Fetal ovarian cysts management and ovarian prognosis: a report of 82 cases

Background/Purpose

Fetal ovarian cysts are frequently complicated by intracystic hemorrhage without associated clinical signs, which is often secondary to ovarian torsion leading to loss of the ovary. The aim of this study was to evaluate ovarian outcome and the place of prenatal management and surgery in the first few days of life in order to save the ovary.

Methods

Between January 1987 and June 2006, 82 fetal ovarian cysts in 79 patients were managed and clinically and ultrasonographically followed up for several months (median, 11 months; range, 6 months to 10 years) in all of the cases where the ovary was not removed. The ultrasonographic results regarding the ovarian parenchyma were broken down into 3 categories: follicular ovary, homogeneous ovary, and undetected ovary.

Results

Twenty-seven cysts remained simple throughout their evolution, and 55 were complicated by intracystic hemorrhage usually several weeks before birth. Overall, after disappearance of the cyst, a follicular ovary was detected in only 39% of the cases (32/82) and more often when the cyst was simple than when it presented an intracystic hemorrhage (85% vs 16.4%, χ², P < .0001).

Conclusions

A review of our series confirms the poor ovarian outcome linked to ultrasonographic signs of intracystic hemorrhage. Preventive action by puncture of “simple” cysts is still being studied. The presence of a bilateral cyst can, if pulmonary maturity has been reached, be an argument for inducement of premature birth with a view to performing conservative surgery. After birth, surgery in the first few days of life is only justified if the signs of intracystic hemorrhage appeared in the period very close to birth.     

Successful liver transplant for unresectable hepatoblastoma

Background

Treatment of children with stage III and IV hepatoblastoma has shown little improvement with 5-year survival rates of 64% and 25%, respectively (J Clin Oncol 2000;18:2665-75). A timely and organized treatment program including preoperative chemotherapy combined with living donor liver transplantation and postoperative chemotherapy has been used seeking improved long-term survival in stage III and IV cases.

Methods

A retrospective review of 8 patients with stage III and IV hepatoblastoma unresectable by conventional resection were treated with complete hepatectomy and transplantation. Approval was obtained from our institutional review board.

Results

Since August of 2001, we have treated 6 patients with stage III hepatoblastoma and 2 patients with initial stage IV hepatoblastoma. These patients (age, 23 months-9 years) had all received extensive chemotherapy or prior resections. After chemotherapy, none had gross tumor documented outside of the liver at time of transplantation. All underwent hepatectomy including vena cava resection, in selected cases, with living donor orthotopic liver transplantation. All patients had at least 2 cycles of postoperative chemotherapy. Of 8 patients, 6 are alive and well with normalized alpha-fetoprotein levels. There were 2 late deaths from recurrent disease. Length of follow-up ranged from 7 to 53 months.

Conclusion

Complete hepatectomy with living donor liver transplantation provides optimal surgical treatment in unresectable stage III and initial stage IV disease confined to the liver at resection. This series indicates that children tolerate complete hepatectomy, transplantation, and postoperative chemotherapy well. Referral to a transplant center during the first 3 cycles of chemotherapy appears to offers the best opportunity for long-term survival.     

Protein array technology to detect HER2 (erbB-2)-induced 'cytokine signature' in breast cancer

Identification of genes/proteins that are differentially expressed in HER2 (erbB-2) oncogene-dependent breast carcinomas is essential in elucidating the mechanistic basis of their increased metastastic potential and resistance to several anti-cancer therapies. We here applied human cytokine antibody arrays with the goal of identifying a unique HER2-induced 'cytokine signature' in breast cancer. Human Cytokine Array III (RayBiotech, Inc.), which simultaneously detects 42 cytokines and growth factors on one membrane, was used to determine the profile of cytokines in conditioned media obtained from MCF-7/Her2-18 cells, a MCF-7-derived clone engineered to stably express the full-length human HER2 cDNA controlled by a SV40 viral promoter, and from the MCF-7/neo control sub-line. We identified two inflammatory and pro-angiogenic CXC chemokines with at least a 10-fold increased expression in HER2-overexpressing MCF-7/Her2-18 transfectants when compared to matched control MCF-7/neo cells: CXCL8 (IL-8; Interleukin-8) and CXCL1 and (GRO; Growth-related oncogene). HER2-induced differential overexpression of IL-8 and GRO was validated by ELISA and further confirmed by switching off the HER2 signalling. Treatment with the tyrosine kinase inhibitor gefitinib (Iressa) returned the expression levels of IL-8 and GRO back to the baseline observed in MCF-7 breast cancer cells, which express physiological levels of HER2. To evaluate the diagnostic utility of these findings, cytokine-specific antibody arrays were incubated with sera retrospectively collected from metastatic breast cancer patients. This approach revealed a high similarity between the 'cytokine signature' observed in serum samples and that obtained in media conditioned by breast cancer-derived cell lines. Thus, IL-8 and GRO circulating levels were significantly higher in HER2-positive breast cancer patients compared with HER2-negative patients. These findings reveal for the first time that: a) Enhanced synthesis and secretion of members of the IL-8/GRO chemokine family, which have recently been linked to oestrogen receptor (ER) inaction, increased cell invasion and angiogenesis, may represent a new pathway involved in the metastatic progression and endocrine resistance of HER2-overexpressing breast carcinomas, and b) Circulating levels of IL-8 and GRO cytokines may represent novel biomarkers monitoring breast cancer responses to endocrine treatments and/or HER2-targeted therapies.     

Efficiency of tazobactam/piperacillin in lethal peritonitis is enhanced after preconditioning of rats with O3/O2-pneumoperitoneum

Insufflation of ozonized oxygen into the peritoneum (O3/O2-pneumoperitoneum [O3/O2-PP]) of rats reduced the lethality of peritonitis. We evaluated the prophylactic effect of O3/O2-PP combined with tazobactam/piperacillin (TZP) in polymicrobial lethal peritonitis. Wistar rats were conditioned by daily repeated insufflation of ozone for 5 days, and hematologic parameters were determined. Sepsis was induced by i.p. injection of cecal material derived from donor rats. Simultaneously, TZP was applied at a single dosage of 65 mg/kg or at two dosage schedules of 65 mg/kg each at an interval of 1 h. The conditioning effect of O3/O2-PP on the number of blood cells was measured before inoculation of bacteria. The mRNA levels of proinflammatory cytokine IL-lbeta and TNF-alpha were determined at 4 h post infection in spleen and liver by semiquantitative in situ hybridization analysis. Preconditioning of rats by O3/O2-PP enhanced the number of blood leukocytes and granulocytes and increased the survival rate of septic rats up to 33%. The combination of O3/O2-PP and TZP further enhanced the survival rate up to 93%. This effect was accompanied by a reduced amount of IL-1beta and TNF-alpha mRNA in spleen and liver. In contrast, in non-infected animals the combination of O3/O2-PP and TZP enhanced IL-1beta and TNF-alpha mRNA in the spleen and IL-1beta mRNA in liver when compared with TZP- and sham-treated controls. The preconditioning effect of O3/O2-PP seems to support the biological effectiveness of TZP by altering the immune status before and during the onset of sepsis. The combined therapy could be a simple, preoperative intervention for abdominal surgery to reduce postoperative morbidity and mortality.