vNOTES (vaginal natural orifice transluminal surgery) gynecologic procedures in morbidly and super-morbidly obese women: five year experience.

PURPOSE: To analyze our experience with vNOTES gynecologic procedures in women with morbid and super morbid obesity to determine feasibility and compare outcomes with standard minimally invasive techniques. METHODS: Gynecologic procedures performed by three surgeons on women with a body mass index (BMI) ≥ 40 kg/m2 from 2017 to 2023. A subset of women with a BMI ≥ 50 kg/m2 was also analyzed. RESULTS: 103 women with a BMI ≥ 40 kg/m2 were identified (Class IV), 19 of whom had a BMI ≥ 50 kg/m2 (Class V). For the entire population the mean BMI was 45.7 kg/m2 (40-62). 29 women were nulliparous and 23 had at least one prior cesarean delivery. 51 had no prior abdominal surgery. The procedures performed were hysterectomy and removal of adnexae in 77 patients, hysterectomy alone in six, adnexal surgery alone in nine, and hysterectomy with adnexectomy and lymph nodes in five. Two surgeries were converted to laparoscopy and five to laparotomy. Average surgical time was 87 min (30-232). Average blood loss was 82 mL (10-400). Mean uterine weight was 206 g (29-2890). 53 procedures were performed as outpatient, 44 had overnight observation, four had a length of stay of 2 days, one each for 4 days and 5 days. The laparoscopies occurred in one patient with an obliterated cul-de-sac and in one patient for lymph node removal. The laparotomies occurred for adnexal adhesions in one, bleeding in two, a cystotomy in one requiring urology consultation, and an obliterated cul-de-sac One patient developed a postoperative vaginal cuff hematoma not requiring intervention. CONCLUSION: vNOTES gynecologic procedures are feasible in this high-risk population and may result in shorter recovery times and fewer complications than standard laparoscopy or transvaginal surgery. What does this study add to the clinical work: VNOTES approach is feasible in morbidly obese women and may have distinct advantages over conventional laparoscopic, vaginal or open techniques.

Radiation treatment for refractory endometriosis: a 38-year-old female presenting with vaginal bleeding.

BACKGROUND: Endometriosis is typically managed with a medical or surgical approach, though some patients have medically refractory disease and are poor surgical candidates. CASE PRESENTATION: A 39-year-old woman presented to our facility with uncontrolled bleeding and pain from an endometriotic mass at the vaginal cuff. She had a history of abdominal hysterectomy with bilateral salpingo-oophorectomy, now with medically refractive and inoperable disease due to prior history of vesicovaginal fistula. We prescribed 30 Gy in 10 fractions with 10 MV and 18 MV photons to the target. At follow-up our patient reported a complete resolution of bleeding and pelvic pain. CONCLUSION: Radiation treatment can be an effective treatment for refractory endometriosis.

Metformin Promotes Anti-tumor Biomarkers in Human Endometrial Cancer Cells.

Metformin (MET) is increasingly implicated in reducing the incidence of multiple cancer types in patients with diabetes. However, similar effects of MET in non-diabetic women with endometrial cancer (EC) remain unknown. In a pilot study, obese non-diabetic women diagnosed with type 1, grade 1/2 EC, and consenting to participate were randomly assigned to receive MET or no MET (control (CON)) during the pre-surgical window between diagnosis and hysterectomy. Endometrial tumors obtained at surgery (MET, n = 4; CON, n = 4) were analyzed for proliferation (Ki67), apoptosis (TUNEL), and nuclear expression of ERα, PGR, PTEN, and KLF9 proteins in tumor glandular epithelial (GE) and stromal (ST) cells. The percentages of immunopositive cells for PGR and for KLF9 in GE and for PTEN in ST were higher while those for ERα in GE but not ST were lower, in tumors of MET vs. CON patients. The numbers of Ki67- and TUNEL-positive cells in tumor GE and ST did not differ between groups. In human Ishikawa endometrial cancer cells, MET treatment (60 µM) decreased cell numbers and elicited distinct temporal changes in ESR1, KLF9, PGR, PGR-B, KLF4, DKK1, and other tumor biomarker mRNA levels. In the context of reduced KLF9 expression (by siRNA targeting), MET rapidly amplified PGR, PGR-B, and KLF4 transcript levels. Our findings suggest that MET acts directly in EC cells to modify steroid receptor expression and signaling network and may constitute a preventative strategy against EC in high-risk non-diabetic women.

Use of Metformin in Obese Women With Type I Endometrial Cancer Is Associated With a Reduced Incidence of Cancer Recurrence.

OBJECTIVES: Recent evidence suggests that hyperinsulinemia associated with obesity may be a significant risk factor for the development of endometrial cancer. Metformin is used in type II diabetes to lower circulating insulin levels. We sought to examine our obese patients with endometrial cancer and examine those who were on metformin to determine any impact on their cancer course. METHODS: A retrospective review of all women with the diagnosis of endometrial cancer and a body mass index of 30 kg/m(2) or higher during a 6-year period (2005-2011) at our institution was conducted. Records were reviewed for standard demographic data, use of metformin, cancer characteristics, treatment, and cancer follow-up. RESULTS: A total of 351 women were identified who were obese and diagnosed as having endometrial cancer. Of these, 64 were on metformin (M+) at the time of diagnosis of endometrial cancer. The women on metformin had a significantly higher mean body mass index (44.6 vs 41.6, P < 0.05). Age, grade, stage, and adjuvant therapy did not differ between the 2 groups. Recurrence occurred in 15.3% of the M- women versus 7.8% of the M+ women (not significant). However, for those patients with type I endometrial cancer, only 1 patient (1.9%) who was on metformin recurred versus 10.3% who were not on the drug (P = 0.05). With a minimum of 24 months of follow-up, 89.1% of metformin users were alive and free of disease versus 83.9% of nonusers (not significant). CONCLUSIONS: Obese women who developed endometrial cancer while on metformin did not seem to have pathologic risk factors different from those not on metformin. However, the type I cancer patients on metformin were less likely to recur than those not on the drug. This suggests that a prospective trial of metformin at the time of diagnosis of endometrial cancer in the obese population may be warranted.

Novel Use of Proteomic Profiles in a Convex-Hull Ensemble Classifier to Predict Gynecological Cancer Patients' Susceptibility to Gastrointestinal Mucositis as Side Effect of Radiation Therapy.

BACKGROUND: Whole-pelvis radiation therapy is common practice in the post-surgical treatment of cervical and endometrial cancer. Gastrointestinal mucositis is an adverse side effect of radiation therapy, and is a primary concern in patient management. We investigate whether proteomic information obtained from blood samples drawn from patients scheduled to receive radiation therapy for gynecological cancers could be used to predict which patients are most susceptible to radiation-induced gastrointestinal mucositis, in order to improve the individualization of radiation therapy. METHODS: We use 132 proteins measured on 17 gynecological cancer patients in a convex-hull-based, selective-voting ensemble classifier to classify each patient into one of two classes: patients who would not (class 1) or would (class 2) develop gastrointestinal mucositis. We employ 20 repetitions of 10-fold cross-validation to measure classification accuracy. RESULTS: We achieved a 95% confidence interval on average prediction accuracy of (0.711, 0.771) using pre-radiation proteomic profiles to predict which patients would experience gastrointestinal mucositis. Pathway analysis of the 12 most prominent proteins indicated that they could be assembled into a single interaction network with direct associations. The function associated with the highest number of these 12 proteins was cell-to-cell signaling and interaction. CONCLUSIONS: Pre-radiation proteomic profiles have the potential to classify cervical/endometrial cancer patients with high accuracy as to their susceptibility to gastrointestinal mucositis following radiation therapy. Further study of the network of 12 identified proteins is warranted with a larger patient sample to confirm that these proteins are predictive of gastrointestinal mucositis in this patient population.

Ovarian tumor ascites CD14+ cells suppress dendritic cell-activated CD4+ T-cell responses through IL-10 secretion and indoleamine 2,3-dioxygenase.

The observation that Th17 infiltration in ovarian cancer correlates with markedly improved survival has prompted the question of whether ovarian tumor antigen-specific Th17 responses could be stimulated by tumor vaccination. Dendritic cells (DCs) treated with IL-15 and an inhibitor of p38 MAPK signaling (DC(IL-15/p38inhib)) bias T-cell responses toward a Th1/Th17 phenotype, raising the prospect of therapeutic vaccination; however, significant barriers remain. Tumor vaccines, including DC vaccination, usually stimulate immune responses, but the lack of clinical responses in cancer patients has been disappointing. Possible reasons may include an inability of antitumor T cells to migrate into the tumor microenvironment, and an inability of T cells to retain effector function in the face of tumor-associated immune suppression. We found that ovarian tumor antigen-specific CD4(+) T cells induced by DC(IL-15/p38inhib) migrated in response to CXCL12 and CCL22 (both highly expressed in ovarian cancer) and to ascites CD14(+) myeloid cells. Cocultures showed that ascites CD14(+) cells markedly suppressed antigen-specific CD4(+) T responses, but suppression could be alleviated by treatment with anti-IL-10 or inhibition of indoleamine 2,3-dioxygenase. These results suggest that the efficacy of DC vaccination against ovarian cancer may be boosted by agents that inhibit tumor-associated CD14(+) myeloid cell suppression or indoleamine 2,3-dioxygenase activity.

Radiation lethality potentiation in total body irradiated mice by a commonly prescribed proton pump inhibitor, Pantoprazole sodium.

PURPOSE: Pantoprazole sodium (Protonix) is a proton pump inhibitor (PPI) widely used to treat peptic ulcer and gastroesophageal reflux due to its ability to inhibit gastric acid secretion. Therefore, a large group of the population exposed to total body irradiation (TBI) in the event of a nuclear disaster would be on this or similar medications. We investigated the effect of pantoprazole on TBI-induced lethality in mice. METHODS AND MATERIALS: Male CD2F1 mice were exposed to various doses of uniform TBI using a (137)Cs irradiator. Pantoprazole was administered by twice daily subcutaneous injection in saline from 4 days before to 5 days after irradiation. Effects on gastric pH, and gastrointestinal (GI) and hematopoietic toxicity were evaluated. RESULTS: Pantoprazole administration significantly exacerbated 30 day lethality and gastrointestinal toxicity. Median survival after 9.0 Gy TBI was reduced from 22 days to 12 days (p = 0.006). Pantoprazole adversely effected intestinal crypt survival and mucosal surface area. In contrast, equivalent doses of a histamine type-2(H2) receptor blocker (cimetidine) did not alter TBI-induced lethality. CONCLUSION: The adverse effect of pantoprazole on TBI-induced lethality is highly important because of the widespread use of PPI in the general population, as well as use of these drugs for acid suppression in individuals exposed to radiation. Further studies of the mechanisms underlying the adverse effect of PPI after exposure to TBI are clearly warranted. Until results from such studies are available, other acid-suppressing strategies should be preferred in the context of radiation exposure.

Oral interleukin 11 as a countermeasure to lethal total-body irradiation in a murine model.

Countermeasures against radiation are critically needed. Ideally, these measures would be easy to store, easy to administer and have minimal toxicity. We used oral delivery of interleukin 11 (IL11) in mice exposed to lethal doses of total-body irradiation (TBI). Animals were given IL11 by gavage at various daily doses beginning 24 h after TBI, which continued for 5 days. At a TBI of 9.0 Gy, mice treated with IL11 had a 70% survival at 30 days compared with control group survival of 25% (P = 0.035). At 10.0 Gy, treated animals had 50% survival at 30 days compared with no survivors in the control group. Treated animals had significant improvement in intestinal mucosal surface area and crypt survival. In addition bacterial translocation of coliform bacteria was significantly less in the treated animals. Systemic absorption of IL11 was low in treated animals and effects on the hematopoietic cells were not seen. Serum citrulline levels rebounded significantly faster after irradiation in the IL11 treated animals, indicating quicker recovery of small intestine health. These data suggest that IL11 given orally protects the intestinal mucosa from radiation damage and that this compound is beneficial as a mitigating agent even when started 24 h after radiation exposure.

Multimodal hyperspectroscopy as a triage test for cervical neoplasia: pivotal clinical trial results.

OBJECTIVE: To prospectively evaluate a new non invasive device that combines fluorescence and reflectance spectroscopy in a population in women at risk for cervical dysplasia. METHODS: A total of 1607 women were evaluated with multimodal hyperspectroscopy (MHS), a painless test with extremely high spectral resolution. Subjects who were referred to colposcopy based on abnormal screening tests or other referral criteria underwent the MHS test and also had a sample taken for additional cytology and presence of high risk human papilloma virus (HPV) prior to undergoing biopsy. RESULTS: Sensitivity of MHS for cervical intraepithelial neoplasia (CIN) 2+ was 91.3% (252/276). Specificity, or the potential reduction in referrals to colposcopy and biopsy, was 38.9% (222/570) for women with normal or benign histology and 30.3% (182/601) for women with CIN1 histology. Two year follow-up data, collected for a subgroup of 804 women, revealed 67 interval CIN2+ that originally were diagnosed at enrollment as normal or CIN1. MHS identified 60 of these (89.6%) as positive for CIN2+ prior to their discovery during the two year follow-up period. CONCLUSIONS: MHS provides an immediate result at the point of care. Recently, the limitations of cytology have become more obvious and as a consequence greater emphasis is being placed on HPV testing for cervical cancer screening, creating a need for an inexpensive, convenient and accurate test to reduce false positive referrals to colposcopy and increase the yield of CIN2+ at biopsy. MHS appears to have many of the attributes necessary for such an application.

Krüppel-like factor 9 loss-of-expression in human endometrial carcinoma links altered expression of growth-regulatory genes with aberrant proliferative response to estrogen.

Endometrial cancer is the most commonly diagnosed female genital tract malignancy. Krüppel-like factor 9 (KLF9), a member of the evolutionarily conserved Sp family of transcription factors, is expressed in uterine stroma and glandular epithelium, where it affects cellular proliferation, differentiation, and apoptosis. Deregulated expression of a number of Sp proteins has been associated with multiple types of human tumors, but a role for KLF9 in endometrial cancer development and/or progression is unknown. Here, we evaluated KLF9 expression in endometrial tumors and adjacent uninvolved endometrium of women with endometrial carcinoma. KLF9 mRNA and protein levels were lower in endometrial tumors coincident with decreased expression of family member KLF4 and growth-regulators FBJ murine osteosarcoma viral oncogene homolog (FOS) and myelocytomatosis viral oncogene homolog (MYC) and with increased expression of telomerase reverse transcriptase (TERT) and the chromatin-modifying enzymes DNA methyltransferase 1 (DNMT1) and histone deacetylase 3 (HDAC3). Expression of estrogen receptor alpha (ESR1) and the tumor-suppressor phosphatase and tensin homolog deleted in chromosome 10 (PTEN) did not differ between tumor and normal tissue. The functional relevance of attenuated KLF9 expression in endometrial carcinogenesis was further evaluated in the human endometrial carcinoma cell line Ishikawa by siRNA targeting. KLF9 depletion resulted in loss of normal cellular response to the proliferative effects of estrogen concomitant with reductions in KLF4 and MYC and with enhancement of TERT and ESR1 gene expression. Silencing of KLF4 did not mimic the effects of silencing KLF9 in Ishikawa cells. We suggest that KLF9 loss-of-expression accompanying endometrial carcinogenesis may predispose endometrial epithelial cells to mechanisms of escape from estrogen-mediated growth regulation, leading to progression of established neoplasms.

Lower extremity glandography (LEG): a new concept to identify and enhance lymphatic preservation.

BACKGROUND: Lower extremity edema remains a major postoperative complication after inguinal lymphadenectomy for vulvar cancer. This study documents the lymphatic drainage of the vulva versus the lymphatic drainage of the lower extremity coming through the femoral triangle. METHODS: Seven patients underwent either unilateral or bilateral inguinal lymphadenectomy in conjunction with a radical vulvar resection. Preoperatively, patients had technetium-99 injected into the vulvar cancer. Isosulfan blue was injected into the medioanterior thigh 10 cm below the inguinal ligament. The femoral triangle was opened, and a neoprobe was used to locate the "hot" node bearing the technetium-99. Gentle dissection located the blue lymphatic channel and any blue lymph nodes. The blue and hot nodes were resected and submitted separately. The patients then underwent a complete inguinal lymphadenectomy. RESULTS: A total of 11 groin dissections were performed. In 9 of the 11 groins, the hot node was identified, and in 8 of the 11 groins, blue node or lymphatic channel was identified. The hot nodes were uniformly located on the superior medial aspect of the femoral triangle. The blue nodes were uniformly located on the lateral aspect of the femoral triangle just anterior to the femoral artery or vein. Three patients had hot lymph nodes containing cancer. Of those 3 patients, one had an additional node positive. None of the blue lymph nodes contained cancer. CONCLUSIONS: This procedure demonstrates the alternative lymphatic drainage of the leg versus the vulva. Larger studies are necessary to document the exclusivity of these 2 drainage systems. Preservation of the lymphatic drainage of the leg may result in decreased lymphedema.

Local administration of interleukin-11 ameliorates intestinal radiation injury in rats.

Intestinal radiation injury is dose limiting during abdominal and pelvic radiotherapy and critical for the outcome after accidental whole-body radiation exposure. The multifunctional cytokine, interleukin-11 (IL-11), ameliorates the intestinal radiation response, but its clinical use is hampered by severe toxicity after systemic administration. This study addressed whether protection against intestinal radiation injury can be achieved by intraluminal administration of IL-11. Male rats underwent surgical transposition of a 4-cm small bowel loop to the scrotum. For repeated intraluminal drug administration, an ileostomy, proximal to the bowel loop in the scrotum, was created. The transposed intestinal loop was exposed to 5 Gy fractions on 9 consecutive days. Recombinant human IL-11 (rhIL-11; 2 mg/kg/d) or vehicle was given through the ileostomy from 2 days before until 2 weeks after irradiation. At 2 weeks, structural, cellular, and molecular aspects of intestinal radiation injury were assessed. rhIL-11 ameliorated structural manifestations of radiation enteropathy, including radiation injury score (6.5 +/- 0.6 in the vehicle group versus 4.0 +/- 0.3 in the IL-11 group; P = 0.001), mucosal surface area loss (0.2 +/- 0.1 versus 0.5 +/- 0.03; P < 0.0001), and intestinal wall thickening (842 +/- 66 microm versus 643 +/- 54 microm; P = 0.02), reduced postradiation transforming growth factor-beta overexpression, and reduced numbers of ED2-positive cells. Postirradiation mucosal mast cell numbers were partially restored by rhIL-11. These data show that local administration of rhIL-11 ameliorates early intestinal radiation injury and support further development of rhIL-11 to reduce manifestations of intestinal radiation injury in the clinic.

Metastatic uterine leiomyosarcoma regression using an aromatase inhibitor.

BACKGROUND: Metastatic and disseminated uterine leiomyosarcoma has limited chemotherapeutic options. CASE: A 45-year-old nulligravida was originally diagnosed with a primary uterine leiomyosarcoma and treated with a total abdominal hysterectomy, followed by six courses of adjuvant platinum and doxorubicin chemotherapy. Three years later she developed multiple metastatic tumor nodules in the lungs. Because of the estrogen receptor positivity of the leiomyosarcoma by immunohistochemistry, she was treated with 1 mg of anastrozole daily. Progressive tumor regression was demonstrated by serial imaging in all metastatic lung tumor deposits, with an objective response lasting at least 12 months. CONCLUSION: Uterine leiomyosarcoma metastatic to the lungs regressed with the use of the anastrozole aromatase inhibitor.

Overexpression of epidermal growth factor type-1 receptor (EGF-R1) in cervical cancer: implications for Cetuximab-mediated therapy in recurrent/metastatic disease.

OBJECTIVES: To evaluate and compare epidermal growth factor type-1 receptor (EGF-R1) expression in short term and established cervical cancer cell lines generated from primary and metastatic/recurrent sites of disease. To evaluate the sensitivity of cervical cancer cell lines to treatment with a chimeric MAb against EGFR-1 (Cetuximab). METHODS: EGFR-1 expression was evaluated by flow cytometry on 22 cervical cancer cell lines including 14 primary cervical cancer cell lines obtained from cervical biopsies (11 patients) and recurrent sites of disease (three patients) as well as eight established cell lines. Tumor cell lines were tested for sensitivity to Cetuximab-mediated complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) in 51Cr release assays. Finally, Cetuximab-mediated inhibition of cell proliferation was also tested. RESULTS: Fourteen out of fourteen (100%) primary tumors and seven out of eight (87.5%) established cervical cancer cell lines expressed EGFR-1 by flow cytometry. Cell lines from recurrent/metastatic sites of disease expressed higher levels of EGFR-1 when compared to those obtained from primary sites (p>0.05). Minimal CDC was detected in the majority of cervical cancer cell lines exposed to complement+/-Cetuximab in the absence of peripheral blood lymphocytes (PBL). In contrast, cervical tumor cell lines were found highly sensitive to Cetuximab-mediated ADCC when challenged with PBL from either healthy donors or cervical cancer patients. Importantly, ADCC was further increased in the presence of complement. Finally, tumor proliferation was significantly inhibited by Cetuximab in all cervical tumors tested. CONCLUSIONS: EGFR-1 is highly expressed in primary and recurrent cervical tumors. Cetuximab might be a novel and attractive therapeutic strategy in patients harboring chemotherapy-resistant, recurrent, or metastatic cervical cancer.

Radical trachelectomy with laparoscopic lymphadenectomy: review of oncologic and obstetrical outcomes.

PURPOSE OF REVIEW: Fertility preservation in early cervical cancer by radical trachelectomy is gaining in acceptance as more cases are published in the literature. Controversies regarding technique and patient management are beginning to emerge as the procedure moves from being a new surgery to a part of standard of care. RECENT FINDINGS: As the number of cases reported in the literature increases, the effectiveness of radical trachelectomy for treating selected early-stage cancers continues to gain support. The survival of selected patients appears to be no different than that of similar patients treated with radical hysterectomy. Central recurrence in the residual cervix is a very rare event as long as the specimen has cleared the cancer. Patient selection criteria have evolved, and a more liberal use of the procedure is warranted. The effectiveness of trachelectomy in preserving fertility has now been demonstrated in series of 50 and 56 pregnancies occurring after the procedure. These larger series detail pregnancy outcomes and will be invaluable information to our patients who wish to maintain their ability to bear children. Subtle differences in technique between centers may account for different pregnancy outcomes. As more physicians begin to perform radical trachelectomy, controlled trials will be necessary to refine the procedure in order to continue to improve obstetric and oncologic outcomes. SUMMARY: Radical trachelectomy will continue to increase in popularity as more physicians become willing to learn the technique. It should routinely be offered to young women with early cervix cancer who desire to maintain their fertility.

Adjuvant therapy of completely resected dysgerminoma with carboplatin and etoposide: a trial of the Gynecologic Oncology Group.

OBJECTIVE: This study was designed to evaluate the effect of adjuvant chemotherapy with carboplatin and etoposide in patients with completely resected stage IB-III dysgerminoma. METHODS: Eligible patients were treated with three courses of carboplatin 400 mg/m(2) on day 1 plus etoposide 120 mg/m(2) on days 1, 2, and 3 every 4 weeks for three courses. RESULTS: Forty-two patients were entered on this trial, of whom 39 were eligible. No patient suffered a recurrence of dysgerminoma, but one patient ultimately died of lung adenocarcinoma. One patient was excluded on pathology review (elements of endodermal sinus tumor were present) developed recurrent tumor and died despite further therapy. As expected, the regimen was well tolerated. Median follow-up of surviving patients is 7.8 years (range: 2.86 months to 10.92 years). CONCLUSION: The regimen used in this study is an alternative to cisplatin, etoposide, and bleomycin (BEP) for selected patients for whom minimizing toxicity (particularly neuropathy) is critical or for whom reduction in the number of treatment days is important.

Anastrozole, an aromatase inhibitor, and medroxyprogesterone acetate therapy in premenopausal obese women with endometrial cancer: a report of two cases successfully treated without hysterectomy.

BACKGROUND: Hormonal therapy for endometrial cancer is occasionally warranted in the premenopausal woman who is interested in maintaining fertility. Combining progesterone with an agent that eliminates the adipose production of estrogen will theoretically be more effective than progesterone alone. CASES: Two cases of reproductive-aged women with grade 1 endometrial cancer who were treated with medroxyprogesterone acetate and anastrozole daily for 3 and 6 months subsequently reverted to normal endometrium. CONCLUSION: Progesterone combined with the elimination of adipose production of estrogen may be an effective therapy in well-differentiated endometrial cancer in the obese premenopausal woman.

Extraperitoneal laparoscopic lymph node staging: the University of Southern California experience.

OBJECTIVES: To describe our experience with extraperitoneal lymph node staging in gynecologic oncology. MATERIALS AND METHODS: The extraperitoneal approach was performed to assess the lymph node histology in patients with gynecologic malignancies. The nodes are approached from a lateral approach after dissecting open the extraperitoneal space bluntly and with insufflation. Bilateral aortic nodes are taken from a left-sided or right-sided approach depending on the patient's characteristics. RESULTS: Forty-six patients underwent this procedure over a 2.5-year period. Thirty-seven patients had cervical cancer. The median BMI was 27.1 (17.7-38.1). The median lymph node yield was 14 (0-60). Two patients had disruption of the peritoneum such that the aortic lymphadenectomy had to be completed transperitoneally. No patients required laparotomy. No patients required transfusion. DISCUSSION: This technique permits histologic evaluation of the retroperitoneal nodes with minimal risk of intraabdominal adhesions. Recovery is rapid and further therapy can be prescribed shortly. The data on the nodes can assist in treatment planning.

Radiation therapy with and without extrafascial hysterectomy for bulky stage IB cervical carcinoma: a randomized trial of the Gynecologic Oncology Group.

OBJECTIVE: To evaluate, in a randomized clinical trial, the role of adjuvant hysterectomy after standardized radiation in improving progression-free survival and survival for patients with "bulky" stage IB cervical cancer. METHODS: A total of 256 eligible patients with exophytic or "barrel" shaped tumors measuring > or = 4 cm were randomized to either external and intracavitary irradiation (RT, N = 124) or attenuated irradiation followed by extrafascial hysterectomy (RT + HYST, N = 132). Twenty-five percent of patients had tumors with a maximum diameter of > or =7 cm. RESULT: Tumor size was the most pronounced prognostic factor followed by performance status 2 and age at diagnosis. Hysterectomy did not increase the frequency of reported grade 3 and 4 adverse effects (both groups, 10%). The majority of these adverse effects were from the gastrointestinal or genitourinary tracts exclusively. There was a lower cumulative incidence of local relapse in the RT + HYST group (at 5 years, 27% vs. 14%). There were no statistical differences in outcomes between regimens except for the adjusted comparison of progression-free survival, although all indicated a lower risk in the adjuvant hysterectomy regimen (unadjusted relative risk [URR] of progression, 0.77, P = 0.07; URR of death, P = 0.26, both one tail). CONCLUSION: Overall, there was no clinically important benefit with the use of extrafascial hysterectomy. However, there is good evidence to suggest that patients with 4-, 5-, and 6-cm tumors may have benefitted from extrafascial hysterectomy (URR of progression; 0.58; URR of death, 0.60).

Radical vaginal trachelectomy and pelvic lymphadenectomy for preservation of fertility in early cervical carcinoma.

OBJECTIVE: The aim of this study was to examine our experience with radical vaginal trachelectomy in women with early cervical cancers who desire to maintain fertility. METHODS: Women who underwent radical vaginal trachelectomy with pelvic lymphadenectomy over a 6-year period are the basis of this report. Subjects were selected for this treatment on the basis of favorable cervical tumors and a desire to maintain fertility. All subjects were informed that this therapy did not represent standard treatment for early stage cervical cancer. Obstetrical and oncologic outcomes were evaluated. RESULTS: Twenty-one women underwent this procedure. The median age was 30 years (range 23-41); 14 were nulligravid and 16 were nulliparous. Mean tumor diameter was 1.1 cm (range 0.3-3.0). Mean operative time was 318 min, with a mean blood loss of 293 cc, and average hospital stay was 3 days. Three patients had transient neuropathy postoperatively. No patient required laparotomy. Two patients had completion of radical vaginal hysterectomy for an inability to clear the cancer with trachelectomy and 1 had postoperative radiation for high-risk features on final pathology. With an average follow-up of 31.5 months, there have been no recurrences. Three women have become pregnant: 1 woman delivered twins at 24 weeks, 1 woman delivered a singleton at term, and 1 patient had rupture of membranes and chorioamnionitis at 20 weeks gestation. CONCLUSIONS: Radical vaginal trachelectomy with pelvic lymphadenectomy permits preservation of fertility in selected patients. To date, with more than 150 cases reported in the literature, recurrence rates are comparable to those seen with radical hysterectomy.