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Biomedical subjects

David Chang

Publications and source records attributed to David Chang.

At least 19 recordsLinked to original sources

Pharmacotherapy for fecal incontinence: a review.

Fecal incontinence is a common clinical problem that often is frustrating to the patient and treating physician. Nonsurgical management for fecal incontinence includes dietary manipulation, Kegel exercises, perianal skin care, and biofeedback therapy. Pharmacotherapies often are used to assist in management of fecal incontinence. A variety of pharmacotherapies have been utilized for the management of fecal incontinence; limited data from randomized, placebo-controlled trials are available. This is a review of the existing literature on clinical trials of several classes of drugs and other medical therapies that may be beneficial for patients with fecal incontinence. The information in this article was obtained by a MEDLINE search for all clinical trials of drug therapy for fecal incontinence. These treatments and the existing data on their use are summarized. Treatments reviewed include stool bulking agents, with an emphasis on the most promising effect obtained with calcium polycarbophil, constipating agents, including loperamide, codeine, amitriptyline, atropine, and diphenoxylate agents injected into the anal sphincter, drugs to enhance anal sphincter function, including topical phenylepherine and oral sodium valproate, and trials of fecal disimpaction. A new classification to easily remember the treatment categories for this condition, based on the "ABCs of treatment for fecal incontinence," has been introduced into the structure of this review.

Chronic Disease↗

Human immunodeficiency virus and hepatitis testing and prevalence among surgical patients in an urban university hospital.

BACKGROUND: Human immunodeficiency virus (HIV), hepatitis B, and hepatitis C represent significant public health problems in an urban community. Early diagnosis and treatment of these infections can improve survival and allow for preventive strategies to reduce further transmission within a community. The aim of this study was to evaluate the surgical setting as a potential opportunity for early diagnosis of HIV, hepatitis B, and hepatitis C among trauma and non-trauma patients. METHODS: We performed a retrospective review of patients presenting for surgery over a 10-year period (July 1994 to July 2004) in an urban, university-based general surgical practice that includes all trauma services, as well as emergency department, inpatient, and outpatient surgical consultations. Data collected included diagnosis, operation, age, race, history of intravenous drug abuse, and HIV, hepatitis B, and hepatitis C test results. RESULTS: Among 2876 patients presenting for surgery, testing for blood-borne pathogens was less likely among trauma patients (21%, 79/380) compared to non-trauma patients (47%, 1183/2496) (P < .001). Among patients tested, the incidence of blood-borne pathogens was similar in the two groups: HIV (26% trauma vs 24% non-trauma, not significant [NS]), hepatitis B (4% trauma vs 3% non-trauma, NS), hepatitis C (33% trauma vs 41% non-trauma, NS), and co-infection with HIV and hepatitis C (18% trauma vs 12% non-trauma, NS). In both groups, blood-borne pathogens were associated with intravenous drug abuse (P < .01). CONCLUSION: HIV, hepatitis B, and hepatitis C are common in an urban community among both trauma and non-trauma surgical patients, although testing is less common among trauma patients. Testing of patients during a surgical admission may represent an excellent opportunity for early disease-specific services and preventive interventions.

AIDS Serodiagnosis↗

Disparities in colon cancer presentation and in-hospital mortality in Maryland: a ten-year review.

BACKGROUND: Much attention has focused on in-hospital treatment disparities in colon cancer outcomes. Little is known about the effect of prehospital factors on outcomes. We hypothesized that racial and socioeconomic disparities exist in the presentation of colon cancer and that these disparities affect in-hospital outcomes. METHODS: Ten-year data on colon cancer patients were obtained from the Maryland Hospital Discharge Database. Life-threatening symptoms at presentation served as a proxy for delay in diagnosis. Patients with the primary diagnosis of colon cancer treated with surgical resection were included. Outcomes of interest were obstruction, hemorrhage, perforation, and in-hospital mortality. RESULTS: A total of 14,291 patients had primary colon cancer, and 13,031 underwent resection. Among this group, 52% were male, 22% were African American (AA), and mean age of AA was 66.0 years versus non-AA mean age of 70.5 years (P < .001). Overall, 27.6% of patients presented with life-threatening symptoms. In-hospital mortality rate was 3.8%. Symptomatic patients had a 2-fold higher rate of in-hospital mortality (odds ratio [OR], 6.06 vs. 2.89, P < .001). Multivariate analysis demonstrated that AA were more likely to have life-threatening symptoms at presentation independent of socioeconomic status (SES) (OR, 1.36). In addition, AA had a higher in-hospital mortality, both overall (OR, 1.39) and in the higher SES (OR, 1.81). CONCLUSIONS: Racial disparities exist in the rate of presentation with life-threatening symptoms that may be a proxy for a delay in diagnosis. These findings were independent of SES, implying that factors beyond health care access may account for poorer outcomes among AA.

Black or African American↗

Prognostic indicators for patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma.

BACKGROUND: This study evaluates clinical, radiological and histopathological prognostic indicators for survival of patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma (DMPM). METHODS: Sixty-two consecutive patients with DMPM underwent cytoreduction and perioperative intraperitoneal chemotherapy at the Washington Cancer Institute. Twenty-six clinical, radiological and histopathological parameters were analyzed in univariate and multivariate analyses using overall survival as an endpoint. RESULTS: The overall survival was 79 months (range 1-143 months), with 1-, 3- and 5-year survival rates of 84%, 58% and 50%, respectively. The following 14 prognostic variables were significant for survival in the univariate analysis: gender (P = .045), peritoneal cancer index (P = .038), completeness of cytoreduction score (P = .010), interpretive CT findings of the small bowel and mesentery (P = .001), mesothelioma cell type (P < .001), mesothelioma nuclear size (P < .001), nuclear/cytoplasmic ratio (P < .001), mitotic count (P < .001), atypical mitosis (P < .001), chromatin pattern (P < .001), cellular necrosis (P < .001), perineural invasion (P = .037), stroma pattern (P < .001) and depth of invasion (P = .014). In the multivariate analysis, the only factor that was independently associated with an improved survival after cytoreduction and perioperative intraperitoneal chemotherapy was mesothelioma nuclear size. CONCLUSIONS: Mesothelioma nuclear size was the dominant factor determining overall survival in patients with DMPM. A histopathological staging system based on measurement of the nuclear size was proposed.

Antineoplastic Combined Chemotherapy Protocols↗

An outcomes analysis of patients undergoing body contouring surgery after massive weight loss.

BACKGROUND: Although published reports about technical management of massive weight loss patients are beginning to appear, risk factors for complications following body contouring operations are not known. METHODS: A retrospective analysis of massive weight loss patients who had body contouring operations between March of 1998 and October of 2004 was performed. Demographic and surgical factors were analyzed. Outcome measures included seroma, wound dehiscence, thromboembolic complications, blood transfusion after surgery, and extended lengths of stay (>2 days). RESULTS: A total of 139 patients were analyzed; 82.7 percent of them were female; mean age was 41 years. On multiple logistic regression, male gender was associated with significant risks for wound dehiscence (odds ratio, 6.4; p = 0.01). There were also trends toward increased risk for wound dehiscence with hypothyroidism (odds ratio, 4.3; p = 0.06) and Ehlers-Danlos syndrome (odds ratio, 18.7; p = 0.05). In terms of risk of blood transfusion, asthma and having three or more procedures were the two variables that emerged with significant association (odds ratio, 16.8 and 13.7, respectively; both p < 0.01). Increased length of stay to greater than 2 days was also significantly associated with having three or more procedures (odds ratio, 4.72; p < 0.01). CONCLUSIONS: Male gender, hypothyroidism, and Ehlers-Danlos syndrome may be risk factors for wound dehiscence following body contour operations for massive weight loss. Asthma may be a marker of poor general health status, and asthmatic patients are at increased risk for requiring blood transfusions. Having three or more procedures is associated with an increased risk of blood transfusion and increased length of stay.

Adult↗

A prospective randomized clinical trial of phacoemulsification vs manual sutureless small-incision extracapsular cataract surgery in Nepal.

PURPOSE: To compare the efficacy and visual results of phacoemulsification vs manual sutureless small-incision extracapsular cataract surgery (SICS) for the treatment of cataracts in Nepal. DESIGN: Prospective, randomized comparison of 108 consecutive patients with visually significant cataracts. METHODS: settings: Outreach microsurgical eye clinic. patients: One hundred eight consecutive patients with cataracts were assigned randomly to receive either phacoemulsification or SICS. intervention Cataract surgery with implantation of intraocular lens. main outcome measures: Operative time, surgical complications, uncorrected and best-corrected visual acuity (BCVA), astigmatism, and central corneal thickness (CCT). RESULTS: Both surgical techniques achieved excellent surgical outcomes with low complication rates. On postoperative day 1, the groups had comparable uncorrected visual acuity (UCVA) (P = 0.185) and the SICS group had less corneal edema (P = 0.0039). At six months, 89% of the SICS patients had UCVA of 20/60 or better and 98% had a best-corrected visual acuity (BCVA) of 20/60 or better vs 85% of patients with UCVA of 20/60 or better and 98% of patients with BCVA of 20/60 or better at six months in the phaco group (P = 0.30). Surgical time for SICS was much shorter than that for phacoemulsification (P < .0001). CONCLUSION: Both phacoemulsification and SICS achieved excellent visual outcomes with low complication rates. SICS is significantly faster, less expensive, and less technology dependent than phacoemulsification. SICS may be the more appropriate surgical procedure for the treatment of advanced cataracts in the developing world.

Aged↗

Resected periampullary adenocarcinoma: 5-year survivors and their 6- to 10-year follow-up.

BACKGROUND: Many studies have reported 5-year survival data after pancreaticoduodenectomy for periampullary adenocarcinoma. This study evaluates 10-year survival in patients surviving 5 years after initial surgery. METHODS: We reviewed all patients undergoing pancreaticoduodenectomy for periampullary adenocarcinoma from April 1970 to July 1999 at a single institution. All 5-year survivors were identified, and their subsequent 5-year survival was compared with the actuarial survival of the general population starting at 70 years of age. RESULTS: Nine hundred fifteen patients underwent pancreaticoduodenectomy for periampullary adenocarcinoma. Follow-up was complete on 890 patients. There were 201 (23%) 5-year survivors with a median age of 65 years at initial surgery; 51% were male and 92% were Caucasian. For the 5-year survivors, the carcinoma origin was pancreatic in 46%, ampullary in 25%, distal bile duct in 17%, and duodenal in 12%. For all 5-year survivors, the subsequent 5-year actuarial survival rate was 65%, with a median survival after achieving the 5-year landmark of 7.9 additional years. The subsequent 5-year survival by site of tumor origin was 55% for pancreatic, 66% for ampullary, 74% for bile duct, and 85% for duodenal cancer. For the age-matched population, the 5-year survival rate was 87% (P<.001 when compared with those with all periampullary cancers). CONCLUSIONS: While the 5-year survival rate for all patients with resected periampullary adenocarcinoma is only 23%, these data imply that attainment of the 5-year survival landmark carries with it an improved survival for the subsequent 5 years. While the survival rate was less than that of the age-matched population, 65% of 5-year survivors survived 5 more years, bringing them to the 10-year postresection landmark.

Adenocarcinoma↗

Serum response factor MADS box serine-162 phosphorylation switches proliferation and myogenic gene programs.

Phosphorylation of a cluster of amino acids in the serum response factor (SRF) "MADS box" alphaI coil DNA binding domain regulated the transcription of genes associated with proliferation or terminal muscle differentiation. Mimicking phosphorylation of serine-162, a target of protein kinase C-alpha, with an aspartic acid substitution (SRF-S162D) completely inhibited SRF-DNA binding and blocked alpha-actin gene transcription even in the presence of potent myogenic cofactors, while preserving c-fos promoter activity because of stabilization of the ternary complex via Elk-1. Introduction of SRF-S162D into SRF null ES cells permitted transcription of the c-fos gene but was unable to rescue expression of myogenic contractile genes. Transition of proliferating C2C12 myoblasts to postfusion myocytes after serum withdrawal was associated with a progressive decline in SRF-S162 phosphorylation and an increase in alpha-actin gene expression. Hence, the phosphorylation status of serine-162 in the alphaI coil may constitute a novel switch that directs target gene expression into proliferation or differentiation programs.

Actins↗

Prospective morbidity and mortality assessment of cytoreductive surgery plus perioperative intraperitoneal chemotherapy to treat peritoneal dissemination of appendiceal mucinous malignancy.

BACKGROUND: Appendiceal mucinous neoplasms present, in most patients, with peritoneal dissemination at the time of initial diagnosis. Patients may have a borderline tumor showing disseminated peritoneal adenomucinosis or an aggressive malignancy identified as peritoneal mucinous adenocarcinoma. Patients with these diagnoses were treated by cytoreductive surgery and perioperative intraperitoneal chemotherapy. METHODS: A database was established in 1998 that prospectively evaluated the morbidity and mortality of this group of patients. By using common toxicity grading criteria, 8 categories were scored on a grade of I to V. Grade IV indicated that the adverse event required urgent and definitive intervention: often a return to the operating room or to the surgical intensive care unit. Grade V indicated that the adverse events resulted in the patient's death. Adverse events were tabulated for each cytoreduction performed in these appendiceal malignancy patients. RESULTS: There were 356 procedures in patients taken to the operating room who received cytoreductive surgery with peritonectomy procedures plus heated intraoperative intraperitoneal chemotherapy. Only patients who had this combined treatment at our institution were included in the analysis. The total 30-day or in-hospital mortality was 2.0%. Nineteen percent of procedures were accompanied by at least one grade IV adverse event, and 11.1% of patients returned to the operating room. The most common category of grade IV complications was hematological (28%), followed by gastrointestinal (26%). CONCLUSIONS: The mortality of 2.0% and the overall grade IV morbidity of 19% in these patients may be acceptable in light of modern standards for the management of gastrointestinal cancer.

Adenocarcinoma, Mucinous↗

Alarming surge in nonsurvivable urban trauma and the case for violence prevention.

HYPOTHESIS: A growing proportion of urban trauma mortality is characterized by devastating and likely nonsurvivable injuries. DESIGN: Consecutive samples from prospectively collected registry data. SETTING: University level I trauma center. PATIENTS: All trauma patients from January 1, 2000, to March 31, 2005. MAIN OUTCOME MEASURES: Data for trauma patients, including locale of death and mechanism of injury, comparing early (years 2000 through 2003) and late (2004 and 2005) periods. RESULTS: A total of 11 051 trauma visits were registered during the study period with 366 deaths for an overall mortality of 3.3%. Penetrating injury occurred in 26.7% of patients; however, 71.9% of trauma mortalities (263 patients) died with penetrating injuries. Of the patients who died, 48.3% demonstrated severe penetrating injuries (Abbreviated Injury Score >/=4) to the head while 32.7% presented with severe penetrating chest injuries. There was a significant increase in the mortality rate over time (3.0% [early] vs 4.3% [late], P<.01). In parallel, emergency department mortality (patients dead on arrival and those not surviving to hospital admission) increased from 1.7% to 3.1% (P<.005), yet postadmission mortality remained constant (1.3% [early] vs 1.2% [late], P = .77). When emergency department mortality and the subsequent hospital mortality of patients with gunshot wounds to the head were combined, this represented 82.6% of all trauma mortalities in the late period. This was increased from 69.7% during the early period (P<.01). CONCLUSIONS: While in-hospital mortality has remained the same, the proportion of nonsurvivable traumatic injuries has increased. In a mature trauma system, this provides a compelling argument for violence prevention strategies to reduce urban trauma mortality.

Adult↗

Sharpless surgery: a prospective study of the feasibility of performing operations using non-sharp techniques in an urban, university-based surgical practice.

CONTEXT: Percutaneous injuries occur frequently during surgical procedures and represent a significant occupational hazard to operating room personnel. OBJECTIVES: To evaluate the feasibility of performing select general surgical procedures using a combination of non-sharp devices and techniques to replace the conventional use of scalpels and needles. DESIGN, SETTING, AND PARTICIPANTS: Candidate procedures for which sharpless techniques could replace conventional scalpels and suture needles were identified preoperatively in an urban, university-based general surgical practice over a 1-year period (June 2003-June 2004). Non-sharp techniques included monomeric 2-octyl cyanoacrylate adhesive, electrocautery, tissue stapler, and minimally invasive instrumentation. Conventional scalpels and suture needles were readily available and used whenever necessary. MAIN OUTCOME MEASURES: We rated the feasibility of performing specific procedures without sharps. We also documented the rate of overall reversion to sharps during operations on patients that had been identified preoperatively as candidates for sharpless surgery. RESULTS: Of 358 procedures performed in the general surgery university practice, 91 were identified preoperatively as appropriate for sharpless surgery. Of these, 86.8% (79/91) were completed without the use of sharps, including 13/22 (59.1%) open laparotomy procedures, 20/22 (90.9%) laparoscopic procedures, and 46/47 (97.8%) soft tissue procedures. Intraoperative reversion to sharps occurred in 12 cases when deemed necessary by the surgeon. CONCLUSIONS: Select common procedures can be performed entirely with sharpless techniques, eliminating the risk to surgical personnel associated with intraoperative percutaneous injuries.

Academic Medical Centers↗

Pancreaticoduodenectomy in the very elderly.

It is estimated that by 2050, there will be a 300% increase in the elderly population (> or =65 years) and a corresponding increase in elderly patients presenting for surgical evaluation. Surgical decision-making in this population can be difficult because outcomes in the elderly are poorly defined. We reviewed 2698 consecutive pancreaticoduodenectomies (PDs) at our institution over a 35-year period (April 1970 through March 2005), with the last 1000 resections being done in the last 4 years. Data collected included surgical indication, mortality (defined as 30-day or in-hospital mortality), complications, and survival. Patients were divided by age into three groups (<80, 80-89, and > or =90 years) and evaluated using multiple logistic regression. Two hundred seven patients > or =80 years old underwent a PD (7.7% of 2698). Patients 80-89 years of age had a mortality rate of 4.1% (8 of 197) and a complication rate of 52.8% (99 of 197), whereas patients < or =79 years of age had a mortality of 1.7% and a complication rate of 41.6% (P < 0.05). There were no perioperative deaths among the 10 patients > or =90 years of age, and their complication rate was 50% (5 of 10). One-year survival for patients 80-89 years of age was 59.1%, and that for patients > or =90 years was 60%. Age was not an independent risk factor for perioperative mortality and morbidity following PD after adjusting for preoperative comorbidities. We demonstrate that PD can be safely performed in patients over 80 years of age and conclude that age alone should not be a contraindication to pancreatic resection. The advent of improved surgical outcomes and an aging population will likely result in a significant increase in the number of PDs performed in the next few decades.

Age Factors↗

Generation and characterization of monoclonal antibodies to human keratinocyte growth factor receptor.

Keratinocyte growth factor receptor (KGFR) and fibroblast growth factor receptor (FGFR) 2c share identical amino acid sequences, except for a 46-amino acid domain in the extracellular region. Monoclonal antibodies (MAbs) specific to KGFR have not been reported nor are commercially available. In this study, we generated murine MAbs specific to KGFR in non-obese diabetic (NOD) mice using a modified Repeated Immunizations at Multiple Sites (RIMMS) technology. Stable cell lines expressing the full-length human KGFR or FGFR2c were produced to facilitate the identification of KGFR-specific MAbs. Following the initial screening of hybridoma clones with a fluorescence-based, confocal cell detection method and ELISA, KGFR-specific MAbs were selected and confirmed by flow cytometry and Western blot analyses. Antagonistic MAbs were identified using a cell-based functional assay. These KGFR MAbs will be important reagents for studying the biological function and tissue distribution of this receptor in normal and pathological conditions.

Amino Acid Sequence↗

Periampullary and pancreatic incidentaloma: a single institution's experience with an increasingly common diagnosis.

BACKGROUND: While incidental masses in certain organs have received particular attention, periampullary and pancreatic incidentalomas (PIs) remain poorly characterized. METHODS: We reviewed 1944 consecutive pancreaticoduodenectomies (PD) over an 8-year period (April 1997 to October 2005). A total of 118 patients (6% of all PDs) presented with an incidental finding of a periampullary or pancreatic mass. The PI patients were analyzed and compared with the rest of the cohort (NI, nonincidentaloma group, n = 1826). RESULTS: Thirty-one percent of the PI patients (n = 37) had malignant disease (versus 76% of the NI patients, P < 0.001), 47% (n = 55) had premalignant disease, and the remaining 22% (n = 26) had little or no risk for malignant progression. The 3 most common diagnoses in the PI group were IPMN without invasive cancer (30%), cystadenoma (17%), and pancreatic ductal adenocarcinoma (10%). The PI group had a higher overall complication rate (55% versus 43%, P = 0.02), due in part to a significantly increased rate of pancreatic fistulas (18.4% PI versus 8.5% NI, P < 0.001). Patients in the PI group with malignant disease had a superior long-term survival (median, 30 months, P = 0.01) compared with patients in the NI group with malignant disease (median, 21 months). CONCLUSIONS: Incidentally discovered periampullary and pancreatic masses comprise a substantial proportion of patients undergoing PD. Roughly three fourths of these lesions are malignant or premalignant, and amenable to curative resection. Resected malignant PIs have favorable pathologic features as compared with resected malignant NIs, and resection of these early lesions in asymptomatic individuals is associated with improved survival, compared with patients with symptomatic disease.

Adolescent↗

Prognostic significance of histomorphologic parameters in diffuse malignant peritoneal mesothelioma.

CONTEXT: Diffuse malignant peritoneal mesothelioma is currently regarded as a rare and lethal primary tumor arising from the peritoneal membrane. In the past, treatment plans with variable combinations of surgery and systemic chemotherapy were associated with a median survival of approximately 1 year. Standardized treatments using cytoreductive surgery and perioperative intraperitoneal chemotherapy have extended this survival. OBJECTIVE: To critically analyze the prognostic significance of histomorphologic parameters as a determinant of survival. DESIGN: Sixty-two consecutive patients with diffuse malignant peritoneal mesothelioma in whom data were prospectively accumulated were retrospectively analyzed by 14 different histomorphologic parameters. The influences of these pathologic characteristics on survival were critically statistically evaluated. RESULTS: In a univariate analysis, histologic type, nuclear/nucleolar size, stroma, depth of invasion into the bowel, atypical mitoses, mitotic index, necrosis, lymph node involvement, and chromatin patterns were found to be significant. In the multivariate analysis, histologic type and nuclear/nucleolar size remained as determinant histomorphologic characteristics. Use of biphasic/sarcomatoid histologic type as a poor prognostic characteristic was limited in that only 8% of patients showed this histology. CONCLUSIONS: Histomorphologic parameters carry prognostic significance in predicting the survival of patients with diffuse malignant peritoneal mesothelioma when treated in a standardized fashion using cytoreductive surgery and perioperative intraperitoneal chemotherapy. Nuclear/nucleolar size was found to be a reliable histomorphologic assessment available to assess prognosis in these patients.

Cell Nucleolus↗

Triangular fibrocartilage complex tears: a review.

Triangular fibrocartilage complex (TFCC) tears are a common source of ulnar sided wrist pain. Originally described by Palmer, in 1981, as a complex of several structures, our understanding of the anatomy and the function of the TFCC has been refined by histologic studies. The TFCC plays an important role in load bearing across the wrist as well as in distal radioulnar joint (DRUJ) stabilization. A thorough knowledge of the anatomy as well as the Palmer classification system helps to guide treatment options.

Arthroscopy↗