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1.
Surgery ; 175(3): 712-717, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37848355

ABSTRACT

BACKGROUND: Time to treatment has been identified as a quality metric, with longer time to treatment associated with poorer outcomes. Genetic evaluation is an integral part of treatment counseling for patients with breast cancer. With expanding indications for genetic testing and consideration of expansion of genetic testing to all patients with a personal history of breast cancer, this study aims to evaluate the effect of genetic evaluation on the time interval from initial surgical visit to surgery. METHODS: A retrospective review of patients undergoing upfront surgery for stage 0-3 breast cancer from June 2022 to December 2022. Patient demographics, treatment characteristics, National Comprehensive Cancer Network criteria for genetic testing, and results were obtained. RESULTS: The study included 492 patients (489 females). Eighty-one (16.2%) were ≤50 years of age at diagnosis. In total, 281 patients (57.1%) met National Comprehensive Cancer Network criteria for genetic testing and 199 consulted with a genetic counselor (72.4%). Seventy-six patients (27.6%) not meeting National Comprehensive Cancer Network criteria pursued genetic counseling. In total, 218 patients (79.3%) referred for genetic counseling completed testing. Mean turnaround time to genetic testing result was 11 days (range, 6-66 days). Twenty-six patients (11.9%) had a pathogenic or likely pathogenic variant. Twenty-four of these patients met National Comprehensive Cancer Network testing criteria (92.3%) and 2 did not (7.7%). The time to treatment for patients undergoing genetic testing was 33 vs 34 days in those without testing (P = .45). Three patients (11.5%) with pathogenic or likely pathogenic variants altered their initial surgical plan due to their genetic testing results. Seven patients with pathogenic or likely pathogenic variant results returning postoperatively did not undergo additional surgery. CONCLUSION: Hereditary breast cancer evaluation and genetic testing did not appear to delay time to treatment for patients with breast cancer in our study cohort.


Subject(s)
Breast Neoplasms , Female , Humans , Breast Neoplasms/genetics , Breast Neoplasms/surgery , Breast Neoplasms/diagnosis , Genetic Predisposition to Disease , Genetic Testing/methods , Genetic Counseling , Retrospective Studies
2.
Ann Surg Oncol ; 31(3): 1423-1427, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38127215

ABSTRACT

This ASO perspective reviews the findings of a randomized, phase II clinical trial evaluating adjuvant trastuzumab emtansine (T-DM1) compared with paclitaxel and trastuzumab (TH) in stage I human epidermal growth factor receptor 2-positive breast cancer, as reported recently by the ATEMPT trial investigators. Patients treated with T-DM1 had better disease-free survival but did not have fewer treatment toxicities. The T-DM1-treated group had higher rates of treatment discontinuations, therefore long-term follow-up will be required to evaluate survival differences between T-DM1 and TH.


Subject(s)
Breast Neoplasms , Female , Humans , Adjuvants, Immunologic/therapeutic use , Ado-Trastuzumab Emtansine/adverse effects , Ado-Trastuzumab Emtansine/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Paclitaxel , Receptor, ErbB-2/metabolism , Trastuzumab/adverse effects , Trastuzumab/therapeutic use , Treatment Outcome , Clinical Trials, Phase II as Topic , Randomized Controlled Trials as Topic
4.
Ann Surg Oncol ; 30(10): 5990-5996, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37567976

ABSTRACT

BACKGROUND: Alternative service delivery models are critically needed to address the increasing demand for genetics services and limited supply of genetics experts available to provide pre-test counseling. METHODS: We conducted a prospective randomized controlled trial of women with stage 0-III breast cancer not meeting National Comprehensive Cancer Network (NCCN) criteria for genetic testing. Patients were randomized to pre-test counseling with a Chatbot or a certified genetic counselor (GC). Participants completed a questionnaire assessing their knowledge of breast cancer genetics and a survey assessing satisfaction with their decision regarding pre-test counseling. RESULTS: A total of 39 patients were enrolled and 37 were randomized to genetic counseling with an automated Chatbot or a GC; 19 were randomized to Chatbot and 18 to traditional genetic counseling, and 13 (38.2%) had a family member with breast cancer but did not meet NCCN criteria. All patients opted to undergo genetic testing. Testing revealed six pathogenic variants in five patients (13.5%): CHEK2 (n = 2), MSH3 (n = 1), MUTYH (n = 1), and BRCA1 and HOXB13 (n = 1). No patients had a delay in time-to-treatment due to genetic testing turnaround time, nor did any patients undergo additional risk reducing surgery. There was no significant difference in median knowledge score between Chatbot and traditional counseling (11 vs. 12, p = 0.09) or in median patient satisfaction score (30 vs. 30, p = 0.19). CONCLUSION: Satisfaction and comprehension in patients with breast cancer undergoing pre-test genetic counseling using an automated Chatbot is comparable to in-person genetic testing. Utilization of this technology can offer improved access to care and a much-needed alternative for pre-test counseling.


Subject(s)
Breast Neoplasms , Genetic Counseling , Humans , Female , Genetic Counseling/psychology , Breast Neoplasms/diagnosis , Artificial Intelligence , Prospective Studies , Genetic Testing
6.
Ann Surg Oncol ; 29(10): 6115-6131, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35876929

ABSTRACT

BACKGROUND: Little is known about the experience of the male breast cancer patient. Mastectomy is often offered despite evidence that breast-conserving surgery (BCS) provides similar outcomes. METHODS: Two concurrent online surveys were distributed from August to October 2020 via social media to male breast cancer (MBC) patients and by email to American Society of Breast Surgeon members. The MBC patients were asked their opinions about their surgery, and the surgeons were asked to provide surgical recommendations for MBC patients. RESULTS: The survey involved 63 MBC patients with a mean age of 62 years (range, 31-79 years). Five MBC patients (7.9 %) stated that their surgeon recommended BCS, but 54 (85.7 %) of the patients underwent unilateral, and 8 (12.7 %) underwent bilateral mastectomy. Most of the patients (n = 60, 96.8 %) had no reconstruction. One third of the patients (n = 21, 33.3 %) felt somewhat or very uncomfortable with their appearance after surgery. The response rate was 16.5 % for the surgeons. Of the 438 surgeons who answered the survey, 298 (73.3 %) were female, 215 (51.7 %) were fellowship-trained, and 244 (58.9 %) had been practicing for 16 years or longer. More than half of surgeons (n = 259, 59.1 %) routinely offered BCS to eligible men, and 180 (41.3 %) stated they had performed BCS on a man with breast cancer. Whereas 89 (20.8 %) of the surgeons stated that they routinely offer reconstruction to MBC patients, 87 (20.3 %) said they do not offer reconstruction, 96 (22.4 %) said they offer it only if the patient requests it, and 157 (36.6 %) said they never consider it as an option. CONCLUSIONS: The study found discordance between MBC patients' satisfaction with their surgery and surgeon recommendations and experience. These data present an opportunity to optimize the MBC patient experience.


Subject(s)
Breast Neoplasms, Male , Breast Neoplasms , Surgeons , Breast Neoplasms/surgery , Breast Neoplasms, Male/surgery , Female , Humans , Male , Mastectomy , Mastectomy, Segmental , Middle Aged , Surveys and Questionnaires
7.
Gynecol Oncol Rep ; 40: 100951, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35392128

ABSTRACT

Objective s: To evaluate travel distance in women with advanced or recurrent epithelial ovarian cancer (OC) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) and the subsequent impact upon outcomes. Methods: An IRB-approved single-institution prospective registry was queried for women with OC who underwent HIPEC from 1/1/2009-12/1/2020. Demographic, oncologic, and surgical data were recorded. The patient's home zip code was compared to the institutional zip code to determine travel distance using Google Maps. Patients were divided into three strata for analysis: 1) local: ≤50 miles, 2) regional: 51-99 miles, and 3) distant: ≥100 miles and univariate analysis was performed. Results: Of 127 women, the median distance travelled was 57.0 miles (IQR: 20.6, 84.6). There were no significant differences in mild (28.3% vs. 26.3 vs. 24.1%), moderate (21.7% vs. 15.8% vs. 17.2%) or severe postoperative complications (11.7% vs. 5.3% vs. 17.2%) (p = 0.75) for local, regional and distant patients, respectively. There was no difference in progression-free survival (17.4 vs. 22.2 vs. 12.8 months, p > 0.05) or overall survival (57.3 vs. 61.6 vs. 29.2 months, p > 0.05) for local, regional or distant patients, respectively. Conclusions: This study demonstrates that women with OC are willing to travel for HIPEC, with over 50% traveling > 50 miles. Our results suggest that women who travel for HIPEC procedures are not at increased risk for perioperative complications or worse oncologic outcomes than those local to HIPEC centers.

8.
J Surg Oncol ; 125(4): 589-595, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34855221

ABSTRACT

BACKGROUND AND OBJECTIVES: Screening for breast cancer in highly penetrant mutation carriers during pregnancy and lactation is challenging and consensus guidelines are lacking. This study evaluates the lapse in screening and the interval pregnancy-associated breast cancer rate. METHODS: A single-institution retrospective cohort study of pregnant and lactating patients with known pathogenic germline mutations was performed. Lapse in screening was defined as the interval between the last screening imaging exam obtained before last menstrual period and the subsequent screening imaging. RESULTS: Out of 685 patients, 42 had 1-3 evaluable pregnancies (54 total - 28 managed in High Risk Breast Clinic and 26 by OB/GYN). Mutations were observed in patients in BRCA1 (49%), BRCA2 (36%), CDH1 (5%), CHEK2 (2%), ATM (2%), NF1 (3%), and MSH2 (3%). The average screening lapse was 25 [19, 30] months for patients followed in the High Risk Clinic versus 32.5 [21, 65.75] months for patients followed with Routine Care (p = 0.035). We identified three cases of pregnancy-associated breast cancer (interval cancer rate 6%). CONCLUSIONS: Patients with highly penetrant mutations are at risk for the development of interval pregnancy-associated breast cancer. Development of consistent screening guidelines and adherence to those guidelines is needed for this patient population.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/diagnosis , Early Detection of Cancer/statistics & numerical data , Genetic Predisposition to Disease , Germ-Line Mutation , Lactation , Adult , Breast Neoplasms/genetics , Breast Neoplasms/psychology , Early Detection of Cancer/psychology , Female , Follow-Up Studies , Genetic Testing/statistics & numerical data , Humans , Pregnancy , Prognosis , Retrospective Studies
9.
Gynecol Oncol ; 162(3): 645-651, 2021 09.
Article in English | MEDLINE | ID: mdl-34247768

ABSTRACT

OBJECTIVE(S): To evaluate the incidence and associated risk factors for anastomotic failure following interval debulking surgery (IDS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in women with advanced ovarian cancer. METHODS: We performed a retrospective cohort study in women with stage III/IV high-grade ovarian cancer treated with neoadjuvant chemotherapy followed by IDS with colorectal resection and HIPEC from 2017 to 2020. These patients were compared to a historical control cohort who underwent IDS with colorectal resection without HIPEC from 2009 to 2016. Data was collected for demographics, surgical variables, and perioperative outcomes. The univariate analysis compared progression-free survival and overall survival. RESULTS: 61 women were identified; 21 (34.4%) underwent IDS with HIPEC from 2017 to 2020, and 40 underwent IDS alone from 2009 to 2016. None of the patients who had IDS with HIPEC had protective ileostomy, compared to 10.0% of those who received had IDS alone (n = 4)(p = 0.29). The cumulative incidence of anastomotic leak rate was 8.2% (n = 5). There was no significant difference in anastomotic leak rate for women who underwent IDS with HIPEC (9.5%, n = 2) versus without HIPEC (7.5%, n = 3) (p = 0.99). While there was no difference in PFS (12.2 vs. 13.3 months, log-rank p = 0.31), OS (9.4 vs. 40.6 months, log-rank p = 0.013) was significantly decreased following postoperative anastomotic leak. CONCLUSIONS: In this retrospective series of women with advanced ovarian cancer, HIPEC was not associated with increased risk for anastomotic leak at the time of IDS with colorectal resection and reanastomosis. While further study is needed, HIPEC alone should not preclude colorectal resection or dictate practices for colonic diversion in IDS.


Subject(s)
Anastomotic Leak/etiology , Carcinoma, Ovarian Epithelial/therapy , Cytoreduction Surgical Procedures/adverse effects , Hyperthermic Intraperitoneal Chemotherapy/adverse effects , Ovarian Neoplasms/therapy , Aged , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/surgery , Cohort Studies , Cytoreduction Surgical Procedures/methods , Female , Humans , Hyperthermic Intraperitoneal Chemotherapy/methods , Middle Aged , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Perioperative Period , Retrospective Studies
10.
Gynecol Oncol ; 162(2): 368-374, 2021 08.
Article in English | MEDLINE | ID: mdl-34083027

ABSTRACT

OBJECTIVE(S): To evaluate the impact of frailty on postoperative complications following cytoreductive surgery (CRS) with hyperthermic intra-peritoneal chemotherapy (HIPEC) in women with advanced or recurrent gynecologic cancer. METHODS: An IRB-approved single-institution prospective registry was queried for women who underwent CRS with HIPEC for advanced or recurrent gynecologic cancer from 1/1/2014-12/31/2020. Frailty was defined as a modified Frailty Index (mFI) score of ≥2. Logistic regression was used to assess the impact of mFI upon the rate of moderate or higher (≥ grade 2) Accordion postoperative complications. RESULTS: Of 141 women, 81.6% (n = 115) were non-frail with mFI of 0-1 and 18.4% (n = 26) were frail with mFI ≥2. The incidence of ≥ grade 2 complications was 21.2% (n = 14) for mFI = 0, 26.5% (n = 13) for mFI = 1, 64.7% (n = 11) for mFI = 2 and 100.0% (n = 9) for patients with mFI ≥3. The incidence of re-operation (1.7% vs. 11.5%, p = 0.044), ICU admission (13.2% vs. 34.6%, p = 0.018), acute kidney injury (6.3% vs. 30.8%, p = 0.001), and respiratory failure (0.9% vs. 19.2%, p < 0.001) were significantly lower amongst non-frail vs. frail women. On multivariable analysis, mFI ≥2 was associated with significantly increased ≥ grade 2 complications versus mFI of 0-1 (OR 9.4, 95% CI 3.3, 26.4, p < 0.001). Age (OR 1.04, 95% CI 1.00, 1.09, p = 0.07), surgical indication (recurrent vs. primary) (OR 0.71, 95% CI 0.30, 1.7, p = 0.44) and Surgical Complexity Score of Intermediate or High vs. Low (OR 1.5, 95% CI 0.67, 3.5, p = 0.31) were not associated with ≥grade 2 complications. CONCLUSIONS: Frailty, defined by the modified frailty index, is predictive of ≥grade 2 postoperative complications following CRS with HIPEC in women with gynecologic cancer. Frailty screening before CRS with HIPEC may assist patient selection and improve postoperative outcomes.


Subject(s)
Cytoreduction Surgical Procedures/adverse effects , Frailty/diagnosis , Genital Neoplasms, Female/therapy , Hyperthermic Intraperitoneal Chemotherapy/adverse effects , Neoplasm Recurrence, Local/therapy , Postoperative Complications/epidemiology , Aged , Clinical Decision-Making/methods , Feasibility Studies , Female , Frailty/etiology , Genital Neoplasms, Female/complications , Genital Neoplasms, Female/diagnosis , Humans , Middle Aged , Neoplasm Recurrence, Local/complications , Neoplasm Recurrence, Local/diagnosis , Neoplasm Staging , Patient Selection , Postoperative Complications/etiology , Retrospective Studies , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Severity of Illness Index
11.
Int J Gynecol Cancer ; 31(7): 1021-1030, 2021 07.
Article in English | MEDLINE | ID: mdl-34006567

ABSTRACT

OBJECTIVE: To evaluate perioperative outcomes in elderly versus non-elderly women with advanced or recurrent epithelial ovarian cancer undergoing surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A single-institution prospective registry was analyzed for women with ovarian cancer who underwent surgery with HIPEC from January 2014 to December 2020. Elderly age was defined as ≥65 years at surgery. Complications were defined according to the Accordion scale. Univariate and multivariable analysis was used to compare progression-free survival and overall survival. RESULTS: Of 127 women who underwent surgery with HIPEC, 33.1% (n=42) were ≥65 and 17.3% (n=22) were ≥70 years old. The median age for non-elderly and elderly patients were 55.7±8.3 versus 72.0±5.4 years, respectively (p<0.001). The majority of non-elderly versus elderly patients underwent HIPEC at the time of interval cytoreductive surgery following neoadjuvant chemotherapy (52.9% vs 73.8%, p=0.024). There were no differences in moderate (15.3% vs 26.2%) or severe postoperative complications (10.6% vs 11.9%, p=0.08), acute kidney injury (7.1% vs 16.7%, p=0.12), and length of stay (5.0 vs 5.0 days, p=0.56) for non-elderly versus elderly patients. With a median follow-up of 20 months (95% CI 9.1 to 32.7 months), there was no difference in progression-free survival (18.8 vs 15.7 months, p=0.75) or overall survival (61.6 months vs not estimable, p=0.72) for non-elderly versus elderly patients. Comparing patients 65-69 versus ≥70 years, progression-free survival (33.0 vs 12.5 months, p=0.002) was significantly improved in patients aged 65-69, without difference in overall survival (not estimable vs 36.0 months, p=0.91). On multivariable analysis, age ≥65 did not impact progression-free survival (p=0.74). CONCLUSIONS: In this prospective registry of women with ovarian cancer, perioperative morbidity is not increased for non-elderly versus elderly patients following surgery with HIPEC. While age should not exclude patients from surgery with HIPEC, additional research is needed regarding oncologic benefits in elderly women.


Subject(s)
Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/surgery , Cytoreduction Surgical Procedures/methods , Hyperthermic Intraperitoneal Chemotherapy/methods , Aged , Aged, 80 and over , Female , Humans , Perioperative Period , Prospective Studies , Registries , Treatment Outcome
12.
Gynecol Oncol ; 161(2): 389-395, 2021 05.
Article in English | MEDLINE | ID: mdl-33551202

ABSTRACT

OBJECTIVE(S): To identify recurrence patterns and outcomes in women with advanced or recurrent epithelial ovarian cancer (EOC) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: This is an IRB-approved single-institution cohort study of women who underwent CRS+HIPEC for advanced or recurrent EOC followed in a prospective registry from 1/12/2014-3/1/2020. Recurrence locations were defined as pelvic, upper abdominal (UA) and/or extra-peritoneal (EP). Univariate analysis assessed associations between recurrence location, progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 92 women with EOC underwent interval (56.5%; n=52) or recurrent CRS+HIPEC (43.5%; n=40). For interval CRS+HIPEC, recurrence locations were pelvic in 50.0% (n=15), UA in 23.3% (n=7) and EP in 56.7% (n=17); 40.0% (n=12) were EP alone. Similarly, for recurrent CRS+HIPEC, recurrence locations were pelvic (22.5%, n=9), UA (5.0%, n=2) and EP (60.0%, n=24); 66.7% (n=20) were EP alone. For both interval and recurrent CRS+HIPEC, median PFS was 10.5 vs. 13.0 months for pelvic and UA vs. EP only recurrences (p=0.02). Similarly, median OS was 29.2 months for pelvic and UA and not reached for EP only (p=0.05). For interval CRS+HIPEC, there was no difference in median PFS (10.6 vs. 11.7 months, p=0.68) and OS (27.1 vs. 24.8 months, p=0.96) for pelvic and UA vs EP alone. However, for recurrent CRS+HIPEC, pelvic and UA sites of recurrence were associated with reduced PFS (10.0 vs. 18.1 months, p=0.03) and OS (33.6 months vs. not reached, p=0.02) vs. EP only. CONCLUSIONS: In women with advanced or recurrent EOC undergoing CRS+HIPEC, one-half of patients experience their first recurrence outside of the peritoneal cavity. Providers must be aware of the risk of EP failure in patients treated with CRS+HIPEC.


Subject(s)
Abdominal Neoplasms/secondary , Carcinoma, Ovarian Epithelial/secondary , Cytoreduction Surgical Procedures , Hyperthermic Intraperitoneal Chemotherapy , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Pelvic Neoplasms/secondary , Abdominal Neoplasms/diagnosis , Abdominal Neoplasms/mortality , Adult , Aged , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Ovarian Epithelial/diagnosis , Carcinoma, Ovarian Epithelial/mortality , Carcinoma, Ovarian Epithelial/therapy , Female , Follow-Up Studies , Humans , Middle Aged , Ovarian Neoplasms/mortality , Pelvic Neoplasms/diagnosis , Pelvic Neoplasms/mortality , Registries , Retrospective Studies , Survival Analysis , Treatment Outcome
13.
Gynecol Oncol ; 161(1): 194-201, 2021 04.
Article in English | MEDLINE | ID: mdl-33468319

ABSTRACT

OBJECTIVES: To evaluate the incidence of intra-operative metabolic and electrolyte abnormalities and subsequent impact on peri-operative outcomes in women with gynecologic cancer undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). METHODS: An IRB-approved single institution retrospective cohort study was performed in women with gynecologic cancer who underwent CRS + HIPEC. Patient demographics, intra-operative electrolyte and metabolic values and peri-operative outcomes were recorded. To assess the association of pH and lactate upon post-operative outcomes, patients were divided in four quartiles for both variables and univariate analysis was performed. RESULTS: 100 consecutive women who underwent CRS + HIPEC from 2017 to 2020 were identified. Intra-operative blood transfusion and pressor support were required in 40% and 86%, respectively. The rate of ICU admission was 17%. Longer operative time (7.0 vs. 5.3 h, p = 0.002), increased blood loss (400.0 vs. 200.0 mL, p = 0.02) and transfusion (70.6% vs. 34.1%, p = 0.005) were associated with ICU admission. Compared to patients in the highest quartile of pH, lower median pH, (7.211 vs. 7.349, p < 0.001) was associated with increased rates of ICU admission, prolonged intubation (36.0% vs. 0.0%, p < 0.05, respectively) and any post-operative complication (72.0% vs. 28.0%, p = 0.01). Similarly, need for prolonged intubation (40% vs. 0%, p = 0.04) and VTE (13.0% vs. 0%, p = 0.01) were increased in women with the highest quartile of lactate levels compared to the lowest (4.7 vs 1.9, p < 0.001). CONCLUSIONS: Intra-operative acidosis is associated with higher incidence of ICU admission and peri-operative complications following CRS + HIPEC in women with gynecologic cancer. These data support the importance of adequate intra-operative resuscitation and timely correction of hemodynamic and metabolic abnormalities.


Subject(s)
Cytoreduction Surgical Procedures/methods , Genital Neoplasms, Female/therapy , Hyperthermic Intraperitoneal Chemotherapy/methods , Acidosis/etiology , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cisplatin/administration & dosage , Cohort Studies , Combined Modality Therapy , Cytoreduction Surgical Procedures/adverse effects , Doxorubicin/administration & dosage , Female , Humans , Hyperthermic Intraperitoneal Chemotherapy/adverse effects , Middle Aged , Mitomycin/administration & dosage , Paclitaxel/administration & dosage , Perioperative Period , Retrospective Studies
14.
Gynecol Oncol ; 160(1): 45-50, 2021 01.
Article in English | MEDLINE | ID: mdl-33067001

ABSTRACT

OBJECTIVE: To determine peri-operative outcomes in women with advanced epithelial ovarian cancer (EOC) undergoing interval debulking surgery (IDS) with hyperthermic intraperitoneal chemotherapy (HIPEC) via minimally invasive interval debulking surgery (MIS) or laparotomy (LAP). METHODS: A single institution, retrospective cohort study was performed in women with EOC who underwent IDS with HIPEC from 2017 to 2019 via MIS or LAP. Peri-operative outcomes were compared using univariate analysis. RESULTS: In total, 50 eligible women were identified; ten (20.0%) underwent MIS + HIPEC and 40 (80.0%) LAP + HIPEC. The median age of patients in the MIS group was 71.1 vs. 64.2 years in LAP (p = 0.031). There was no significant difference in pre-operative complete radiographic response following NACT (p = 0.18). Notably, there was no difference in the rate of R0 resection (70.0% vs. 77.5%; p = 0.39). There was no significant difference in ICU admission, estimated blood loss, operative time, or use of vasopressors between the cohorts. Similarly, there was no difference in 30-day adverse events for MIS vs. LAP, but length of stay was decreased for those who underwent minimally invasive procedures (3 vs. 4 days, p = 0.016). Time to initiation of chemotherapy following surgery was not significantly different between groups (26.2 days vs 32.0 days, p = 0.090). With median follow-up of 15.1 months, there was no difference in recurrence free survival (median 15.0 vs 17.2 months log-rank, p = 0.30) for MIS vs. LAP. CONCLUSIONS: In this retrospective cohort study, we demonstrate that in women with advanced EOC, HIPEC with MIS at the time of IDS following NACT is feasible. Our institutional experience demonstrates similar rates of R0 cytoreduction, compared to LAP. An MIS approach should not prevent surgeons from utilizing HIPEC where indicated for management of advanced EOC.


Subject(s)
Carcinoma, Ovarian Epithelial/surgery , Carcinoma, Ovarian Epithelial/therapy , Cytoreduction Surgical Procedures/methods , Hyperthermic Intraperitoneal Chemotherapy , Ovarian Neoplasms/surgery , Ovarian Neoplasms/therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial/drug therapy , Cisplatin/administration & dosage , Cohort Studies , Feasibility Studies , Female , Humans , Laparotomy/methods , Middle Aged , Minimally Invasive Surgical Procedures/methods , Neoadjuvant Therapy , Ovarian Neoplasms/drug therapy , Paclitaxel/administration & dosage , Retrospective Studies
15.
J Gynecol Obstet Hum Reprod ; 50(5): 101844, 2021 May.
Article in English | MEDLINE | ID: mdl-32590110

ABSTRACT

INTRODUCTION: Hyperthermic intraperitoneal chemotherapy following cytoreductive surgery (CRS) is a treatment strategy that has been evaluated in recurrent ovarian cancer. The aim of this study was to examine if survival was similar regardless of platinum sensitivity. METHODS: A retrospective study of women with recurrent platinum sensitive or resisteant epithelial ovarian cancer who were treated with cytoreductive surgery (CRS) and HIPEC between the years 2010-2018 was performed. Recurrence free (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Thirty-five (72.9 %) were platinum sensitive (PS) and 13 (27.1 %) were platinum resistant (PR). The complete cytoreduction (R0) rate was higher in the PS patients as compared to PR (85.7 % vs 53.8 %; p = 0.017). Median follow-up was 16.9 (range, 11.7-34.5) months. The median recurrence free survival in the patients who had a R0 resection was 22.3 months in PS and 11.1 months in PR patients (p = 0.017), respectively. Median overall survival was 26.9 months in the PR patients, while it had not been reached in the PS patients. In the patients with PS recurrence, the mean treatment free interval (TFI) prior to HIPEC was 1.6 years and following HIPEC, 40 % of those patients were recurrence free at 2 years. In the patients with PR recurrence, the mean TFI prior to HIPEC was 4.6 months and following HIPEC, 61.5 % of those patients had a longer TFI, with a mean increase of 10.1 months. CONCLUSION: Although surgery is not considered standard treatment in PR ovarian cancer, in carefully selected patients, surgery with HIPEC could extend the treatment-free interval.


Subject(s)
Carcinoma, Ovarian Epithelial/drug therapy , Hyperthermic Intraperitoneal Chemotherapy/methods , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Ovarian Epithelial/mortality , Carcinoma, Ovarian Epithelial/surgery , Cisplatin/administration & dosage , Combined Modality Therapy/methods , Cytoreduction Surgical Procedures , Disease-Free Survival , Doxorubicin/administration & dosage , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Follow-Up Studies , Humans , Hyperthermic Intraperitoneal Chemotherapy/mortality , Kaplan-Meier Estimate , Middle Aged , Mitomycin/administration & dosage , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/surgery , Ovarian Neoplasms/mortality , Ovarian Neoplasms/surgery , Paclitaxel/administration & dosage , Retrospective Studies , Time Factors
16.
Gynecol Oncol ; 159(3): 699-705, 2020 12.
Article in English | MEDLINE | ID: mdl-32950250

ABSTRACT

OBJECTIVE(S): To determine whether antibiotic treatment (ABX) during platinum chemotherapy (PC) for epithelial ovarian cancer (EOC) impacts progression-free survival (PFS) and overall survival (OS). STUDY DESIGN: Retrospective single institution cohort study in women with newly diagnosed stage III/IV EOC (n = 424) who underwent cytoreductive surgery (CRS) and PC from 2009 to 2015. ABX for >48 h, including ABX against gram-positive (anti-G + ABX) bacteria were recorded. The impact of ABX on PFS and OS was assessed using univariate and multivariable Cox regression models. RESULTS: Of 424 eligible women, 34.7% (n = 147) received ABX, with 11.3% (n = 48) treated with anti-G + ABX. ABX decreased PFS (17.4 vs. 23.1 months, HR 1.50, 95% CI 1.20-1.88, p < 0.001) and OS (45.6 vs. 62.4 months, HR 1.63, 95% CI 1.27-2.08, p < 0.001) compared to no ABX. Similarly, anti-G + ABX worsened PFS (16.5 vs. 23.1 months; HR 1.85, 95% CI 1.33-2.55) and OS (35.0 vs. 62.4 months; HR 2.12, 95% CI 1.50-3.0, p < 0.001). On multivariable analysis, all ABX and anti-G + ABX significantly worsened PFS (HR 1.31, 95% CI 1.04-1.65, p = 0.02), (HR 1.50, 95% CI 1.07-2.10, p = 0.02) and OS (HR 1.52, 95% CI 1.18-1.96, p = 0.001), (HR 1.83, 95% CI 1.27-2.62, p = 0.001) respectively. Increased Clavien Dindo score was associated with worsened PFS (1-2 - HR 1.52, 95% CI 1.14-2.03, p = 0.004; 3-4 - HR 1.86, 95% CI 1.27-2.72, p = 0.001) but not OS (1/2 - HR 1.35, 95% CI 0.97-1.88, p = 0.08; 3/4 - HR 1.53, 95% CI 1.00-2.34, p = 0.05); residual disease (p < 0.05) and neoadjuvant chemotherapy (p < 0.001) were associated with worse PFS and OS. CONCLUSION(S): In this retrospective cohort study of women with advanced EOC undergoing PC, ABX treatment was associated with decreased PFS and OS. Mechanistic studies are needed to investigate the negative impact of ABX upon PC response in EOC.


Subject(s)
Anti-Bacterial Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Ovarian Epithelial/mortality , Gram-Positive Bacterial Infections/drug therapy , Neoplasm Recurrence, Local/epidemiology , Ovarian Neoplasms/mortality , Aged , Carcinoma, Ovarian Epithelial/diagnosis , Carcinoma, Ovarian Epithelial/pathology , Carcinoma, Ovarian Epithelial/therapy , Chemotherapy, Adjuvant , Cisplatin/therapeutic use , Cyclophosphamide/therapeutic use , Cytoreduction Surgical Procedures , Female , Follow-Up Studies , Humans , Incidence , Middle Aged , Neoadjuvant Therapy , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Progression-Free Survival , Retrospective Studies
17.
J Minim Invasive Gynecol ; 27(6): 1405-1413, 2020.
Article in English | MEDLINE | ID: mdl-31812614

ABSTRACT

STUDY OBJECTIVE: To compare the feasibility of opportunistic bilateral salpingectomy (OBS) at the time of vaginal hysterectomy (VH) for benign disease in patients with and without relative contraindications (RCs) to the vaginal approach and to evaluate the factors that contribute to the inability to perform OBS. DESIGN: Retrospective chart review. SETTING: Tertiary medical center. PATIENTS: Women undergoing hysterectomy for benign indications between November 2014 and October 2017 who were consented for either VH with or without removal of tube(s) and/or bilateral salpingectomy. INTERVENTIONS: RCs to the vaginal approach are defined as lack of prolapse (cervix high, cervix not visualized, cervix tucked underneath pubis, or minimal descent), enlarged uterus (≥250 g or a size of a ≥12-week uterus), nulliparity, obesity (body mass index ≥30 kg/m2), previous cesarean section (CS), known adhesions, and known adnexal pathologic condition. MEASUREMENTS AND MAIN RESULTS: A total of 258 patients underwent VH and attempted to undergo OBS within the study period; of these, 112 patients (43.4%) had no RC, and 146 patients (56.6%) had ≥1 RCs. Overall, successful salpingectomy was performed in 86.8% of patients. There was no significant difference in the rate of success in patients without or with ≥1 RCs (84.9% vs 89%, p = .15). Salpingectomy was unsuccessful in 13.2% of patients (n = 34). In a multivariable logistic regression analysis, the odds of unsuccessful OBS were 3.83 times higher in patients without prolapse (confidence interval [CI], 0.99-14.76; p = .051), 2.71 times higher in patients with obesity (CI, 1.23-5.94; p = .013), and 3.07 times higher in patients with previous CS (CI, 1.17-8.08; p = .023) as compared to patients without any relative contraindications. An enlarged uterus was associated with successful salpingectomy (odds ratio, 0.28; 95% CI, 0.08-0.94; p = .039) compared with a normal-sized uterus. When excluding enlarged uterus, patients with 2 to 3 RCs had 11.24 and 6.8 higher odds of an unsuccessful OBS than patients with no (CI, 3.73-33.87; p <.001) and 1 RC (CI, 2.36-19.63; p <.001), respectively. There were no differences in postoperative stay or rates of readmission among patients with or without successful salpingectomy at the time of VH. CONCLUSION: OBS is associated with a high overall rate of success in patients with and without traditional RCs to VH. Lack of prolapse, obesity, and previous CS were associated with failed attempt at salpingectomy. Patients with ≥2 RCs to VH should be counseled about the high likelihood of failed salpingectomy.


Subject(s)
Contraindications, Procedure , Genital Diseases, Female/surgery , Hysterectomy, Vaginal/adverse effects , Salpingectomy/methods , Adult , Feasibility Studies , Female , Genital Diseases, Female/epidemiology , Humans , Hysterectomy/adverse effects , Hysterectomy/methods , Hysterectomy/statistics & numerical data , Middle Aged , Pregnancy , Retrospective Studies , Salpingectomy/adverse effects , Salpingectomy/statistics & numerical data , Treatment Outcome
18.
J Minim Invasive Gynecol ; 26(7): 1234-1252.e1, 2019.
Article in English | MEDLINE | ID: mdl-31039407

ABSTRACT

STUDY OBJECTIVE: Hysterectomy for uterine leiomyoma(s) is associated with significant morbidity including blood loss. A systematic review and meta-analysis was conducted to identify nonhormonal interventions, perioperative surgical interventions, and devices to minimize blood loss at the time of hysterectomy for leiomyoma. DATA SOURCES: Librarian-led search of Embase, MEDLINE, Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases from 1946 to 2018 with hand-guided updates. METHODS OF STUDY SELECTION: Included studies reported on keywords of hysterectomy, leiomyoma, and operative blood loss/postoperative hemorrhage/uterine bleeding/metrorrhagia/hematoma. The review excluded a comparison of route of hysterectomy, morcellation, vaginal cuff closure, hormonal medications, vessel sealing devices for vaginal hysterectomy, and case series with <10 patients. TABULATION, INTEGRATION, AND RESULTS: Surgical blood loss, postoperative hemoglobin (Hb) drop, hemorrhage, transfusion, and major and minor complications were analyzed and aggregated in meta-analyses for comparable studies in each category. A total of 2016 unique studies were identified, 33 of which met the inclusion criteria, and 22 were used for quantitative synthesis. The perioperative use of misoprostol in abdominal hysterectomy (AH) was associated with a lower postoperative Hb drop (0.59 g/dL; 95% confidence interval [CI], 0.39-0.79; p < .01) and blood loss (-96.43 mL; 95% CI, -153.52 to -39.34; p < .01) compared with placebo. Securing the uterine vessels at their origin in laparoscopic hysterectomy (LH) was associated with decreased intraoperative blood loss (-69.07 mL; 95% CI, -135.20 to -2.95; p = .04) but no significant change in postoperative Hb (0.24 g/dL; 95% CI, -0.31 to 0.78; p = .39) compared with securing them by the uterine isthmus. Uterine artery ligation in LH before dissecting the ovarian/utero-ovarian vessels was associated with lower surgical blood loss compared with standard ligation (-27.72 mL; 95% CI, -35.07 to -20.38; p < .01). The postoperative Hb drop was not significantly different with a bipolar electrosurgical device versus suturing in AH (0.26 g/dL; 95% CI, -0.19 to 0.71; p = .26). There was no significant difference between an electrosurgical bipolar vessel sealer (EBVS) and conventional bipolar electrosurgical devices in the Hb drop (0.02 g/dL; 95% CI, -0.15 to 0.20; p = .79) or blood loss (-50.88 mL; 95% CI, -106.44 to 4.68; p = .07) in LH. Blood loss in LH was not decreased with the LigaSure (Medtronic, Minneapolis, MN) impedance monitoring EBVS compared with competing EBVS systems monitoring impedance or temperature (2.00 mL; 95% CI, -8.09 to 12.09; p = .70). No significant differences in hemorrhage, transfusion, or major complications were noted for all interventions. CONCLUSION: Perioperative misoprostol in AH led to a reduction in surgical blood loss and postoperative Hb drop (moderate level of evidence by Grading of Recommendations, Assessment, Development and Evaluation guidelines) although the clinical benefit is likely limited. Remaining interventions, although promising, had at best low-quality evidence to support their use at this time. Larger and rigorously designed randomized trials are needed to establish the optimal set of perioperative interventions for use in hysterectomy for leiomyomas.


Subject(s)
Blood Loss, Surgical/prevention & control , Hysterectomy , Leiomyoma/surgery , Perioperative Care/methods , Uterine Neoplasms/surgery , Female , Humans , Treatment Outcome
19.
Int J Mol Sci ; 18(9)2017 Sep 09.
Article in English | MEDLINE | ID: mdl-28891935

ABSTRACT

Environmental exposure to estrogens and estrogen like contaminants during early development is thought to contribute to the risk of developing breast cancer primarily due to an early onset of puberty; however, exposure during key developing windows may also influence the risk of developing the disease. The goal of this study was to ask whether in utero exposure to the metalloestrogen cadmium alters mammary gland development due to acceleration of puberty onset or to an effect on early development of the mammary gland. The results show that, in addition to advancing the onset of puberty, in utero exposure to the metalloestrogen cadmium altered mammary gland development prior to its effect on puberty onset. In utero exposure resulted in an expansion of the number of mammosphere-forming cells in the neonatal mammary gland and an increase in branching, epithelial cells, and density in the prepubertal mammary gland. In the postpubertal mammary gland, there was a further expansion of the mammary stem/progenitor cell population and overexpression of estrogen receptor-alpha (ERα) that was due to the overexpression and altered regulation of the ERα transcripts derived from exons O and OT in response to estradiol. These results suggest that in utero exposure to cadmium increases stem/progenitor cells, cell density, and expression of estrogen receptor-alpha that may contribute to the risk of developing breast cancer.


Subject(s)
Cadmium/toxicity , Estrogen Receptor alpha/genetics , Mammary Glands, Human/growth & development , Maternal Exposure/adverse effects , Prenatal Exposure Delayed Effects/pathology , Animals , Cells, Cultured , Epithelial Cells/cytology , Epithelial Cells/metabolism , Estrogen Receptor alpha/metabolism , Female , Humans , Mammary Glands, Human/metabolism , Mammary Glands, Human/pathology , Pregnancy , Prenatal Exposure Delayed Effects/genetics , Prenatal Exposure Delayed Effects/metabolism , Rats , Rats, Sprague-Dawley , Stem Cells/cytology , Stem Cells/metabolism
20.
Nature ; 548(7669): 537-542, 2017 08 31.
Article in English | MEDLINE | ID: mdl-28783722

ABSTRACT

Somatic gene mutations can alter the vulnerability of cancer cells to T-cell-based immunotherapies. Here we perturbed genes in human melanoma cells to mimic loss-of-function mutations involved in resistance to these therapies, by using a genome-scale CRISPR-Cas9 library that consisted of around 123,000 single-guide RNAs, and profiled genes whose loss in tumour cells impaired the effector function of CD8+ T cells. The genes that were most enriched in the screen have key roles in antigen presentation and interferon-γ signalling, and correlate with cytolytic activity in patient tumours from The Cancer Genome Atlas. Among the genes validated using different cancer cell lines and antigens, we identified multiple loss-of-function mutations in APLNR, encoding the apelin receptor, in patient tumours that were refractory to immunotherapy. We show that APLNR interacts with JAK1, modulating interferon-γ responses in tumours, and that its functional loss reduces the efficacy of adoptive cell transfer and checkpoint blockade immunotherapies in mouse models. Our results link the loss of essential genes for the effector function of CD8+ T cells with the resistance or non-responsiveness of cancer to immunotherapies.


Subject(s)
Genes, Essential/genetics , Immunotherapy , Neoplasms/genetics , Neoplasms/therapy , T-Lymphocytes, Cytotoxic/drug effects , T-Lymphocytes, Cytotoxic/immunology , Adoptive Transfer , Animals , Antigen Presentation/genetics , Apelin/metabolism , Apelin Receptors/genetics , Apelin Receptors/metabolism , CRISPR-Cas Systems/genetics , Cell Line, Tumor , Female , Genome/genetics , Histocompatibility Antigens Class I/immunology , Humans , Interferon-gamma/immunology , Janus Kinase 1/metabolism , Knowledge Bases , Melanoma/genetics , Melanoma/immunology , Melanoma/metabolism , Melanoma/therapy , Mice , Mutation , Neoplasms/immunology , Neoplasms/metabolism , Reproducibility of Results , T-Lymphocytes, Cytotoxic/metabolism
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