Israel Medical Association Journal

Background: Predictive biomarkers for personalized treatment of neoplasms are suggested to be a major advancement in oncology and are increasingly used in clinical practice, albeit based on level II evidence. Target Now® (TN) employs immunostaining and RNA expression on tumor samples to identify potentially beneficial or ineffective drugs. 

Objectives: To explore retrospectively the predictive value of TN for patients with colorectal and gastric carcinomas. 

Methods: The study group comprised colorectal and gastric carcinoma patients with TN test reports. We identified chemotherapy regimens given for stage IV disease for which TN reports indicated prediction. Protocols were classified as having clinical benefit (CB; i.e., stable disease or any objective response) or progressive disease, and this was compared with the TN prediction. 

Results: Nineteen patients – 12 colorectal and 7 gastric carcinomas – met the inclusion criteria. There were 26 evaluable treatment protocols; of 18 with a CB 15 were predicted to have a CB while 3 were predicted to have a lack of CB. Of eight protocols that had no CB, seven were predicted to have a CB and one was predicted to have a lack of CB. A chi-square test was non-significant (P = 0.78). An exploratory analysis yielded a positive predictive value of 68% and a sensitivity of 83% for the TN test. 

Conclusions: This study emphasizes the need for larger multicenter studies to validate the TN test before it is adopted into clinical practice. 

 

Background: In recent years several reports have been published describing dogs’ ability to detect, by scent, patients with cancer. This ability is based on the sniffing of volatile organic elements that are secreted by malignant cells, react to them. 

Objectives: To evaluate the ability of trained dogs to detect (i) breast cancer cell cultures (MCF7) compared to the control pseudo-normal keratinocyte cell line (HaCaT), and then (ii) melanoma (BG) and (iii) type 2 epithelial lung carcinoma (A549) malignant cell cultures to which they were not previously exposed in the course of their training.

Methods: Cell cultures were prepared in a standard manner. Two Belgian Shepherd dogs were trained and then tested in a single-blind test (for dogs and trainers) on their ability to detect the "target specimen," a MCF7 breast cancer cell culture. Following this, the ability of the dogs to detect cancer cell cultures that they were not previously exposed to (i.e., A549, BG) was tested. In each test round, four specimens placed in identical blocks were arranged in a line with one meter between them: one target specimen (MCF7, A549, BG), two control specimens (HaCaT), and a sample containing cell culture medium only.

Results: The two dogs picked out all the target specimens of MCF7 breast cancer cell cultures that they were trained to detect (10/10) as well as all the target specimens that they were not previously exposed to [A549 (5/5) and BG (5/5)], but did not pick out the control specimens or the cell culture medium. Thus, the sensitivity, specificity, and positive and negative predictive values for both dogs were 100%.

Conclusions: The results of this study support the assumption that cancer cells have a unique odor pattern, and that this odor pattern is common to different types of cancer.

 

Background: Anal cancer is a relatively uncommon disease, accounting for only 4% of cancers of the lower gastrointestinal tract. 

Objectives: To summarize the single-center experience in the treatment of anal carcinoma using various radiation techniques.

Methods: We conducted a retrospective chart review of consecutive patients who were treated for anal cancer between the years 2002 and 2011. The data extracted included demographics, type of radiation technique, treatment-associated acute toxicity, and patterns of failure and survival. For statistical analysis purposes, the patients were divided into two groups according to radiotherapy technique: 2D (group A) and 3D (group B).

Results: A total of 42 patients – 25 (59.5%) females and 17 males (40.5%) – underwent definitive chemo-radiation treatment (CRT) for anal cancer. Group A comprised 26 patients and group B 14 patients. Toxicity did not differ significantly between the groups, only in grade 1-2 skin toxicity which was more common in group B. There were significant differences in the unplanned interruptions in treatment, in both the number of patients who needed a treatment break and the number of days needed (more in group A). There were no differences in treatment response and patterns of failure between these two techniques, or in overall survival between the two groups. 

Conclusions: Our study results are consistent with reported large randomized trials, indicating that current treatments for anal carcinomas are associated with high grade acute toxicity that may result in significant treatment interruptions. The 2D technique was associated with significantly more treatment interruptions, but did not differ from 3D with regard to treatment efficacy. 

 

Background: The efficacy of video-assisted thoracoscopic surgery lobectomy in patients with previous coronary artery bypass grafting (CABG) surgery is controversial.

Objectives: To investigate whether skeletonized left internal mammary artery (LIMA) mobilization contributes to the development of severe adhesions, which will affect what type of lung surgery (open or closed procedure) will be required in the future.

Methods: Eight patients (mean age 73.9 years) with previous CABG surgery using a LIMA to left anterior descending (LAD) graft underwent left-sided lobectomy for operable non-small cell lung carcinoma. 

Results: The lobectomy by thoracotomy rate was 62.5% (5 patients), generally in patients with tumors in the left upper lobe or in patients post-neoadjuvant chemotherapy, while the video-assisted thoracic surgery lobectomy rate was 37.5% (3 patients). Mean hospital stay was 8.3 days. There was no mortality or major morbidity, apart from six minor complications in four patients (50%) (air leak, atrial fibrillation, atelectasis, pneumonia). 

Conclusions: Patients with operable non-small cell lung carcinoma following CABG surgery who need left upper lobe resection do not benefit from the video-assisted thoracoscopic surgery technique due to significant adhesions between the LIMA to LAD graft and the lung. The method of preserving a small portion of the lung on the LIMA to LAD graft may help during left upper lobe resections. Adhesions in the left pleural space after LIMA mobilization appear to generally minimally affect left lower lobe video-assisted thoracoscopic surgery.

 

Background: QT segment prolongation is a high risk factor for fatal arrhythmias. Several studies have indicated a possible relation between low testosterone levels and QT interval prolongation. 

Objectives: To compare the QT interval length in elderly patients with prostate carcinoma who were on anti-testosterone treatment and those who were not.

Methods: We screened the electrocardiograms (ECGs) of 100 prostate cancer patients divided into two groups: 50 patients on anti-testosterone drug treatment and 50 patients not. QT interval length was measured according to the accepted methods.

Results: The mean QTc 12 leads in the entire group was 0.45 ± 0.04 sec, which is close to the upper limit. Mean QTc was actually longer in the control group and there was no QTc difference between the groups after adjustment for possible confounders. Prolonged QTc 12-lead ECG (48% in treated and 54% in non-treated) and lead L2 QT interval (50% in treated and 56% in non-treated) did not differ significantly between the groups. The analysis of QTc 12-lead ECG indicated no significant effects of anti-testosterone drug treatment. Only the use of furosemide was associated with QT prolongation. 

Conclusions: The results of this preliminary study do not support our initial concern of an alarmingly prolonged QT interval in the anti-testosterone treated group. However, further prospectively designed studies are needed. In the meanwhile we call for a close follow-up of the QT interval length in patients receiving anti-testosterone treatment. 

 

Thrombosis is a common phenomenon in patients with malignancies. It is believed that thrombosis is multifactorial and that in addition to mechanisms directly associated with cancer and its treatment, it may also be related to the interaction between the immune system and clotting. The present work describes four cancer patients (three adults and one child) whose clinical course was characteristic of catastrophic antiphospholipid syndrome (CAPS) in intensive care units of the National Cancer Institute of Rio de Janeiro. The presence of findings similar to those in CAPS can be attributed to an unbalanced interaction between the immune system and coagulation.

Background: Serum lactate dehydrogenase (LDH) is elevated in various diseases. 

Objectives: To analyze serum LDH as a distinguishing clinical biomarker and as a predictor of in-hospital outcome in admitted medical patients.

Methods: We analyzed a cohort of all 158 patients with very high isolated LDH (LDH ≥ 800 IU/ml – without concomitant elevations of alanine aminotransferase and aspartate aminotransferase) – admitted to our internal medicine department during a 3 year period. Epidemiologic and clinical data, as well as the final diagnosis and outcome were recorded and compared with those of a cohort of all 188 consecutive control patients.

Results: Very high isolated LDH was a distinguishing biomarker for the presence of cancer (27% vs. 4% in the LDH group and controls respectively, P < 0.0001), liver metastases (14% vs. 3%, P < 0.0001), hematologic malignancies (5% vs. 0%, P = 0.00019), and infection (57% vs. 28%, P < 0.0001). Very high isolated LDH was a marker for a severe prognosis, associated with more admission days (9.3 vs. 4.1, P < 0.0001), significantly more in-hospital major complications, and a high mortality rate (26.6% vs. 4.3%, P < 0.0001). Finally, very high isolated LDH was found in a multivariate regression analysis to be an independent predictor of mortality.

Conclusions: The presence of very high isolated LDH warrants thorough investigation for the presence of severe underlying disease, mostly metastatic cancer, hematologic malignancies and infection. Moreover, it is a marker for major in-hospital complications and is an independent predictor of mortality in admitted medical patients.