Epidemiological, clinical, and pathological characteristics of invasive breast cancer in Bedouin and Jewish women in southern Israel: a retrospective comparative study.

BACKGROUND: Invasive breast cancer (IBC) is a leading cause of cancer-related death among women in Israel, regardless of ethnicity. This study compared IBC epidemiological, clinical, and pathological characteristics in Bedouin and Jewish patients in southern Israel. METHODS: Medical records of 1514 Jewish and 191 Bedouin women with IBC treated at Soroka University Medical Center between 2014 and 2021 were analyzed retrospectively. Baseline measures and tumor characteristics were compared between groups. Overall survival (OS) and disease-free survival (DFS) were analyzed using log-rank test. Multivariate analysis was performed using the Cox proportional hazard model. RESULTS: Bedouin patients exhibited a significantly younger age at diagnosis (median 48 vs. 62 years, p < 0.001), larger tumor size (median 2.5 vs. 2.13 cm, p < 0.001), and higher metastasis rate (18.8% vs. 12.7%, p = 0.03) compared to Jewish patients. In early-stage (non-metastatic) disease, Jewish and Bedouin patients had comparable overall survival (OS) rates (127 vs. 126 months, p = 0.2), consistent across stages 1 to 3. However, among patients with metastatic disease, Bedouins exhibited significantly longer OS (76.6 vs. 37.8 months, p = 0.006). Disease-free survival (DFS) showed no ethnic differences (not reached vs. 122 months, p = 0.31). There were no significant differences in OS between Bedouin and Jewish patients undergoing various treatment modalities for early-stage disease: surgery, adjuvant radiotherapy, chemotherapy, and systemic neoadjuvant therapy. CONCLUSION: Breast cancer among Bedouin women in southern Israel manifests at a younger age, with larger tumors and more advanced stages than in Jewish women. However, recent data indicate no differences in OS and DFS between the ethnic groups despite past disparities in prognosis.

Lamotrigine therapy in patients after bariatric surgery: Potentially hampered solubility and dissolution.

Bariatric surgery is an effective treatment of obesity and related comorbidities. With surgery, the stomach undergoes major anatomical/physiological changes that may affect the oral exposure of drugs, especially marginally soluble weak bases, such as lamotrigine. The aim of this work was to study the solubility/dissolution of lamotrigine in conditions simulating the stomach before vs. after bariatric surgery. Lamotrigine solubility was studied in-vitro, as well as ex-vivo in gastric content aspirated from patients before vs. after bariatric surgery. We then compared the dissolution kinetics of various marketed lamotrigine products in pre- vs. post-operative stomach conditions, different in volume, pH, agitation strength and speed. Decreased lamotrigine solubility with increasing pH (from 1.37 ± 0.09 (pH = 1) to 0.22 ± 0.03 mg/mL (pH = 7)) was obtained. Twelve-fold higher lamotrigine solubility was revealed in gastric content aspirated before vs. after surgery (8.5 ± 0.7 and 0.7 ± 0.01 mg/mL, respectively). Dissolution studies showed that only the lowest dose (25 mg) fully dissolved in the post-surgery stomach conditions, while at higher doses, lamotrigine tablet dissolution was impaired. Neither fast-dissolving tablet, nor tablet crushing, helped resolving this problem. Based on these results, and given that dissolution of the drug dose governs the subsequent absorption, close monitoring of this essential drug is advised after bariatric surgery.

Stomach pH before vs. after different bariatric surgery procedures: Clinical implications for drug delivery.

Stomach pH may vary following bariatric surgery, with implications for drug delivery/bioavailability. Yet, this parameter has not been studied. In this work, gastric content was aspirated from patients before, immediately after, and the day after different bariatric procedures, and pH was immediately measured. Compared to pre-surgery (1.8), pH was increased one day after one-anastomosis gastric bypass (OAGB) and sleeve gastrectomy (LSG) by 3-4 pH units; pH immediately after these procedures was in between the other 2 time points. Post-OAGB pH was significantly higher than post-LSG (6.4 and 4.9, respectively). Prior adjustable gastric band did not significantly alter baseline pH. We then performed drug dissolution studies of the antiplatelet drugs dipyridamole and aspirin, mimicking pre-surgery, post-LSG and post-OAGB conditions, implementing our pH results and other relevant physiological parameters. Dipyridamole, a weak base, completely dissolved (100% of dose) under pre-surgery conditions, while dissolution was hampered under post-LSG (5%) and post-OAGB (0.25%) conditions, due to solubility limit. Aspirin was not released from enteric-coated tablet under pre-surgery or post-LSG gastric conditions, however, >75% dissolved within 15 min under post-OAGB gastric conditions, indicating potential failure of enteric coating, depending on the bariatric procedure. In conclusion, special care should be taken when using pH-dependent drugs and drug products after bariatric surgery, and the use of pH-independent formulations should be preferred. Overall, this research revealed the interim gastric pH after different bariatric procedures, and potentially important effects on post-bariatric oral drug delivery and treatment.

Increased Paracetamol Bioavailability after Sleeve Gastrectomy: A Crossover Pre- vs. Post-Operative Clinical Trial.

Oral drug bioavailability may be significantly altered after laparoscopic sleeve gastrectomy (LSG), the most popular bariatric procedure worldwide. Paracetamol (acetaminophen) is the post-bariatric analgesic/antipyretic drug of choice. In this work we studied and analyzed the LSG effects on systemic bioavailability and pharmacokinetics of paracetamol after oral administration of solid vs. liquid dosage form. A 4-armed, pharmacokinetic, crossover trial was performed in patients enrolled for LSG. Single paracetamol dose (500 mg), as caplet (n = 7) or syrup (n = 5), was administered before vs. 4-6 months post-LSG. Bioavailability was enhanced after LSG; in the caplet groups, average AUC0-t increased from 9.1 to 18.6 µg·h/mL with AUC0-t difference of 9.5 µg·h/mL (95% CI 4.6-14.5, p = 0.003). Cmax increased from 1.8 (95% CI 1.2-2.5) to 4.2 µg/mL (3.6-4.8) after LSG (p = 0.032). In the syrup groups, AUC0-t increased from 13.4 to 25.6 µg·h/mL, with AUC0-t difference of 12.2 µg·h/mL (95% CI 0.9-23.5, p = 0.049). Cmax changed from 5.4 (95% CI 2.5-8.4) to 7.8 µg/mL (6.1-9.6), and systemic bioavailability was complete (102%) after the surgery. Overall, decreased paracetamol exposure in obesity, with recovery to normal drug levels (caplet) or even higher (syrup) post-LSG, was revealed. In conclusion, attention to paracetamol effectiveness/safety in obesity, and after bariatric surgery, is prudent.

Predictors for choledocholitiasis in patients undergoing endoscopic ultrasound.

AIM: Biliary lithiasis is common in most western countries. Symptomatic patients will also have choledocholithiasis in 10% of the cases. For patients with intermediate probability of CBD stones, the recommended imaging studies are endoscopic ultrasound (EUS) or MRCP. This study aims to identify early factors that can be used as predictors for the presence of CBD stones, and by that to find which patient should undergo ERCP without an early EUS. METHODS: This is a retrospective cohort study including all patients who underwent EUS for suspected choledocholithiasis at the Soroka University Medical Center (SUMC) in the years 2009-2014. Data collection was performed by manual surveillance of patients' computerized files and data gathering after approval by the Soroka Institutional Review Board Results: One hundred seventy-five (175) patients were included in the study. The average age was 57, and 111 patients were women (64.2%). Sixty-two patients (35%) had common bile duct stones by EUS and underwent an ERCP. Eighty-two percent of those 62 patients were found to have CBD stones at ERCP. Patients found positive for CBD stones by EUS were older than those who were negative (52 vs. 71 respectively, p < .001). These patients were also found to have a higher prevalence of ischemic heart disease and congestive heart failure. Common bile duct dilatation ≥8mm and gallstones presence in abdominal ultrasonography were more common in patients found positive for CBD stones by EUS than in those who were found negative (45% vs. 24% p < .05, and 81% vs. 66% p < .05, respectively). Alkaline phosphatase (ALP) serum levels higher than 300 IU/L were found to be the only independent predictor for the existence of CBD stones (OR = 2.98, p = .001(. When ALP serum levels lower than 150 IU/L or GGT lower than 150 IU/L were measured, the probability of having CBD stones was low (NPV of 90% and 87%, respectively). CONCLUSIONS: ALP serum levels higher than 300 IU/L are an independent predictor for the presence of CBD stones. EUS is an excellent screening tool for choledocholithiasis before performing ERCP. In most patients who undergo an early EUS, a subsequent diagnostic ERCP will not be needed.