Sentinel lymph node (SLN) isolated tumor cells (ITCs) in otherwise stage I/II endometrioid endometrial cancer: To treat or not to treat?

OBJECTIVES: To assess associations between treatment and recurrence-free survival (RFS) among patients with isolated tumor cells (ITCs) in sentinel lymph nodes (SLN) and otherwise stage I/II endometrioid endometrial cancer (EC). METHODS: A multi-institutional retrospective study of patients with SLN ITCs (<200 cells and < 0.2 mm) was performed. Only patients with otherwise stage I/II EC, endometrioid histology, and no evidence of micro-or macrometastases were included. Univariate and multivariable Cox proportional hazard models were used to evaluate associations between treatment, tumor characteristics, and RFS. RESULTS: 175 patients were included. Median follow up time was 31 months. 39% stage IB and 12% stage II disease. 76 (43%) received no adjuvant therapy or vaginal brachytherapy only (NAT/VBT), 21 (12%) had external beam radiation (EBRT), and 78 (45%) received chemotherapy +/- radiation. Patients who received chemotherapy more often had tumors with deep myoinvasion, lymphovascular space invasion (LVSI), and higher grade. Nine (5.1%) patients recurred; 5 distant, 3 retroperitoneal, and 1 vaginal. Extra-vaginal recurrences were similar in patients with or without chemotherapy (5.2% vs 3.8%, p = 0.68). After controlling for stage, LVSI and grade, chemotherapy and EBRT were not associated with RFS (HR = 0.63, 95%CI 0.11-3.52, and HR = 0.90, 95%CI 0.22-3.61, respectively). Type of lymph node dissection and ITC detection method were not associated with RFS. CONCLUSIONS: Risk of retroperitoneal and/or distant recurrence is low (4.6%) for patients with stage I/II endometrioid EC and ITCs in SLNs regardless of treatment. Our preliminary data suggests that adjuvant therapy may not be significantly associated with RFS. However, longer follow-up time and a larger sample size are needed before definitive recommendations regarding adjuvant therapy for patients with EC and only ITCs in SLN can be made.

Pathologic and clinical tumor size discordance in early-stage cervical cancer: Does it matter?

OBJECTIVE: The objective of this study was to assess the rate of discordance between clinical and pathologic tumor size for women with stage IB1 cervical cancer (FIGO 2009 criteria), assess risk factors for discordance, and determine the impact of discordance on oncologic outcomes. METHODS: This was a secondary analysis of a prior multi-institutional retrospective review of patients diagnosed with stage IB1 (FIGO 2009 staging) cervical cancer undergoing radical hysterectomy between 2010 and 2017. Demographic, clinicopathologic, and oncologic data were collected. Pathologic upstaging was defined as having a preoperative diagnosis of stage IB1 cervical cancer with pathology demonstrating a tumor size >4 cm. Demographic and clinicopathologic data was compared using chi-square, fisher exact or 2-sided t-test. Survival was estimated using the Kaplan-Meier method. RESULTS: Of the 630 patients, 77 (12%) were upstaged. Patients who were upstaged had lower rates of preoperative conization (p < .001) or preoperative tumor sizes ≤2 cm (p < .001). Upstaged patients had increased odds of deep stromal invasion, lymphovascular space invasion, positive margins and positive lymph nodes. Almost 88% of upstaged patients received adjuvant therapy compared to 29% of patients with tumors ≤4 cm (odds 18.49, 95% CI 8.99-37.94). Finally, pathologic upstaging was associated with an increased hazard of recurrence (hazard ratio [HR] 1.95, 95% CI 1.03-3.67) and all-cause death (HR 2.31, 95% CI 1.04-5.11). CONCLUSIONS: Pathologic upstaging in stage IB1 cervical cancer is relatively common. Upstaging is associated with an 18-fold increased risk of receipt of adjuvant therapy. Patients undergoing preoperative conization and those with tumors <2 cm had lower risks of upstaging. Improvement in preoperative assessment of tumor size may better inform primary treatment decisions.

Robot-assisted versus open radical hysterectomy: A multi-institutional experience for early-stage cervical cancer.

OBJECTIVE: To compare perioperative and clinico-pathological outcomes of patients with early-stage cervical cancer who underwent robot-assisted radical hysterectomy (RRH) and open radical hysterectomy (ORH). METHODS: This retrospective multi-center study abstracted demographic, clinico-pathological and perioperative outcomes data from medical records of 491 cervical cancer patients treated with RRH (n = 259) ORH (n = 232) between 2005 and 2011 at two American and one Norwegian University Cancer Centres. RESULTS: Mean estimated blood loss (EBL) and transfusion rates were less for RRH than for ORH (97 vs. 49 mL, p < 0.001, and 3% vs. 7%, p = 0.018, respectively). Mean length of hospital stay (LOS) was significantly shorter in RRH versus ORH (1.8 vs. 5.1 days, p < 0.001). Mean operative time was longer for RRH than ORH (220 vs. 156 min, p < 0.001). Although overall complications were similar (p = 0.49), intra-operative complications were less common in the RRH group than ORH (4% vs. 10%, p = 0.004). In multivariate regression analyses longer operative time, less EBL and intra-operative complications, shorter LOS, and more pre-operative cone were significantly associated with RRH versus ORH. Recurrence and death rates were not statistically different for the two groups at a mean follow-up time of 39 months (p = 1.00 and p = 0.48, respectively). CONCLUSIONS: RRH had improved clinical outcomes compared to ORH in the treatment of early-stage cervical cancer in terms of EBL, intra-operative complications, transfusion rates, LOS, and pre-operative cone. Disease recurrence and survival were comparable for the two procedures.

Primary peritoneal low-grade serous carcinoma forming a mass in the colon mimicking a colonic primary carcinoma: a case report.

Primary carcinomas of Müllerian origin involving the colon is not an uncommon phenomenon, with most cases reportedly associated with endometriosis. On the other hand, a primary peritoneal low-grade serous carcinoma presenting as a dominant mass in the colon and causing clinical symptoms mimicking a primary colonic carcinoma has not been reported in the literature to the best of the authors' knowledge. A case of a 66-year-old female patient who presented clinically with rectal bleeding and a rectosigmoid mass is described. The final histologic examination revealed a peritoneal low-grade serous carcinoma forming a dominant mass in the rectosigmoid colon. Of particular interest was a microscopic spectrum of serous epithelial proliferation in the peritoneal cavity and lymph nodes with morphologic features reminiscent of non-invasive and invasive implants in ovarian borderline serous tumors, which most likely denoted the precursors of the tumor in the colon.

Hyperactive EGF receptor, Jaks and Stat3 signaling promote enhanced colony-forming ability, motility and migration of cisplatin-resistant ovarian cancer cells.

We present evidence that the cisplatin-resistant human ovarian cancer lines, A2780S/CP1 (S/CP1), A2780S/CP3 (S/CP3) and A2780S/CP5 (S/CP5), derived by subjecting the sensitive A2780S ovarian cancer line to multiple rounds of cisplatin treatments followed by recovery and are resistant to 1, 3 and 5 µM cisplatin, respectively, have increased colony-forming ability and altered morphology that is consistent with enhanced motility, migration and invasiveness in vitro. The malignant phenotype progresses with increasing resistance and is associated with hyperactive epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (Erk)1/2 and janus kinases (Jaks), aberrant signal transducer and activator of transcription (Stat) 3 activation promoted by EGFR and Jaks, and epithelial-mesenchymal transition (EMT) in vitro. Survivin and FLIP anti-apoptotic factors, vascular endothelial growth factor (VEGF) and matrix metalloproteinase activities are also elevated in the resistant cells. Accordingly, the ectopic expression of constitutively-active Stat3C in the sensitive A2780S cells diminished cisplatin sensitivity. The inhibition of EGFR or Stat3 activity repressed Survivin, VEGF and Vimentin expression and the colony-forming potential, viability, motility and migration of the resistant cells, and sensitized them to cisplatin. Analysis of human ovarian cancer patients' tumor tissues shows aberrantly-active EGFR and Stat3 that in certain cases correlate with Vimentin over-expression. Intra-peritoneal mouse xenograft studies revealed, compared with the sensitive A2780S line that had low tumor incidence restricted to the ovary, a high tumor incidence for the resistant S/CP3 and S/CP5 lines that formed tumor nodules at several locations on the small intestine and colon, and which responded poorly to cisplatin, but were sensitive to concurrent treatment with cisplatin and EGFR or Stat3 inhibitor. Hyperactive EGFR signaling through Stat3 and the Jak-Stat3 activity together promote ovarian cancer progression to cisplatin resistance and therefore represent targets for preventing the development of cisplatin resistance and the recurrent disease during cisplatin therapy in ovarian cancer.

Correlation of extreme drug resistant assay results and progression-free survival following intraperitoneal chemotherapy for advanced ovarian cancer.

The aim of this study was to determine if in vitro extreme drug resistance (EDR) to platinum and/or taxane chemotherapy was predictive of patient response to intraperitoneal (I.P.) chemotherapy in patients with stage III or recurrent epithelial ovarian cancer (EOC). Fifty-six patients were retrospectively identified who underwent optimal cytoreductive surgery for primary or recurrent eOC and then received at least three cycles of either intravenous (I.V.) or I.P. chemotherapy with platinum and paclitaxel-based chemotherapy. EDR to platinum and/or paclitaxel was determined using a commercially available assay (Oncotech, Inc., Tustin, CA). The primary outcome measure was progression-free survival (PFS). Twenty-nine (52%) patients received I.P. chemotherapy and 27 (48%) received I.V. chemotherapy. The patients were well matched in terms of age, stage, grade and histology. Ten (35%) patients in the I.OP. arm and ten (37%) patients in the I.V. arm showed EDR to either platinum and/or paclitaxel. Median PFS for all I.P. chemotherapy patients was 23 months, compared with 13 months for those receiving I.V. chemotherapy (p = 0.04). Patients with EDR to platinum and/or taxane who underwent I.V. chemotherapy had a median PFS of 13.5 months, whereas those who underwent I.P. treatment had a median PFS of 15 months (p = 0.69). Median overall survival had not been reached at the time of analysis.No significant difference in PFS was noted between patients who underwent I.P. and those who underwent I.V. chemotherapy when EDR was predicted to either platinum or paclitaxel or both. These data suggest that the decision to offer I.P. chemotherapy, with the attendant increase in morbidity, in the setting of EDR to platinum and/or taxane chemotherapy, may not be beneficial. Prospective studies, preferably analyzing platinum or taxane EDR individually, are required to validate these observations.

Robotic surgery in gynecology.

Advanced laparoscopic procedures for gynecologic surgery have not been widely adopted in clinical practice despite nearly 20 years of improvements in laparoscopic technology. The da Vinci robotic surgical system was cleared for use in gynecologic surgery in the U.S in 2005. Many surgeons have embraced da Vinci technology over conventional laparoscopy because of its technologic advantages of wristed instrumentation, high definition 3-D optics, ergonomics, and autonomy of camera control. Furthermore, many surgeons with limited advanced laparoscopic skills have successfully converted their practice from primarily laparotomy to minimally invasive surgery using the da Vinci System. The purpose of this article is to review the development of robotic procedures in gynecology through the current literature. This article reviews recent peer-reviewed literature concerning robotic-assisted laparoscopic procedures including hysterectomy, myomectomy, radical hysterectomy, pelvic and aortic lymphadenectomy, trachelectomy, parametrectomy, tubal anastamosis, sacrocolpopexy, and others. The majority of this literature consists of descriptive retrospective case series from the investigator's early experience; in fact these early reports represent innovation of a new operative technique. Some reports compare outcomes to open and standard laparoscopic procedures. Future prospective studies comparing complications, pain, return to routine activity, and long-term clinical outcomes with open and laparoscopic procedures will be necessary to completely appreciate the impact of robotic technology.

An evaluation of Groshong central venous catheters on a gynecologic oncology service.

One hundred ten women with gynecologic malignancies underwent 116 subclavian vein Groshong catheter insertions at the bedside under local anesthesia and intravenous sedation. Three (2.6%) additional patients had unsuccessful insertions because of an inability to access the subclavian vein or thread the guidewire. Fluoroscopy was not used. There was one delayed pneumothorax and no insertion-related infections. The 111 single-lumen catheters used primarily for the administration of chemotherapy are the subject of this report. The mean age of patients was 60 (range 13 to 89) years and their average Gynecologic Oncology Group performance score was 1.1 (range, 0 to 3). Diagnoses include 74 ovarian, 19 cervical, 13 uterine, and 5 other gynecologic malignancies. Hyperalimentation was administered in 16 (14%) patients. Grade IV neutropenia occurred in 57 (51%) patients and 44 (40%) received granulocyte colony-stimulating factor during therapy. The average lifespan of catheters was 247 (range, 37 to 703) days, and 39 (35%) women died from disease with their catheter in situ at a mean time of 288 days. Thirty-seven (33%) catheters were removed after completion of chemotherapy at an average time of 239 (range, 78 to 448) days. As of 1/1/94, 22 patients continued to use their catheters at a mean of 313 (range, 182 to 509) days. The remaining 13 (11.7%) catheters were removed due to complications (7 episodes of bacteremia, 3 tunnel infections, 2 catheter migration/thromboses, and 1 catheter laceration). Twenty episodes of fever in 17 (15.3%) patients were evaluated with blood cultures in the absence of a tunnel infection. None of the 10 culture negative cases resulted in catheter removal, whereas 7 of 10 patients with bacteremia had catheters removed. Exit site infections occurred in 23 (21%) patients and were resolved with local measures and oral antibiotics. The risk of exit site cellulitis was 3.3% per month. When compared to placement of permanent central venous access devices at our institution in the operating room or radiology suite, bedside placement of Groshong catheters resulted in a savings of $1448 and $231 per case, respectively.

The efficacy and safety of the cytobrush during pregnancy.

The safety and efficacy of abrasive cytology, using the cytobrush, were evaluated in 300 pregnant patients. When compared to conventional cytology obtained with a cotton-tipped applicator there was no difference in adverse pregnancy events. Smear adequacy (containing endocervical cells) was statistically (P less than 0.01) and clinically increased from 21 to 86%. The use of abrasive cervical cytology was associated with a twofold increase in the incidence of abnormal smears.

Surgical aspects of cervical cancer.

Surgery maintains an important role in the diagnosis and treatment of premalignant as well as early invasive and recurrent cervical cancer. Although the indications for and benefits of surgical staging remain to be determined, specific procedures frequently are necessary to manage treatment-related complications. The authors review the indications, morbidity, and outcome of these procedures.

Surgical staging of uterine cancer: an analysis of perioperative morbidity.

Surgical staging documented extrauterine disease in 27.9% of 168 patients with apparent early-clinical-stage uterine cancer. An analysis of operative time (78 +/- 21 min), blood loss (332 +/- 160 cc), and surgical site infection risks (4.7%) indicated little additional risk of lymphadenectomy. The long-term risk of lymphocyst (1.3%) or lymphedema (0.7%) was small. The histologic information obtained from staging was utilized to rationally guide the need for adjunctive teletherapy. The overall risk of recurrence (median follow-up, 26 months) with surgical Stage I disease was 2.6%.

Identification of human papillomavirus type 16 in primary and recurrent cervical cancer following radiation therapy.

Formalin-fixed, paraffin-embedded tissue blocks from 13 women with cervical carcinoma that recurred following radiation therapy were evaluated for the presence of human papillomavirus (HPV) by in situ hybridization using ribonucleic acid 35S-labeled probes for HPV types 6, 11, 16, and 18. Ten of thirteen patients also had pretreatment biopsies from their primary tumors available for analysis. HPV 16 was detected in both primary and recurrent lesions in 4 women. In 1 case, HPV was detected in the primary tumor and not in the recurrence. HPV 16 was also present in three recurrent cancers from which primary lesions were not available for probing. Radiation therapy did not alter the hybridization signal strength or pattern, suggesting that the HPV genome copy number was not significantly affected. The persistence of HPV 16 in recurrent cervical carcinoma is consistent with the theory that HPV plays a role in maintaining the malignant state.

The use of in situ hybridization to show human papillomavirus deoxyribonucleic acid in metastatic cancer cells within lymph nodes.

Southern blot hybridization has been used to identify human papillomavirus types in both primary tumors and lymph node metastases. However, this technique requires fresh-frozen tissue and is incapable of localizing deoxyribonucleic acid sequences to specific cell types in the tumor sample. In contrast, in situ hybridization precisely locates viral sequences within tumor cells while preserving cellular architecture. Further, in situ hybridization requires only small samples of formalin-fixed, paraffin-embedded tissues. Five lymph nodes (from four patients) containing metastatic cervical squamous tumor cells (identified with hematoxylin and eosinophil staining) were analyzed with in situ hybridization techniques with human papillomavirus type 16 deoxyribonucleic acid probes labeled with sulfur 35. The primary cervical cancer from all four patients had been shown to contain human papillomavirus type 16 sequences by Southern blot. Three specimens from two patients clearly showed the presence of human papillomavirus type 16 sequences within the nuclei of metastatic tumor cells, whereas two specimens were nondiagnostic most likely as a result of the small volume of cancer relative to the size of the lymph node. This information indicates that it is the tumor cells themselves that contain viral deoxyribonucleic acid and provides additional evidence linking human papillomavirus with cervical carcinogenesis.

Hysterectomy with extended surgical staging and radiotherapy versus hysterectomy alone and radiotherapy in stage I endometrial cancer: a comparison of complication rates.

Extended surgical staging (ESS) has been added to total hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) in patients with clinical Stage I endometrial cancer in order to better define patterns of metastatic spread and the response to treatment. Adjuvant radiotherapy has a demonstrated efficacy in decreasing central recurrence in Stage I disease. The combined use of radical surgery and pelvic radiotherapy for cervical cancer patients results in an increased incidence of complications. This study compares major complication rates in Stage I endometrial cancer patients who underwent either TAHBSO with ESS or TAHBSO alone followed by adjuvant external beam radiotherapy (RT). Records of 52 patients with clinical stage I endometrial cancer were reviewed. Thirty-two patients underwent TAHBSO plus ESS and 20 patients had TAHBSO alone. All patients received postoperative, whole pelvis external radiotherapy. Four patients suffered complications potentially related to treatment which required rehospitalization, and all 4 were in the group which had undergone ESS. A comparison of complication rates between the ESS + RT group (4/37 or 10.8%) and TAHBSO + RT group (0/20) suggested a trend toward significance (P less than 0.10). Treatment protocols using extended surgical staging prior to adjuvant radiotherapy in Stage I endometrial cancer should examine complications potentially related to this combination, to further define treatment risks and benefits.

Monitoring the course of cervical carcinoma with the squamous cell carcinoma serum radioimmunoassay.

Serum samples were collected from 611 gynecologic patients for measurement of squamous cell carcinoma antigen levels using the Abbott Laboratories squamous cell carcinoma antigen radioimmunoassay kit. Sixteen of 83 patients (19.3%) with cervical dysplasia and 72 of 135 (53.3%) with primary or recurrent cervical carcinoma had levels above 2.4 ng/mL. In contrast, only seven of 373 women (1.9%) without genital tract squamous cell intraepithelial neoplasia or carcinoma had squamous cell carcinoma antigen levels above 2.4 ng/mL. Fifty-six patients with cervical cancer were followed for correlation of squamous cell carcinoma antigen levels to disease course, and 20 had persistent or recurrent disease after therapy; rising squamous cell carcinoma antigen levels predicted disease in 15 of these 20 patients with recurrence (13 of 15 with elevated pre-treatment levels and two of five with normal pre-treatment levels). Rising squamous cell carcinoma antigen levels preceded the clinical detection of disease in ten patients by a mean of 4.6 months (range 2-7.5 months); in the remaining five, squamous cell carcinoma antigen levels were elevated only when disease recurrence was documented. Although measurement of squamous cell carcinoma antigen levels is not a sensitive screening method for cervical cancer (sensitivity 53.3%), the test has good specificity (94.3%); the majority of patients with false-positive elevations had other genital tract squamous cell neoplasias. The squamous cell carcinoma antigen assay may be a useful aid for monitoring the disease course of cervical carcinoma.

Melanosis of the cervix.

Benign and malignant melanotic cervical lesions are rare and require biopsy to rule out melanoma. Reported is a case of cervical melanosis, defined as benign epithelial pigmentation.

Psammoma bodies in a cervicovaginal smear associated with an intrauterine device. A case report.

Psammoma bodies were found in a cervicovaginal smear, presumably related to the patient's use of an intrauterine device. Colposcopy, endocervical and uterine curettage, and laparoscopy with pelvic washings ruled out other conditions that may be associated with psammoma bodies.