Mani Nassir

Preoperative HE4 and ROMA values do not improve the CA125 diagnostic value for borderline tumors of the ovary (BOT) - a study of the TOC Consortium

BackgroundBorderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants.ObjectiveThe aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants.MethodsRetrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease.ResultsThere were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples.ConclusionsBoth HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants.

Detection of soluble EpCAM (sEpCAM) in malignant ascites predicts poor overall survival in patients treated with catumaxomab

EpCAM is an attractive target for cancer therapy and the EpCAM-specific antibody catumaxomab has been used for intraperitoneal treatment of EpCAM-positive cancer patients with malignant ascites. New prognostic markers are necessary to select patients that mostly benefit from catumaxomab. Recent data showed that soluble EpCAM (sEpCAM) is capable to block the effect of catumaxomab in vitro. This exploratory retrospective analysis was performed on archived ascites samples to evaluate the predictive role of sEpCAM in catumaxomab-treated patients. Sixty-six catumaxomab-treated patients with an available archived ascites sample were included in this study and tested for sEpCAM by sandwich ELISA. All probes were sampled before treatment start and all patients received at least one catumaxomab infusion. Overall survival, puncture-free survival and time to next puncture were compared between sEpCAM-positive and -negative patients. We detected sEpCAM in ascites samples of 9 patients (13.6%). These patients showed a significantly shorter overall survival. The prognostic significance of sEpCAM in ascites was particularly strong in patients with ovarian cancer. Puncture-free survival and time to next puncture were not significantly different between sEpCAM-positive and -negative patients. We propose sEpCAM in malignant ascites as a potential predictive marker in cancer patients treated with catumaxomab. Prospective studies with larger patients samples are urgently needed to confirm these findings and studies testing dose-intensified catumaxomab in patients with sEpCAM-positive ascites should be envisaged.

Prediction of clinical response to drugs in ovarian cancer using the chemotherapy resistance test (CTR-test)

BackgroundIn order to validate if the test result of the Chemotherapy Resistance Test (CTR-Test) is able to predict the resistances or sensitivities of tumors in ovarian cancer patients to drugs, the CTR-Test result and the corresponding clinical response of individual patients were correlated retrospectively. Results were compared to previous recorded correlations.MethodsThe CTR-Test was performed on tumor samples from 52 ovarian cancer patients for specific chemotherapeutic drugs. Patients were treated with monotherapies or drug combinations. Resistances were classified as extreme (ER), medium (MR) or slight (SR) resistance in the CTR-Test. Combination treatment resistances were transformed by a scoring system into these classifications.ResultsAccurate sensitivity prediction was accomplished in 79% of the cases and accurate prediction of resistance in 100% of the cases in the total data set. The data set of single agent treatment and drug combination treatment were analyzed individually. Single agent treatment lead to an accurate sensitivity in 44% of the cases and the drug combination to 95% accuracy. The detection of resistances was in both cases to 100% correct. ROC curve analysis indicates that the CTR-Test result correlates with the clinical response, at least for the combination chemotherapy. Those values are similar or better than the values from a publication from 1990.ConclusionsChemotherapy resistance testing in vitro via the CTR-Test is able to accurately detect resistances in ovarian cancer patients. These numbers confirm and even exceed results published in 1990. Better sensitivity detection might be caused by a higher percentage of drug combinations tested in 2012 compared to 1990. Our study confirms the functionality of the CTR-Test to plan an efficient chemotherapeutic treatment for ovarian cancer patients.

Enigmatic meningitis in a patient with T cell lymphoma.

Dear Editor, Infections with Strongyloides stercoralis are distributed globally, but are particularly prevalent in tropical/subtropical regions. Larvae of S. stercoralis can persist for decades in infected hosts [1]. Immunosuppression could promote autoinfection resulting in a hyperinfection syndrome, which is characterized by increased numbers of migrating larvae, an enhanced risk of bacterial dissemination from the gastrointestinal tract and a dismal prognosis [2, 3]. A 44-year-old male, descent from the Ivory Coast, presented in our emergency room with severe headache, but without fever, meningism, or any other neurological abnormalities. The white blood cell count (WBC) was slightly elevated (14.5/nL). Prior to admission, the patient had received CHOEP-chemotherapy for non-leukemic, stage IV peripheral T cell lymphoma (not otherwise specified according to the WHO classification). The patient had a 16-year-long history of recurrent headaches. Since receiving chemotherapy, headaches worsened requiring morphine. Upon admission, the cerebrospinal fluid (CSF) contained 18,853 WBC/μL (99 % neutrophils), 1305 mg/dL protein, and 15 mg/dL glucose, and gram and India ink stain was negative. The number of CD4-positive cells was decreased (180/μL). Empirical therapy with ceftriaxone, ampicillin, and acyclovir was started. A drug-induced, aseptic meningitis was first suspected, but CSF cultures were positive for Streptococcus gallolyticus subsp. pasteurianus. There was only minor improvement, although the CSF cell count had decreased down to 32/μL. Despite continuation of antibiotic therapy with adequate modifications, CSF and blood stream cultures continued to be positive: Enterococcus faecium (CSF, day 7), Klebsiella pneumoniae (blood stream, day 19), and E. faecium (CSF, day 36; blood stream, day 40). During the course, the patient developed intestinal atony. Endoscopy showed ulcerative lesions in the colon and massive duodenal fibrin exsudation. Histopathological examination revealed larvae within the duodenal and gastric mucosa (Fig. 1a), accompanied by T cell lymphoma infiltrates in the gastric mucosa. Numerous larvae of S. stercoralis were visible in stool samples after Baermann enrichment (Fig. 1b). Upon recognition of a S. stercoralis hyperinfection syndrome, the patient received oral ivermectin (200 μg/kg b.i.d.) for 19 days. Stool specimens were first negative for larvae after 11 days. Serology was positive for HTLV-1 and negative for HIV and hepatitis C. Furthermore, serology detected antibodies against HBc antigen, CMV, and EBV, but absence of IgM and HBs antigen indicated past infections with these viral agents. Additional immunophenotyping of the lymphoma revealed a co-expression of CD4 and CD25 suggestive for an adult T cell lymphoma. Interestingly, S. stercoralis serum antibodies were undetectable and the eosinophil count was always within the normal range. Unfortunately, the patient developed progressive deterioration, which precluded further antineoplastic therapy. He died 55 days after admission due to lymphoma progression. Infections with S. stercoralis could present with subtle symptoms and unusual manifestations carrying the risk of misdiagnoses or delayed recognition, particularly in nonendemic areas where most healthcare professionals are unfamiliar with this disease. Increasing numbers of individuals * Stefan Schwartz stefan.schwartz@charite.de

Inflammatory bowel disease (IBD)-like disease in a case of a 33-year old man with glycogenosis 1b

BackgroundInflammatory bowel disease (IBD)-like conditions in glycogen storage disease (GSD) type Ib have been predominantly described in children. Signs and symptoms of GSD type Ib are hypoglycemia, pancytopenia and hepatosplenomegaly. Based on few published cases, there is evidence that granulocyte-colony stimulating factor (G-CSF) in patients with glycogenosis–related pancytopenia might ameliorate the IBD-like disease through leukocyte increase.Case presentationHere we firstly describe a case of an adult 33-year-old Caucasian male patient with GSD type Ib accompanied with IBD-like disease with persistent pancytopenia despite moderate-dose G-CSF treatment. Recent vomiting and abdominal discomfort were due to a high-grade stenosis in the transverse colon. A dose increase of the G-CSF successfully normalized his leukocyte count. However, the stenosis worsened and surgical therapy was needed.ConclusionWe suggest that symptomatic patients with GSD type Ib should undergo endoscopic examination in order to detect IBD-like disease and to initiate early treatment.