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Biomedical subjects

Charles Cha

Publications and source records attributed to Charles Cha.

15 recordsLinked to original sources

Safety of carotid endarterectomy in a high-risk population: lessons from the VA and Connecticut.

BACKGROUND: The safety and efficacy of carotid endarterectomy (CEA) have been demonstrated in randomized trials, but these studies excluded patients thought to be at higher risk for poor outcomes. We sought to determine whether patients undergoing CEA in Veteran Affairs Hospitals (VA) were at higher risk and had different outcomes, compared with patients in nonfederal hospitals. STUDY DESIGN: Records of all CEA performed in the VA Connecticut Healthcare System between October 1997 and September 2002 were examined and compared with CEA performed in all nonfederal Connecticut hospitals (CT). RESULTS: There were 7,089 CEAs performed (VA, 140; CT, 6,949). VA patients had increased comorbidity scores and symptomatic presentation (39% versus 14%; p < 0.0001). Perioperative mortality rates were 1.4% (VA) and 0.3% (CT) (p = 0.06). Perioperative stroke (VA, 1.4% versus CT, 0.9%; p = 0.15) and cardiac complication (VA, 2.9% versus CT, 2.1%; p = 0.54) rates were similar. Multivariate analysis demonstrated that perioperative mortality correlated with symptomatic presentation (odds ratio 11.7, p < 0.0001), but not performance, in a VA hospital (p = 0.23); patients treated at the VA were also not at higher risk for stroke (p = 0.94) or cardiac complications (p = 0.90). CONCLUSIONS: Despite increased severity of illness and symptomatic presentation, VA patients had similar perioperative outcomes compared with patients undergoing CEA in nonfederal hospitals in the state of Connecticut. These results suggest not only that patients undergoing vascular surgery at the VA may form a higher-risk population compared with patients receiving care in non-VA hospitals, but that these high-risk patients can undergo CEA safely.

Comorbidity↗

Less common neoplasms of the pancreas.

Recently, there has been an increased recognition of neoplasms of the pancreas other than ductal adenocarcinoma. Although not as well studied or characterized as pancreatic adenocarcinoma there are many distinct lesions which exhibit diverse biological behaviors and varying degrees of malignancy. These lesions include: endocrine neoplasms, cystic tumors, solid pseudopapillary tumors, acinar cell carcinoma, squamous cell carcinoma, primary lymphoma of the pancreas, and metastatic lesions to the pancreas. These less common neoplasms are being diagnosed more frequently as the number and sensitivity of diagnostic imaging studies increase. This review article discusses the clinical course, diagnosis, and treatment of these less common, but quite relevant, neoplasms of the pancreas.

Adenocarcinoma, Mucinous↗

Updates on esophageal and gastric cancers.

Esophageal and gastric cancers are both common and deadly. Patients present most often after disease progression and survival is therefore poor. Due to demographic variability and recent changes in disease incidence, much emphasis has been placed on studying risk factors for both esophageal and gastric cancers. However, with increasing understanding of these diseases, low survival rates persist and continued intensive studies are necessary to optimize treatment plans. This review article discusses updates in the evolving epidemiology, clinical presentation, risk factors, and diagnostic and treatment modalities of esophageal and gastric cancers.

Combined Modality Therapy↗

Hospital-based factors predict outcome after carotid endarterectomy.

OBJECTIVE: Patient, hospital, and surgeon factors affect outcome after carotid endarterectomy (CEA). The nature and importance of hospital-specific factors, especially those unrelated to procedural volume, that affect post-CEA outcome remains poorly defined. We used a statewide database to determine the impact of several hospital-associated factors on outcome after CEA. METHODS: Hospital factors were established by telephone survey and validated by repeated survey as well as by the Connecticut Hospital Association, Connecticut state, and individual hospital internet Websites. All CEA in Connecticut non-federal hospitals between 1991 and 2002 were examined, including perioperative mortality, stroke, and cardiac complications. Multivariable logistic regression was used to analyze data. RESULTS: There were 14,288 CEAs performed with 0.5% mortality, 1.3% stroke, and 2.4% cardiac complications. The only hospital factor independently predictive of perioperative mortality was few number of hospital beds (less than 132 beds; odds ratio (OR) 2.78, P = 0.032). Factors predictive of perioperative stroke included few number of beds (OR 1.96, P = 0.001) and absence of a critical pathway (OR 1.39, P = 0.038). Factors predictive of perioperative cardiac complications included few number of beds (OR 3.01, P = 0.003), absence of a critical pathway (OR 1.50, P = 0.001), and absence of dedicated vascular recovery beds (OR 1.35, P = 0.03). Combined mortality, stroke, or cardiac complications were independently predicted by few hospital beds (OR 4.58, P = 0.002), absence of a critical pathway (OR 1.81, P < or = 0.0001), or inability to perform cardiac angiography (OR 3.92, P = 0.024). CONCLUSIONS: Hospital-based factors, such as greater bed capacity, use of critical pathways, ability to perform cardiac angiography, or presence of a dedicated vascular recovery unit predict reduced perioperative mortality, stroke and cardiac complications from CEA. These results suggest that hospital-associated factors do impact surgical outcome and that surgeons need to optimize these factors, extrinsic to the patient and surgeon, to provide maximal quality of care.

Endarterectomy, Carotid↗

Short interfering RNA-mediated gene silencing of vascular endothelial growth factor: effects on cellular proliferation in colon cancer cells.

HYPOTHESIS: By using short interfering RNA (siRNA) to inhibit the in vitro expression of vascular endothelial growth factor (VEGF) A, we hope to further investigate the presence of an autocrine loop in colon cancer cells. We hypothesize that VEGF inhibition will result in decreased cellular proliferation. DESIGN: Human colon cancer cells were evaluated for the expression of VEGF and VEGF receptor 2 (VEGFR-2). In vitro assessments were then made of the ability of anti-VEGF siRNA to knock down expression of VEGF and the subsequent effect this decreased expression had on colon cancer cell proliferation. SETTING: Surgical oncology research laboratory. INTERVENTIONS: Human colon cancer cells from the RKO cell line were transfected with siRNA targeting the coding region of VEGF. MAIN OUTCOME MEASURES: Enzyme-linked immunosorbent assay, Northern blot analysis, and real-time quantitative polymerase chain reaction were performed to establish the ability of siRNA to decrease VEGF production. Proliferation assays were run on transfected and wild-type cells to establish concomitant decrease in VEGF expression and cellular proliferation. RESULTS: The RKO colon cancer cells expressed both VEGF and VEGFR-2. Those cells transfected with siRNA targeting VEGF showed a 94% knockdown in VEGF expression and a 67% decrease in cellular proliferation. CONCLUSION: Colon cancer cells expressing VEGF and VEGFR-2 may possess an autocrine growth pathway that can be effectively targeted using RNA interference as an antiangiogenic therapy.

Apoptosis↗

Malnutrition after vascular surgery: are patients with chronic renal failure at increased risk?

BACKGROUND: The deleterious effects of perioperative malnutrition on recovery after general surgery are established. Since the effects of perioperative malnutrition on recovery after vascular surgery are not known, we examined the effects of nutritional status, and risk factors predictive of malnutrition, on outcome after vascular surgery. METHODS: The records of all open index vascular cases (abdominal aortic aneurysm [AAA] repair, carotid endarterectomy [CEA], lower extremity bypass) performed at the Veterans Affairs (VA) Connecticut between July 2004 and June 2005 were reviewed. The primary outcome was mortality; secondary outcomes included infection and nutritional risk index (NRI) scores. RESULTS: Sixty-eight open vascular cases were performed during the study period. Nutritional depletion developed in 55% of patients and was more likely in patients undergoing AAA (85%) or bypass (77%) than CEA (30%; P = .0005). Patients who developed malnutrition had similar mortality as patients who did not develop postoperative malnutrition (6.1% vs. 3.7%; P = .68); however, malnourished patients had higher rates of postoperative infection (24.2% vs. 3.7%; P = .03). Chronic renal failure was the only patient-associated risk factor predictive of postoperative nutritional depletion (odds ratio 5.9, confidence interval 1.0 to 33.6; P = .04). CONCLUSIONS: Patients undergoing major open vascular surgery have high rates of postoperative malnutrition, with patients undergoing AAA repair having the highest rates of postoperative malnutrition and infection. Patients with chronic renal failure undergoing vascular surgery are associated with increased risk for postoperative malnutrition and may be a group to target for perioperative risk factor modification and nutritional supplementation.

Aortic Aneurysm, Abdominal↗

Differential responsiveness of early- and late-passage endothelial cells to shear stress.

BACKGROUND: The incidence of vascular disease increases with age. Because atherosclerosis and neointimal hyperplasia colocalize in areas of disturbed shear stress, the effects of orbital shear stress (SS) on endothelial cell proliferation, protein kinase B (Akt) activation, and functional activity were analyzed using a senescence model. METHODS: Early- (p3 to 7) and late- (p28 to 32) passage bovine aortic endothelial cells were exposed to orbital SS (210 rpm) or static conditions (0 to 5 days). Cell proliferation was directly counted and confirmed with proliferating cell nuclear antigen reactivity. Phosphorylated and total Akt were assessed with Western blotting. Endothelial cell-induced smooth muscle cell migration was assessed with a Boyden chamber. RESULTS: Late-passage endothelial cells demonstrated no increase in orbital SS stimulated proliferation compared with early-passage cells (P = .42). Late-passage endothelial cells demonstrated decreased Akt phosphorylation in response to SS compared with early passage cells (n = 6, P = .01). Late-passage cells induced 26% less smooth muscle cell migration than early-passage cells (n = 3, P = .03). CONCLUSIONS: Late-passage endothelial cells demonstrate decreased proliferation, Akt phosphorylation, and secretion of smooth muscle cell chemoattractants in response to orbital SS compared with early passage cells. These results suggest that late-passage endothelial cells respond to SS differently than early-passage cells and confirm the utility of the in vitro senescence model.

Aging↗

Molecular mechanisms in hepatocellular carcinoma development.

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. It usually develops in patients with chronic viral hepatitis, aflatoxin exposure, or excessive alcohol use. Most patients with HCC present with advanced disease and have a poor prognosis. The implementation of antiviral drugs and the availability of a vaccine for hepatitis B should help reduce the incidence of HCC. Considerable effort has now focused on unraveling the molecular pathogenesis of HCC in order to design better treatments, or to prevent the disease altogether. However, so far, the pathogenesis of HCC appears to be quite heterogeneous among patients. In particular, several mechanisms of tumorigenesis seem to be involved, including loss of tumor suppressor gene function, oncogene activation, direct viral effects, DNA methylation, and angiogenesis. It is not clear which events are critical in tumor initiation versus tumor progression. RNA expression arrays and proteomics hold promise to provide further clues about this common and complex cancer.

Carcinoma, Hepatocellular↗

Multiple gastrointestinal stromal tumors and synchronous ileal carcinoids.

BACKGROUND: A 74-year-old African-American male presented with a 3-day history of hematemesis and melena. The patient reported no abdominal pain, constitutional symptoms, bright red blood per rectum, constipation, or diarrhea. His physical examination and medical history were unremarkable except for benign prostatic hypertrophy. An esophagogastroduodenoscopy showed a 3 x 2 x 2 cm smooth round mass in the cardia, 2 cm distal to the gastroesophageal junction. Biopsy of the mass revealed an ulcerated tumor composed of spindle cells. Immunohistochemistry showed positive staining for a number of biochemical markers, including KIT, Ki-67 and smooth muscle actin, but was negative for the markers S100 and desmin. A gastric-wedge resection revealed an ulcerated 4.5 cm mass in the stomach, and exploration of the abdomen revealed two ileal carcinoid tumors, jejunal diverticula and reactive mesenteric lymphadenopathy. INVESTIGATIONS: Esophagogastroduodenoscopy, biopsy, CT scan, immunohistochemistry, DNA microarray analysis and quantitative reverse transcriptase-PCR. DIAGNOSIS: Multiple gastrointestinal stromal tumors occurring concomitantly with ileal carcinoids. MANAGEMENT: Gastric-wedge resection and segmental resection.

Aged↗

Gastric carcinoid.

PURPOSE OF REVIEW: Gastric carcinoid tumors are rare lesions but have been the focus of much scientific investigation. The incidence of gastric carcinoid appears to be increasing without a corresponding increase in survival, despite utilization of the latest available therapies. Therefore, there is great interest in furthering the understanding of the biologic basis of these tumors, delineating the connection between hypergastrinemia and gastric carcinoids, and most importantly, improving upon current treatment options. RECENT FINDINGS: This review discusses the current biologic understanding of gastric carcinoid tumors, including the role of hypergastrinemia on enterochromaffin-like cell proliferation and its relation to acid-suppressive therapy. Numerous diagnostic and therapeutic modalities including endoscopic ultrasound, somatostatin receptor scintigraphy, long-acting octreotide, hepatic artery embolization, endoscopic mucosal resection, and surgical resection have also been the focus of recent investigations. SUMMARY: Despite the many advances that have been made in both the basic science and clinical arenas, the optimal treatment of gastric carcinoid tumors is still a matter of debate. As the understanding of the biologic basis of gastric carcinoid tumors increases, the treatment will likely be a multimodal approach tailored to individual tumor biology and will incorporate a variety of diagnostic and therapeutic modalities.

Antineoplastic Agents↗

Long-term results with resection of radiation-induced soft tissue sarcomas.

INTRODUCTION: Radiation therapy is increasingly used as adjuvant treatment of many childhood and adult malignancies. Radiation-induced sarcoma is a well recognized if uncommon event. The objective of this study is to determine the prevalence and long-term outcome for patients who develop radiation-induced sarcomas. METHODS: From July 1982 to December 2001, 4884 adult patients with sarcoma were admitted and treated at our institution and recorded in a prospective database. There were 123 (2.5%) patients who had radiation-induced soft tissue sarcomas. Survival was determined by Kaplan-Meier analysis. Patient, tumor, and treatment characteristics were tested for their prognostic significance by log rank and the Cox proportional hazards model. RESULTS: The median interval between radiation and development of sarcoma was 103 (6 to 534) months. In 114 patients with radiation-induced sarcoma who underwent curative resection, the 5-year actuarial survival was 41%, with a median survival of 48 months at a median follow-up of 36 months for survivors. The most common malignancy for which radiation was used was breast cancer (29%), followed by lymphoma (16%) and prostate cancer (15%). Malignant fibrous histiocytoma (23%) was the most common histologic diagnosis, followed by fibrosarcoma (15%) and angiosarcoma (15%). High-grade tumors (n = 85; 79%), age > 60 years (n = 61; 50%), and gross positive resection margin (n = 36; 32%) were predictive of poor sarcoma-specific survival on univariate and multivariate analysis. CONCLUSIONS: The increasing utilization of adjuvant radiation therapy, especially for early-stage breast cancer mandates long-term follow-up to detect radiation-induced sarcoma. Surgical resection remains the primary therapy, but 5-year survival remains approximately 40%.

Adult↗

Predictors and patterns of recurrence after resection of hepatocellular carcinoma.

BACKGROUND: The majority of patients with hepatocellular carcinoma (HCC) who undergo complete tumor resection subsequently develop tumor recurrence. The objectives of this study were to determine the risk factors for recurrence of HCC after hepatectomy and to examine the outcomes once tumor recurrence occurs. STUDY DESIGN: From February 1990 to May 2001 a total of 164 patients underwent liver resection for HCC at our institution and were prospectively followed. Time to recurrence and survival after recurrence were determined by Kaplan-Meier analysis. Patient, tumor, and treatment characteristics were tested for their prognostic significance by univariate and multivariate analysis using the logrank test and the Cox proportional hazards model, respectively. RESULTS: The median patient age was 64 years (range 21 to 87 years) and 106 patients (65%) were male. After a median followup of 26 months, 90 patients (55%) have developed recurrent cancer. Among them, 75 patients (83%) had tumor detectable in the liver, which was the only site of disease in 67 (74%). In all, 15 patients (20%) had extrahepatic disease (7 lung, 4 peritoneum, 2 pancreas, 1 bone, and 1 brain). The median time to recurrence was 24 months (range 1 to 274 months). Predictors of recurrence on univariate analysis were tumor size greater than 5 cm, more than one tumor, cirrhosis, vascular invasion (microscopic or macroscopic), and tumor satellites. On multivariate analysis only tumor size greater than 5 cm (p = 0.04) and vascular invasion (p = 0.01) predicted recurrence. The median survival after recurrence was 11 months (range 0 to 60 months). Of the 90 patients who developed tumor recurrence 49 (67%) were able to undergo additional ablative or surgical therapy (33 embolization, 9 ethanol injection, and 14 re-resection). On multivariate analysis vascular invasion in the original tumor predicted poor survival after recurrence (p = 0.009). CONCLUSIONS: The liver is the predominant site of first recurrence after resection of hepatocellular carcinoma, and once recurrence occurs survival is limited. The current study underscores the need for effective adjuvant therapy for patients with HCC treated with partial hepatectomy.

Actuarial Analysis↗

Primary thyroid lymphoma: can the diagnosis be made solely by fine-needle aspiration?

BACKGROUND: Primary malignant lymphoma of the thyroid accounts for <5% of all thyroid malignancies and is primarily treated with chemotherapy and external beam radiation. With the advent of modern immunophenotypic analyses, fine-needle aspiration (FNA) can potentially obviate the need for surgical procedures. METHODS: To investigate the utility of FNA, data from 23 consecutive patients with primary malignant thyroid lymphoma evaluated at the Johns Hopkins Hospital from July 1985 to April 2000 were analyzed. RESULTS: Patients were categorized into two groups: those diagnosed before 1993 (group 1, n = 12) and those diagnosed after 1993 (group 2, n = 11). Although patients in group 1 were slightly older, there were no other differences between the groups with regard to sex, tumor grade, or tumor stage. Although no patient in group 1 was successfully diagnosed by FNA alone, seven patients (63%) in group 2 were diagnosed solely by FNA (P =.019, chi(2) analysis). Therefore, all 12 patients in group 1, but only 4 of 11 patients in group 2, required open surgical biopsy. CONCLUSIONS: Primary thyroid lymphoma is an uncommon malignancy usually treated nonsurgically once the diagnosis is established. In most patients with malignant lymphoma of the thyroid, FNA, should obviate the need for open surgical biopsy.

Adult↗

Surgery and ablative therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, responsible for an estimated one million deaths annually. The incidence in the United States has steadily increased over the past two decades. Although HCC has historically had a dismal prognosis, it is now being detected earlier as a result of improved radiologic imaging and surveillance. This affords the opportunity to treat patients with curative intent, and may improve survival. Partial hepatectomy and transplantation each provide potentially curative therapy for selected patients with HCC. Transplantation is indicated when there is severe underlying liver dysfunction. Local ablative therapy, such as ethanol injection, hepatic artery embolization, and radiofrequency ablation, offer palliation for patients when surgery is not feasible. The rational application of the myriad of therapies to a patient with HCC is designed to maximize both quality of life and survival.

Anti-Infective Agents, Local↗