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1.
Cureus ; 16(2): e53526, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38314387

ABSTRACT

Congenital pulmonary airway malformations (CPAM) compose the major part of congenital lung malformations (CLM) and have traditionally been treated by pulmonary lobectomy. In terms of surgical strategy, lobectomy has conventionally been the preferred treatment for CPAM localized to a single lobe. More recently, alternative approaches including lung-sparing resections (LSR), such as wedge or non-anatomic resections and segmentectomy, have been suggested. In asymptomatic CPAM early surgical resection is often shown to reduce infection and malignancy development. We describe two patients who were diagnosed with CPAM when being evaluated for respiratory tract infection. Patient 1 (P1) was a two-month-old infant weighing 4 kg with glucose-6-phosphate dehydrogenase (G6PD) deficiency and Patient 2 (P2) was a toddler aged one year, nine months weighing 9 kg. P1 underwent LSR for the CPAM diagnosed in the left upper lobe of the lung with conventional mechanical ventilation whilst right upper lobectomy was performed in P2 using one/single lung ventilation. In both cases, LSR and right upper lobectomy led to an uneventful postoperative recovery with no complications reported.

4.
Gynecol Oncol ; 165(1): 82-89, 2022 04.
Article in English | MEDLINE | ID: mdl-35216808

ABSTRACT

OBJECTIVE: To determine the clinical characteristics of patients who attained pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) and to identify specific predictive or prognostic factors associated with pCR. METHODS: Two distinct populations of patients who underwent NACT followed by interval tumor reductive surgery (TRS) were used in this retrospective study. The first contained 472 patients from a single institution. The second contained only pCR patients (67); those identified from population one, plus 44 obtained through collaborative institutions. Cox analysis and log-rank tests were performed to assess associations between clinical characteristics and pCR outcome, recurrence-free survival (RFS), and overall survival (OS). RESULTS: The median RFS and OS in our pCR-only population was 24.2 and 80.8 months, respectively, with a median follow-up time of 32.4 months. In our single institution population, 23 patients attained pCR (4.9%) and had longer RFS compared to non-pCR patients with viable microscopic, optimal, or suboptimal residual disease (24.3 vs. 12.1 vs. 11.6 vs. 9.6 months, p = 0.025, 0.012, 0.008, respectively), and longer OS compared to those with optimal or suboptimal residual disease (54.5 vs. 29.4 vs. 25.7 months, p = 0.027, 0.007, respectively). Patients were more than three-fold likely to attain pCR if their CA125 value was normal at the time of surgery (OR 3.54, 95% CI: 1.14-11.05, p = 0.029). CONCLUSIONS: Women with pCR after NACT have significantly longer RFS compared to those with residual viable tumor at the time of interval tumor-reductive surgery, and CA125 is plausible biomarker for identifying these extreme responders preoperatively.


Subject(s)
Neoadjuvant Therapy , Ovarian Neoplasms , Carcinoma, Ovarian Epithelial/drug therapy , Chemotherapy, Adjuvant , Female , Humans , Neoplasm Staging , Neoplasm, Residual/pathology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Retrospective Studies
5.
Cell Rep ; 38(4): 110301, 2022 01 25.
Article in English | MEDLINE | ID: mdl-35081345

ABSTRACT

Anti-angiogenic therapies, such as anti-VEGF antibodies (AVAs), have shown promise in clinical settings. However, adaptive resistance to such therapies occurs frequently. We use orthotopic ovarian cancer models with AVA-adaptive resistance to investigate the underlying mechanisms. Genomic profiling of AVA-resistant tumors guides us to endothelial p130cas. We find that bevacizumab induces cleavage of VEGFR2 in endothelial cells by caspase-10 and that VEGFR2 fragments internalize into the nucleus and autophagosomes. Nuclear VEGFR2 and p130cas fragments, together with TNKS1BP1 (tankyrase-1-binding protein), initiate endothelial cell death. Blockade of autophagy in AVA-resistant endothelial cells retains VEGFR2 at the membrane with bevacizumab treatment. Targeting host p130cas with RGD (Arg-Gly-Asp)-tagged nanoparticles or genomic ablation of vascular p130cas in p130casflox/floxTie2Cre mice significantly extends the survival of mice with AVA-resistant ovarian tumors. Higher vascular p130cas is associated with shorter survival of individuals with ovarian cancer. Our findings identify opportunities for new strategies to overcome adaptive resistance to AVA therapy.


Subject(s)
Crk-Associated Substrate Protein/metabolism , Drug Resistance, Neoplasm/physiology , Endothelial Cells/metabolism , Ovarian Neoplasms/pathology , Angiogenesis Inhibitors/pharmacokinetics , Animals , Bevacizumab/pharmacology , Female , Humans , Mice , Ovarian Neoplasms/metabolism , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor Receptor-2/metabolism
9.
Am J Obstet Gynecol ; 224(2): 191.e1-191.e15, 2021 02.
Article in English | MEDLINE | ID: mdl-32805208

ABSTRACT

BACKGROUND: The incidence of complex atypical hyperplasia and early-stage endometrioid endometrial cancer is increasing, in part owing to the epidemic of obesity, which is a risk factor tightly linked to the development of endometrial hyperplasia and cancer. The standard upfront treatment for complex atypical hyperplasia and early-stage endometrial cancer is hysterectomy. However, nonsurgical treatment of early-stage endometrial neoplasia may be necessary owing to medical comorbidities precluding surgery or desired future fertility. OBJECTIVE: This study aimed to evaluate the efficacy of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and grade 1 endometrioid endometrial carcinoma. STUDY DESIGN: A single-institution, single-arm, phase II study of the levonorgestrel intrauterine device (52 mg levonorgestrel, Mirena) was conducted in patients with complex atypical hyperplasia or grade 1 endometrioid endometrial cancer. The primary endpoint was pathologic response rate at 12 months, including complete or partial response. Quality of life and toxicity were assessed. Molecular analyses for proliferation markers, hormone-regulated genes, and wingless-related integration site pathway activation were performed at baseline and 3 months. RESULTS: A total of 57 patients were treated (21 endometrial cancer, 36 complex atypical hyperplasia). The median age was 48.0 years, and the median body mass index was 45.5 kg/m2. Of the 47 evaluable patients, 12-month response rate was 83% (90% credible interval, 72.7-90.3)-37 were complete responders (8 endometrial cancer; 29 complex atypical hyperplasia), 2 were partial responders (2 endometrial cancer), 3 had stable disease (2 endometrial cancer; 1 complex atypical hyperplasia), and 5 had progressive disease (3 endometrial cancer; 2 complex atypical hyperplasia). After stratification for histology, the response rate was 90.6% for complex atypical hyperplasia and 66.7% for grade 1 endometrioid endometrial cancer. Notably, 4 patients (9.5%) experienced relapse after the initial response. Adverse events were mild, primarily irregular bleeding and cramping. Quality of life was not negatively affected. At 3 months, exogenous progesterone effect was present in 96.9% of responders (31 of 32) vs 25% of nonresponders (2 of 8) (P=.001). Nonresponders had higher baseline proliferation (Ki67) and lower dickkopf homolog 3 gene expression than responders (P=.023 and P=.030). Nonresponders had significantly different changes in secreted frizzled-related protein 1, frizzled class receptor 8, and retinaldehyde dehydrogenase 2 compared with responders. CONCLUSION: The levonorgestrel intrauterine device has a substantial activity in complex atypical hyperplasia and grade 1 endometrioid endometrial cancer, with a modest proportion demonstrating upfront progesterone resistance. Potential biomarkers were identified that may correlate with resistance to therapy; further exploration is warranted.


Subject(s)
Carcinoma, Endometrioid/drug therapy , Contraceptive Agents, Hormonal/administration & dosage , Endometrial Hyperplasia/drug therapy , Endometrial Neoplasms/drug therapy , Intrauterine Devices, Medicated , Levonorgestrel/administration & dosage , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adult , Aged , Aged, 80 and over , Aldehyde Dehydrogenase 1 Family/genetics , Aldehyde Dehydrogenase 1 Family/metabolism , Biomarkers/metabolism , Biomarkers, Tumor/metabolism , Body Mass Index , Carcinoma, Endometrioid/metabolism , Carcinoma, Endometrioid/pathology , Endometrial Hyperplasia/metabolism , Endometrial Hyperplasia/pathology , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Female , Gene Expression , Humans , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Ki-67 Antigen/genetics , Ki-67 Antigen/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Middle Aged , Neoplasm Grading , Neoplasm Staging , Quality of Life , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , Retinal Dehydrogenase/genetics , Retinal Dehydrogenase/metabolism , Treatment Outcome , Wnt Signaling Pathway/genetics , Young Adult
10.
Gynecol Oncol ; 158(3): 653-658, 2020 09.
Article in English | MEDLINE | ID: mdl-32709538

ABSTRACT

OBJECTIVE: Low-grade serous carcinoma of the ovary/peritoneum (LGSC) is relatively chemoresistant in the adjuvant, neoadjuvant, and recurrent settings. We sought to expand our prior work and evaluate response rates of women with LGSC to neoadjuvant chemotherapy (NACT) compared to women with high-grade serous carcinoma of the ovary/peritoneum (HGSC). METHODS: Thirty-six patients with LGSC who received NACT were matched to patients with HGSC. A single radiologist re-reviewed pre- and post-NACT imaging for response using RECIST 1.1. Pre- and post-NACT CA-125 values were compared using paired t-tests. Kaplan-Meier estimates of progression free survival (PFS) and overall survival (OS) were performed. RESULTS: All patients received neoadjuvant platinum-based regimens. LGSC patients received a median of 5 cycles (range 3-9), HGSC patients received a median of 4 cycles (range 3-9). Interval cytoreductive surgery was performed in 29/36 (81%) of LGSC and 32/36 (89%) HGSC patients. Complete cytoreduction was reported and achieved in 11/29 (38%) of LGSC patients and 24/32 (75%) of HGSC patients (p = 0.002). Median pre- and post-treatment CA-125 levels for LGSC patients were 295.5 U/mL and 144 U/mL (52% decrease) (p < 0.001). The median pre- and post-treatment CA-125 levels for HGSC patients were 767.5 and 35.6 (96% decrease) (p < 0.001). For LGSC patients, 4/36 (11%) had partial response (PR), 30/36 (83%) had stable disease (SD), and 2/36 (6%) had progressive disease (PD). In HGSC patients, 27/36 (75%) had PR, and 9/36 (25%) SD. Median PFS for LGSC patients was 18.5 months and median OS was 47.4 months. CONCLUSIONS: This study provides further evidence of relative chemoresistance of LGSC in patients treated with NACT.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cystadenocarcinoma, Serous/drug therapy , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Bridged-Ring Compounds/administration & dosage , CA-125 Antigen/metabolism , Cystadenocarcinoma, Serous/metabolism , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/surgery , Drug Resistance, Neoplasm , Female , Humans , Ki-67 Antigen/metabolism , Membrane Proteins/metabolism , Middle Aged , Neoadjuvant Therapy , Organoplatinum Compounds/administration & dosage , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Peritoneal Neoplasms/metabolism , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/surgery , Progression-Free Survival , Response Evaluation Criteria in Solid Tumors , Taxoids/administration & dosage , Young Adult
11.
Gynecol Oncol ; 154(3): 524-530, 2019 09.
Article in English | MEDLINE | ID: mdl-31353053

ABSTRACT

OBJECTIVE: To determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment. METHODS: Patients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression. Descriptive statistics summarized surveys, and paired changes were analyzed using signed rank tests. Random-intercept Tobit models examined immune response. RESULTS: Median age was 59.9; 88.5% were stage IIIC/IV; and 38.5% underwent primary debulking. Thirty-two patients were enrolled; 3 excluded because they never took propranolol; an additional 3 didn't meet inclusion criteria, leaving 26 evaluable. Eighteen of 26 (69%), 90% credible interval (CI) of 53-81%, completed 6 chemotherapy cycles plus propranolol (an 82% posterior probability that the true proportion of success is ≥60%). Among the 23 patients with baseline and six month follow up data, overall QOL, anxiety, and depression improved (P < 0.05) and leukocyte expression of pro-inflammatory genes declined (P = 0.03) after completion of therapy. Decrease from baseline of serum IL-6 and IL-8 preceded response to chemotherapy (P < 0.0014). Change from baseline IL-10 preceded complete response. CONCLUSION: Use of propranolol during primary treatment of EOC is feasible and treatment resulted in decrease in markers of adrenergic stress response. In combination with chemotherapy, propranolol potentially results in improved QOL over baseline.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Ovarian Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Propranolol/administration & dosage , Adrenergic beta-Antagonists/administration & dosage , Aged , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial/genetics , Carcinoma, Ovarian Epithelial/immunology , Carcinoma, Ovarian Epithelial/surgery , Chemotherapy, Adjuvant , Cytokines/blood , Cytokines/genetics , Cytokines/immunology , Feasibility Studies , Female , Gene Expression/drug effects , Gene Expression/immunology , Humans , Leukocytes/drug effects , Leukocytes/immunology , Longitudinal Studies , Middle Aged , Neoadjuvant Therapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/immunology , Ovarian Neoplasms/surgery , Paclitaxel/administration & dosage , Pilot Projects , Prospective Studies , Quality of Life
12.
Gynecol Oncol ; 152(3): 501-508, 2019 03.
Article in English | MEDLINE | ID: mdl-30876495

ABSTRACT

OBJECTIVE: To compare symptom burden and functional recovery in women undergoing primary cytoreductive surgery (PCS) or neoadjuvant chemotherapy (NACT) and interval cytoreductive surgery (ICS) within an enhanced recovery after surgery program (ERAS). METHODS: Symptom burden was measured using the MD Anderson Symptom Inventory-Ovarian Cancer, a 27-item validated tool that was administered preoperatively, daily while hospitalized, and weekly for 8 weeks after hospital discharge. Mixed-effect modeling was performed. RESULTS: 196 patients (71 PCS, 125 ICS) participated. Patients in the PCS group were younger, median age of 59 vs. 63 in ICS group. Median length of stay was 4 days for PCS and 3 days for ICS group. PCS pts had a significantly higher median surgical complexity score (4 vs. 2, p = 0.002), and longer median surgical time (257 min vs. 220 min, p = 0.03). While patients undergoing PCS had significantly different symptom burden profiles prior to surgery compared to those undergoing ICS, there were no significant differences in symptoms in the immediate in-hospital and extended post-hospital discharge period. Irrespective of the timing of surgery in relation to chemotherapy, patients undergoing intermediate or high complexity surgery had more nausea, fatigue, and higher total interference scores compared to patients undergoing low complexity surgery. CONCLUSION: Within a center with a standardized, systematic method for patient selection for PCS and a standardized ERAS care pathway, there were not significant differences in surgery-related symptoms related to recovery between patients undergoing PCS or ICS. However, patient-reported symptom burden and symptom interference did meaningfully differentiate based on surgical complexity score.


Subject(s)
Cytoreduction Surgical Procedures/methods , Gynecologic Surgical Procedures/methods , Ovarian Neoplasms/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Female , Humans , Middle Aged , Neoadjuvant Therapy , Ovarian Neoplasms/drug therapy , Patient Reported Outcome Measures , Perioperative Care/methods , Tumor Burden , Young Adult
13.
Obstet Gynecol ; 132(3): 545-554, 2018 09.
Article in English | MEDLINE | ID: mdl-30095787

ABSTRACT

OBJECTIVE: To estimate the effects of a laparoscopic scoring algorithm to triage patients with advanced ovarian cancer to immediate or delayed debulking to improve complete gross surgical resection rates and determine the resulting clinical outcomes. METHODS: We prospectively performed laparoscopic assessment on patients with suspected advanced-stage ovarian cancer from April 2013 to December 2016 to determine primary resectability at tumor reductive surgery. Patients with medically inoperable or distant metastatic disease received neoadjuvant chemotherapy. Two-surgeon scoring was performed in a blinded fashion using a validated scoring method. Patients with predictive index value scores less than 8 were offered primary surgery and those with scores 8 or greater received neoadjuvant chemotherapy. Univariate and multivariate analysis was performed for effects on progression-free survival. RESULTS: Six hundred twenty-one patients presenting with presumed advanced ovarian cancer were evaluated during the study period and 488 patients met inclusion criteria. Two hundred fifteen patients underwent laparoscopic scoring, of whom 125 had predictive index value scores less than 8 and 84 had predictive index value scores 8 or greater. Blinded two-surgeon predictive index value scoring resulted in bivariate discordance in only 2% of patients. Tumor cytoreduction led to no gross residual disease (R0 resection) in 88% of patients in the primary surgery group and 74% in the neoadjuvant chemotherapy group. Patients triaged to primary surgery had an improved progression-free survival of 21.4 months versus 12.9 months in those patients undergoing neoadjuvant chemotherapy (P<.001). Median progression-free survival by treatment group and residual disease status was as follows: primary surgery-R0 23.5 months; primary surgery-R1 (any gross residual disease) 17.6 months; neoadjuvant chemotherapy-R0 15.5 months; and neoadjuvant chemotherapy-R1 12.9 months (P<.001). On multivariate analysis for progression-free survival, baseline CA 125 (P=.001) and gross residual disease at tumor reductive surgery (P=.01) were significantly associated with progression-free survival. CONCLUSION: Laparoscopic triage assessment allowed for a personalized approach to the management of patients with advanced ovarian cancer and resulted in high complete surgical resection rates at tumor reductive surgery.


Subject(s)
Cytoreduction Surgical Procedures , Ovarian Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Algorithms , Female , Humans , Laparoscopy , Middle Aged , Prospective Studies
14.
J Gynecol Oncol ; 29(5): e68, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30022632

ABSTRACT

OBJECTIVE: To determine the effect of surgeon experience on intraoperative, postoperative and long-term outcomes among patients undergoing pelvic exenteration for gynecologic cancer. METHODS: This was a retrospective analysis of all women who underwent exenteration for a gynecologic malignancy at MD Anderson Cancer Center, between January 1993 and June 2013. A logistic regression was used to model the relationship between surgeon experience (measured as the number of exenteration cases performed by the surgeon prior to a given exenteration) and operative outcomes and postoperative complications. Cox proportional hazards regression was used to model survival outcomes. RESULTS: A total of 167 exenterations were performed by 19 surgeons for cervix (78, 46.7%), vaginal (43, 25.8%), uterine (24, 14.4%), vulvar (14, 8.4%) and other cancer (8, 4.7%). The most common procedure was total pelvic exenteration (69.4%), incontinent urinary diversion (63.5%) and vertical rectus abdominis musculocutaneous reconstruction (42.5%). Surgical experience was associated with decreased estimated blood loss (p<0.001), intraoperative transfusion (p=0.009) and a shorter length of stay (p=0.03). No difference was noted in the postoperative complication rate (p=0.12-0.95). More surgeon experience was not associated with overall or disease specific survival: OS (hazard ratio [HR]=1.02; 95% confidence interval [CI]=0.97-1.06; p=0.46) and DSS (HR=1.01; 95% CI=0.97-1.04; p=0.66), respectively. CONCLUSION: Patients undergoing exenteration by more experienced surgeons had improvement in intraoperative factors such as estimated blood loss, transfusion rates and length of stay. No difference was seen in postoperative complication rates, overall or disease specific survival.


Subject(s)
Clinical Competence , Genital Neoplasms, Female/surgery , Pelvic Exenteration/standards , Workload/statistics & numerical data , Adult , Aged , Aged, 80 and over , Blood Loss, Surgical/prevention & control , Blood Transfusion/statistics & numerical data , Female , Follow-Up Studies , Humans , Length of Stay/statistics & numerical data , Middle Aged , Pelvic Exenteration/adverse effects , Pelvic Exenteration/statistics & numerical data , Postoperative Complications , Texas , Treatment Outcome
15.
Obstet Gynecol ; 132(2): 281-290, 2018 08.
Article in English | MEDLINE | ID: mdl-29995737

ABSTRACT

OBJECTIVE: To investigate the effect of an enhanced recovery after surgery (ERAS) program on perioperative outcomes with an emphasis on opioid consumption and patient-reported outcomes in the immediate and extended postoperative periods. METHODS: We initiated our ERAS program as part of a quality improvement initiative in November 2014. We compared clinical outcomes among a cohort of 607 women undergoing open gynecologic surgery before or after implementation of ERAS. For 293 patients, patient-reported outcomes were compared using the MD Anderson Symptom Inventory-Ovarian Cancer. RESULTS: Median age was 58 years (range 18-85 years). Median length of stay decreased by 25% for patients in the ERAS pathway (P<.001). Overall, patients in the ERAS group had a 72% reduction in median opioid consumption and 16% were opioid-free during admission up to postoperative day 3 (P<.001). There was no difference in pain scores (P=.80). Patients on ERAS reported less fatigue (P=.01), interference with walking (P=.003), and total interference (composite score of physical and affective measures) during hospitalization (P=.008). After discharge, those on the ERAS pathway demonstrated a significantly shorter median time to return to no or mild fatigue (10 vs 30 days, P=.03), mild or no interference with walking (5 vs 13 days, P=.003), and mild to no total interference (3 vs 13 days, P=.02). There were no significant differences in complications, rates of readmission, or reoperation between the pre- and post-ERAS groups. CONCLUSION: Implementation of an ERAS program was associated with significantly decreased opioid use after surgery and improvement in key patient-reported outcomes associated with functional recovery after surgery without compromising pain scores.


Subject(s)
Analgesics, Opioid/administration & dosage , Gynecologic Surgical Procedures/methods , Patient Reported Outcome Measures , Postoperative Complications/epidemiology , Quality Improvement , Adolescent , Adult , Aged , Aged, 80 and over , Analgesics, Opioid/therapeutic use , Fatigue , Female , Genital Neoplasms, Female/surgery , Humans , Length of Stay , Middle Aged , Pain Measurement , Pain, Postoperative/drug therapy , Pain, Postoperative/epidemiology , Perioperative Care , Physical Functional Performance , Postoperative Period , Treatment Outcome
16.
Article in English | WPRIM (Western Pacific) | ID: wpr-717078

ABSTRACT

OBJECTIVE: To determine the effect of surgeon experience on intraoperative, postoperative and long-term outcomes among patients undergoing pelvic exenteration for gynecologic cancer. METHODS: This was a retrospective analysis of all women who underwent exenteration for a gynecologic malignancy at MD Anderson Cancer Center, between January 1993 and June 2013. A logistic regression was used to model the relationship between surgeon experience (measured as the number of exenteration cases performed by the surgeon prior to a given exenteration) and operative outcomes and postoperative complications. Cox proportional hazards regression was used to model survival outcomes. RESULTS: A total of 167 exenterations were performed by 19 surgeons for cervix (78, 46.7%), vaginal (43, 25.8%), uterine (24, 14.4%), vulvar (14, 8.4%) and other cancer (8, 4.7%). The most common procedure was total pelvic exenteration (69.4%), incontinent urinary diversion (63.5%) and vertical rectus abdominis musculocutaneous reconstruction (42.5%). Surgical experience was associated with decreased estimated blood loss (p < 0.001), intraoperative transfusion (p = 0.009) and a shorter length of stay (p = 0.03). No difference was noted in the postoperative complication rate (p = 0.12–0.95). More surgeon experience was not associated with overall or disease specific survival: OS (hazard ratio [HR] = 1.02; 95% confidence interval [CI] = 0.97–1.06; p = 0.46) and DSS (HR = 1.01; 95% CI = 0.97–1.04; p = 0.66), respectively. CONCLUSION: Patients undergoing exenteration by more experienced surgeons had improvement in intraoperative factors such as estimated blood loss, transfusion rates and length of stay. No difference was seen in postoperative complication rates, overall or disease specific survival.


Subject(s)
Female , Humans , Pregnancy , Cervix Uteri , Genital Neoplasms, Female , Length of Stay , Logistic Models , Pelvic Exenteration , Postoperative Complications , Pregnancy Outcome , Rectus Abdominis , Retrospective Studies , Surgeons , Urinary Diversion
17.
Ann Surg Oncol ; 24(2): 362-368, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27573526

ABSTRACT

BACKGROUND: Surgical site infections (SSIs) lead to increased patient morbidity and healthcare costs. Our objective was to decrease the SSI rate following gynecologic surgery. METHODS: Adult patients undergoing abdominal surgery for gynecologic malignancy or benign disease received the following: patient education; preoperative antibacterial soap; appropriate antibiotic prophylaxis; change of gloves and use of clean instruments at surgical closure; surgical dressing for 48 h; and a post-discharge phone call. The baseline SSI rate was determined retrospectively (1 April 2014-30 June 2014), while the post-intervention SSI rate was determined prospectively (16 February 2015-15 October 2015). The main outcome was the overall SSI rate with secondary outcomes, including the rate of superficial, deep, incisional and organ space infection, as well as the cost effectiveness of the bundle. RESULTS: A total of 232 baseline and 555 post-intervention patients were included in the study. No differences were observed between the baseline and post-intervention groups with regard to median body mass index (BMI), surgical approach, receipt of preoperative chemotherapy and/or radiation therapy, and cases including bowel surgery. Overall, the SSI rate decreased significantly from baseline [12.5 %] to post-intervention [7.4 %] (odds ratio [OR] 0.56, 90 % confidence interval [CI] 0.37-0.85; p = 0.01). A 40 % decrease was noted in the rate of superficial and deep infections (9.5 vs. 5.9 %; OR 0.60, 90 % CI 0.38-0.97; p = 0.04) and SSIs after open surgery (21.4 vs. 13.2 %; OR 0.56, 90 % CI 0.34-0.92; p = 0.03). The estimated cost of the intervention was $19.26/case and the net total amount saved during the post-intervention period was $65,625 month. CONCLUSIONS: This bundled intervention led to a significant decrease in the overall SSI rate and was cost effective. The largest decreases in SSIs were in incisional infections and following open surgery.


Subject(s)
Antibiotic Prophylaxis , Digestive System Surgical Procedures/adverse effects , Genital Neoplasms, Female/surgery , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Female , Follow-Up Studies , Humans , Incidence , Middle Aged , Prognosis , Prospective Studies , Retrospective Studies , Risk Factors , Surgical Wound Infection/etiology , Texas/epidemiology
18.
Biotechniques ; 61(5): 249-259, 2016.
Article in English | MEDLINE | ID: mdl-27839510

ABSTRACT

High affinity aptamer-based biomarker discovery has the advantage of simultaneously discovering an aptamer affinity reagent and its target biomarker protein. Here, we demonstrate a morphology-based tissue aptamer selection method that enables us to use tissue sections from individual patients and identify high-affinity aptamers and their associated target proteins in a systematic and accurate way. We created a combinatorial DNA aptamer library that has been modified with thiophosphate substitutions of the phosphate ester backbone at selected 5´dA positions for enhanced nuclease resistance and targeting. Based on morphological assessment, we used image-directed laser microdissection (LMD) to dissect regions of interest bound with the thioaptamer (TA) library and further identified target proteins for the selected TAs. We have successfully identified and characterized the lead candidate TA, V5, as a vimentin-specific sequence that has shown specific binding to tumor vasculature of human ovarian tissue and human microvascular endothelial cells. This new Morph-X-Select method allows us to select high-affinity aptamers and their associated target proteins in a specific and accurate way, and could be used for personalized biomarker discovery to improve medical decision-making and to facilitate the development of targeted therapies to achieve more favorable outcomes.


Subject(s)
Aptamers, Nucleotide/analysis , Biomarkers, Tumor/analysis , Ovarian Neoplasms/metabolism , Aptamers, Nucleotide/chemistry , Aptamers, Nucleotide/metabolism , Biomarkers, Tumor/chemistry , Biomarkers, Tumor/metabolism , Female , Humans , Laser Capture Microdissection , Mass Spectrometry
19.
BBA Clin ; 6: 76-81, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27453821

ABSTRACT

BACKGROUND: Ovarian cancer patients have a high risk of developing venous thrombosis. The membrane lipid bilayer of platelets and platelet-derived microparticles (PMP) provides a platform for assembly of coagulation proteins and generation of blood clots. METHODS: We compared the lipid composition of platelets and PMPs in patients with ovarian cancer to those in healthy subjects. We used shotgun lipidomics to quantify 12 classes and 177 species of lipids. RESULTS: We found a significant change in 2 classes of lipids in platelets and PMPs isolated from ovarian cancer patients: higher phosphatidylinositol and lower lyso-phosphatidylcholine. The level of 28 species of lipids was also significantly altered in the direction of an increase in the pro-coagulant and a reduction in the anticoagulant lipids. We found that cancer platelets expressed less lipid phosphate phosphatase 1 (LPP1), a key enzyme in phospholipid biosynthesis pathways, than normal platelets. The reduction in LPP1 might contribute to the changes in the lipid profile of cancer platelets. CONCLUSION: Our results support a procoagulant lipid profile of platelets in ovarian cancer patients that can play a role in the increased risk of venous thrombosis in these patients. GENERAL SIGNIFICANCE: As far as we are aware, our study is the first study on platelet lipidomics in ovarian cancer. The importance of our findings for the future studies are: 1) a similar change in lipid profile of platelets and PMP may be responsible for hypercoagulability in other cancers, and 2) plasma level of high-risk lipids for venous thrombosis may be useful biomarkers.

20.
J Oncol Pract ; 12(10): e878-e883, 2016 10.
Article in English | MEDLINE | ID: mdl-27460495

ABSTRACT

PURPOSE: Surgical site infections (SSIs) are associated with patient morbidity and increased health care costs. Although several national organizations including the University HealthSystem Consortium (UHC), the National Surgical Quality Improvement Program (NSQIP), and the National Healthcare Safety Network (NHSN) monitor SSI, there is no standard reporting methodology. METHODS: We queried the UHC, NSQIP, and NHSN databases from July 2012 to June 2014 for SSI after gynecologic surgery at our institution. Each organization uses different definitions and inclusion and exclusion criteria for SSI. The rate of SSI was also obtained from chart review from April 1 to June 30, 2014. SSI was classified as superficial, deep, or organ space infection. The rates reported by the agencies were compared with the rates obtained by chart review using Fisher's exact test. RESULTS: Overall SSI rates for the databases were as follows: UHC, 1.5%; NSQIP, 8.8%; and NHSN, 2.8% (P < .001). The individual databases had wide variation in the rate of deep infection (UHC, 0.7%; NSQIP, 4.7%; NHSN, 1.3%; P < .001) and organ space infection (UHC, 0.4%; NSQIP, 4.4%; NHSN, 1.4%; P < .001). In agreement with the variation in reporting methodology, only 19 cases (24.4%) were included in more than one database and only one case was included in all three databases (1.3%). CONCLUSION: There is discordance among national reporting agencies tracking SSI. Adopting standardized metrics across agencies could improve consistency and accuracy in assessing SSI rates.


Subject(s)
Surgical Wound Infection/epidemiology , Databases, Factual , Government Agencies , Humans , Quality of Health Care , United States/epidemiology
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