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D S Chi

Publications and source records attributed to D S Chi.

At least 19 recordsLinked to original sources

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↗

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↗

Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease.

Endothelial cells, by virtue of their capacity to express adhesion molecules and cytokines, are intricately involved in inflammatory processes. Endothelial cells have been shown to express interleukin-1 (IL-1), IL-5, IL-6, IL-8, IL-11, IL-15, several colony-stimulating factors (CSF), granulocyte-CSF (G-CSF), macrophage CSF (M-CSF) and granulocyte-macrophage CSF (GM-CSF), and the chemokines, monocyte chemotactic protein-1 (MCP-1), RANTES, and growth-related oncogene protein-alpha (GRO-alpha). IL-1 and tumor necrosis factor-alpha (TNF-alpha) produced by infiltrating inflammatory cells can induce endothelial cells to express several of these cytokines as well as adhesion molecules. Induction of these cytokines in endothelial cells has been demonstrated by such diverse processes as hypoxia and bacterial infection. Recent studies have demonstrated that adhesive interactions between endothelial cells and recruited inflammatory cells can also signal the secretion of inflammatory cytokines. This cross-talk between inflammatory cells and the endothelium may be critical to the development of chronic inflammatory states. Endothelial-derived cytokines may be involved in hematopoiesis, cellular chemotaxis and recruitment, bone resorption, coagulation, and the acute-phase protein synthesis. As many of these processes are critical to the maturation of an inflammatory and reparative state, it appears likely that endothelial-derived cytokines play a crucial role in several diseases, including atherosclerosis, graft rejection, asthma, vasculitis, and sepsis. Genetic and pharmacologic manipulation of endothelial-derived cytokines provides an additional approach to the management of chronic inflammatory diseases.

Arteriosclerosis↗

Laparoscopy in gynecologic malignancies.

One of the cornerstones of gynecologic cancer surgery is the assessment and removal of the retroperitoneal lymph nodes. Numerous reports have demonstrated that, when performed by highly skilled individuals, laparoscopic lymphadenectomies can be performed safely. This has led to the investigation of laparoscopy in the surgical staging and treatment of patients with ovarian, cervical, and endometrial cancers. This very promising approach has the potential to revolutionize numerous aspects of the management of gynecologic malignancies. However, it must be emphasized that the use of laparoscopy for gynecologic malignancies is still in its infancy. Studies that provide complication rates and long-term results are just beginning to be reported. More clinical data are necessary before the laparoscopic techniques are accepted as new surgical standards. Ongoing, prospective clinical trials will help answer many of the questions regarding the safety and efficacy of gynecologic laparoscopy. Until more data accumulate, operative laparoscopy will remain a promising, but unproven, tool in the management of patients with gynecologic malignancies.

Endometrial Neoplasms↗

Primary intravenous paclitaxel and platinum chemotherapy for high-risk Stage I epithelial ovarian carcinoma.

OBJECTIVE: To evaluate the efficacy of intravenous (i.v.) paclitaxel and platinum chemotherapy in patients with high-risk Stage I epithelial ovarian carcinoma. METHODS: We performed a retrospective chart review of all patients with Stage I ovarian cancer treated at our institution between March 1993 and June 1995. RESULTS: Twenty patients received adjuvant paclitaxel-containing chemotherapy for Stage I ovarian carcinoma after comprehensive surgical staging. Five patients (25%) had Stage IA disease and 15 patients (75%) had Stage IC disease. Tumor grades were: 1, five patients (25%); 2, nine patients (45%); and 3, six patients (30%). Histologic cell types were: clear-cell, ten (50%); endometrioid, five (25%); mucinous, three (15%); and serous, two (10%). Nineteen patients (95%) were treated with i.v. paclitaxel and platinum chemotherapy. One patient (5%) received i.v. paclitaxel alone. Eighteen patients (90%) had five cycles of chemotherapy, while two patients (10%) had three. The 96 total cycles were associated with nine episodes (9%) of significant toxicity: fever, four (4%); severe nausea and vomiting, two (2%); Clostridium difficile enteritis, one (1%); congestive heart failure, one (1%); and anemia, requiring blood transfusion, one (1%). With a median follow-up of 36 months (range 24-50 mos), all 20 patients are alive, and 19 (95%) are disease-free. The one patient (5%) treated with i.v.++paclitaxel alone developed an abdominal recurrence 22 months after diagnosis. CONCLUSION: Primary i.v.++paclitaxel and platinum chemotherapy in patients with high-risk Stage I epithelial ovarian carcinoma is reasonably well tolerated and may improve survival. Larger studies with long-term follow-up are needed.

Adenocarcinoma↗

Multifunctional cytokine expression by human coronary endothelium and regulation by monokines and glucocorticoids.

Human endothelium is capable of expressing a variety of molecules, including cytokines and growth factors, critical to inflammation. This aspect of coronary endothelium has not been studied in detail. In this study, we report, for the first time, expression of multifunctional cytokines by human coronary artery endothelial cells (HCAEC) and their regulation by inflammatory cytokines and glucocorticoids. We also compared expression of cytokine transcripts in two additional cell lines derived from pulmonary artery (HPAEC) and umbilical vein (HUVEC) endothelium. HCAEC expressed transcripts for interleukin 5 (IL-5), IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) constitutively. Induction of IL-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and MCP-1 was seen following treatment with TNFalpha. We found no expression of IL-1RA, IL-2, IL-4, IL-13, TNF-alpha, or IFN-gamma in HCAEC. IL-1beta and TNF-alpha synergistically induced IL-6 and GM-CSF and additively induced IL-8 and MCP-1 production, while IL-2, IL-10, IFN-alpha, and IFN-gamma had little or no additional effects. Interestingly, no IL-1alpha or IL-5 protein product was found even after maximal stimulation of HCAEC. No significant differences were seen in the profile of cytokine genes expressed by HCAEC, HPAEC, or HUVEC. Glucocorticoids inhibited IL-8 production from all three cell lines. This study demonstrates that human coronary endothelial cells are capable of expressing a wide variety of multifunctional cytokines which may be of relevance to vascular inflammation.

Cell Line↗

Identification of H. pylori in saliva by a nested PCR assay derived from a newly cloned DNA probe.

A novel probe was developed from genomic DNA of Helicobacter pylori ATCC type strain 43629. It hybridized with all 73 H. pylori clinical isolates tested but not with any of 183 non-H. pylori DNAs in dot blot hybridization. Typing tests revealed 41 different HaeIII-digestion patterns from 57 H. pylori strains tested. Based on the sequence of the probe, a nested PCR was developed that detected as little as 2 fg of H. pylori DNA or approximately equivalent to one cell. No PCR products were amplified from any of 21 non-H. pylori strains tested. Using this nested PCR, H. pylori DNA was detected in 33 of 45 (73%) saliva samples collected from patients with gastric H. pylori infection. These data suggest that the probe is useful for typing H. pylori and that the nested PCR is a valuable tool for detecting H. pylori DNA in saliva.

DNA Fingerprinting↗

The role of surgery in the management of ovarian cancer: primary and interval cytoreductive surgery.

Ovarian cancer remains the number one cause of mortality in gynecologic malignancies and the fifth most common cause of death among all malignancies in women. Unfortunately, recent data confirm that only approximately 90% of "apparent" early ovarian cancer are inadequately staged, and only approximately 80% of patients with advanced-stage disease are adequately staged. Interval debulking surgery, a newer treatment modality, appears to have a promising role for patients who cannot be adequately debulked at their initial surgery. Second-look laparotomy continues to be the most accurate way to document responses to chemotherapy in protocol settings, but additional clinical trials with newer second-line chemotherapy will be necessary before definitive statements can be made with regard to survival advantages in patients who undergo second-look laparotomy.

Clinical Trials as Topic↗

The role of whole-pelvic irradiation in the treatment of early-stage uterine carcinosarcoma.

Thirty-eight patients with Stage I and II uterine carcinosarcoma were treated by surgery with and without whole-pelvic irradiation (WPI) at our institution from 1975 to 1993. Ten patients (8 Stage I and 2 Stage II) were treated with surgery alone, while 28 patients (20 Stage I and 8 Stage II) received WPI in addition to surgery. With a median follow-up of 75 months (range 25-220 months), a trend toward a decreased rate of pelvic recurrence in those receiving WPI (6/28, 21%) compared to those treated with surgery alone (5/10, 50%) was observed (P = 0.09). There was no difference in the rate of distant recurrence between those receiving WPI (12/28, 43%) and those who did not (4/10, 40%) (P = 0.9). There was also no difference in the 2- and 5-year Kaplan-Meier survival estimates for the patients receiving WPI (79 and 59%, respectively) compared to those who did not receive WPI (60 and 60%, respectively) (P = 0.84). In this small series, the addition of whole-pelvic irradiation to primary surgery did not improve survival; however, a trend toward improved pelvic control was observed, suggesting a possible benefit for pelvic irradiation that should be studied in future trials.

Aged↗

Hepatic resection for metastatic gynecologic carcinomas.

OBJECTIVE: To report a series of cases of hepatic resection for metastatic gynecologic carcinomas. METHODS: We reviewed the records of all patients who underwent hepatic resection for metachronous liver metastases from gynecologic carcinomas at our institution from 1986 to 1996. RESULTS: Twelve patients were identified with a median age of 60 years (range 30-73 years). The primary sites of carcinoma were as follows: ovary, 7 (58%); cervix, 2 (17%); endometrium, 2 (17%); and fallopian tube, 1 (8%). The median disease-free interval before the diagnosis of liver metastasis was 32 months (range 1-243 months). The types of liver resections were as follows: trisegmentectomy, 4 (33%); lobectomy, 4 (33%); segmentectomy, 3 (25%); and wedge resection, 1 (8%). To remove all visible tumor with adequate margins, additional surgery included the following: resection of a portion of the diaphragm, 5 (42%); wedge resection of the right lung, 3 (25%); resection of a portion of the pericardium, 2 (17%); and adrenalectomy, 1 (8%). One patient (8%) had pulmonary wedge resections of bilateral pulmonary metastases. There was no perioperative mortality. Ten patients (83%) received additional chemotherapy. With a median follow-up of 25 months (range 8-94 months), the median survival time is 27 months. Three patients (25%) have no evidence of tumor recurrence at 8, 17, and 38 months of follow-up. Nine patients (75%) have had tumor recurrence at a median of 12 months from the time of surgery. CONCLUSIONS: Hepatic resection of metachronous metastases from gynecologic carcinomas can be performed safely and may help prolong survival in carefully selected patients.

Adult↗