Israel Medical Association Journal

Background: Tumor treating fields (TTFields) are low-intensity, intermediate frequency electric fields that affect proliferating cells. TTFields are FDA approved for treatment of newly diagnosed and recurrent glioblastoma. Combining TTFields with immunotherapy is a rational approach due to their different mechanisms of action (MOA) and to the ability of TTFields to induce immunogenic cell death. Conversely, TTFields may interfere with immune functions critical for effective T-cell responses.

Objectives: To evaluate the effects of TTFields on pivotal antitumoral T-cell functions.

Methods: T-cells from healthy donor peripheral blood (PB) or from viably dissociated human glioblastoma samples were cultured under normal or TTFields conditions, with or without superantigen stimulation. Multiparametric flow cytometry (8-color) was used to assess T-cell responses by monitoring select pivotal functions: proliferation (CFSE), IFNγ secretion, cytotoxic degranulation (CD107a), and activation/exhaustion (PD-1). Cellular viability was assessed in a dedicated assay. A chimeric antigen receptor (CAR) T-cell-based assay directly evaluated cellular cytotoxicity.

Results: Activated PB T-cells and tumor-infiltrating T-cells (TILs) preserved all monitored anti- tumoral functions under TTFields, apart from proliferation. This finding also applied specifically to PD-1 + TILs, comprised predominantly of tumor antigen-specific cells. Activated T-cells that attempted to proliferate under TTFields demonstrated decreased viability, in line with TTField MOA. Small or no reduction in viability was found in T-cells that did not attempt to proliferate, whether activated or resting.

Conclusions: All monitored anti-tumoral T cell functions, except for proliferation, were unhindered by TTFields. Our results support further investigation into combinations of TTFields with T-cell based immunotherapeutic approaches.

Background: Dialysate purity contributes to the inflammatory response that afflicts hemodialysis patients.

Objectives: To compare the clinical and laboratory effects of using ultrapure water produced by a water treatment system including two reverse osmosis (RO) units in series, with a system that also includes an ultrapure filter (UPF).

Methods: We performed a retrospective study in 193 hemodialysis patients during two periods: period A (no UPF, 6 months) and period B (same patients, with addition of UPF, 18 months), and a historical cohort of patients treated in the same dialysis unit 2 years earlier, which served as a control group.

Results: Mean C-reactive protein, serum albumin and systolic blood pressure worsened in period B compared to period A and in the controls.

Conclusions: A double RO system to produce ultrapure water is not inferior to the use of ultrapure filters.

Background: Right hydronephrosis secondary to acute appendicitis is an under-reported phenomenon with only several case reports published.

Objectives: To assess the incidence of this phenomenon in our database of patients diagnosed with acute appendicitis.

Methods: Data were collected on 1092 patients who underwent surgery due to acute appendicitis between 2003 and 2007 in our tertiary medical center. The data entailed demographic, surgical, and hospitalization parameters including ultrasound or computed tomography examinations and presence of right hydronephrosis prior to surgery.

Results: Out of 1092 patients, appendicitis was eventually diagnosed in 87.4% of the patients. Only 594 (54%) had preoperative imaging performed prior to surgery (ultrasound or computed tomography). Out of these 594 patients, 21 (3.5%) had a new right hydronephrosis diagnosed and all had appendicitis with 15/21 (71%) having a retrocecal appendix. Of those with retrocecal appendix, 10 were pregnant women (48%). Erythrocyturia was present in 15/21 patients (71%) and in 10/11 of patients (91%) after excluding those who were pregnant. No significant differences were seen in patients with hydronephrosis regarding age, hospitalization, and surgery time. In all patients, an ultrasound was performed 2 weeks after surgery demonstrating the disappearance of hydronephrosis. Median follow-up time was 41.7 months (range 14.8–118.4 months).

Conclusions: Our study shows that 3.5% of our cohort had right hydronephrosis secondary to acute appendicitis. Although this presentation is very rare, physicians should be aware of this phenomenon and the risk for delayed diagnosis and treatment of acute appendicitis.

Background: Diagnosis of abdominal lymphadenopathy is challenging when not accompanied by peripheral lymphadenopathy. Computed tomography-guided core-needle biopsy has largely replaced open procedures in recent years, but this approach is limited by access to the anatomic region and the amount of tissue acquired.

Objective: To demonstrate the feasibility of the laparoscopic approach in obtaining abdominal lymph node biopsies and to evaluate the diagnostic adequacy of the technique.

Methods: We reviewed the data of patients who underwent laparoscopic lymph node biopsy between 2014 and 2014 in our department. Demographics, intra-operative parameters and postoperative course were examined, as were histological reports. Postoperative complications were categorized according to the Clavien-Dindo(CD) classification.

Results: Between 2004 and 2014, 57 laparoscopic biopsies were performed for intra-abdominal lymphadenopathy. One case was a repeated attempt due to limited histologic material. The mean age was 49.5 ± 19.6 years. There were two conversions to open laparotomy, one due to small bowel injury and the other due to a sizable mass. Overall, 56 cases had full clinical data: 48 cases (85.7%) had CD=0, six (10.7%) had CD=1, one postoperative severe complication (CD=3) and one mortality (CD=5), which was related to preexisting hepatic insufficiency. Mean hospital stay was 1.6 days. Overall, adequate tissue samples were acquired in 96.7% and only 3 of these cases resulted in inconclusive diagnoses.

Conclusions: Laparoscopic lymph node biopsy is a viable alternative to the currently available methods of tissue retrieval. It provides an access for nodes which are inaccessible percutaneously, and may allow a superior diagnostic yield.

A flowering plant of variegated ingredients and psychoactive qualities, cannabis has long been used for medicinal and recreational purposes. Currently, cannabis is approved in several countries for indications of symptomatic alleviation. However, limited knowledge on the benefits and risks precludes inclusion of cannabis in standard treatment guidelines. This review provides a summary of the available literature on the use of cannabis and cannabinoid-based medicines in palliative oncology. Favorable outcomes are demonstrated for chemotherapy-induced nausea and vomiting and cancer-related pain, with evidence of advantageous neurological interactions. Benefit in the treatment of anorexia, insomnia and anxiety is also suggested. Short- and long-term side effects appear to be manageable and to subside after discontinuation of the drug. Finally, cannabinoids have shown anti-neoplastic effects in preclinical studies in a wide range of cancer cells and some animal models. Further research is needed before cannabis can become a part of evidence-based oncology practice.

Background: Various vena cava filters (VCF) are designed with the ability to be retrieved percutaneously. Yet, despite this option most of them remain in the inferior vena cava (IVC). 

Objectives: To report our experience in the placement and retrieval of three different types of VCFs, and to compare the indications for their insertion and retrieval as reported in the literature.

Methods: During a 5 year period three types of retrievable VCF (ALN, OptEase, and Celect) were inserted in 306 patients at the Rabin Medical Center (Beilinson and Hasharon hospitals). Indications, retrieval rates, median time to retrieval, success and complications rate were viewed and assessed in the three groups of filter types and were compared with the data of similar studies in the literature.

Results: Of the 306 VCFs inserted, 31 (10.1%) were retrieved with equal distribution in the three groups. In most patients the reason for filter insertion was venous thromboembolic events (VTE) and contraindications to anticoagulant therapy. Mean age was 68.38 ± 17.5 years (range 18–99) and was noted to be significantly higher compared to similar studies (53–56 years) (P < 0.0001). Multi-trauma patients were significantly older (71.11 ± 14.99 years) than post-pulmonary embolism patients (48.03 ± 20.98 years, P < 0.0001) and patients with preventive indication (26.00 ± 11.31, P < 0.0001). The mean indwelling time was 100.6 ± 103.399 days. Our results are comparable with the results of other studies, and there was no difference in percentage of retrieval or complications between patients in each of the three groups. 

Conclusions: In 1 of 10 patients filters should be removed after an average of 3.5 months. All three IVC filter types used are safe to insert and retrieve.

 

Background: Physical restraints are a common, albeit controversial, tool used in the acute care setting. 

Objectives: To determine the prevalence of physical restraint use in an acute care hospital. Secondary objectives were to determine whether physical restraints are used more commonly in night shifts, identify patient risk factors for physical restraint use, and establish if staff-to-patient ratio correlated with physical restraint use.

Methods: An observational cross-sectional study was conducted over 3 months in 2013 in the medical, surgical and intensive care units in a mid-sized general hospital. All the physically restrained patients in each observation were added to the registry. At each observation one department was selected for comparison and all non-restrained patients were added to the registry.

Results: The study population comprised 2163 patients. Seventy-six were restrained and 205 were included as case-controls. The prevalence of physical restraint use was 3.51% (95%CI = 2.79–4.37%). Physical restraint use was more common in night shifts than day shifts: 4.40% vs. 2.56% (P = 0.03). Male gender, dependency, invasive ventilation, invasive tubes (nasogastric tube or urine catheter), and bedsores were all significantly correlated with restraint use. Staff-to-patient ratios were not significantly correlated with use of physical restraints.

Conclusions: Physical restraints are relatively common in acute care wards. The use of physical restraints seems to correlate with certain patient characteristics but not with staff-to-patient ratios, and seems more common at night. 

 

Background: Trachea esophageal puncture (TEP) is performed following total laryngectomy to allow speech and communication. The most common reason for long-term speech failure in this population is hypertonicity of the constrictor muscle.

Objectives: To present our experience with the treatment of aphonic patients after total laryngectomy and TEP and suggest a protocol for treatment.

Methods: Of 50 patients who underwent total laryngectomy and TEP, 6 suffered from aphonia after surgery. All patients underwent radiotherapy with or without chemotherapy. Delay in speech continued for more than 6 months after surgery. The patients received percutaneous lidocaine injection to the neopharynx in different locations around the stoma in order to map the hypertonic segments in the neopharynx.

Results: Lidocaine injection immediately enabled free speech in five patients. One patient (patient 6) suffered from aphonia and from severe dysphagia and required a feeding tube. This patient succeeded to pronounce abbreviations after lidocaine injection. Another (patient 4) gained permanent ability to speak following a single lidocaine injection; this patient was not injected with botolinium toxin (BTX). For the other five, lidocaine had a transient effect on speech. These patients received BTX percutaneous injections. After BTX injections four regained free speech within 14 days. The fifth patient (patient 6) gained a conversational voice and experienced improvement in swallowing only after additional intensive speech therapy.

Conclusions: Percutaneous lidocaine and BTX injections represent first-line treatment in this population, with good success and minimal complications. 

Background: A growing number of Eritrean and Sudanese refugees seek medical assistance in the labor and delivery ward of our facility. Providing treatment to this unique population is challenging since communication is limited and pregnancy follow-up is usually absent.

Objectives: To compare the perinatal outcome of refugees and Israeli parturients.

Methods: The medical and financial records of all refugees delivered between May 2010 and April 2011 were reviewed. Perinatal outcome was compared to that of native Israeli controls.

Results: During this period 254 refugees were delivered (2.3% of deliveries). Refugees were significantly younger and leaner. They had significantly more premature deliveries under 37 weeks (23 vs. 10, P = 0.029) and under 34 weeks gestation (9 vs. 2, P = 0.036) with more admissions to the neonatal intensive care unit (15 vs. 5, P = 0.038). Overall cesarean section rate was similar but refugees required significantly more urgent surgeries (97% vs. 53%, P = 0.0001). Refugees had significantly more cases of meconium and episiotomies but fewer cases of epidural analgesia. There were 2 intrauterine fetal deaths among refugees, compared to 13 of 11,239 deliveries during this time period (P = 0.036), as well as 7 pregnancy terminations following sexual assault during their escape. Sixty-eight percent of refugees had medical fees outstanding with a total debt of 2,656,000 shekels (US$ 767,250).

Conclusions: The phenomenon of African refugees giving birth in our center is of unprecedented magnitude and bears significant medical and ethical implications. Refugees proved susceptible to adverse perinatal outcomes compared to their Israeli counterparts. Setting a pregnancy follow-up plan could, in the long run, prevent adverse outcomes and reduce costs involved in treating this population.