Inherited alterations of TGF beta signaling components in Appalachian cervical cancers.

PURPOSE: This study examined targeted genomic variants of transforming growth factor beta (TGFB) signaling in Appalachian women. Appalachian women with cervical cancer were compared to healthy Appalachian counterparts to determine whether these polymorphic alleles were over-represented within this high-risk cancer population, and whether lifestyle or environmental factors modified the aggregate genetic risk in these Appalachian women. METHODS: Appalachian women's survey data and blood samples from the Community Awareness, Resources, and Education (CARE) CARE I and CARE II studies (n = 163 invasive cervical cancer cases, 842 controls) were used to assess gene-environment interactions and cancer risk. Polymorphic allele frequencies and socio-behavioral demographic measurements were compared using t tests and χ2 tests. Multivariable logistic regression was used to evaluate interaction effects between genomic variance and demographic, behavioral, and environmental characteristics. RESULTS: Several alleles demonstrated significant interaction with smoking (TP53 rs1042522, TGFB1 rs1800469), alcohol consumption (NQO1 rs1800566), and sexual intercourse before the age of 18 (TGFBR1 rs11466445, TGFBR1 rs7034462, TGFBR1 rs11568785). Interestingly, we noted a significant interaction between "Appalachian self-identity" variables and NQO1 rs1800566. Multivariable logistic regression of cancer status in an over-dominant TGFB1 rs1800469/TGFBR1 rs11568785 model demonstrated a 3.03-fold reduction in cervical cancer odds. Similar decreased odds (2.78-fold) were observed in an over-dominant TGFB1 rs1800469/TGFBR1 rs7034462 model in subjects who had no sexual intercourse before age 18. CONCLUSIONS: This study reports novel associations between common low-penetrance alleles in the TGFB signaling cascade and modified risk of cervical cancer in Appalachian women. Furthermore, our unexpected findings associating Appalachian identity and NQO1 rs1800566 suggests that the complex environmental exposures that contribute to Appalachian self-identity in Appalachian cervical cancer patients represent an emerging avenue of scientific exploration.

Endometrial stromal sarcoma: analysis of recurrence following adjuvant treatment.

OBJECTIVE: Endometrial stromal sarcoma (ESS) is a rare and indolent form of uterine cancer with ill-defined post-operative treatment guidelines. The goal of this study was to evaluate the rate of recurrence and the effect of various adjuvant treatment modalities. METHODS: Patients with ESS at 4 institutions were identified (1986-2007). Patient demographics, pathology, treatment, and follow-up information were collected. Chi-square statistical analysis was performed. RESULTS: Forty-three patients with ESS were identified. All patients initially underwent hysterectomy. Twenty-eight (66.7%) had early stage, 12 (28.6%) had advanced stage ESS, and 2 (4.8%) had no staging information. Eight patients received pelvic and or vaginal cuff radiation treatment, with or without chemotherapy. Sixteen of 43 patients experienced a recurrence at an average of 100.5months. Thirty-three patients were treated with progestin therapy alone or followed expectantly. Complete outpatient records were available for 28 of these patients. Sixteen patients (57%) were followed expectantly while 12 (43%) received progestins. Patients receiving progestins vs. expectant management had a lower rate of recurrence in stage 1 (14.3% vs 38.5%, p=0.26) and all stages (33% vs 50%, p=0.38). Twenty-three of 28 (82.1%) patients underwent initial oophorectomy. Eight of 23 (34.8%) had a recurrence, compared to 4 of 5 (80%) in those who retained their ovaries (p=0.06). CONCLUSIONS: ESS is a rare cancer that is difficult to study. We found removal of the adnexa and post-operative treatment with progestin therapy decreased recurrence rates. These two treatment strategies should be considered in the treatment of patients with all stages of ESS.

Intraperitoneal chemotherapy for recurrent epithelial ovarian cancer is feasible with high completion rates, low complications, and acceptable patient outcomes.

OBJECTIVES: Three large randomized clinical trials have shown a survival benefit for patients treated with intraperitoneal (IP) compared with intravenous chemotherapy for advanced stage epithelial ovarian cancer (EOC). However, the use of IP chemotherapy in recurrent EOC is controversial. The purpose of this study was to determine outcomes, completion rates, and frequency of complications in patients with platinum-sensitive recurrent EOC treated with IP chemotherapy. METHODS: A retrospective, single-institution analysis of women who received IP chemotherapy for recurrent EOC from January 2003 to April 2010 was conducted. Study patients were identified from the Tumor Registry and office records. Demographic factors, stage, histology, surgical findings, cytoreduction status, and subsequent therapies were abstracted. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier methods. RESULTS: Fifty-six women who received IP chemotherapy for their first EOC recurrence were identified. The mean age of patients was 56.7 years (range, 40-79 y). Fifty-five patients (98.3%) had previously completed at least 6 cycles of intravenous chemotherapy. Of all patients, 87.5% were initially diagnosed with advanced stage disease (stage IIA-IV). All patients underwent secondary cytoreduction at the time of IP port placement. Moreover, 67.9% of patients were considered optimally cytoreduced (<1 cm residual disease) at the end of the secondary debulking surgery. Forty-two patients (75%) were able to successfully complete at least 6 cycles of IP chemotherapy. Reasons for noncompletion were disease progression, allergic reaction, renal failure, pain, severe nausea and vomiting, death, and patient refusal. Six patients (10.7%) developed port complications including pain around port site, port malfunction, and port erosion into small bowel. Median PFS since the initiation of IP chemotherapy was 10.5 months (95% confidence interval, 7.5-16.4 months) and median OS was 51 months (95% confidence interval, 40.8-61.1 months). CONCLUSIONS: Intraperitoneal chemotherapy is a feasible option for patients with recurrent EOC, with high completion rates, low frequency of complications, and acceptable PFS and OS.

Radical hysterectomy for early stage cervical cancer: laparoscopy versus laparotomy.

OBJECTIVES: Gynecologic oncologists have recently begun using laparoscopic techniques to treat early stage cervical cancer. We evaluated a single institution's experience of laparoscopic radical hysterectomy and staging compared with laparotomy. METHODS: A retrospective chart review identified stage IA2 and IB1 cervical cancer patients who underwent laparoscopic radical hysterectomy and pelvic lymph node dissection from July 2003 to April 2009. A 2:1 cohort of patients treated with laparotomy were matched by stage. RESULTS: Nine laparoscopic patients (3 stage IA2, 6 stage IB1) with 18 matched controls (6 and 12) were identified. Demographics for each group were similar. None had positive margins or lymph nodes. An average of 11.2 vs.13.9 pelvic lymph nodes (P=0.237) were removed. Average operating time was 231.7 vs. 207.2 minutes (P=0.434), and average estimated blood loss was 161.1 vs. 394.4mL (P=0.059). Average length of stay was 2.9 vs. 5.5 days (P=0.012). No transfusions or operative complications were noted in the laparoscopic group vs. 3 each in the open group (P=0.194). No laparoscopic patients and 5 open patients had a postoperative wound infection (P=0.079). No recurrences were noted. CONCLUSIONS: Laparoscopic radical hysterectomy is a feasible alternative to laparotomy for early stage cervical cancer. Similar surgical outcomes are achieved with significantly less morbidity.

Intraperitoneal catheter leads to prolongation of the time to normalization of serum CA125 levels.

OBJECTIVE: The intraperitoneal (IP) catheter has the potential to cause peritoneal irritation, which may contribute to an elevated CA125 level. We hypothesize that patients undergoing IP chemotherapy may have elevated CA125 values when compared with patients receiving intravenous (IV) chemotherapy. METHODS: From February 2006 to July 2007, optimally debulked patients with stage III and stage IV ovarian carcinoma from a single institution were offered an outpatient IV/IP chemotherapy regimen modified from Gynecologic Oncology Group 172. They were matched to a cohort of similar patients who received IV paclitaxel and carboplatin. Demographic data and CA125 levels were collected before each cycle of chemotherapy and after the removal of the IP catheter. Statistical analysis was completed using a chi2 test with a significance level of P < 0.05. RESULTS: Fifty patients received the standard IV regimen, and 38 patients completed the modified IV/IP regimen. There was no statistical difference in the median CA125 values between the 2 groups during the treatment. After 6 cycles of therapy, 68.4% (26/38) of the IP cohort had a normal CA125 level before IP catheter removal compared with 78% (39/50) in the IV chemotherapy cohort (P = 0.44). After removal of the IP catheter, 86.8% (33/38) of the patients had a normal CA125 value (68.4% vs 86.8%, P = 0.049). CONCLUSIONS: After removal of the IP catheter, an additional 18.2% (7/38) of patients in the IP group had normalized their CA125 level. Because CA125 levels at the end of the treatment have prognostic significance, the role of the IP catheter in an elevated CA125 level must be considered.

Completion of intraperitoneal chemotherapy in advanced ovarian cancer and catheter-related complications.

OBJECTIVE: Combination intravenous/intraperitoneal (IV/IP) chemotherapy has been shown in three randomized trials to be superior to IV therapy alone in the treatment of advanced ovarian cancer with respect to overall survival (OS). We sought to evaluate the effect of dose modification of IP therapy on completion rates. METHODS: From November 1999 until August 2008, all optimally debulked, advanced stage ovarian cancer patients who received adjuvant IP chemotherapy at a single institution were reviewed. The primary endpoint was completion of 6 cycles of IP chemotherapy. This rate was compared to published results from GOG 172. A secondary analysis evaluated completion of chemotherapy based on IP catheter type. Statistical analysis was performed with a chi square test with a significance level of p<0.05. RESULTS: One hundred and three patients received IP chemotherapy during this period. Seventy-five patients received the modified IV/IP chemotherapy regimen. Sixty-two patients (83%) completed all 6 cycles in our cohort compared to 119 patients (42%) reported in GOG 172 (p=0.0001). Fifty-five patients had a fenestrated catheter (F) and 48 had a non-fenestrated (NF) catheter. Eight patients in each cohort discontinued treatment, for a completion rate of 85.5% in NF and 82.3% in F (p=0.79). CONCLUSIONS: The dose modifications utilized in this study allowed for completion of 6 cycles of adjuvant IP chemotherapy in 83% of patients. Choice of catheter type did not affect completion rates. Continued monitoring of outcomes is planned to compare PFS and OS. The high completion rate may increase acceptance of IP chemotherapy in the community setting.

Heterotopic pregnancy presenting at 18 weeks' gestational age: a case report.

BACKGROUND: Heterotopic pregnancy is a rare event that usually presents in the first 6-8 weeks of pregnancy. CASE: A 35-year-old primigravida was referred to the hospital at 18+ weeks' gestational age for evaluation of chronic abdominal pain. Ultrasound revealed a heterotopic pregnancy. The patient underwent surgery for removal of the ectopic pregnancy. CONCLUSION: Heterotopic pregnancy can present at any time during pregnancy and should be considered in any pregnant woman with abdominal pain.

Which ovarian masses need intervention?

Ovarian cancer is deadly if not detected early, but it is only one of many causes of pelvic masses, which are common. The physician's job is to determine if a mass is likely to be malignant and needing surgical evaluation. The best predictors of malignancy are a combination of factors that include the patient's age, family history, menopausal status, symptoms, findings on physical examination and imaging studies, and blood level of the cancer biomarker CA125.

Yolk sac tumor of the ovary associated with endometrioid carcinoma with metastasis to the vagina: a case report.

BACKGROUND: Mixed yolk sac tumors of the ovary are biologically aggressive even in early stage disease. CASE: A 41-year-old woman presented with a large pelvic mass and anterior vaginal wall tumor. At surgery vaginal biopsies were performed followed by an exploratory laparotomy with resection of the mass. Pathology of the ovary revealed a primary yolk sac tumor associated with poorly differentiated endometrioid and undifferentiated carcinoma with vaginal metastasis only. She was initiated on bleomycin, etoposide, and cisplatin, with three additional cycles of etoposide and cisplatin. Initially the patient experienced a complete response, however her disease recurred and she currently is dead of her disease. CONCLUSION: To our knowledge this is the first case of a mixed ovarian germ cell tumor with vaginal metastasis.