Tracheoesophageal fistula development following radiotherapy and tyrosine kinase inhibitors in a patient with advanced follicular thyroid carcinoma: a case-based review.

INTRODUCTION: Tracheoesophageal fistulas (TEF) are a rare complication that can occur in patients with radioactive iodine refractory metastatic follicular thyroid carcinoma (FTC) following treatment with radiotherapy (RT) and tyrosine kinase inhibitors (TKI). METHODS: We describe the case of a TEF development in a 69-year-old male who underwent targeted therapy TKIs and adjuvant RT for radioactive iodine refractory FTC. RESULTS: In the case, staging investigations revealed a metastatic, poorly differentiated FTC refractory to radioactive iodine. After 2 years of disease control on Lenvatinib, the patient's condition progressed, necessitating a switch to Cabozantinib. Soon after, they presented with haemoptysis secondary to invasion of the primary thyroid tumour into the trachea. Radical radiotherapy (45 Gy/30 fractions) was also administered to the thyroid gland, ultimately complicated by radiation necrosis. Four months post-completion of RT and recommencing TKI, the patient presented with haemoptysis and hoarseness secondary to recurrent laryngeal nerve compression and tracheal invasion, as well as dysphagia secondary to oesophageal compression. Following an acute presentation with intractable throat pain, investigations revealed a TEF. Surgical and endoscopic management was deemed inappropriate given the patient's rapid deterioration and anatomical position of the TEF, and therefore a palliative approach was taken. CONCLUSION: This case report highlights a rare cause of TEF development in a patient having TKI therapy post-RT for advanced FTC. It highlights the importance of monitoring TEF development in this cohort of patients. It demonstrates the importance of patient counselling and education regarding treatment options and the rare side effects of treatments.

Age alone is not a barrier to efficacy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: analysis of 1138 patients from the UK and Ireland Colorectal Peritoneal Metastases Registry.

BACKGROUND: The management of colorectal peritoneal metastases continues to be a challenge but recent evidence suggests cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve survival. Uncertainty about the relationship between age and tumour biology makes patient selection challenging particularly when reported procedure related morbidity is high and impact on survival outcomes unknown. The UK and Ireland Colorectal Peritoneal Metastases Registry was reviewed to assess the influence of age on efficacy of CRS and HIPEC. METHODS: A review of outcomes from the UK and Ireland Colorectal Peritoneal Metastases Registry was performed. Data from 2000 to 2021 were included from five centres in the UK and Ireland, and the cohort were sub-divided into three age groups; <45 years, 45-65 years and >65 years old. Primarily, we examined post-operative morbidity and survival outcomes across the three age groups. In addition, we examined the impact that the completeness of cytoreduction, nodal status, or adverse pathological features had on long-term survival. RESULTS: During the study period, 1138 CPM patients underwent CRS HIPEC. 202 patients(17.8%) were <45 years, 549 patients(48.2%) aged 45-65 years and 387 patients(34%) >65 years. Overall, median length of surgery (CRS and HIPEC), median PCI score and rate of HIPEC administration was similar in all three groups, as was overall rates of major morbidity and/or mortality. Complete cytoreduction rates (CC0) were similar across the three cohorts; 77%, 80.6% and 81%, respectively. Median overall survival for all patients was 38 months following complete cytoreduction. CONCLUSION: Age did not appear to influence morbidity or long-term survival following CRS and HIPEC. When complete cytoreduction is achieved survival outcomes are good. The addition of HIPEC can be performed safely and may reduce local recurrence within the peritoneum.

Options in Bariatric Surgery: Modeled Decision Analysis Supports One-Anastomosis Gastric Bypass as the Treatment of Choice when Type 2 Diabetes Is Present.

BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) represent significant healthcare burdens. Surgical management is superior to traditional medical therapy. Laparoscopic sleeve gastrectomy (LSG) and gastric bypass (both Roux-en-Y (RYGB) and one anastomosis gastric bypass (OAGB) are the most commonly performed metabolic procedures. It remains unclear which gives the optimal quality-of-life pay-off in the context of T2DM. This study compares LSG, RYGB, and OAGB in the management of T2DM and obesity using modeled decision analysis. Alternative approaches were assessed considering efficacy of interventions, post-operative complications, and quality of life outcomes to determine the optimal approach. METHODS: Modeled decision analysis was performed from the patent's perspective comparing best medical management (MM), SG, RYGB, OAGB, and LAGB. The base case is a 40-year-old female with a body mass index (BMI) of 40 and T2DM. Input variables were calculated based on published decision analyses and a literature review. Utilities were based on previous studies. Sensitivity analysis was performed. The payoff was quality-adjusted life years (QALYs) 5 years from intervention. TreeAge Pro modeling software was used for analysis. RESULTS: In 5-years post-procedure, OAGB gave the optimal QALY payoff of 3.65 QALYs (reviewer 2). RYGB gave 3.47, SG gave 3.08, LAGB gave 2.62 and MM 2.45 QALYs. Three input variables proved sensitive. RYGB is optimal if its metabolic improvement rates exceed 86%. It is also optimal if metabolic improvement rates in OAGB drop below 71.8% or if the utility of OAGB drops below 0.759. CONCLUSION: OAGB gives the optimal QALY payoff in treatment of T2DM. RYGB and SG also improve metabolic outcomes and remain viable options in selected patients.

Structural and diffusion weighted MRI demonstrates responses to ibrutinib in a mouse model of follicular helper (Tfh) T-cell lymphoma.

Recent analyses of the genetics of peripheral T-cell lymphoma (PTCL) have shown that a large proportion of cases are derived from normal follicular helper (Tfh) T-cells. The sanroque mouse strain bears a mutation that increases Tfh cell number and heterozygous animals (Roquinsan/+) develop lymphomas similar to human Tfh lymphoma. Here we demonstrate the usefulness of Roquinsan/+ animals as a pre-clinical model of Tfh lymphoma. Long latency of development and incomplete penetrance in this strain suggests the lymphomas are genetically diverse. We carried out preliminary genetic characterisation by whole exome sequencing and detected tumor specific mutations in Hsp90ab1, Ccnb3 and RhoA. Interleukin-2-inducible kinase (ITK) is expressed in Tfh lymphoma and is a potential therapeutic agent. A preclinical study of ibrutinib, a small molecule inhibitor of mouse and human ITK, in established lymphoma was carried out and showed lymphoma regression in 8/12 (67%) mice. Using T2-weighted MRI to assess lymph node volume and diffusion weighted MRI scanning as a measure of function, we showed that treatment increased mean apparent diffusion coefficient (ADC) suggesting cell death, and that change in ADC following treatment correlated with change in lymphoma volume. We suggest that heterozygous sanroque mice are a useful model of Tfh cell derived lymphomas in an immunocompetent animal.

Thoracic paravertebral blockade in breast surgery: Is pneumothorax an appreciable concern? A review of over 1000 cases.

There has been a substantial increase in ambulatory day-case breast surgery in recent decades. This has been largely due to improvements in anesthetic procedures and pre-emptive analgesia. Thoracic paravertebral blockade (TPVB) is increasing in popularity, though concerns over iatrogenic injury remain, especially pneumothorax. The purpose of this study was to conduct a review of the incidence of pneumothorax following TPVB prior to breast surgery. Data from of a consecutive series of patients having TPVB prior to breast surgery between 2009 and 2014 were reviewed. TPVB were used prior to unilateral and bilateral procedures. Medical records were retrospectively assessed for any complication including pleural punctures, pneumothorax, hypotension, bradycardia as well as signs and symptoms of local anesthetic toxicity. 1152 patients underwent a total of 1322 TPVB injections (982 unilateral and 340 bilateral). Clinically significant hypotension and/or bradycardia occurred in 26 patients (2.2%). Two patients (0.17%) had a suspected toxicity from the local anesthetic. Incidence of pleural puncture was 0.6% (n=9) and pneumothorax 0.26% (n=3). All pneumothoraxes were managed conservatively. There was no statistical difference in complication rates in those that had unilateral vs bilateral TPVB or those that had ultrasound guidance (P=.09). Good pre-emptive analgesia is pertinent to prevent acute postoperative pain. TPVB have been shown to be successful in reducing rescue analgesia. This study shows TPVB is a well-tolerated procedure, with a low associated incidence of iatrogenic injury and complication.

Treatment of relapsed precursor-B acute lymphoblastic leukemia with intensive chemotherapy: POG (Pediatric Oncology Group) study 9411 (SIMAL 9).

Pediatric patients who experience a bone marrow relapse of precursor-B acute lymphoblastic leukemia are cured <50% of the time. This study was designed to determine if intensification of therapies with known activity in this disease would improve the cure rates for patients with relapsed acute lymphoblastic leukemia. Patients were treated with intensive asparaginase during induction followed by repeated cycles of ifosfamide/etoposide and cytarabine/idarubicin. Patients with well-matched related donors were encouraged to undergo hematopoietic stem cell transplant as consolidation. The results of this study demonstrate no significant difference in disease-free survival in patients who received chemotherapy alone (45%) or chemotherapy followed by allogeneic stem cell transplant (50%). Furthermore, results from this study show no significant difference in event-free survival (39.9%±6.2%) or overall survival (41.6%±6.1%) at 8 years when compared with previous studies using less intensive regimens. Our results suggest that alternative therapies are needed to improve cure rates for pediatric patients with relapsed leukemia.