Varying concentrations of tyrosine kinase inhibitors in chronic myeloid leukemia patients following bariatric surgery: a case series.

Bariatric surgery is increasingly performed to treat severe obesity. As a result of anatomical and physiological changes in the gastrointestinal tract, the pharmacokinetics (PK) of oral drugs can be altered, affecting their efficacy and safety. This includes the class of tyrosine kinase inhibitors (TKIs) which are used to treat chronic myeloid leukemia (CML). This case series describes the clinical course of four CML cases with a history of bariatric surgery. The patients used various TKIs (nilotinib, dasatinib, bosutinib, ponatinib, and imatinib) for which 15 drug levels were measured. The measured TKI concentrations were in part subtherapeutic, and highly variable when compared to mean levels measured in the general population. Multiple drug levels were measured in these patients, as the clinicians were aware of the possible impact of bariatric surgery. The drug levels were used as additional input for clinical decision-making. All four patients required TKI switches and/or dose modifications to achieve an effective and tolerable treatment. Eventually, adequate clinical and molecular remissions were achieved in all cases. In summary, TKI concentrations of patients undergoing bariatric surgery may be subtherapeutic. Moreover, there is substantial interindividual and intraindividual variation, which may be explained by the complex interference of bariatric surgery and associated weight loss. For clinical practice, therapeutic drug monitoring is advised in patients with a history of bariatric surgery in case of suboptimal response or loss of response.

Postoperative Outcomes of Bascom Cleft Lift Versus Excision With Secondary Wound Healing for Pilonidal Sinus Disease: A Multicenter Retrospective Analysis.

BACKGROUND: Pilonidal sinus disease impacts patient's quality of life. In the Netherlands, it is often treated with excision and secondary healing, which is associated with high recurrence rates and poor wound healing. The Bascom cleft lift, an alternative technique, has shown favorable healing times and recurrence rates. OBJECTIVE: The present study aims to compare successful wound healing, time to healing, complications, and recurrence rate between excision with secondary wound healing and Bascom cleft lift. DESIGN: This is a multicenter retrospective study. SETTINGS: Three institutions in the Rotterdam region of the Netherlands participated in the study. PATIENTS: Patients who underwent excision with secondary healing or Bascom Cleft Lift between July 2015 and August 2021 were included. MAIN OUTCOME MEASURES: Primary endpoints included the rate of successful wound healing and the time to achieve healing. Secondary endpoints included postoperative complications and recurrence rate within twelve months after surgery. RESULTS: Out of 272 patients, 128 underwent Bascom cleft lift and 144 patients excision and secondary healing. Recurrent PSD (47.7% vs 22.2%) and abscess history (53.1% vs 40.3%) were more common in the Bascom cleft lift group compared to excision with secondary wound healing. The median follow-up period at the outpatient clinic was 43 days. Wound healing was 84.4% after Bascom cleft lift vs. 32.6% after excision and secondary healing (p < 0.001), with median time to wound healing of 55 days and 101 days, respectively (p < 0.001). Complications were 28.9% for Bascom cleft lift vs. 13.2% for excision and secondary healing (p = 0.003). Recurrent disease was 6.3% after Bascom Cleft Lift and 11.8% after excision and secondary healing (p = 0.113). LIMITATIONS: It has a retrospective design which makes it prone to selection bias and residual confounding. Additionally, the study's short follow-up period further adds to these limitations as longer follow-up may better identify true recurrence rates. Finally, a deficiency is the absence of collected patient satisfaction data, which is nowadays a common scientific issue. CONCLUSIONS: This retrospective study shows that Bascom cleft lift is superior to excision and secondary healing given the higher percentage of patients with successful wound healing within a shorter time. See Video Abstract.

A Dutch Survey on Medication Adjustments after Metabolic and Bariatric Surgery: Experiences of Bariatric Surgeons, Internists, Pharmacists, and General Practitioners.

BACKGROUND: As metabolic and bariatric surgery (MBS) can alter the pharmacokinetics of drugs, post-bariatric surgery patients may require medication adjustments and monitoring. To improve pharmacotherapy in these patients, we aimed to understand the beliefs, attitudes, knowledge, and concerns of healthcare professionals who treat these patients. METHODS: A survey by means of an online questionnaire was divided into six sections. It was sent to bariatric surgeons, internists, pharmacists, and general practitioners in the Netherlands. RESULTS: Out of 229 returned surveys, 222 were included. Virtually all respondents (98%) expected MBS to influence the effect of medication. Both reduced efficacy (23%) and more adverse events or medication-related complications (21%) were recognized. Two-thirds of the respondents felt competent to prescribe or to provide advice regarding medication in post-bariatric surgery patients. Most of the respondents (95%) believed that other healthcare professionals should be aware of the contraindication "bariatric surgery". Of the respondents, 37% indicated that they were not aware of the medication advice incorporated in the electronic health record systems. Almost half of the respondents (48%) indicated that they documented changes in drug effects. Most respondents answered that these ought to be registered in the pharmacovigilance database or national registry. CONCLUSIONS: The majority of prescribers and pharmacists believe that patients will receive better pharmacotherapy if healthcare professionals take MBS into account. However, not all prescribers think they are competent to act adequately. To improve this, information on changed drug effects after MBS should be more widely shared among healthcare professionals via resources that are easily accessible.

Impact of bariatric surgery on oral anticancer drugs: an analysis of real-world data.

PURPOSE: The number of patients with bariatric surgery who receive oral anticancer drugs is rising. Bariatric surgery may affect the absorption of oral anticancer drugs. Strikingly, no specific drug dosing recommendations are available. We aim to provide practical recommendations on the application of oral anticancer drugs in patients who underwent bariatric surgery. METHODS: Patients with any kind of bariatric surgery were extracted retrospectively in a comprehensive cancer center. In addition, a flowchart was proposed to assess the risk of inadequate exposure to oral anticancer drugs in patients who underwent bariatric surgery. Subsequently, the flowchart was evaluated retrospectively using routine Therapeutic drug monitoring (TDM) samples. RESULTS: In our analysis, 571 cancer patients (0.4% of 140.000 treated or referred patients) had previous bariatric surgery. Of these patients, 78 unique patients received 152 oral anticancer drugs equaling an overall number of 30 unique drugs. The 30 different prescribed oral anticancer drugs were categorized as low risk (13%), medium risk (67%), and high risk (20%) of underdosing. TDM plasma samples of 25 patients (82 samples) were available, of which 21 samples post-bariatric surgery (25%) were below the target value. CONCLUSIONS: The proposed flowchart can support optimizing the treatment with orally administered anticancer drugs in patients who underwent bariatric surgery. We recommend performing TDM in drugs that belong to BCS classes II, III, or IV. If more risk factors are present in BCS classes II or IV, a priori switches to other drugs may be advised. In specific cases, higher dosages can be provided from the start (e.g., tamoxifen).

Sinus laser-assisted closure (SiLaC®) for pilonidal disease: results of a multicentre cohort study.

BACKGROUND: An emerging and promising minimally invasive treatment for pilonidal disease (PD) is sinus laser-assisted closure (SiLaC®). Previous studies have shown encouraging results concerning safety, patient satisfaction, wound healing and acceptable recurrence rates. This study investigated outcomes for a large cohort of PD patients treated with SiLaC®. METHODS: A multicentre cohort study with a prospective design and partial retrospective data collection for patients with PD treated with SiLaC® in three hospitals in the Netherlands (Albert Schweitzer Hospital, Flevoziekenhuis and Medical Centre Zuiderzee) from January 1st 2017 to March 1st 2020. The primary outcome was recurrence. Secondary outcomes were incidence of complete wound closure, time until wound closure, postoperative complications, ability to perform daily activities and reported patient satisfaction. RESULTS: A total of 311 patients were included with a median follow-up of 10 months (range 1-52 months). The recurrence rate after one SiLaC® treatment was 26% with 7% experiencing incomplete wound closure, resulting in an initial success rate of 66% after one SiLaC® procedure. This increased to 92% and 98% after two and three SiLaC® procedures, respectively. Mean time until wound closure was 6 weeks (range 1-24 weeks). Seven patients (2%) were still unsuccessfully treated after three SiLaC® treatments and required additional and extensive surgery. Mean time to perform regular daily activities including working was 6 days (range 0-42 days) and the vast majority of patients (84%) did not require painkillers or only paracetamol. Twelve patients (4%) developed a postoperative wound infection. The mean satisfaction score was 9 (range 5-10). CONCLUSIONS: SiLaC® is a promising minimally invasive treatment for PD with high patient satisfaction and an acceptable success rate. These results suggest that SiLaC® could be used as a safe and effective primary treatment for PD.

The Use of Intraperitoneal Bupivacaine in Laparoscopic Roux-en-Y Gastric Bypass: a Double-blind, Randomized Controlled Trial.

BACKGROUND: Several studies have shown a reduction in postoperative pain and length of hospital stay when using intraperitoneal local anesthetics during laparoscopic surgery. In morbidly obese patients, respiratory depression due to opioid use is a serious side effect. Any different type of analgesia is therefore clinically relevant. OBJECTIVE: To assess the effect of intraperitoneal bupivacaine on postoperative pain after laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Between March and November 2017, 130 patients were included and randomly assigned to receive 20 ml or 0 ml of 2.5% bupivacaine hydrochloride sprayed onto the diaphragm. Pain scores for abdominal and shoulder pain were conducted using the visual analogue scale (VAS) for pain score at 0, 1, 6, and 24 h postoperatively. The length of hospital stay and use of analgesics was recorded in digital patient records. The primary outcome is the pain scores and the secondary outcomes are postoperative use of opioids or antiemetics and length of hospital stay. RESULTS: The study and control group contained respectively 66 and 61 patients. Patient characteristics were equal in both groups (p < 0.05), except for age. No significant reduction of postoperative pain or opioid use was seen with the use of intraperitoneal bupivacaine. There was also no significant reduction in the use of antiemetics and length of hospital stay. CONCLUSION: The use of intraperitoneal bupivacaine in LRYGB does not show a statistically significant reduction in postoperative pain or postoperative opioid use. Therefore, using intraperitoneal bupivacaine has no clinical relevance and should no longer be used in LRYGB.

Iatrogenic subtotal stenosis of the right subclavian artery treated with percutaneous transluminal angioplasty.

This report describes a rare vascular complication of surgical placement of a marking clip and a possible approach to problem solving. A 55-year-old patient presented with loss of sensation in the fingers and loss of peripheral pulsations in the right arm 4 days after right upper lobectomy for a pT2N1 moderately differentiated adenocarcinoma of the lung. Duplex examination and computed tomography were performed the same day and showed a subtotal stenosis of the right subclavian artery, which was caused by the surgical placement of a metal clip to mark the surgical boundary. Selective angiography was subsequently performed. Percutaneous transluminal angioplasty (PTA) successfully dilated the stenosis and pushed the clip off. Flow in the right subclavian artery (RSA) was completely restored as were neurology and peripheral pulses. In conclusion, arterial stenosis by a surgical (marking) clip may be feasibly treated with PTA.

Survival analysis of pseudomyxoma peritonei patients treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

OBJECTIVE: To evaluate the survival of patients with pseudomyxoma peritonei (PMP) treated by cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), and to identify factors with prognostic value. SUMMARY BACKGROUND DATA: PMP is a clinical syndrome characterized by progressive intraperitoneal accumulation of mucous and mucinous implants, usually derived from a ruptured mucinous neoplasm of the appendix. Survival is dominated by pathology. METHODS: A total of 103 patients (34 men and 69 women) treated at The Netherlands Cancer Institute between 1996 and 2004 were identified. Survival was calculated from date of initial treatment and corrected for a second procedure. PMP was pathologically categorized into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and an intermediate subtype (PMCA-I). Clinical and pathologic factors were analyzed to identify their prognostic value for survival. RESULTS: Median follow-up was 51.5 months (range, 0.1-99.5 months). Recurrence developed in 44%. A second procedure for recurrence was performed in 11 patients. The median disease-free interval was 25.6 months (95% confidence interval [CI], 14.8-43.6 months). The 3-year and 5-year disease-free survival probability was 43.6% (95% CI, 34.4%-55.2%) and 37.4% (95% CI, 28.2%-49.5%), respectively. The disease-specific 3-year and 5-year survival probability was 70.9% (95% CI, 62.0%-81.2%) and 59.5% (95% CI 48.7%-72.5%), respectively. Factors associated with survival were pathological subtype, completeness of cytoreduction, and degree and location of tumor load (P < 0.05). The main prognostic factor, independently associated with survival, was the pathologic subtype (P < 0.01). CONCLUSION: Cytoreductive surgery in combination with intraoperative HIPEC is a feasible treatment strategy for PMP in terms of survival. The pathologic subtype remains the dominant factor in survival. Patients should be centralized to improve survival by a combination of surgical experience and adequate patient selection.

Progression of pseudomyxoma peritonei after combined modality treatment: management and outcome.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment strategy for pseudomyxoma peritonei (PMP) with curative intent. The aim of this study was to determine the patterns of failure in patients who underwent such a procedure and to evaluate management and outcome of progressive disease. METHODS: After exclusion of patients with overt malignancy, progression was studied in 96 PMP patients treated primarily by CRS with HIPEC. Location, pathology, management and outcome were recorded. RESULTS: Median follow-up was 51.5 months (0.1-99.5). Median progression free survival (PFS) was 28.2 months (95% CI 18.3->). Progressive disease was mainly located sub hepatic (38%) or in multiple regions (36%). Pathological dedifferentiation was observed in 8 patients (20%). The choice of treatment depended on pathology, extent of disease and PFS. Seventeen patients were treated for progression by second CRS with (n=8) or without HIPEC (n=10). The 3-years overall survival (OS) probability after this treatment was 100% and 53.3% (95% CI 28.2-100%), respectively. Fifteen patients with (slow) progression were observed. Three-years OS probability of these patients was 66.0% (95% CI 43.4-100%). All patients treated for progression by systemic chemotherapy only (n=6) had died of disease after a median follow up of 14.8 (9.8-33.6) months. A longer PFS after primary treatment was associated with longer OS after progression (P = 0.04). CONCLUSIONS: Progressive PMP after primary CRS with HIPEC is probably the result of technical failure and/or tumor biology. Management of progressive PMP can be valuable for selected patients and should depend primarily on the PFS.