article↗