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D S Chi

Publications and source records attributed to D S Chi.

At least 19 recordsLinked to original sources

What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)?

OBJECTIVE: Recent studies have suggested that the definition of optimal cytoreduction for advanced EOC should be changed from the current Gynecologic Oncology Group threshold of < or =1 cm residual disease to no gross residual disease owing to improved survival of patients (pts) rendered macroscopically disease-free. The objective of this study was to analyze survival rates at very specific residual disease diameters to determine the optimal goal of primary cytoreduction for bulky stage IIIC EOC. METHODS: A prospectively kept database was used to identify and review the records of all pts with Stage IIIC EOC who underwent primary cytoreductive surgery at our institution between January 1989 and December 2003. To analyze a homogeneous cohort of cases, we excluded pts with stage IIIC disease based on nodal metastasis alone (without bulky abdominal tumor), fallopian tube or primary peritoneal carcinomas, and borderline tumors. Standard statistical analyses were utilized. RESULTS: The study cohort included 465 pts. The median age was 60 years (range, 25-87), and the median follow-up was 38 months (range, 1-199). Univariate and multivariate analyses, which included various prognostic factors, identified amount of residual disease as a significant prognostic factor (P < 0.001). Median overall survival in relation to the 5 residual disease categories was: no gross residual, 106 months; gross < or =0.5 cm, 66 months; 0.6-1.0 cm, 48 months; 1-2 cm, 33 months; >2 cm, 34 months. Statistical comparison between the 5 residual disease categories revealed 3 distinct groups with significantly different survival rates (P < 0.01). These 3 groups were: (1) no gross residual; (2) gross < or =1 cm residual; and (3) >1 cm residual. Although the difference in survival did not reach statistical significance, within the gross < or =1 cm residual group, there was a trend toward improved survival in pts left with smaller volume, < or =0.5 cm residual compared with those with 0.6-1.0 cm residual (P = 0.06). CONCLUSION: Our data suggest that removal of all evidence of macroscopic disease is associated with prolonged survival and should be the goal of primary cytoreductive surgery. If complete gross resection is not feasible, however, cytoreduction to as minimal residual tumor as possible should be the focus of cytoreductive efforts, as each incremental decrease in residual disease below 1 cm may be associated with an incremental improvement in overall survival.

Adult↗

Moraxella catarrhalis induces mast cell activation and nuclear factor kappa B-dependent cytokine synthesis.

Human mast cells are often found perivascularly and at mucosal sites and may play crucial roles in the inflammatory response. Recent studies have suggested a prominent role for mast cells in host defense. In this study, we analyzed the effects of a common airway pathogen, Moraxella catarrhalis and a commensal bacterium, Neiserria cinerea, on activation of human mast cells. Human mast cell leukemia cells (HMC-1) were activated with either phorbol myristate acetate (PMA) and calcium ionophore or with varying concentrations of heat-killed suspensions of bacteria. Supernatants were assayed for the cytokines interleukin-4 (IL-4), granulocyte macrophage colony stimulating factor (GM-CSF), IL-6, IL-8, IL-13 and monocyte chemotactic protein-1 (MCP-1). Nuclear proteins were isolated and assayed by electrophoretic mobility shift assay (EMSA) for nuclear factor kappaB (NF-kappaB) nuclear binding activity. In some experiments, NF-kappaB inhibitor, Bay-11 was added to determine functional significance. Both M. catarrhalis and N. cinerea induced mast cell activation and selective secretion of two key inflammatory cytokines, IL-6 and MCP-1. This was accompanied by NF-kappaB activation. Neither spun bacterial supernatants nor bacterial lipopolysaccharide induced cytokine secretion, suggesting need for direct bacterial contact with mast cells. Scanning electron microscopy revealed active aggregation of bacteria over mast cell surfaces. The NF-kappaB inhibitor, Bay-11, inhibited expression of MCP-1. These findings suggest the possibility of direct interactions between human mast cells and common bacteria and provide evidence for a novel role for human mast cells in innate immunity.

Cell Line, Tumor↗

The human mast cell: functions in physiology and disease.

Mast cells are multifunctional, tissue-dwelling cells capable of secreting a wide variety of mediators. They develop from bone marrow-derived progenitor cells, primed with stem cell factor (SCF), which mediates its actions by interacting with the SCF receptor or c-kit on the cell surface. Mast cells continue their maturation and differentiation in peripheral tissue, developing into two well described subsets of cells, MCT and MCTC cells, varying in content of tryptase and chymase as well as in immunobiology. Mast cells are activated by numerous stimuli, including antigen (acting via the high affinity IgE receptor, Fc?RI), superoxides, complement proteins, neuropeptides and lipoproteins resulting in activation and degranulation. Following activation, these cells express mediators such as histamine, leukotrienes and prostanoids, as well as proteases, and many cytokines and chemokines, pivotal to the genesis of an inflammatory response. Recent data suggests that mast cells may play an active role in such diverse diseases as atherosclerosis, malignancy, asthma, pulmonary fibrosis and arthritis. Mast cells directly interact with bacteria and appear to play a vital role in host defense against pathogens. Drugs, such as glucocorticoids, cyclosporine and cromolyn have been demonstrated to have inhibitory effects on mast cell degranulation or mediator release.

Arteriosclerosis↗

The role of laparoscopy in second-look evaluations for ovarian cancer.

BACKGROUND: The aim of this study was to evaluate the accuracy and safety of laparoscopic second-look operations in patients with ovarian cancer. METHODS: We retrospectively reviewed the medical records of all patients who have undergone laparoscopic second-look procedures for ovarian cancer at our institution. RESULTS: From July 1993 to December 1998, 150 patients underwent laparoscopic second-look operations. The mean age of patients was 53 years (range, 25-78 years). The majority of patients (87%) had Stage III or IV disease at initial surgery; the remainder were Stage II or unstaged. Eighty-two patients (54%) had had optimal cytoreduction at the time of their initial surgery. All patients had completed primary chemotherapy and were clinically disease-free based on imaging studies and CA-125 levels at the time of second look. Sixty-nine patients (46%) were found to have pathologically negative second looks; thus, the rate of positive second-look evaluations was 54%. The rate of conversion to laparotomy was 18/150 (12%). In 3 cases this was secondary to bowel injury; one patient sustained a bladder injury; the remainder of conversions to laparotomy were for secondary cytoreduction. There was only 1 case where the patient was found to have extensive adhesions and laparoscopy was abandoned. The overall rate of major complications was 2.7%. CONCLUSIONS: In our experience, laparoscopy is a safe and accurate method of second-look assessment in patients with ovarian cancer. The incidence of complications is low, particularly in this group of patients, all of whom have undergone prior abdominal surgery. The rate of negative evaluations and the rate of recurrences in patients with negative second looks are equivalent to those described in studies of second-look assessment by laparotomy.

Adult↗

Identification of prognostic factors in advanced epithelial ovarian carcinoma.

OBJECTIVE: The Gynecologic Oncology Group (GOG) has demonstrated that age, tumor grade, and size and number of residual lesions after primary cytoreductive surgery are significant prognostic factors in advanced ovarian carcinoma. Recent studies have reported numerous other clinical features as having prognostic value. We sought to identify the independent prognostic factors for survival in a cohort of patients with advanced ovarian cancer. METHODS: We performed a retrospective chart review of all patients with stage III and IV ovarian carcinoma who received their primary treatment at our institution between 1987 and 1994. RESULTS: A total of 295 patients were identified, 282 of whom were evaluable. Of these 282 patients, 214 (76%) have died of disease or other causes. The median follow-up is 32 months (range: 1-139). Eighteen factors were evaluated for prognostic significance. Significant factors in univariate analysis included patient age, gravidity (0 vs > 0), parity (0 vs > 0), preoperative albumin level, preoperative total protein level, ascites (presence vs absence), disease stage (IIIA/IIIB vs IIIC vs IV), number of residual lesions (< or =20 vs >20), and diameter of largest residual tumor nodule (< or = 1 cm vs 1-2 cm vs > 2 cm). However, on multivariate analysis, only patient age (P < 0.001), ascites (P = 0.001), and size of residual disease (P = 0.005) retained prognostic significance. Substage of disease was of borderline significance (P = 0.086). CONCLUSION: Although numerous clinical variables have recently been reported to have prognostic value in advanced ovarian carcinoma, only patient age, presence or absence of ascites, and diameter of the largest residual tumor nodule proved to be of statistical significance in our analysis.

Adult↗

Surgical management of advanced or recurrent endometrial cancer.

Most patients who have endometrial cancer are diagnosed with early stage disease and have excellent long-term survival. For patients who have evidence of metastatic disease at surgery, there is a survival benefit to be gained if all gross evidence of disease can be resected. Even in cases in which complete gross excision cannot be attained, surgical debulking to small-volume residual disease leads to an improved prognosis compared with patients left with bulky residual disease. Patients with endometrial cancer who have not previously received pelvic irradiation and develop isolated pelvic recurrences can be effectively treated with pelvic radiotherapy. The treatment options for patients who develop recurrent disease are limited. Hormonal and chemotherapeutic treatments typically do not provide durable responses. In carefully selected patients with isolated central recurrences, pelvic exenteration is the only potential option for cure. Long-term survival has been achieved although complication rates are significant. Further investigation into the techniques of IORT may increase the pool of patients for whom surgically based salvage therapy may be offered.

Disease-Free Survival↗

The benefit of a special elective gynecologic oncology program for obstetrics and gynecology residents.

OBJECTIVE: To assess the benefit of a special elective gynecologic oncology program for Obstetrics and Gynecology (Ob/Gyn) residents. METHODS: We reviewed our housestaff records from July 1992 to June 1998 and the National Residency Matching Program (NRMP) subspeciality match results for gynecologic oncology from its inception in 1994 to 1999. RESULTS: From July 1992 to June 1998, a total of 146 residents participated in our elective program. Of the 104 candidates who went through our program and subsequently participated in the NRMP, 55 (53%) obtained match positions. After completion of the elective, 42 of the 146 residents (29%) did not participate in the NRMP for gynecologic oncology and therefore were not eligible to obtain match appointments. During the study period, there were 255 other residents in the United States who applied for gynecologic oncology fellowship positions through the NRMP and did not participate in our program. Of these 255 candidates, 137 (54%) matched. CONCLUSION: The percentage of residents who went through our program, participated in the NRMP, and obtained fellowships did not differ significantly from the percentage of residents who matched without participating in the program. However, almost one-third of the residents who went through our program did not participate in the NRMP. The reasons for their lack of participation were not formally evaluated, but are likely related to a personal decision to pursue another carrer pathway, a decision facilitiated by their experience in our program. Therefore, it appears that the main benefits of the program are to help potential candidates decide whether or not to pursue a career in gyencologic oncology and to aid fellowship programs in identifying exceptional candidates for subspecialty training.

Fellowships and Scholarships↗

Clinicopathologic features of BRCA-linked and sporadic ovarian cancer.

CONTEXT: Most hereditary ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. Attempts to define the clinical significance of BRCA mutation status in ovarian cancer have produced conflicting results, especially regarding survival. OBJECTIVE: To determine whether hereditary ovarian cancers have distinct clinical and pathological features compared with sporadic (nonhereditary) ovarian cancers. DESIGN AND SETTING: Retrospective cohort study of a consecutive series of 933 ovarian cancers diagnosed and treated at our institution, which is a comprehensive cancer center as designated by the National Cancer Institute, over a 12-year period (December 1986 to August 1998). PATIENTS: The study was restricted to patients of Jewish origin because of the ease of BRCA1 and BRCA2 genotyping in this ethnic group. From the 189 patients who identified themselves as Jewish, 88 hereditary cases were identified with the presence of a germline founder mutation in BRCA1 or BRCA2. The remaining 101 cases from the same series not associated with a BRCA mutation and 2 additional groups (Gynecologic Oncology Group protocols 52 and 111) with ovarian cancer from clinical trials (for the survival analysis) were included for comparison. MAIN OUTCOME MEASURES: Age at diagnosis, surgical stage, histologic cell type and grade, and surgical outcome; and response to chemotherapy and survival for advanced-stage (II and IV) cases. RESULTS: Hereditary cancers were rarely diagnosed before age 40 years and were common after age 60 years, with mean age at diagnosis being significantly younger for BRCA1- vs BRCA2-linked patients (54 vs 62 years; P=.04). Histology, grade, stage, and success of cytoreductive surgery were similar for hereditary and sporadic cases. The hereditary group had a longer disease-free interval following primary chemotherapy in comparison with the nonhereditary group, with a median time to recurrence of 14 months and 7 months, respectively (P<.001). Those with hereditary cancers had improved survival compared with the nonhereditary group (P=.004). For stage III cancers, BRCA mutation status was an independent prognostic variable (P=.03). CONCLUSIONS: Although BRCA-associated hereditary ovarian cancers in this population have surgical and pathological characteristics similar to those of sporadic cancers, advanced-stage hereditary cancer patients survive longer than nonhereditary cancer patients. Age penetrance is greater for BRCA1-linked than for BRCA2-linked cancers in this population.

Adult↗

The ability of preoperative serum CA-125 to predict optimal primary tumor cytoreduction in stage III epithelial ovarian carcinoma.

PURPOSE: The aim of this study was to determine the ability of preoperative serum CA-125 to predict optimal primary tumor cytoreduction in patients with Stage III epithelial ovarian carcinoma. METHODS: We performed a retrospective chart review of 100 consecutive patients with Stage III ovarian carcinoma who had a serum CA-125 drawn prior to primary cytoreductive surgery. We used a receiver operating characteristic curve to determine the CA-125 level with the maximal prognostic power in predicting optimal versus suboptimal cytoreduction. RESULTS: The median CA-125 level for the 100 patients was 819 U/ml (range 5.6-26,200 U/ml). Optimal cytoreduction (diameter of largest residual tumor nodule < or =1 cm) was obtained in 45 cases (45%). The probability of performing optimal cytoreduction decreased with increasing CA-125 levels. A preoperative CA-125 level of 500 U/ml was identified as the value with the most predictive power. Optimal cytoreduction was achieved in 33 of the 45 cases (73%) with a CA-125 less than 500 U/ml compared to only 12 of the 55 cases (22%) with a CA-125 greater than 500 U/ml. Using a threshold level of 500 U/ml, the preoperative serum CA-125 level was able to predict optimal versus suboptimal cytoreduction with a sensitivity of 78%, specificity of 73%, positive predictive value of 78%, and negative predictive value of 73%. CONCLUSION: The probability of performing optimal cytoreduction in patients with Stage III ovarian carcinoma and a preoperative CA-125 greater than 500 U/ml was approximately one in five. These patients may be candidates for initial laparoscopic evaluation to obtain a confirmatory tissue diagnosis and to determine resectability.

Adult↗

Advanced ovarian cancer.

State-of-the-art treatment for advanced ovarian cancer requires a multimodality approach. Aggressive surgical debulking with the goal of optimal cytoreduction is the initial step. After primary cytoreductive surgery, standard treatment for patients with stage III and IV disease is systemic combination chemotherapy consisting of six cycles of paclitaxel and carboplatin. Approximately 70% of patients enter a clinical remission with this approach, yet less than 30% remain disease free. Options following primary therapy include observation or second surgical assessment if no clinical evidence of disease is present. Novel strategies for consolidation are needed. Second-look surgery can be performed safely and effectively laparoscopically, and this is the most accurate means of identifying patients who appear to be clinically free of disease but actually harbor persistent cancer. Although this procedure is an extremely accurate means of identifying these patients, women who have pathologically negative second-look surgery are still at risk for relapse. Patients can receive additional treatment following second-look surgical assessment via the intraperitoneal route if they are pathologically negative or if they have microscopic or small volume disease. Alternatively, additional systemic chemotherapy can be given with non-cross-resistant systemic agents, but no current standard approach for consolidation therapy exists for patients following the completion of primary treatment. Unfortunately, most patients relapse. Multiple agents with similar activity in phase II trials are available to treat patients with advanced recurrent disease. Combination therapy in this setting has not been shown to have significantly superior progression-free or overall survival compared with single agents. The selection of treatment for patients with recurrent disease is currently based on a determination of the treatment-free interval since last treatment, as well as the route, schedule, and expected side effects of the agent.

Antineoplastic Combined Chemotherapy Protocols↗

The molecular role of mast cells in atherosclerotic cardiovascular disease.

Human atherosclerosis has many characteristics of an inflammatory disorder. Recent data suggest that mast cells might be important in the pathogenesis of atherosclerotic disease. By secretion of pro-inflammatory cytokines, mast cells can assist in the recruitment of monocytes and lymphocytes into vascular tissue, thereby propagating the inflammatory response. Mast cell enzymes might activate pro-metalloproteinases, thereby destabilizing atheromatous plaques. Mast cells can facilitate foam cell formation by promoting cholesterol accumulation. However, mast cell tryptase could slow thrombus formation at sites of plaque rupture by interfering with coagulation. Therefore, mast cells can modulate coronary artery disease by both facilitatory and inhibitory pathways.

Arteriosclerosis↗

Vulnerable plaque.

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Arteriosclerosis↗

Splenectomy in recurrent epithelial ovarian cancer.

OBJECTIVE: To report a series of patients with recurrent epithelial ovarian cancer who underwent splenectomy for isolated parenchymal metastases. METHODS: We performed a retrospective review of all patients who had a splenectomy for ovarian cancer at our institution during the period 1991 to 1997. RESULTS: Six patients were identified who had a splenectomy performed for recurrent epithelial ovarian cancer confined to the splenic parenchyma. All had initial cytoreductive surgery for Stage III disease followed by platinum-based chemotherapy. Five patients underwent second-look surgery and four of them had pathologically confirmed persistent disease. All five patients who underwent second-look surgery had an intraperitoneal (ip) port placed and received platinum-based ip chemotherapy. Computed tomography (CT) scan performed during the posttreatment surveillance period demonstrated recurrent disease confined to the spleen in all six patients. Splenectomy was performed at a median of 57 months (range 28-88 months) after the initial surgery. The only major complication was a diaphragmatic tear necessitating chest tube placement. With a median follow-up of 25.5 months (range 6-65 months), all six patients are alive and free of disease. CONCLUSION: Splenectomy is a safe and feasible procedure in recurrent epithelial ovarian cancer. Isolated parenchymal splenic metastasis may occur as a late recurrence in epithelial ovarian cancer and splenectomy should be considered a part of the management of this group of patients.

Chemotherapy, Adjuvant↗

The accuracy of frozen-section diagnosis in metastatic breast and colorectal carcinoma to the adnexa.

OBJECTIVE: The objective of our study was to describe the accuracy of intraoperative frozen-section diagnosis of carcinoma metastatic to the adnexa in women with a history of breast or colorectal carcinoma. METHODS: We conducted a retrospective chart review of all patients with a history of breast or colorectal carcinoma who developed histologically proven pelvic or abdominal metastases between 1988 and 1995. In those patients whose final histologic review revealed carcinoma metastatic to the adnexa, the accuracy of the intraoperative frozen-section diagnosis of the adnexal tumor was compared to the final diagnosis. RESULTS: Forty-three patients were identified and in 36 patients the frozen section was obtained from the adnexa. Twenty-one patients (58.3%) had metastatic breast carcinoma and 15 (41.7%) had metastatic colorectal carcinoma to the adnexa. Carcinoma in the adnexa was correctly diagnosed by frozen section in 35 of 36 patients (97.2%). Metastatic carcinoma was identified at frozen section in 17 of 21 patients (81%) with metastatic breast cancer and 13 of 15 patients (86.7%) with metastatic colorectal cancer. In 3 of 21 patients (14.3%) with metastatic breast cancer and in 2 of 15 patients (13.3%) with metastatic colorectal cancer, the frozen-section diagnosis was carcinoma of uncertain origin. One patient had a false-negative frozen section because the small focus of metastatic breast cancer was not sampled at the time of frozen section. CONCLUSION: Intraoperative frozen-section evaluation correctly diagnosed carcinoma in the adnexa in 97% of patients, and in over 80% of cases, the carcinoma was diagnosed as being metastatic in origin.

Adnexa Uteri↗

Ten-year follow-up of ovarian cancer patients after second-look laparotomy with negative findings.

OBJECTIVE: To determine long-term survival and predictors of recurrence in patients with platinum-treated ovarian cancer who were followed for 10 years after second-look laparotomy with negative findings. METHODS: Records were reviewed of 91 consecutive patients with negative findings on second-look laparotomy after platinum-based chemotherapy between January 1978 and January 1987. Statistical analysis used Kaplan-Meier survival curves, Cox proportional hazards, and multiple logistic regression. RESULTS: Mean age of patients was 57 (range 30-79) years. Distribution by stage and grade was as follows: stage I, ten; II, 18; III, 57; IV, six; grade 1, 18; 2, 28; 3, 45. Forty-seven of 91 women had optimal initial cytoreduction. Recurrence-free survival rates for all subjects were 75% at 2 years, 55% at 5 years, and 52% at 10 years. For women with stage I disease, the recurrence-free survival rate was 90% at 2, 5, and 10 years. For women with stage II disease, recurrence-free survival rates were 78, 72, and 66% at 2, 5, and 10 years, respectively. Patients with stage III or IV disease had recurrence-free survival rates of 72, 44, and 40% at 2, 5, and 10 years, respectively. Risk of recurrent disease was related to tumor stage (relative risk [RR] 2.02; 95% confidence interval [CI] 1.2, 3.3; P = .005), grade (RR 2.00; 95% CI 1.3, 3.2; P = .004), and presence of a residual tumor of more than 2 cm at the end of initial surgery (RR 3.19; 95% CI 1.2, 8.5; P = .02). CONCLUSION: Ovarian cancer patients face an appreciable risk of recurrence in the first 5 years after second-look laparotomy with negative findings after platinum-based chemotherapy, but those who remain disease free at 5 years have excellent long-term survival rates. Tumor stage, grade, and presence of a residual tumor of more than 2 cm after initial surgery are significant predictors of recurrence.

Adult↗

Gynecologic cancer and laparoscopy.

Numerous technologic and surgical advances have led to the application of operative laparoscopic techniques to gynecologic cancers. Operative laparoscopy has been described in the surgical staging and treatment of patients with ovarian, cervical, and endometrial cancers. it seems to be a very promising approach with the potential to revolutionize numerous aspects of the management of gynecologic malignancies. Since 1996, the SGO has offered an operative laparoscopy course to all gynecologic oncology fellowship programs. Boike and colleagues report that faculty and fellows from 25 different fellowship programs have attended the 2-day course. In questionnaires filled out at the completion of the course, more than 85% of respondents believed that operative laparoscopic procedures were equivalent to open techniques and should be taught in fellowship programs. Despite the enthusiasm for the use of endoscopy in patients with gynecologic malignancies, its potential is unconfirmed and its hazards unknown. Reports regarding complications and long-term results are just now beginning to be published. More clinical data must be collected before the minimally invasive techniques can be accepted as new surgical standards. Ongoing prospective clinical trials will help to answer many of the questions regarding safety and efficacy. Pending the completion of additional trials, operative laparoscopy will remain a promising but unproven tool in the management of patients with gynecologic cancer.

Clinical Trials as Topic↗

Evaluation of two string tests for obtaining gastric juice for culture, nested-PCR detection, and combined single- and double-stranded conformational polymorphism discrimination of Helicobacter pylori.

We have compared two gastric string tests for obtaining gastric juice for culture of Helicobacter pylori and for nested-PCR detection and PCR-based combined single- and double-stranded conformational polymorphism (SDSCP) discrimination of infecting strains. String test specimens were obtained from one seropositive volunteer for 13 consecutive weeks. The distal 10 cm of each string was suspended in 1 ml saline and quantitatively cultured. An additional nine volunteers with histories of upper-gastrointestinal complaints were given a string test for culture and nested-PCR assay. H. pylori isolates and/or gastric juice from each volunteer were extracted for DNA and analyzed by PCR-based SDSCP. Quantitative culture showed that the Entero-test was four times as sensitive as the Gastro-test but was more prone to contamination by oral flora. However, the two string tests are equally sensitive by PCR assays. Thus, the Gastro-test is more suitable for culture detection of H. pylori, since it is less prone to oral contamination and its shorter length is better tolerated. SDSCP analysis of H. pylori DNA from four PCR-positive volunteers without requiring culture showed four distinct profiles, indicating different infecting strains. SDSCP analysis of strains isolated before and after treatment of one volunteer had the same SDSCP profile, suggesting endogenous reinfection by the same strain.

Female↗