Dr. Litkouhi joined the Stanford Women's Cancer Center in 2019. He was previously faculty at Yale and Harvard universities, and co-chief of gynecologic oncology at John Theurer Cancer Center in Hackensack, NJ. His expertise is in gynecologic surgery and medical and surgical management of gynecologic cancers. He is the program director of the gynecologic oncology fellowship program at Stanford. He has been the recipient of numerous patient-care and teaching awards.
- Gynecologic Oncology
- Gynecologic Cancers
- Ovarian cancer
- Uterine and endometrial cancer
- Cervical cancer
- Vulvar and vaginal cancer
- Gynecologic pre-cancers
- Pelvic Tumors
- Pelvic surgery
- Laparoscopic surgery
- Robotic surgery
- Sentinel lymph node mapping
Clinical Associate Professor, Obstetrics & Gynecology - Gynecologic Oncology
Program Director, Gynecologic Oncology Fellowship, Stanford University School of Medicine (2019 - Present)
Medical Education: Icahn School of Medicine at Mount Sinai (2000) NY
Board Certification: American Board of Obstetrics and Gynecology, Gynecologic Oncology (2011)
Board Certification: American Board of Obstetrics and Gynecology, Obstetrics and Gynecology (2009)
Fellowship: Brigham and Women's Hospital Gynecologic Oncology Fellowship (2007) MA
Residency: Yale New Haven Obstetrics and Gynecology Residency (2004) CT
Reactivated disseminated tuberculosis in pregnancy: Case report and review of the literature.
Case reports in women's health
2023; 37: e00475
This case report describes the evaluation and management of a 32-year-old woman who presented shortly after a fetal demise at 23weeks of gestation with multiple symptoms, including bloody vaginal discharge. Although the initial diagnostic concern was for metastatic malignancy, the patient was ultimately determined to have disseminated tuberculosis. Genital tuberculosis is common worldwide, yet guidelines for evaluation are limited. This report highlights the relationship between pregnancy-reactivated tuberculosis, and guides clinicians on diagnostic and management considerations in the peripartum period.
View details for DOI 10.1016/j.crwh.2022.e00475
View details for PubMedID 36582263
Technetium Tc 99m tilmanocept fails to detect sentinel lymph nodes in endometrial cancer.
Gynecologic oncology reports
2022; 43: 101054
Technetium Tc 99m tilmanocept is a synthetic radiotracer specifically designed for sentinel lymph node (SLN) mapping that has been FDA-approved in breast cancer, melanoma, and head and neck cancer. No published studies exist for the use of this radiotracer in endometrial cancer.The primary objective was to determine the detection rate of bilateral SLNs in endometrial cancer with the concurrent use of technetium Tc 99m tilmanocept and ICG.An open-label, single cohort, prospective feasibility study was conducted with participants receiving preoperative cervical injections of technetium Tc 99m tilmanocept followed by subsequent imaging and SPECT/CT. Intraoperative ICG injections were administered for all patients with near-infrared imaging used to visualize lymphatic vessels and nodes. A laparoscopic gamma counter was used to detect radioactive SLN intraoperatively.All six evaluated patients had FIGO grade 1 or 2 endometrioid histology. Stage IA/IB were in 33% and 66% of patients, respectively. Tilmanocept did not map any SLN in the first six patients but instead showed retention of the tracer in the cervical stroma, leading to study discontinuation for futility. ICG mapped bilateral SLN in all patients with the most common location being the external iliac region, followed by the obturator and common iliac areas. All patients had CD206 positive staining throughout the full wall thickness of ectocervix, transformation zone, endocervix, and lymphatic vessels. No patients experienced adverse events.Technetium Tc 99m tilmanocept did not detect SLN in early stage endometrial cancers and is unlikely to improve bilateral detection rate compared to ICG alone. ICG remains a standard technique for SLN detection in low stage, low grade endometrial cancer.
View details for DOI 10.1016/j.gore.2022.101054
View details for PubMedID 35958955
View details for PubMedCentralID PMC9361318
Prospective molecular classification of endometrial carcinomas: institutional implementation, practice, and clinical experience.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
The comprehensive genomic analysis of endometrial carcinoma (EC) by The Cancer Genome Atlas (TCGA) led to the discovery of four distinct and prognostically significant molecular subgroups. Molecular classification has the potential to improve risk-stratification when integrated with clinicopathologic features and has recently been included in national and international patient management EC guidelines. Thus, the adoption of molecular classification into routine pathologic and clinical practice is likely to grow significantly in the upcoming years. Establishing an efficient and standardized workflow for performing molecular classification on ECs, and reporting both the molecular and histologic findings in an integrative manner, is imperative. Here we describe our effort to implement rapid and routine molecular classification on all ECs diagnosed at our institution. To this effect, we performed immunohistochemistry as a surrogate marker for identifying genetic and/or epigenetic alterations in DNA mismatch repair (e.g., MLH1, PMS2, MSH6, MSH2), and TP53 genes. In addition, we have developed and employed a single-gene POLE SNaPshot assay, which is a rapid and analytically sensitive method for detecting select POLE exonuclease domain mutations (EDMs). We report our molecular testing workflow and integrative reporting system as well as the clinicopathologic and molecular features of 310 ECs that underwent routine molecular classification at our institution. The 310 ECs were molecularly classified as follows: 15 (5%) POLE mutant (POLEmut), 79 (25%) mismatch repair-deficient (MMRd), 135 (44%) no specific molecular profile (NSMP), and 81 (26%) p53 abnormal (p53abnl). This work provides an initial framework for implementing routine molecular classification of ECs.
View details for DOI 10.1038/s41379-021-00963-y
View details for PubMedID 34743187
Stage III uterine serous carcinoma: modern trends in multimodality treatment.
Journal of gynecologic oncology
2020; 31 (4): e53
To examine outcomes in a modern treatment era for stage III uterine serous carcinoma (USC).Fifty women were retrospectively identified as 2009 International Federation of Gynecology and Obstetrics stage III USC patients who received radiotherapy (RT) at our institution between 1/2003-5/2018. The patients were divided into 2 cohorts: 20 in the early era (2003-2010) and 30 in the modern era (2011-2018). Patient characteristics were compared using χ² tests for categorical variables and t-tests for continuous variables. Recurrence free survival (RFS) and overall survival (OS) were analyzed with Kaplan-Meier estimates, the log-rank test, and Cox proportional hazards.The modern era differed from the early era in the increased use of volume-directed external beam RT (EBRT) as opposed to vaginal brachytherapy (VB) alone (33.3% vs 5.0%, p=0.048), minimally invasive surgery (56.7% vs. 25%, p=0.027), sentinel node sampling (26.7% vs. 0%, p=0.012), computed tomography imaging in the perioperative period (63.3% vs. 30%, p=0.044), and human epidermal growth factor receptor 2/neu testing (96.7% vs. 55%, p=0.001). Median follow-up for early and modern eras was 37.27 and 33.23 months, respectively. The early vs. modern 3-year RFS was 33% and 64% (p=0.039), respectively, while the 3-year OS was 55% and 90% (p=0.034). Regional nodal recurrence more common among the patients who received VB only (p=0.048).Modern era treatment was associated with improved RFS and OS in patients with stage III USC. Regional nodal recurrences were significantly reduced in patients who received EBRT.
View details for DOI 10.3802/jgo.2020.31.e53
View details for PubMedID 32266802
View details for PubMedCentralID PMC7286763
Randomized Phase II Trial of Carboplatin-Paclitaxel Compared with Carboplatin-Paclitaxel-Trastuzumab in Advanced (Stage III-IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis.
Clinical cancer research : an official journal of the American Association for Cancer Research
PURPOSE: Uterine-serous-carcinoma (USC) is an aggressive variant of endometrial cancer. On the basis of preliminary results of a multicenter, randomized phase II trial, trastuzumab (T), a humanized-mAb targeting Her2/Neu, in combination with carboplatin/paclitaxel (C/P), is recognized as an alternative in treating advanced/recurrent HER2/Neu-positive USC. We report the updated survival analysis of NCT01367002.PATIENTS AND METHODS: Eligible patients had stage III to IV or recurrent disease. Participants were randomized 1:1 to receive C/P for six cycles ± T followed by maintenance T until progression or toxicity. Progression-free survival (PFS) was the primary endpoint; overall survival (OS) and toxicity were secondary endpoints.RESULTS: Sixty-one patients were randomized. After a median-follow-up of 25.9 months, 43 progressions and 38 deaths occurred among 58 evaluable patients. Updated median-PFS continued to favor the T-arm, with medians of 8.0 months versus 12.9 months in the control and T-arms (HR = 0.46; 90% CI, 0.28-0.76; P = 0.005). Median-PFS was 9.3 months versus 17.7 months among 41 patients with stage III to IV disease undergoing primary treatment (HR = 0.44; 90% CI, 0.23-0.83; P = 0.015), and 7.0 months versus 9.2 months among 17 patients with recurrent disease (HR = 0.12; 90% CI, 0.03-0.48; P = 0.004). OS was higher in the T compared with the control arm, with medians of 29.6 months versus 24.4 months (HR = 0.58; 90% CI, 0.34-0.99; P = 0.046). The benefit was most notable in those with stage III to IV disease, with survival median not reached in the T-arm versus 24.4 months in the control arm (HR = 0.49; 90% CI, 0.25-0.97; P = 0.041). Toxicity was not different between arms.CONCLUSIONS: Addition of T to C/P increased PFS and OS in women with advanced/recurrent HER2/Neu-positive USC, with the greatest benefit seen for the treatment of stage III to IV disease.
View details for DOI 10.1158/1078-0432.CCR-20-0953
View details for PubMedID 32601075
Vulvar sarcoma outcomes by histologic subtype: a Surveillance, Epidemiology, and End Results (SEER) database review.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
Vulvar cancers account for 5% of all gynecologic malignancies; only 1%-3% of those vulvar cancers are primary vulvar sarcomas. Given the rarity of vulvar sarcomas, outcome data specific to histopathologic subtypes are sparse. The aim of this study was to identify clinical and pathologic factors of primary vulvar sarcomas that are associated with survival and may inform treatment decisions.The Surveillance, Epidemiology, and End Results (SEER) database was searched for women diagnosed with vulvar sarcoma between 1973 and 2018. We identified 315 patients and reviewed their demographic, clinicopathologic, surgical, and survival information. Statistical analyses included χ2 and t-tests, Kaplan-Meier survival, and Cox regression analyses.The most common histopathologies of vulvar sarcomas were dermatofibrosarcomas (85/315, 27%) and leiomyosarcomas (72/315, 22.9%). Rhabdomyosarcomas (18/315, 5.7%), liposarcomas (16/315, 5.1%), and malignant fibrous histiocytomas (16/315, 5.1%) were less frequent. The majority of patients underwent surgery (292/315, 92.7%), which included lymph node dissections in 21.6% (63/292). Survival and lymph node involvement varied significantly with histologic subtype. The 5-year disease-specific survival for dermatofibrosarcomas, liposarcomas, and fibrosarcomas was 100% and only 60.3% and 62.5% for malignant fibrous histiocytomas and rhabdomyosarcomas, respectively. None of the patients with (dermato)fibrosarcomas, liposarcomas, or leiomyosarcomas had positive lymph nodes, in contrast to rhabdomyosarcomas and malignant fibrous histiocytomas with 77.8% and 40% positive lymph nodes, respectively. The 5-year disease-specific survival for women with positive lymph nodes was 0%.Vulvar sarcomas are heterogeneous with survival highly dependent on the histopathologic subtype. While surgical excision is the mainstay of treatment for all vulvar sarcomas, staging lymphadenectomy should be deferred for (dermato)fibrosarcomas, liposarcomas, and leiomyosarcomas as there were no cases of lymph nodes metastases.
View details for DOI 10.1136/ijgc-2020-001516
View details for PubMedID 32641392
Outcomes and relapse patterns of stage IB grade 2 or 3 endometrial cancer treated with adjuvant vaginal brachytherapy.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
2020; 30 (1): 48-55
Risk factors for pelvic recurrence in early stage endometrial cancer are poorly understood. We sought to describe outcomes, patterns of failure, and risk factors for recurrence among patients with grade 2-3 endometrial cancer with deep myometrial invasion who were treated with vaginal brachytherapy as sole adjuvant therapy after hysterectomy and lymph node dissection.We retrospectively reviewed the records of stage I patients with grade 2-3 endometrioid histology and ≥50% myometrial invasion treated at an academic institution from January 2005 to December 2017. Only patients with endometrioid histology were included. Mixed histologies, including papillary serous or clear cell components, were excluded. Further exclusion criteria were International Federation of Gynecology and Obstetrics stage IB grade 1 patients, follow-up time less than 3 months, receipt of pelvic irradiation or any form of systemic therapy (chemotherapy, aromatase inhibitor). Overall survival, disease-free survival, and pelvic recurrence-free survival were calculated with Kaplan-Meier methods. Multivariable Cox proportional hazards regression was used to analyze factors associated with overall survival and disease-free survival.Among 131 consecutive patients identified, 111 (85%) patients met the inclusion criteria. The majority (98.2%) underwent lymph node dissection with ≥10 lymph nodes removed in 78.9%. With a median follow-up of 36 months (IQR 12-70 months), the 3-year overall survival, disease-free survival, and pelvic recurrence-free survival were 89.6%, 90.1%, and 92.8%, respectively. Histologic grade 3, older age, and lymphovascular invasion were not associated with inferior outcomes; however, lower uterine segment involvement (p=0.031), tumor size >4 cm (p=0.024), and <10 lymph nodes removed (p=0.032) were associated with reduced disease-free survival on multivariable analysis. Pelvic recurrence occurred in 12 (11%) patients, most often in the setting of synchronous distant disease (n=9), and was significantly more likely with lower uterine segment involvement.Among patients with stage IB grade 2-3 endometrial cancer treated with vaginal brachytherapy, the risk factors for recurrence (larger tumor size and lower uterine segment involvement) in conjunction with established risk factors (high grade, ≥50% myometrial invasion, and lymphovascular invasion) may identify a group of high-risk patients who might benefit from pelvic radiotherapy.
View details for DOI 10.1136/ijgc-2019-000675
View details for PubMedID 31722964
MRI of cervical cancer with a surgical perspective: staging, prognostic implications and pitfalls.
Abdominal radiology (New York)
2019; 44 (7): 2557-2571
Magnetic resonance imaging (MRI) of the pelvis is the most reliable imaging modality for staging, treatment planning, and follow-up of cervical cancer; and its findings may now be incorporated into the International Federation of Gynecology and Obstetrics Federation (FIGO) 2018 clinical staging of cervical cancer. It is imperative that radiologists are familiar with the imaging appearance of the different stages of cervical cancer as well as the post-treatment changes and imaging pitfalls given the respective clinical manifestations, treatment regimens, and prognosis of an accurate diagnosis. In addition to the different stages of cervical cancer, we address the imaging techniques for diagnosis, staging and treatment implications as well as the changes of the new FIGO staging system.The use of MRI to diagnose and stage cervical cancer is steadily increasing and the new FIGO stagi ng system, previously based on clinical examination, now allows the staging or change of staging based on the imaging findings. MRI can evaluate the extent of disease because of its excellent contrast resolution for pelvic tissues and organs, high accuracy and detailed elaboration of the cervical/uterovaginal anatomy.Relevant anatomy, including normal MRI appearance of the cervix, parametria and pelvic ligaments; different stages of cervical cancer on MRI with prognostic and therapeutic implications; MRI sequences, other imaging modalities used in the staging and follow-up, treatment of different stages and the appearance of the cervix and cervical cancer post-treatment. Since clinical implications and therapeutic strategies for cervical cancer treatment vary tremendously according to degree of tumor extension, familiarity with relevant MRI techniques and findings is essential for radiologists. It is important that radiologists interpreting pelvic MRI are aware with the different stages of cervical cancer to provide useful information regarding treatment and prognosis. Pitfalls regarding the interpretation of tumor extension can interfere with an accurate diagnosis and have significant therapeutic implications.
View details for DOI 10.1007/s00261-019-01984-7
View details for PubMedID 30903231
Serial Uterine Artery Embolization for the Treatment of Placenta Percreta in the First Trimester: A Case Report.
Cardiovascular and interventional radiology
2018; 41 (8): 1280-1284
Two patients with placenta percreta underwent uterine artery embolization (UAE) for abnormally invasive placenta (AIP) in the first trimester. Patient 1 had a 9-week cervical ectopic, while Patient 2 had a 9-week cesarean scar pregnancy. Elective termination of pregnancy was performed in both patients. UAE was performed with tris-acryl gelatin microspheres as well as gelfoam until stasis and was repeated in cases of revascularization. Both patients were followed with US/MRI/MRA scans and β-hCG levels. Revascularization occurred in both patients following UAE, requiring multiple embolizations to achieve complete placental involution. Serial bland UAE may be an effective technique in the treatment of first-trimester AIP, with the distinct advantage of maintaining a patient's fertility.Level IV.
View details for DOI 10.1007/s00270-018-1929-9
View details for PubMedID 29556708
View details for PubMedCentralID PMC6428058
Occult Gynecologic Cancer in Women Undergoing Hysterectomy or Myomectomy for Benign Indications.
Obstetrics and gynecology
2018; 131 (4): 642-651
To estimate the prevalence of corpus uteri, cervix uteri, and ovarian malignancy in women undergoing hysterectomy or myomectomy for presumed benign indications.We conducted a secondary analysis of data from the 2014-2015 American College of Surgeons National Surgical Quality Improvement Program. Adult women undergoing hysterectomies and myomectomies without evidence for known or suspected cancer at the beginning of surgery were identified from the database. Our primary outcome measure was pathology-confirmed malignancy in the corpus uteri, cervix uteri, and ovary. We performed adjusted logistic regression analysis to examine the association of patient characteristics with the risk for malignancy.Our sample included 24,076 women undergoing hysterectomy and 2,368 women undergoing myomectomy. Malignancy of the corpus uteri was found in 1.44% (95% CI 1.29-1.59%) of the women undergoing hysterectomy. The prevalence varied considerably across surgical routes with the rate being 0.23% (95% CI 0.06-0.58%) in laparoscopic supracervical hysterectomy and 1.89% (95% CI 1.65-2.14%) in total laparoscopic or laparoscopic-assisted vaginal hysterectomy. Older women were significantly more likely to have preoperatively undetected malignancy of the corpus uteri (adjusted odds ratio 6.46, 95% CI 4.96-8.41 for age 55 years or older vs age 40-54 years). Additionally, 0.60% (95% CI 0.50-0.70%) and 0.19% (95% CI 0.14-0.25%) of the women undergoing hysterectomy were found to have malignancy of the cervix uteri and the ovary, respectively. Among patients undergoing myomectomy, 0.21% (95% CI 0.03-0.40%) were found to have malignancy of the corpus uteri with no occult cervical or ovarian cancer identified.Prevalence of occult corpus uteri, cervical, and ovarian malignancy was 1.44%, 0.60%, and 0.19%, respectively, among women undergoing hysterectomy and it varied by patient age and surgical route.
View details for DOI 10.1097/AOG.0000000000002521
View details for PubMedID 29528920
FIGO Stage III Metastatic Gestational Choriocarcinoma Developed From an Antecedent Partial Hydatidiform Molar Pregnancy Bearing a Numerical Chromosomal Aberration 68, XX: A Case Report and Literature Review.
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists
2016; 35 (2): 162-6
A 36-yr-old, gravida 5 para 4 woman presented with uterine bleeding and was discovered to have a 3.7-cm uterine mass with multiple, bilateral, lung metastases. Six months earlier, the patient was diagnosed with a partial hydatidiform mole that demonstrated a rare chromosomal karyotype 68, XX. The patient's serum β-human chorionic gonadotropin was elevated from baseline to 12,039 mIU/mL before the treatment. A total hysterectomy was performed and revealed a markedly hemorrhagic, extensively necrotic choriocarcinoma. The tumor mass invaded to a depth of 1/3 of the uterine wall thickness. Cytogenetic analysis of the choriocarcinoma revealed the same 68, XX karyotype, as observed in the antecedent partial hydatidiform mole. A clinical diagnosis of advanced stage invasive choriocarcinoma was rendered, with a risk factor score of 5. Following the development of chemoresistance to a single-agent (methotrexate) regimen, the patient subsequently received 5 cycles of chemotherapy (EMA-CO), without any major complication. She is currently >5 yr posttreatment and is asymptomatic. Her most recent imaging studies, including scans of chest and brain, show no evidence of disease, and her serum β-human chorionic gonadotropin level has remained consistently below detectable levels.
View details for DOI 10.1097/PGP.0000000000000215
View details for PubMedID 26352546
Institutional review of primary non-hodgkin lymphoma of the female genital tract: a 33-year experience.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
2014; 24 (7): 1250-5
The aim of this is to provide an updated review of the literature and to report our institutional experience with this rare gynecologic malignancy.The medical records of patients with diagnosis of non-Hodgkin lymphoma of the female genital tract from 1980 to 2013 at the Yale-New Haven Hospital were reviewed retrospectively. Histological classification and staging were determined by the World Health Organization and Ann Arbor systems, respectively. Kaplan-Meier was used to calculate the survival.There were 36 patients with diagnosis of non-Hodgkin lymphoma of the female genital tract and followed for a median of 61 months (0-361 months). The median age of diagnosis was 44 years (19-87 years), and 76% (n = 28) were classified as stage IV.Of these, 4 patients were asymptomatic on presentation, and 13 were identified incidentally during surgery/radiography (n = 9), on prenatal ultrasound (n = 1), and on Papanicolaou test (n = 3). The location of the disease included the ovary (n = 6), uterine corpus and cervix (n= 9), vagina (n = 1), a pelvic mass (n = 7), isolated pelvic/para-aortic lymph nodes (n = 3), and/or multiple sites (n = 9). There were 6 cases that were concomitant with other gynecologic malignancies.Diffuse large B-cell lymphoma (n= 18) was the most common histologic type. A total of 28 patients underwent surgery. Combination chemotherapy was used in 34 patients, with concomitant radiation therapy in 7 and stem cell transplantation in 3. A total of 5 patients had recurrent disease.The overall median survival from the diagnosis of lymphoma was 70 months (0.3-361 months) with a 91% 1-year survival, 86% 5-year survival, and a 79% 10-year survival.Our report is the largest published single-institution experience of this disease. It demonstrates a more favorable prognosis and proposes that with early diagnosis and appropriate therapy, radical gynecologic surgery can be avoided.
View details for DOI 10.1097/IGC.0000000000000201
View details for PubMedID 25010039