Overall Survival in Patients with Endometrial Cancer Treated with Dostarlimab plus Carboplatin-Paclitaxel in the Randomized ENGOT-EN6/GOG-3031/RUBY Trial.

BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer. At the first interim analysis, the trial met one of its dual-primary endpoints with statistically significant progression-free survival benefits in the mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. PATIENTS AND METHODS: RUBY is a phase 3, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer who were randomly assigned (1:1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual-primary endpoint. RESULTS: A total of 494 patients were randomized (245 in dostarlimab arm; 249 in placebo arm). In the overall population, with 51% maturity, RUBY met the dual-primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death (HR = 0.69; 95% CI, 0.54-0.89; P = 0.0020) in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32; 95% CI, 0.17-0.63; nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair proficient/microsatellite stable (MMRp/MSS) population (HR = 0.79; 95% CI, 0.60-1.04; nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis. CONCLUSIONS: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful overall survival benefit in the overall population of patients with primary advanced or recurrent endometrial cancer while demonstrating an acceptable safety profile.

Assessment of immune biomarkers and establishing a triple negative phenotype in gynecologic cancers.

OBJECTIVE: Immuno-oncology (IO) has rapidly evolved, with many IO therapies either approved or under investigation for multiple malignancies. Biomarkers exist that can predict response to IO therapies including PD-L1 expression, microsatellite instability (MSI), and total mutation burden (TMB). This paper serves to analyze the presence of these biomarkers across gynecologic cancers. METHODS: A total of 16,300 gynecologic cancer specimens submitted for molecular profiling to Caris Life Sciences were reviewed. Immunohistochemistry was performed using the SP142 anti-PD-L1 clone and assessed for intensity. Next-generation sequencing, immunohistochemistry, and fragment analysis were used to determine MSI status. TMB was measured by counting all non-synonymous missense mutations found per tumor not previously described as germline alterations. Chi-Square, Fisher Exact, and the Kruskal-Wallis test were used to compare cohorts. RESULTS: Of 16,300 specimens, 54.1% were ovarian, 37.2% uterine, 7.2% cervical, 0.3% vulvar, 1.2% vaginal, with 0.1% unspecified. MSI-H was most frequent in uterine cancer (17.7%) and only 1% of ovarian cancers. PD-L1 expression was present in 38.3% of cervical and 62.5% of vulvar cancers, but less than 8% of ovarian and uterine cancers. TMB-H was present in 21.1% cervical, 19.7% uterine, and 5% ovarian cancers. Few specimens exhibited a "triple positive" phenotype - 0.3% ovarian, 1.5% uterine, and 1.5% cervical. Associations were seen between MSI, TMB, and PD-L1 across all cancer types. CONCLUSIONS: The frequency of individual biomarkers pertinent to IO therapy varies by cancer type. HPV-driven genital tract cancers have higher frequencies of PD-L1 expression, MSI-H, and TMBH. Endometrial cancers are characterized by MSI-H and TMB, whereas ovarian cancers have a low frequency of MSI-H and modest PD-L1 or TMBH. The incidence of 'triple positive" cases was less than 2%.

Treatment of patients with recurrent epithelial ovarian cancer for whom platinum is still an option.

BACKGROUND: Ovarian cancer remains the most deadly gynecologic cancer with the majority of patients relapsing within 3 years of diagnosis. Traditional treatment paradigms linked to platinum sensitivity or resistance are currently being questioned in the setting of new diagnostic methods and treatment options. DESIGN: Authors carried out review of the literature on key topics in treatment of recurrent epithelial ovarian cancer (EOC) when platinum is still an option; including secondary surgical cytoreduction, chemotherapy, novel treatment options, and maintenance therapy. A treatment algorithm is proposed. RESULTS: Molecular characterization of EOC is critical to help guide treatment decisions. The role of secondary cytoreductive surgery is currently being evaluated with results from Gynecologic Oncology Group (GOG) 213 and anticipated results from DESKTOP III clinical trials. Chemotherapy backbone has remained relatively unchanged but utilizing non-platinum-based regimens is under investigation. In addition, maintenance therapy with anti-angiogenic therapy and Poly (ADP-ribose) Polymerase (PARP) inhibitors has emerged as the standard of care. Novel combinations, including immunotherapy and anti-angiogenesis agents, may further change the current landscape. CONCLUSIONS: The treatment of recurrent EOC is rapidly changing. Clinical trial design will need to continue to evolve as many novel therapies move to the upfront setting. Ultimately, the treatment of patients with recurrent EOC must incorporate individual patient and tumor factors.

Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer.

OBJECTIVE: The AGO-OVAR16 study was designed to test the efficacy, safety, and tolerability of pazopanib maintenance after first-line chemotherapy in patients with newly diagnosed advanced ovarian cancer (AOC). METHODS: Nine hundred and forty patients with histologically confirmed AOC, International Federation of Gynecology and Obstetrics (FIGO) stage II-IV, were randomized in a 1:1 ratio to receive either 800 mg pazopanib once daily or placebo for up to 24 months, unless there was disease progression, toxicity, withdrawal of consent, or death. The primary endpoint (investigator-assessed progression-free survival [PFS]) was met and previously reported. The results of final analyses of overall survival (OS) are reported here. RESULTS: A third OS interim analysis showed futility and led to study closure and a final OS analysis after last patient last visit. At the time of the final OS analysis, 494 (89.7% of the planned 551) events had occurred. No difference was observed in OS between pazopanib and placebo. The hazard ratio (HR) was 0.960 (95% confidence interval [CI]: 0.805-1.145), and the median OS from randomization was 59.1 months in pazopanib and 64.0 months in placebo arms. For the East Asian patients, similar to the first three interim OS analyses, a numerical negative trend was observed favoring placebo (HR, 1.332; 95% CI: 0.863-2.054). Exploratory analyses showed a trend for a longer time to first subsequent anti-cancer therapy or death with pazopanib over placebo (HR, 0.829; 95% CI: 0.713-0.965), with a median estimate of 19.0 and 14.5 months, respectively. No new safety signals were observed. CONCLUSION: Although pazopanib prolonged PFS, this was not associated with improvement in median OS. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov: NCT00866697.

Quality of life in patients with advanced epithelial ovarian cancer (EOC) randomized to maintenance pazopanib or placebo after first-line chemotherapy in the AGO-OVAR 16 trial. Measuring what matters-patient-centered end points in trials of maintenance therapy.

Background: Health-related quality of life (HRQoL) was a secondary end point in AGO-OVAR 16, which randomized 940 patients with EOC after first-line chemotherapy to maintenance pazopanib (PZ) or placebo (P). Additional post hoc analyses were carried out to investigate additional patient-centered end points. Patients and methods: HRQoL was measured with EORTC-QLQ-C30, QLQ-OV28 and EQ-5D-3L. Pre-specified end points included mean differences in HRQoL between treatment arms. Exploratory analyses included quality-adjusted progression-free survival (QAPFS), impact of specific symptoms and progressive disease (PD) on HRQoL and time to second-line chemotherapy. The objective was to provide clinical perspective to the significant median PFS gain of 5.6 months with PZ. Results: There were statistically significant differences between PZ and P in QLQ-C30 global health status [5.5 points; 95% confidence interval (CI), 0.7-10.4, P = 0.024] from baseline to 25 months, but not EQ-5D-3L (0.018 points; 95% CI - 0.033 to 0.069, P = 0.485). The impact of diarrhea was captured in QLQ-OV28 Abdominal/GI-Symptoms scale (8.1 points; 95% CI 3.6-12.5, P = 0.001). QAPFS was 386 days (95% CI 366-404 days) with PZ versus 359 days (95% CI 338-379 days) with placebo (P = 0.052). PD was associated with a decline in HRQoL (P < 0.0001). Median time to second-line chemotherapy was 19.7 months with PZ and 15.0 months with P [hazard ratio (HR) 0.72, 95% CI 0.69-0.86, P = 0.0001]. Conclusions: There were small to no significant mean score differences in global HRQoL and EQ5D-3L between PZ and placebo, respectively, despite the increased toxicity of PZ. Exploratory end points including QAPFS, impact of specific symptoms on HRQoL during treatment and at PD help place the PFS gain with PZ in context and interpret the results. Additional patient-centered end points should be considered in trials of maintenance therapy in EOC beyond mean differences in HRQoL scores alone, to support the benefit to patients of prolongation of PFS. Clinical Trials Registration Number: NCT00866697.

The emerging role of epidermal growth factor receptor inhibitors in ovarian cancer.

Epidermal growth factor receptor (EGFR) inhibitors are a new biologically targeted therapy, which may offer new hope in the treatment of patients with advanced or recurrent ovarian cancers. In this review, we summarize and discuss the results of research to date on EGFR inhibitors with particular emphasis on ovarian cancer. We reviewed data identified by searches of MEDLINE, PubMed, and abstracts from the proceedings of the American Society of Clinical Oncology meetings from 1998 to 2006, with the search terms "Ovarian Cancer,""EGFR,""gefitinib, ZD1839, Iressa,""erlotinib, OSI-774, Tarceva,""CI-1033,"" GW 572016, lapatinib,""PKI-166,""EKB 569,""anti-EGFR antibodies,""trastuzumab, Herceptin,""cetuximab, Erbitux, IMC-C225,""matuzumab, EMD 72000,""panitumamab, ABX-EGF,""pertuzumab," and "vandetanib, rINN, Zactima, ZD6474." Phase II trials of both small molecule inhibitors of EGFR- and antibody-based inhibitors are currently ongoing in ovarian cancer and emerging data suggest that their activity in unselected women with advanced or recurrent ovarian cancer is modest, when utilized as a single agent. It is possible that these agents will be highly effective in smaller subsets of patients whose tumors are dependent on EGFR signaling, perhaps through activating mutations in EGFR or its downstream pathway. Targeted therapy with EGFR inhibitors is an untapped potential resource in the treatment of advanced or recurrent ovarian cancer. Ongoing trials will elucidate the most effective strategies to use these agents individually or in combination with traditional chemotherapeutic agents.

Allelic loss of sequences from the long arm of chromosome 10 and replication errors in endometrial cancers.

Thirty-seven endometrial cancers were subjected to an allelotype analysis in an attempt to identify chromosomal regions that are lost in a significant portion of tumors and to identify tumors characterized by replication errors. Thirty-nine highly polymorphic microsatellite markers representing all chromosomal arms, excluding the X and the short arms of the acrocentrics, were examined. An average of 20 informative cases were evaluated for each marker. Genetic alterations were detected in 30 of the 37 tumors. Replication errors were identified in 8 tumor specimens. Loss of heterozygosity was observed for loci on all chromosomes examined with the exception of chromosomes 4 and 20. The two most frequent sites of loss were at the marker loci examined on 10q (40%) and 17p (29%). Six additional simple sequence repeat markers from 10q were genotyped in an effort to refine the region of 10q loss. The chromosome 10 markers used in these studies were physically mapped with the use of a panel of somatic hybrids that retain defined portions of chromosome 10. The observed patterns of loss of sequences on 10q suggest a role for a tumor suppressor gene in the 10q23-26 region in the development or progression of endometrial cancers.

Lack of effect of tumor size on the prognosis of carcinoma of the uterine cervix Stage IB and IIA treated with preoperative irradiation and surgery.

PURPOSE: The purpose of this analysis was to evaluate the prognostic significance of cervical tumor size in patients with Stages Ib and IIa carcinoma of the cervix treated with preoperative irradiation and radical or conservative hysterectomy. METHODS AND MATERIALS: This study is a retrospective analysis of 177 patients. One hundred forty-one patients had Stage Ib and 36 patients had Stage IIa carcinoma of the cervix. All patients were treated with preoperative irradiation and surgery. Radiation therapy consisted of external pelvic irradiation and intracavitary brachytherapy; total doses ranged from 30 to 60 Gy to the pelvic sidewall and 60 to 70 Gy to point A. Surgery consisting of radical hysterectomy and lymph node dissection or a conservative hysterectomy and lymph node dissection was performed 4 to 6 weeks after completion of irradiation. RESULTS: The 5-year progression-free survivals were 80% for Stage Ib and 63% for Stage IIa (p = 0.03). The 5-year cumulative pelvic failure rates for Stage Ib were 16% for tumors <3 cm and 9% for tumors >3 cm (p = 0.90). The 5-year cumulative pelvic failure rates for Stage IIa were 22% for tumors <3 cm and 22% for tumors >3 cm (p = 0.75). The corresponding cumulative distant metastasis failure rates at 5 years for Stage Ib were 21% for tumors <3 cm and 21% for tumors >3 cm (p = 0.60). For patients with Stage IIa disease, the 5-year cumulative distant metastasis rates were 33% for tumors <3 cm and 36% for tumors >3 cm (p = 0.70). A multivariate analysis was performed to evaluate prognostic factors for the endpoint of progression-free survival. The variables that were analyzed were patient age, tumor histology, tumor size, clinical stage, point A and pelvic lymph node irradiation dose, and cervical tumor status and pelvic lymph node status at the time of hysterectomy. The variables that were found to be of independent significance for progression-free survival by multivariate analysis were pelvic lymph node irradiation dose (p <0.001), pelvic lymph node status at the time of hysterectomy (p = 0.01), and clinical stage (p = 0.02). Cervical tumor size at the time of diagnosis and the presence of tumor cells in the cervix in the hysterectomy specimen was not an independent prognostic factor by multivariate analysis. The overall severe complication rate was 11% for all patients. CONCLUSIONS: For this population of patients treated with preoperative irradiation and surgery, pelvic lymph node status at the time of hysterectomy and the preoperative irradiation dose to the pelvic lymph nodes are independent predictors of progression-free survival and the development of distant metastasis. The pretreatment cervical tumor size is of less importance for predicting progression-free survival and the development of distant metastasis but clinical stage is an important prognostic variable. These results are in contrast with those of surgery or irradiation alone, in which primary tumor size is a critical prognostic factor for all outcome parameters.

Meigs' syndrome with an elevated CA 125 from benign Brenner tumors.

BACKGROUND: Meigs' syndrome refers to solid, benign ovarian tumors, ascites, hydrothorax, and resolution of these signs after surgery. Meigs' syndrome with an elevated CA 125 secondary to benign Brenner tumors is exceedingly rare. CASE: A postmenopausal woman presented with a large pelvic mass, ascites, and a right pleural effusion. Serum CA 125 was 759 IU/mL. Ascitic fluid, pleural fluid, and fine needle aspiration of the mass were without evidence of malignancy. Exploratory laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy revealed benign Brenner tumors. Immunohistochemical staining for CA 125 showed immunoreactivity in the omentum only. Postoperatively, her signs and symptoms resolved completely and did not recur. CONCLUSION: Cytologic or histologic confirmation of malignancy is imperative in patients with a pelvic mass, ascites, hydrothorax, and elevated CA 125 before initiating chemotherapy.

Radical hysterectomy for cervical cancer in obese women.

OBJECTIVE: To estimate the morbidity, adequacy of surgery, and survival of obese women undergoing radical hysterectomy and pelvic lymphadenectomy. METHODS: Patients with stage I and IIa cervical cancer and a body mass index (BMI) over 30 kg/m(2) and absolute weight greater than 85 kg explored with the intent for radical hysterectomy between 1986 and 1998 were identified. Patient characteristics, surgical, pathologic, and follow-up data were extracted and survival curves were generated. RESULTS: Forty-eight obese women were identified who were explored for radical hysterectomy and pelvic lymph node dissection. The median BMI was 36 kg/m(2), and the median weight was 95 kg. Thirty-five patients (73%) had stage Ib1 disease. Despite the obesity of the study group, none had severe comorbidity. The procedure was completed in 46 patients, and abandoned in two because of metastatic disease. For patients undergoing radical hysterectomy and pelvic lymph node dissection, median blood loss was 800 mL. No patient developed fistulas. Residual tumor was present in 26 (57%) hysterectomy specimens, and margins were without disease in 45 specimens (98%). A median of 26 pelvic lymph nodes were obtained per procedure, and six patients (13%) had positive nodes. Five-year overall and disease-free survival are 84% (95% confidence interval [CI] 70.9, 97.5) and 80% (95% CI 65.2, 93.8), respectively, at a median follow-up of 36 months. CONCLUSION: In this carefully selected obese group, we demonstrate that radical hysterectomy and pelvic lymph node dissection can be performed with adequate surgical resection, acceptable morbidity, and excellent survival.

Randomized comparison of laparoscopic and open lymphadenectomy in pigs.

OBJECTIVE: To compare the efficacy of open and laparoscopic lymphadenectomy and validate an objective model of lymph node retrieval using lymphangiography in pigs. METHODS: Twenty-five pigs weighing 54-75 lbs were randomly assigned by side to open or laparoscopic pelvic and paraaortic lymphadenectomy. Lymph node yield, quantified by a masked pathologist, operative time, complications, blood loss, and other variables were recorded. Lymphangiography was done, and radiographs were taken before and after lymph node harvesting. Statistical analysis used McNemar test for nominal data and paired Student t test or Wilcoxon signed-rank test for continuous variables. RESULTS: Lymph node yields were a mean of 11.5 with a standard deviation of 2.8 for open and 15.3 +/- 3.4 nodes for laparoscopic lymphadenectomy (P = .009). Mean operating time was 26.5 +/- 5.3 minutes for open versus 54.9 +/- 23.7 minutes for laparoscopy (P < .01). Mean blood loss was higher for laparoscopic cases, 35 mL for open versus 58 mL for laparoscopic lymphadenectomy (P = .048). The four major complications were evenly distributed between the two procedures. Lymphangiography was successful in 24 of 25 pigs. A total of 243 lymph nodes were identified with equal distribution by side. Lymphangiographic data correlated well with number of lymph nodes retrieved. CONCLUSION: In this randomized trial, laparoscopic lymphadenectomy was at least as effective as open lymphadenectomy, although operating time and blood loss were greater. Lymphangiography was a reliable, objective mode for documentation and assurance of lymph node recovery.

Use of magnetic resonance imaging in the diagnosis of cortical blindness in pregnancy.

Magnetic resonance imaging (MRI) may be helpful in the assessment of eclampsia and preeclampsia with central nervous system symptomatology such as cortical blindness. We describe a rare case of complete binocular blindness postpartum with no other neurologic deficits, in which MRI abnormalities were undetected on computed tomography. The better soft-tissue discrimination of MRI may visualize important but subtle lesions which ultimately may help to explain the underlying pathophysiologic mechanism in such cases.

Recurrent ovarian tumor with low malignant potential and cardiac metastasis.

BACKGROUND: Up to 20% of ovarian epithelial tumors are classified as being of low malignant potential. Most of these low malignant potential tumors are detected at an early stage and have an excellent prognosis. This is a report of a woman with cardiac metastasis from an ovarian low malignant potential tumor. CASE: This case describes a 53-year-old woman who presented with congestive heart failure and was found to have a recurrent stage III ovarian tumor of low malignant potential. A transesophageal echocardiogram revealed compression of the inferior vena cava and a mass encompassing the right atrium. Findings at autopsy confirmed a low malignant potential ovarian tumor thrombus involving the inferior vena cava and right atrium. CONCLUSION: Ovarian low malignant potential tumors can metastasize in an aggressive manner. A transesophageal echocardiogram may be useful when the diagnosis of cardiac tumor thrombus is considered.

Cancer among first-degree relatives of probands with invasive and borderline ovarian cancer.

OBJECTIVE: The familial clustering of ovarian, breast, endometrial, colon; and prostate cancer was compared in first-degree relatives of probands with invasive and borderline ovarian cancer to determine coaggregation. METHODS: Probands (n=392), who had been patients in the Division of Gynecologic Oncology at Washington University, were ascertained consecutively. Family history on 2192 first-degree relatives was collected by personal interviews of the probands and other family members. Estimates of prevalence of cancers in first-degree relatives of the two proband groups were compared. Survival analysis was used to examine the age-at-onset distribution of each cancer in relatives of invasive probands versus relatives of borderline probands. RESULTS: Among the relatives were 24 cases of ovarian cancer, 46 cases of breast cancer, 13 cases of endometrial cancer, and 25 and 28 cases of colon and prostate cancer, respectively. There were no significant differences in the prevalence of any of these cancers in relatives of the invasive and borderline probands. Cumulative lifetime risk estimates did not differ between the relatives of the two groups for any cancers. Age-at-onset of ovarian cancer did not differ between probands with positive family histories of the five cancers and those with negative histories. The inability to reject the null hypothesis of no differences in the first-degree relatives of our two study groups might be from insufficient power to detect small differences, given our sample size. CONCLUSION: These results suggest that relatives of patients with invasive and borderline ovarian cancer might share similar cancer risks and age-at-onset distributions.

Successful in vitro fertilization pregnancy after conservative management of endometrial cancer.

OBJECTIVE: To report a successful IVF pregnancy in an infertile couple after conservative treatment of endometrial cancer. DESIGN: Case report and literature review. SETTING: University teaching hospital. PATIENT(S): A 29-year-old infertile white woman. MAIN OUTCOME MEASURE(S): Successful pregnancy after conservative management of endometrial cancer. INTERVENTION(S): Grade 1 endometrial adenocarcinoma diagnosed at hysteroscopy, followed by dilatation and curettage (D&C). On follow-up D&C, pathologic examination was normal after high-dose progesterone therapy. The patient subsequently underwent an IVF cycle with transfer of three blastocysts. RESULT(S): The patient delivered triplets by cesarean section. Laparoscopic-assisted vaginal hysterectomy and bilateral salpingo-oophorectomy was then done. No residual endometrial cancer was evident in the hysterectomy specimen, but a 1.1-cm cystic mixed endometrioid and clear cell-type adenocarcinoma was discovered in the left ovary. The patient is doing well after 3 cycles of chemotherapy; her CA-125 level is normal. The triplets are also doing well. CONCLUSION(S): In carefully chosen situations, deferring surgery in infertile patients with endometrial cancer may be a viable option permitting subsequent successful pregnancy.

Analysis of MSH3 in endometrial cancers with defective DNA mismatch repair.

OBJECTIVE: To clarify the origin of defective mismatch repair (MMR) in sporadic endometrial cancers with microsatellite instability (MSI), a thorough mutation analysis was performed on the human mismatch repair gene MSH3. METHODS: Twenty-eight MSI-positive endometrial cancers were investigated for mutations in the human mismatch repair gene MSH3 using single-strand conformation variant (SSCV) analysis of all 24 exons. All variants were sequenced. Loss of heterozygosity was investigated at all MSH3 polymorphisms discovered. A subset of tumors were investigated for methylation of the 5' promoter region of MSH3 using Southern blot hybridization. RESULTS: An identical single-base deletion (delta A) predicted to result in a truncated proteins was discovered in six tumors (21.4%). This deletion occurs in a string of eight consecutive adenosine residues (A8). Because simple repeat sequences are unstable in cells with defective MMR, the observed mutation may be an effect, rather than a cause, of MSI. Evidence of inactivation of the second MSH3 allele in tumors with the delta A mutation would strongly support a causal role for these MSH3 mutations. However, there was no evidence of a second mutation, loss of sequences, or methylation of the promoter region in any of the tumors with the delta A mutation. CONCLUSION: Although the delta A mutation is a frequent event in sporadic MSI-positive endometrial cancers, it may not be causally associated with defective DNA MMR.

Technique for performing direct lymphangiography in pigs.

RATIONALE AND OBJECTIVES: The authors developed a porcine model for direct lymphangiography to be used as a reference for lymph node harvesting. METHODS: A pilot animal was studied first to develop the protocol, which was used successfully in 24 pigs. An indicator dye was first injected into each foot to make the lymphatic vessels visible. Then, ethiodized poppy seed oil was injected directly through cutdowns in both groins. Radiographs were obtained before and after lymph node harvesting. RESULTS: Images were of diagnostic quality in all animals. The pilot animal developed transient respiratory distress, which was thought to be due to the oil-based contrast material. The amount injected was reduced by half, and no episodes occurred thereafter in the study group. There were no other immediate or delayed complications. CONCLUSION: Direct lymphangiography is safe, easy, and reliable in a porcine model.

Adenocarcinoma in a single horn of a bicornuate uterus. A case report.

Adenocarcinoma developed in one horn of a bicornuate uterus. Making such a diagnosis is difficult, and hysteroscopy is helpful.