Pooled analysis of diarrhea events in patients with cancer treated with lapatinib

Purpose To characterize diarrhea events in patients with cancer treated with lapatinib as monotherapy or in combination with capecitabine or taxanes. Patients and methods Eleven clinical trials (phase I, II, or III) in patients with metastatic cancer were analyzed. Lapatinib was administered at doses ranging from 1,000 to 1,500 mg/day as monotherapy (n = 926) or in combination with capecitabine (n = 198) or taxanes (n = 687). Diarrhea events were characterized based on severity, time to onset, duration, required interventions, and clinical outcomes. Results In the pooled analysis of nine studies, diarrhea occurred in 55% of lapatinib-treated patients and 24% of patients not receiving lapatinib. All grade diarrhea occurred in 51% of patients treated with lapatinib monotherapy and 65% treated with lapatinib plus capecitabine. In a separate analysis, 48% of patients treated with lapatinib plus a taxane experienced diarrhea. Overall, most diarrhea events were grade 1/2. Grade 3 events occurred in <10% of patients and grade 4 events were rare (≤1%). Most diarrhea events resolved with conventional approaches and without dose modification. Approximately 40% of patients treated with lapatinib monotherapy or combination therapy experienced a first diarrhea event within 6 days of treatment initiation, with a median duration of 7–9 days. Lapatinib-containing chemotherapy regimens do not cause severe diarrhea when proactive monitoring and intervention is introduced. Conclusion Most diarrhea events in lapatinib-treated patients are low grade, requiring infrequent lapatinib dose modification or interruption. Proactive management of diarrhea is crucial to prevent more serious complications in lapatinib-treated patients. An erratum to this article can be found at     

Outcomes in young women with breast cancer of triple-negative phenotype: the prognostic significance of CK19 expression

PURPOSE: Basal-like carcinoma of the breast is associated with genetic instability and aggressive behavior. In this study, we evaluated the luminal cytokeratin marker CK-19 in young women with breast cancer treated with conservative surgery and radiation therapy (CS+RT). METHODS: Primary tumor specimens from a cohort of 158 young premenopausal women (range, 25-49 years) treated with CS+RT with a median follow-up of 6.25 years were constructed into a tissue microarray. The array was stained for ER, PR, HER2, CK19, and p53. The molecular profiles were correlated with clinical-pathologic factors, overall, local, and distant relapse-free survival. The association between CK19, other co-variables, and outcome was assessed in a multivariate model. RESULTS: Positive expression of ER, PR, HER-2/neu, CK19, and p53 were 33.1%, 34.5%, 10.0%, 79.5%, and 20.9%, respectively. With 20 local relapses and 38 distant metastases, the 10-year overall, breast relapse-free, and distant relapse-free survival were 79.65%, 87.29%, and 67.35%, respectively. Tumor stage and nodal status were associated with distant relapse-free and overall survival. In multivariate analysis, CK19 negativity was a predictor poor local (RR, 3.54; 95% CI, 1.87-7.65; p < 0.01) distant (RR, 1.44; 95% CI, 0.86-2.70; p = 0.17), and overall survival (RR, 1.89; 95% CI, 1.04-3.55; p = 0.03). CONCLUSIONS: Lack of CK19 expression identifies a subset of patients with a significantly higher risk of local relapse. Distant relapse and overall survival rates also correlated with CK19 negativity. Further evaluation of the prognostic significance of basal and luminal cytokeratins in young women with breast cancer is warranted.     

What is the aim of esophageal variceal sclerotherapy--prevention of rebleeding or complete obliteration of veins?

Endoscopic variceal sclerotherapy (EVS) is highly effective in arresting active esophageal variceal bleeding. Subsequent repeated EVS sessions significantly reduce recurrence of bleeding; long-term survival is reported as prolonged or unaltered. In contrast, EVS for preventing first variceal bleeding (prophylactic sclerotherapy) is not recommended, even for high-risk patients, because it enhances mortality by significantly increasing the risk of bleeding in the treated group compared with controls. The risk of variceal rebleeding is maximum within 6 weeks of index bleeding; most patients who survive 6 weeks of variceal bleeding (with or without sclerotherapy) behave like patients who have never bled from varices. Thus, EVS continued beyond 6 weeks, to obliterate the veins completely, is akin to prophylactic sclerotherapy. Significant complications of EVS--its cost, discomfort to patient, and loss of doctor and patient time--should be weighed against doubtful benefit of continuing prolonged EVS beyond 6 weeks, just to completely obliterate esophageal veins. The possibility of better long-term survival with sclerotherapy limited to 6 weeks cannot be excluded, because prophylactic sclerotherapy shortens long-term survival.     

Measurement of CA125, carcinoembryonic antigen, and alpha-fetoprotein in ovarian cyst fluid: diagnostic adjunct to cytology.

This study used CA125, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) to classify ovarian cysts by measuring the levels of the three antigens; this information was useful when fluid obtained through laparoscopic puncture of ovarian cysts was submitted for cytologic examination from patients for whom tissue was unavailable for classification. We studied 136 consecutive cyst fluids (108 benign, 28 malignant) and correlated the findings with the tissue diagnosis. All three antigens were very low (CEA, less than 0.5 ng/ml; CA125, 55-2,143 mu/ml; and AFP, less than 4.8 ng/ml) in follicular and lutein cysts. Markedly elevated CA125 (296-1,950,000 mu/ml) and low CEA (0.5-220 ng/ml) and AFP (less than 4.8 ng/ml) levels were seen in patients with serous neoplasms, both benign and malignant. Elevated CEA (greater than 600 ng/ml) and CA125 (56-65,330 mu/ml) levels were seen in primary mucinous cystadenoma and cystadenocarcinoma. Two patients with colonic carcinoma metastatic to the ovary had an elevated CEA (greater than 600 ng/ml) and a normal CA125. Only one patient, with a malignant teratoma, had an elevated AFP. The adjunctive use of CEA and CA125 is recommended for the classification of ovarian cysts.     

Doppler Ultrasound: A Good and Reliable Predictor of Ovarian Malignancy

Aims

The aim of the present study was to prove the efficiency of Color Doppler and Spectral Doppler in evaluation and characterization of the ovarian neoplasm.

Materials and Methods

In total, 104 patients with adnexal masses were examined sonographically to evaluate for morphologic characteristics, as well as pulsatility indices (PI), and resistance indices (RI) over a period of 2 years, of which 20 were excluded as the masses were not finally proven to be adnexal, and thus 84 patients with ovarian neoplasm were retained as the study subjects. The final diagnosis was based on histopathologic confirmation.

Result

Out of 84 cases, 44 were benign and 40 were malignant. Color Doppler showed vascularity in 97.5 % of malignant tumors in contrast to only 68.1 % of benign tumors. The present study showed that, 87.5 % of malignant tumors had PI less than 0.8 in contrast to only 4.54 % of benign tumors. Similarly, 82.5 % of malignant tumors had RI less than 0.6 in contrast to only 6.81 % of benign tumors.

Conclusion

Multiparameter analysis utilizing B-mode USG along with Color Doppler and Spectral Doppler is the mainstay in diagnosis of patients with ovarian tumors. A good specificity (84.1 %) and sensitivity (97.5 %) with PI and RI values of <1.0 and <0.6, respectively, was achieved with the present study which is highly significant in differentiating between malignant and benign ovarian tumours.     

Effects of Period of Gestation and Position of Fetal Neck on Nuchal Translucency Measurement

Objective

The aim of this study was to determine the effects of period of gestation and position of fetal neck on nuchal translucency measurement.

Materials and Methods

Nuchal translucency was measured in the mid-sagittal plane, with the fetal neck in the flexed, neutral, and extended positions in 100 pregnant women between 11 and 13⁺⁶ weeks. Mean nuchal translucency measurements at different periods of gestation were compared. Differences between the extended and neutral positions (Δ extended nuchal translucency) and those between the flexed and neutral positions (Δ flexed nuchal translucency) were calculated. The repeatability coefficients for the measurements in all the three positions were computed. Statistical analysis was also done.

Results

Nuchal translucency values were 1.050 ± 0.282 mm in the 11th week, 1.243 ± 0.348 mm in the 12th week, and 1.823 ± 0.357 mm in the 13th week (r = 0.747, p < 0.0001). The mean Δ flexed value was 0.233 ± 0.133 mm lesser than the neutral value (p < 0.0001). The mean Δ extended nuchal translucency was 0.305 ± 0.155 mm greater than the neutral value (p < 0.0001). The repeatability coefficient was the lowest in the neutral position (0.17 mm in the neutral position, 0.28 in the flexed position and 0.41 mm in the extended position).

Conclusion

We concluded that the period of gestation and fetal neck position can make a significant difference to nuchal translucency measurement. Repeatability of measurement is more accurate with the fetal neck in the neutral position. These findings have important implications for clinicians using nuchal translucency to screen the obstetric population for Down’s syndrome.     

Pheochromocytoma and pregnancy: report of three cases.

Three cases of pheochromocytoma associated with pregnancy are reported. Two patients had adrenal pheochromocytoma coexistent with normal pregnancy and one patient had a bladder pheochromocytoma coexistent with molar pregnancy (gestational trophoblastic disease). The diagnosis was made antenatally in the two normal pregnancy patients, both underwent planned tumor resection, one at mid-trimester, complicated by postoperative miscarriage, while the other had tumor resection during cesarean section at term. Bladder pheochromocytoma, preoperatively mistaken for invasive trophoblastic tumor, was resected at the time of planned abdominal hysterectomy for molar pregnancy, pheochromocytoma was recognized only after microscopic study of the resected bladder tumor. The three patients survived with no evidence of disease.