Middle cerebral artery peak systolic velocity monitoring of fetal anemia during chemotherapy in pregnancy.

INTRODUCTION: Chemotherapy during pregnancy can increase the risk of fetal anemia. Severe fetal anemia can lead to the development of hydrops fetalis and potentially fetal demise. Hence, it is imperative to implement consistent monitoring methods in the context of chemotherapy treatment. This study aimed to diagnose and monitor fetal anemia using middle cerebral artery peak systolic velocity (MCA-PSV) as a diagnostic tool during chemotherapy in pregnant women. MATERIAL AND METHODS: The study employed a prospective analysis involving a case series of 15 patients diagnosed with cancer during pregnancy and subsequently underwent chemotherapy. MCA-PSV was used to identify fetal anemia. The patients were scheduled for ultrasound examinations of the MCA-PSV. The first examination was performed on the same day as the administration of chemotherapy, while the second occurred on the 10th day after chemotherapy. The measurement technique used in the study was based on the methodology proposed by Mari and Barr. The multiples of the median were calculated using the calculators provided by Medicina Fetal Barcelona. Based on these values anemia severity was determined. When moderate or severe anemia was identified, chemotherapy was individually modified. Additionally, a blood count analysis was conducted immediately after the delivery of the newborn. RESULTS: Five patients were diagnosed with fetal or newborn anemia. With MCA-PSV, we identified moderate fetal anemia in two patients and severe fetal anemia in one. The complete blood count testing of newborns revealed mild anemia in three patients. One case was unrelated to chemotherapy-induced anemia. During treatment, fetal anemia did not corelate with maternal anemia. CONCLUSIONS: In four cases of anemia the combination of cisplatin and iphosphamide was used as a chemotherapy agent. No anemia was observed in other drug combinations. Our findings suggest that MCA-PSV is a reliable method for identifying anemia and should be included in the treatment protocol for chemotherapy-induced fetal anemia.

The current role of radiotherapy and systemic therapy in the multidisciplinary treatment of cholangiocarcinoma.

Cholangiocarcinoma is a cancer with very poor prognosis. The only potentially curative approach is surgical resection of tumor. However, the rate of local and distant recurrence after radical surgery is still high. Benefit of adjuvant therapy is not clearly defined, nevertheless patients at high risk of recurrence are indicated to chemotherapy or chemoradiotherapy. Locally advanced, unresectable disease can also be treated with chemotherapy alone, or with her combination with radiotherapy. Required radiation doses are relatively high, therefore it is necessary to use highly conformal radiation therapy. Treatment of metastatic disease is currently based on systemic therapy, combination of gemcitabine and cisplatin as standard of care. Benefit of targeted molecular therapy is not clear at present, but ongoing research in genetic profiling of tumor may help to improve current clinical practice. Patients with cholangiocarcinoma have to be discussed during multidisciplinary team meetings.

Locally advanced laryngeal cancer: Total laryngectomy or primary non-surgical treatment?

Between January 1997 and December 2013, the Charles University 3rd Medical School and Royal Vinohrady Teaching Hospital Ear, Nose and Throat oncology team treated 185 patients with advanced laryngeal cancer, which, from a surgical perspective, required a total laryngectomy. Overall, ~70% of these patients (n=129) underwent conventional treatment (i.e., total laryngectomy with post-operative radiotherapy), and ~30% (n=56) were treated with larynx preservation protocols (including primary radiotherapy, neoadjuvant chemotherapy followed by radiotherapy or chemoradiotherapy, or primary chemoradiotherapy). Patients treated with laryngeal preservation protocols had a 5-year survival probability of 48%, whereas those treated with total laryngectomy and post-operative radiotherapy had a 5-year survival probability of 63%. This difference was not statistically significant. However, patients who underwent primary surgical treatment survived for a significantly longer period (P<0.010). The sex of the patient did not have a statistically significant impact on patient survival probability. More extensive local disease and more advanced disease stages conferred a lower survival probability, but were not statistically significant; however, a lower survival probability in patients >70 years was identified to be statistically significant (P<0.010). Local disease recurrence and recurrent cervical nodal metastases had a statistically significant impact on the 5-year survival probability (P<0.001). A step wise Cox regression analysis was used to compare the parameters of sex, patient age, tumor extent, disease stage, choice of primary surgery, local recurrence and cervical nodal recurrence. In the first step, local recurrence was selected as the parameter having the greatest effect on survival (P<0.001); patient age >70 years (P<0.001) was selected in the second step; cervical nodal recurrence (P<0.001) in the third step; and disease stage (P<0.010) in the fourth step. Other parameters did not significantly affect survival. The results of the present study confirmed that primary non-surgical treatment is an alternative approach to total laryngectomy, and that an informed patient should determine the treatment approach. The decreased overall survival observed in more extensive tumors suggests that surgical treatment may be a better selection in these cases. Due to increased overall survival, primary non-surgical treatment may be recommended for younger patients. If the patient chooses primary non-surgical treatment, concomitant chemoradiotherapy is recommended. If the patient cannot tolerate cytostatic chemotherapy, radiotherapy alone is recommended.

Circulating tumor cells in patients with breast cancer: monitoring chemotherapy success.

UNLABELLED: Circulating tumor cells (CTCs) are an independent prognostic factor for patients with metastatic breast cancer (MBC). However, the role of CTCs in early breast cancer management is not yet clearly defined. The aim of this study was to assess the CTC-positivity rate in patients undergoing chemotherapy depending on breast cancer stage in the adjuvant and neoadjuvant setting. We evaluated the ability to confirm therapy response by CTC analysis. PATIENTS AND METHODS: CTCs isolated from blood by means of immunomagnetic separation were further characterized by means of reverse transcriptase - polymerase chain reaction (RT-PCR) for epithelial cell adhesion molecule (EPCAM), mucin 1 (MUC1) and v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (HER2) transcripts with the AdnaTest™. This prospective study included 179 patients; altogether 419 blood samples were evaluated. Patients with primary tumors were divided into neoadjuvant (n=38), and adjuvant (n=100) groups. Forty-one patients with MBC were evaluated under palliative treatment. RESULTS: CTC positivity was described in 35% of patients with early breast cancer without detected metastases before neoadjuvant chemotherapy; similarly, a 26% positivity rate was found in the adjuvant group. In patients with MBC, we detected CTCs in 43% of them. After completing the therapy, the CTC positivity rate decreased to 5% in the neoadjuvant group, to 13% in the adjuvant group and to 12% in the MBC group. CTC positivity after the therapy may classify a subgroup of patients at high risk of developing metastatic disease. This was even true when a patient was evaluated as being CTC-negative before chemotherapy. The multivariate analysis evaluating the correlation of CTC positivity with clinicopathological characteristics such as tumor size, nodal involvement, hormone receptor status, HER2 expression and number of metastatic sites revealed no statistically significant relationships. CONCLUSION: CTC status may have a significant impact on early BC management.

Expression of selected proteins in breast cancer brain metastases.

The aim of the study was to assess the immunohistochemical (IHC) profiles of SRC3, Pax2, ER, PgR, Her2, EGFR, CK5/6, and Ki67 proteins in breast-cancer brain metastasis. The study utilized tumor samples from 30 metastatic patients and calculated correlations between all IHC variables. In fourteen cases, primary breast cancers paired with secondary deposits were analyzed. We evaluated the association between IHC status in the primary and secondary deposits, grade, and histotype of the tumors. The examination of the metastatic deposits in all 30 patients resulted in positive detection in the following cases: SRC3 in 20 cases (66.6%), Pax2 in 22 (73.3%), ER in 22 (73.3%), PgR in 25 (83.3%), Her2 in 10 (33.3%), EGFR in 12 (40%), CK5/6 in 7 (23.3%), and Ki67 in 23 (76.6%). Grade 2 was found in 13.3% of all patients, and grade 3 in 86.7%. SRC3 and Pax2 were positive in both G2 and G3. Invasive lobular carcinoma and invasive ductal carcinoma were diagnosed in 23.3% and 76.7% of cases, respectively. There were no differences between the IHC expression of the studied proteins in either grading or histotype of the tumors. In the IHC profiles, which included SRC3, Pax2, ER, PgR, Her2, CK5/6, Ki67, and EGFR, we found no statistically significant differences between the primary cancer and the brain metastasis. In our study of metastatic breast carcinoma deposits, there was no correlation between SRC3, Pax2 status and histotype, and tumor grade. The IHC status of the paired primary and metastatic deposits did not differ in a statistically significant manner.

heterogeneity of dna ploidy in endometrial carcinoma: comparison of different tissue samples obtained during diagnosis and treatment.

AIM: Comparison of DNA ploidy status of different tumour tissue samples (fresh/frozen vs. paraffin-embedded; curettage vs. hysterectomy samples) obtained during diagnosis and treatment of patients with endometrial carcinoma. PATIENTS AND METHODS: DNA ploidy status and conventional prognostic parameters were recorded for 74 patients with endometrial carcinoma prospectively. RESULTS: In 59 (79.7%) patients the DNA status was described as diploid in all analyzed tissue samples. The remaining 15 (20.3%) cases were described as DNA aneuploid in at least one of the corresponding tissue samples. The concordance between DNA ploidy status in fresh vs. paraffin-embedded hysterectomy samples as well as curettage vs. hysterectomy paraffin-embedded samples was high (kappa coefficient κ=0.6348, 95% confidence interval CI=0.3673-0.9023, and p=0.6408, 95% CI=0.3977-0.8838), however, the methods are not interchangeable. CONCLUSION: The DNA ploidy discordance observed in our study group seems to document intratumoral heterogeneity that should be expected when applying DNA ploidy status in the clinical management of endometrial carcinoma.

Cimetidine: an anticancer drug?

Cimetidine, H(2) receptor antagonists, is commonly prescribed for gastric and duodenal ulcer disease. Additionally, cimetidine has been shown to have anticancer effects. This review describes the mechanism of antitumor action of cimetidine including its ability to interfere with tumor cell adhesion, angiogenesis and proliferation; its effect on the immune system; as well as inhibition of postoperative immunosuppression. Its anticancer effect is also compared to that of the other H(2) receptor antagonists as well as outcomes of cimetidine in clinical studies in cancer patients.

A clinically relevant, syngeneic model of spontaneous, highly metastatic B16 mouse melanoma.

We report a syngeneic model of spontaneous metastatic B16-F10 mouse melanoma in C57/BL6 mice with a very high metastatic frequency that mimics clinical metastatic melanoma. The B16 melanoma cells were injected between the skin and cartilage on the dorsal side of the ear. The model generated lymphatic and visceral metastases in all of the tested animals. In mice with large primary tumors, tumor weight correlated with the tumor growth time and also with the number of metastases in lymph nodes and organs. The dorsal ear space between the skin and cartilage enables both lymphatic and hematogenous metastatic spread. The model should be useful to study the mechanism of melanoma metastasis and to develop therapy for this currently untreatable disease.