Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature.

Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with about 222 cases documented in the literature and an incidence of about 11% in living GTN patients. Brain metastasis from GTN was part of a disseminated disease in 90% of patients, single metastases in the brain - 80% and located in the cerebrum - 90%. Brain metastasis was the only manifestation of metastatic GTN in 11.3% of patients, appeared synchronously with metastatic GTN in other sites of the body - 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of metastatic GTN in other sites (most often in the lung) - 58.1%. Overall, 83.9% of patients with brain metastases from GTN had also lung metastases from GTN. Brain metastases from GTN showed a greater tendency to be hemorrhagic compared to brain metastases from other primaries. In patients with brain metastases from GTN, the best outcome was achieved with multimodal therapy including craniotomy, whole brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain metastasis from GTN is a grave disease with a median survival time from diagnosis of brain metastasis of about 12 months.

Can parametrectomy be avoided in early cervical cancer? An algorithm for the identification of patients at low risk for parametrial involvement.

AIMS: To assess the rate of parametrial involvement in a large cohort of patients who underwent radical hysterectomy for cervical cancer and to suggest an algorithm for the triage of patients to simple hysterectomy or simple trachelectomy. METHODS: Multicenter retrospective study of patients with cervical cancer stage I through IIA who underwent radical hysterectomy and pelvic lymphadenectomy. The patients were divided into 2 groups according to whether or not the parametrium was involved. The two groups were compared with regard to the clinical and histopathological variables. Logistic regression of the variables potentially assessable prior to definitive hysterectomy such as age, tumor size, lymph-vascular space invasion (LVSI) and nodal involvement was performed. RESULTS: Five hundred and thirty patients had specific histological data on parametrial involvement and in 58 (10.9%) patients, parametria was involved. Parametrial involvement was significantly associated with older age, tumors larger than 2 cm, deeper invasion, LVSI, involved surgical margins, and the presence of nodal metastasis. By triaging patients with a tumor ≤ 2 cm and no LVSI, the parametrial involvement rate was 1.8% (2/112 patients). With further triage of patients with negative nodes, the rate of parametrial involvement was 0% (0/107 patients). CONCLUSION: Using a pre-operative triage algorithm, patients with early small lesions, no LVSI and no nodal involvement may be spared radical surgical procedures and parametrectomy. Further prospective data are urgently needed.

Brain metastases from cervical carcinoma: overview of pertinent literature.

Brain metastasis from cervical carcinoma is rare with only about 100 cases documented in the literature and an incidence among cervical carcinoma patients of 0.6%. The median interval between diagnosis of cervical carcinoma and brain metastases is 18 months. The brain can be the only site of distant metastasis of cervical carcinoma ("isolated brain metastases") (46.8%) or brain metastasis can be part of a disseminated cervical carcinoma involving also other sites of the body (53.2%). Brain metastasis of cervical carcinoma affects most often the cerebrum (73%) and can be either single (one metastasis) (50.6%) or multiple (> or = two metastases) (49.4%). Treatment of brain metastases has evolved over the years from whole brain radiotherapy (WBRT) alone to multimodal therapy including surgical resection (craniotomy) or stereotactic radiosurgery (SRS) followed by WBRT +/- chemotherapy. The median overall survival after diagnosis of brain metastases is four months; however, a better survival is achieved with multimodal therapy (craniotomy followed by WBRT) compared to craniotomy alone or WBRT alone. The worst survival is observed in patients with no treatment. Although based on a very small number of patients, the best survival is noticed in patients having SRS either alone or in combination with other treatment modality.

A multicenter validation of computerized tomography models as predictors of non- optimal primary cytoreduction of advanced epithelial ovarian cancer.

AIMS: To compare the validity of four predictive models of preoperative computerized tomography (CT) scans in predicting suboptimal primary cytoreduction in patients treated for advanced ovarian cancer. PATIENTS AND METHODS: Preoperative CT scans of patients with stage III/IV epithelial ovarian cancer who underwent primary cytoreductive surgery at one of four medical centers were reviewed by radiologists blinded to surgical outcome. The validity of each set of CT criteria previously published by Nelson, Bristow, Dowdy, and Qayyum as predictors of suboptimal cytoreduction was assessed. RESULTS: Data of 123 patients were evaluated. Optimal cytoreduction (largest diameter of residual tumor < or =1cm) was obtained in 90 (73.2%) patients. All CT models were able to significantly predict surgical outcome (p<0.02). The respective sensitivity, specificity, and accuracy of the CT models to predict sub-optimal cytoreduction was 64%, 64% and 64% for Nelson's criteria, 70%, 64% and 66% for Bristow's criteria, 79%, 60%, and 65% for Dowdy's criteria, and 67% 57% and 60% for Qayyum's criteria. CONCLUSIONS: Apart from Dowdy's criteria, the accuracy rates of CT predictors of suboptimal cytoreduction in the original cohorts could not be confirmed in this cross validation. This study underscores the difficulty in devising universally applicable selection criteria or models that reliably predict surgical outcome across institutions and surgeons.

The influence of meteorological factors on the emergence of preterm delivery and preterm premature rupture of membrane.

OBJECTIVE: To evaluate the influence of changes in the atmospheric state on the incidence of preterm delivery (PTD) and preterm premature rupture of membrane (PPROM). STUDY DESIGN: The hospital records of PTD and/or PPROM over the year 1999 were reviewed. The current meteorological state was described by a set of parameters and their diurnal and seasonal variations. Multivariate analysis, time series approach and Poisson regression were used. RESULT: PTD occurrence was correlated with humidity and maximum temperature (P<0.01), its rise preceded their sharp variations by 3 days (P<0.01). PPROM was influenced by the variations in the weather state: desert heat wave arrival (P=0.093), strong winds, overall daily differences of humidity and temperature (all with P<0.05). CONCLUSION: The rates of PTD and PPROM are affected by an ensemble of meteorological variables, specific for each disorder. Obstetricians should be aware of the influence of unstable weather on PTD and PPROM rates, especially in the spring and autumn.

Recurrent cervical carcinoma after radical hysterectomy and pelvic lymph node dissection: a study of 32 cases.

PURPOSE OF INVESTIGATION: To investigate the characteristics of patients with recurrent cervical carcinoma after radical hysterectomy and pelvic lymph node dissection (RHND), and to evaluate the effect of clinical and surgical pathologic factors on the outcome of these patients. METHODS: Data from the files of 32 patients with recurrent cervical carcinoma after RHND managed at the Soroka Medical Center from 1962 through 2005 were analyzed. RESULTS: These 32 patients represent a recurrence rate of 25.4%. The median recurrence-free interval was 19.3 (range, 1-106) months. The prevailing signs and symptoms were obstructive nephropathy, sacral pain and bowel obstruction. Sixteen (50%) patients had loco-regional recurrence alone, 12 (27.5%) loco-regional plus distant recurrence, and four (12.5%) distant recurrence alone. Treatment modalities included radiotherapy, chemotherapy and various surgical procedures. The 5-year survival rate was 35%, with 22 (68.7%) of the patients dead of disease at the end of follow-up. Univariate analysis demonstrated a significant worsening in survival with each of the following factors: loco-regional plus distant recurrence (p = 0.010), positive pelvic lymph nodes (p = 0.010), tumor size > or = 3 cm (p = 0.013), positive lymph vascular space involvement (p = 0.017) and RHND without bilateral salpingo-oophorectomy (p = 0.042). In a multivariate analysis, extent of recurrent disease (locoregional alone versus loco-regional plus distant recurrence) and pelvic lymph node status (negative vs positive) at RHND were the only significant predictors of survival. Uremia was the most common cause of death. CONCLUSIONS: Recurrent cervical carcinoma after RHND is a grave disease with unfavorable prognosis. In both univariate and multivariate analyses, extent of recurrent disease and pelvic lymph node status at RHND were significant predictors of survival.

Ovarian ossification associated with endometriosis.

BACKGROUND: Bone formation in the ovary, with the exception of developing in the setting of mature cystic teratoma, is exceedingly rare. CASE: A 46-year-old woman with a history of endometriosis and chronic pelvic pain underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. A 3 cm solid heavily calcified mass with a stony hard consistency was detected within the right ovary. Microscopic examination revealed extensive calcification of the right ovarian stroma with formation of abundant mature bone, adjacent to small foci of endometriosis. CONCLUSIONS: Endometriosis can be associated with ovarian ossification, forming an extensively calcified adnexal mass. Conservative treatment with close follow-up may be adequate in patients with a history of endometriosis who present with a small heavily calcified ovarian mass and wish to preserve their fertility.

The influence of weather state on the incidence of preeclampsia and placental abruption in semi-arid areas.

BACKGROUND: Being close to the big deserts of the Sahara and Saudi Arabia, the Negev desert in the south of Israel is meteorologically defined as a semi-arid area. PURPOSE: To investigate the influence of meteorological factors typical for the semi-arid areas on the incidence of preeclampsia (PE) and placental abruption (PA). METHODS: The hospital records of women in confinement who had PE and/or PA between January 1, 1999 and December 31, 1999 were retrospectively reviewed. The current meteorological state was described by temperature, humidity, their overall differences and winds. Multivariate analysis, time series approach and Poisson regression are used. RESULTS: The incidence of PE and PA was increased during the periods of unstable weather. Strong winds were associated with increased frequency of PE (p < 0.002); desert wind of Sharav (specific atmospheric state and motion of big desert air volumes) increased incidence of PA (p < 0.033). Daily overall differences of temperature and humidity were correlated with PE (p < 0.03). An inverse correlation between humidity level and PA was obtained (p = 0.000). Increase in PE incidence preceded sharp variations in temperature with an average of 3-day lag (p < 0.003). CONCLUSIONS: An ensemble of meteorological variables, specific for each disorder, affects frequency of PA and PE occurrence. Obstetricians working in semi-arid areas should be aware of the influence of unstable weather conditions on the incidence of PE and PA, especially, in the spring and autumn seasons.

[Placental site trophoblastic tumor].

Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease (GTD) that originates from the implantation site intermediate trophoblast. It accounts for about 1% of all GTDs, with an estimated incidence of 1 per 100,000 pregnancies. Most patients are in their thirties and the prevailing presenting symptom is abnormal vaginal bleeding. More than half of the patients present with disease limited to the uterus and the remainder present with disease extension beyond the uterus. The overall mortality rate is 25%. The most important adverse prognostic factor is disease extension beyond the uterus. Other adverse prognostic factors are interval from antecedent pregnancy > 2 years, mitotic count > 5 mitotic figures/10 high-power fields, and age > 40 years. Since PSTT is less sensitive to chemotherapy than GTDs originating from cytotrophoblast and syncytiotrophoblast (hydatidiform mole, invasive mole, and choriocarcinoma), hysterectomy is the mainstay of treatment. Systemic multi-agent chemotherapy is administered in the presence of disease extension beyond the uterus and considered in the presence of other adverse prognostic factors. The EP/EMA regimen seems to be the most effective chemotherapy available to date for PSTT. Although PSTT produces less human chorionic gonadotropin (hCG) than choriocarcinoma, beta-hCG is still the best available serum marker for monitoring the response to treatment and for follow-up.

Placental site trophoblastic tumor: report of four cases and review of literature.

Placental site trophoblastic tumor (PSTT) is a rare variant of gestational trophoblastic disease that originates from the implantation site intermediate trophoblast. We report four patients with PSTT and review pertinent literature. Three patients presented with disease confined to the uterus and one patient with disease extension beyond the uterus. Antecedent pregnancy was full-term pregnancy in three patients and termination of a 21-week pregnancy in one patient. Interval from the antecedent pregnancy was <1 year in three patients and 13 years in one patient. Primary treatment was simple hysterectomy in three patients and radical hysterectomy in one patient. Overall, three patients received chemotherapy; one had EP/EMA as adjuvant chemotherapy, one had EMA/CO for rising levels of serum beta-hCG and one had BEP then VIP for recurrent disease. The three patients with disease confined to the uterus have remained after treatment alive and with no evidence of disease, whereas the one patient with disease extension beyond the uterus died of disease despite surgery and aggressive chemotherapy. It is concluded that disease extension beyond the uterus is the most important adverse prognostic factor. Other adverse prognostic factors are interval from antecedent pregnancy >2 years, age >40 years, and mitotic count >5 mitotic figures/10 high-power fields. Because of the relative insensitivity to chemotherapy, hysterectomy is the mainstay of treatment. EP/EMA seems to be the most effective first-line chemotherapy available to date for metastatic and relapsing PSTT.

Number and distribution of pelvic lymph nodes and effect of surgical pathologic factors on pelvic lymph node status in patients with early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection.

PURPOSE OF INVESTIGATION: To report the number and distribution of pelvic lymph nodes and to identify surgical pathologic factors that best predict positive pelvic lymph nodes in patients with early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection (RHND). METHODS: Data from the files of 126 patients with cervical carcinoma treated by RHND at the Soroka Medical Center from 1962 through 2005 were analyzed. RESULTS: The status of pelvic lymph nodes was known in 114 patients. The exact number of lymph nodes removed from the pelvis of each patient was known in 111 patients. The mean number of lymph nodes removed from the pelvis per patient was 26.6 (median 23; range 1-62). Positive pelvic lymph nodes were found in 35 (30.7%) of the patients with a mean of 3.4 (median 2; range, 1-15) positive pelvic lymph nodes per patient. In a univariate analysis, positive lymph vascular space invasion and positive parametrial and/or paracervical involvement were significant predictors of positive pelvic lymph nodes, whereas penetration > or = 50% of the thickness of the cervical wall and grade 2+3 were of borderline significance. In a multivariate analysis, positive lymph vascular space invasion was the strongest and the only significant predictor of positive pelvic lymph nodes, whereas positive parametrial and/or paracervical involvement was of borderline significance. CONCLUSIONS: In patients with early-stage cervical carcinoma treated with RHND, positive lymph vascular space invasion emerged to be the strongest and most significant predictor of positive pelvic lymph nodes.

[Umbilical metastasis: Sister Mary Joseph's nodule].

Sister Mary Joseph (1856-1939), who was superintendent nurse at St. Mary's Hospital in Rochester, Minnesota, U.S.A. (at present Mayo Clinic), observed that patients with intra-abdominal or pelvic malignancy often had an umbilical nodule. In 1949 the English surgeon Hamilton Bailey, in his famous textbook "Demonstrations of Physical Signs in Clinical Surgery", coined the term "Sister Joseph's nodule" for umbilical metastases. To date, more than 400 cases of Sister Mary Joseph's nodule have been described in the literature. The nodule may be painful and ulcerated, sometimes with pus, blood, or serous fluid. It is usually a firm nodule measuring 0.5-2 cm, although some nodules may reach up to 10 cm in size. Tumor may spread to the umbilicus through lymph ducts, blood vessels, contiguous extension, and embryologic remnants. Sister Mary Joseph's nodule can be the first manifestation of an underlying malignancy or an indication of a recurrence in a patient with a previous malignancy. The most common origin of Sister Mary Joseph's nodule in women is ovarian carcinoma and in men--gastric carcinoma. Sister Mary Joseph's nodule has traditionally been considered a sign of advanced primary malignancy with an associated poor prognosis; the average survival time has been reported to be 11 months with < 15% of the patients surviving >2 years. In some patients, however, depending on the state of the primary neoplasm and the patient's general condition, surgery and/or chemotherapy may improve survival.

Intraplacental choriocarcinoma metastasizing to the maternal lung.

BACKGROUND: Although normal pregnancy is the precursor of 25% of cases of maternal choriocarcinoma, intraplacental choriocarcinoma in an otherwise normal placenta associated with viable pregnancy has rarely been reported. CASE: Examination of the placenta after delivery of a pale and small-for-date infant at term revealed intraplacental choriocarcinoma. There was no evidence of metastatic disease in the mother or child, but the mother exhibited postpartum rising levels of beta-HCG. The mother refused chemotherapy and disappeared from follow-up. Nine months later, she presented with metastatic choriocarcinoma of the lung. Eleven courses of the multi-drug EMA CO regimen effected a decrease of beta-HCG to normal and disappearance of lung metastases. To date, 28 months after the end of chemotherapy, the patient is alive and without evidence of gestational trophoblastic disease. Moreover, since then she has given birth to an additional two children. CONCLUSIONS: This case is an example of natural disease progression of intraplacental choriocarcinoma metastasizing to the mother. Furthermore, it supports common knowledge that the multi-drug EMA CO regimen is effective treatment in poor prognosis metastatic choriocarcinoma.

Placental site trophoblastic tumor--a challenging rare entity.

Placental site trophoblastic tumor (PSTT) is a challenging rare variant of gestational trophoblastic disease (GTD) with variable characteristics. Historically, it was first described in 1895 and was considered a benign lesion until Scully and Young recognized its malignant potential in 1981. Current knowledge related to PSTT is largely based on the experience of handling this disease in established trophoblastic disease centers and on the experience of authors who reported small series or singular cases. In contrast to other forms of GTD, it arises from the implantation-site intermediate trophoblast, produces less beta-hCG and is less sensitive to chemotherapy. More than half of the patients present with disease confined to the uterus, whereas the remainder present with disease extension beyond the uterus. Because of the relative insensitivity to chemotherapy, simple hysterectomy is the mainstay of treatment. While the outcome of patients with disease confined to the uterus is usually excellent, most patients with disease extension beyond the uterus experience progression of disease and die despite surgery and aggressive chemotherapy. Other important adverse prognostic factors are interval from antecedent pregnancy > 2 years, age > 40 years and mitotic count > 5 mf/10 HPF Although the ideal chemotherapy regimen for PSTT has yet not been established, it seems that the EP/EMA regimen is the most effective first-line chemotherapy available to date for metastatic and relapsing PSTT. Although PSTT produces less hCG than choriocarcinoma, beta-hCG is still the best available serum marker to follow the disease and treatment course of PSTT.

Surgical pathologic factors in patients with early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection: association with administration of adjuvant radiotherapy and effect on survival.

PURPOSE OF INVESTIGATION: To identify surgical pathologic factors that best correlate with administration of adjuvant radiotherapy and best predict survival in early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection (RHND). METHODS: Data from the files of 126 patients with cervical carcinoma treated by RHND at the Soroka Medical Center from 1962 through 2005 were analyzed. RESULTS: Fifty-four percent of the patients received postoperative adjuvant radiotherapy. In a univariate analysis, each of the following factors: positive pelvic lymph nodes, lower uterine segment involvement, lymph vascular space involvement, penetration > or = 50% of the cervical wall, grade 2+3, parametrial and/or paracervical involvement, vaginal margin involvement, non-squamous histologic type, tumor size > or = 3 cm and Stage IB2 + IIA was significantly associated with administration of radiotherapy. In a multivariate analysis, positiviy of pelvic lymph nodes was persistently the most significant factor associated with administration of radiotherapy. The 5-year survival rate was 82.6% overall. In a univariate analysis, a significant worsening in survival was demonstrated with positivity of pelvic lymph nodes and positivity of lymph vascular space involvement. In a "better fit" model of multivariate analysis, pelvic lymph node status was the strongest and the only significant predictor of survival. CONCLUSIONS: In patients with early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection, pelvic lymph node status is the strongest factor affecting administration of adjuvant radiotherapy and the most significant predictor of survival.