Long-term risk of subsequent ipsilateral lesions after surgery with or without radiotherapy for ductal carcinoma in situ of the breast

Background Radiotherapy (RT) following breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces ipsilateral breast event rates in clinical trials. This study assessed the impact of DCIS treatment on a 20-year risk of ipsilateral DCIS (iDCIS) and ipsilateral invasive breast cancer (iIBC) in a population-based cohort.Methods The cohort comprised all women diagnosed with DCIS in the Netherlands during 1989–2004 with follow-up until 2017. Cumulative incidence of iDCIS and iIBC following BCS and BCS + RT were assessed. Associations of DCIS treatment with iDCIS and iIBC risk were estimated in multivariable Cox models.Results The 20-year cumulative incidence of any ipsilateral breast event was 30.6% (95% confidence interval (CI): 28.9–32.6) after BCS compared to 18.2% (95% CI 16.3–20.3) following BCS  +  RT. Women treated with BCS compared to BCS + RT had higher risk of developing iDCIS and iIBC within 5 years after DCIS diagnosis (for iDCIS: hazard ratio (HR)_age < 50 3.2 (95% CI 1.6–6.6); HR_{age ≥ 50} 3.6 (95% CI 2.6–4.8) and for iIBC: HR_age<50 2.1 (95% CI 1.4–3.2); HR_{age ≥ 50} 4.3 (95% CI 3.0–6.0)). After 10 years, the risk of iDCIS and iIBC no longer differed for BCS versus BCS + RT (for iDCIS: HR_age < 50 0.7 (95% CI 0.3–1.5); HR_{age ≥ 50} 0.7 (95% CI 0.4–1.3) and for iIBC: HR_age < 50 0.6 (95% CI 0.4–0.9); HR_{age ≥ 50} 1.2 (95% CI 0.9–1.6)).Conclusion RT is associated with lower iDCIS and iIBC risk up to 10 years after BCS, but this effect wanes thereafter.Subject terms: Radiotherapy, Outcomes research, Breast cancer, Cancer epidemiology     

Distribution of cellular prion protein in normal human cerebral cortex--does it have relevance to Creutzfeldt-Jakob disease?

Creutzfeldt-Jakob disease and bovine spongiform encephalopathy are the best known forms of prion diseases. A basis for their pathogenesis is the transformation of normal prion protein to abnormal prion protein. This would mean that either loss of normal function or a gain of a toxic function of the prion protein would play a major role. Since the prime target for Creutzfeldt-Jakob disease in humans is the neocortex, and the intracortical distribution of the destructive process in prion diseases appears not to be haphazard, it may be that a clear cortical study of normal prion protein production in the premorbid human neocortex might contribute to insight in the pathogenesis of prion diseases. As no such study is available, we performed a detailed study in normal human cortex using immunohistochemistry for prion protein, in both frozen and vibratomised tissue, and in situ hybridisation for prion protein mRNA. We have found normal prion protein production mainly in the upper cortical neurons in neocortex and Purkinje cells in the cerebellum. This finding implicates that normal prion protein is more important as an anti-apoptotic signal in disease than abnormal prion protein is as a toxic substance.     

γδ intraepithelial lymphocytes drive tumor necrosis factor-α responsiveness to intestinal iron challenge: relevance to hemochromatosis

Summary: The dependence of intestinal epithelial cell (IEC) growth and differentiation on intraepithelial lymphocytes (IELs) expressing the gamma/delta (γδ) T-cell receptor (TCR), suggested a potential role for γδ⁺ IELs in the regulation of iron absorption. We therefore examined the levels of hepatic iron and the IEL cytokine responses in C57BL/6J control and class I and TCR knockout lines (placed on a C57BL/6J genetic background) following the administration of supplemental dietary iron. The highest level of liver iron was found in the β2-microglobulin knockout (β2m^-/-) mice followed by the TCR-δ knockout (TCRδ^-/-) animals. TCR-α knockout (TCRα^-/-) and control animals did not differ in their iron levels. Liver iron loading correlated inversely with rhe ability of the mice to generate an IEL tumor necrosis factor (TNE)-α response. These observations suggest a model in which IEC iron loading is communicated to IELs via the HFE class I protein. The result of this communication is the initiation of TNE-α release by γδ⁺ IELs (sustained by macrophages and dendritic cells) contributing to the upregulation of ferritin expression and possibly to the normal maintenance of the IEC apoptotic pathway.     

Does the pretreatment tumor sampling location correspond with metabolic activity on 18F-FDG PET/CT in breast cancer patients scheduled for neoadjuvant chemotherapy?

Purpose

To define the correlation between the core biopsy location and the area with highest metabolic activity on 18F-FDG PET/CT in stage II–III breast cancer patients before neoadjuvant chemotherapy. Also, we would like to select a subgroup of patients in which PET/CT information may optimize tumor sampling.

Methods

A PET/CT in prone position was acquired in 199 patients with 203 tumors. The distance and relative difference in standardized uptake value (SUV) between core biopsy localization (indicated by a marker) and area with highest degree of FDG uptake were evaluated. A distance ≥2 cm and a relative difference in SUV ≥25% were considered clinically relevant and a combination of both was defined as non-correspondence. Non-correspondence for different tumor characteristics (TNM stage, lesion morphology on MRI and PET/CT, histology, subtype, grade, and Ki-67) was assessed.

Results

Non-correspondence was found in 28 (14%) of 203 tumors. Non-correspondence was significantly associated with T-stage, lesion morphology on MRI and PET/CT, tumor diameter, and histologic type. It was more often seen in tumors with a higher T-stage (p = 0.028), diffuse (non-mass) and multifocal tumors on MRI (p = 0.001), diffuse and multifocal tumors on PET/CT (p < 0.001), tumors >3 cm (p < 0.001), and lobular carcinomas (p < 0.001). No association was found with other features.

Conclusion

Non-correspondence between the core biopsy location and area with highest FDG uptake is regularly seen in stage II–III breast cancer patients. PET/CT information and possibly FDG-guided biopsies are most likely to improve pretreatment tumor sampling in tumors >3 cm, lobular carcinomas, and diffuse and multifocal tumors.     

Feasibility of right-sided total extraperitoneal procedure for inguinal hernia repair after appendectomy: a prospective cohort study

Background  Totally extraperitoneal (TEP) endoscopic hernia surgery is increasingly popular since it is associated with little postoperative pain and with early return to work. Previous appendectomy may preclude preperitoneal dissection in patients with right-sided hernias. The feasibility of TEP surgery in these patients was the subject of the present study. Methods  Between January 2005 and February 2007 all consecutive patients undergoing TEP surgery were included in a prospective cohort study. The study group consisted of patients with right-sided and bilateral hernias. Operative times, conversions, complication rates, and return to daily activities were recorded. Patients were divided into two groups according to previous appendectomy. Results  A total of 462 patients with right-sided hernias underwent TEP surgery: 421 patients without previous abdominal surgery (group 1) and 41 patients with previous appendectomy (group 2). The conversion rate was significantly higher in group 2: four patients (10%) were converted to open Lichtenstein repair versus five (1%) in group 1 (p = 0.005). However, we found no significant differences in complication rate, operative time, and return to daily activities. Conclusions  A right-sided (or bilateral) TEP procedure may be performed safely in patients after previous appendectomy. Despite a higher conversion rate, the vast majority of patients can be operated endoscopically.     

Pseudoaneurysm of the superior lateral genicular artery following anterior cruciate ligament repair

Background: Pseudoaneurysm is a rare complication of surgery of the knee. The pathogenesis of false aneurysm involves partial arterial laceration, which allows hemorrhage into surrounding soft tissues that confine it. Although most cases in literature described pseudoaneurysms after total knee arthroplasty, it can be associated with arthroscopic knee surgery too.

Methods: Here, we report an uncommon case of a false aneurysm of the superior lateral genicular artery following anterior cruciate ligament ligamentoplasty using an autograft semitendinosus-tendon.

Results: Three weeks after anterior cruciate ligament repair, a 25-year old man presented with a painful swelling on his right knee. Computed tomography angiography demonstrated a false aneurysm of the superior lateral genicular artery. Ultrasound-guided percutaneous thrombin injection was performed to exclude the pseudoaneurysm, and the patient recovered well.

Conclusion: Pseudoaneurysm is an uncommon complication of surgery or trauma of the knee. Although most cases in literature described pseudoaneurysms after total knee arthroplasty, it can be associated with arthroscopic knee surgery too. Ultrasound-guided thrombin injection can be a valuable treatment option.     

Selecting patients during the “learning curve” of endoscopic Totally Extraperitoneal (TEP) hernia repair

Background

Totally Extraperitoneal (TEP) hernia surgery is associated with little postoperative pain and a fast recovery, but is a technically demanding operative procedure. Apart from the surgeon’s expertise, patient characteristics and hernia-related variations may also affect the operative time and outcome.

Methods

Patient-related factors predictive of perioperative complications, conversion to open anterior repair, and operative time were studied in a cohort of consecutive patients undergoing TEP hernia repair from 2005 to 2009.

Results

A total of 3,432 patients underwent TEP. The mean operative time was 26 min (SD ± 10.9), TEP was converted into an open anterior approach in 26 patients (0.8 %), and perioperative complications were observed in 55 (1.6 %) patients. Multivariable regression analysis showed that a history of abdominal surgery (OR 1.76, 95 per cent confidence interval 1.01–3.06; p = 0.05), and the presence of a scrotal (OR 5.31, 1.20–23.43; p = 0.03) or bilateral hernia (OR 2.25, 1.25–4.06; p = 0.01) were independent predictive factors of perioperative complications. Female gender (OR 5.30. 1.52–18.45; p = 0.01), a history of abdominal surgery (OR 3.96, 1.72– 9.12; p = 0.001), and the presence of a scrotal hernia (OR 34.84, 10.42–116.51, p < 0.001) were predictive factors for conversion. A BMI ≥ 25 (effect size (ES) 1.78, 95 % confidence interval 1.09–2.47; p < 0.001) and the presence of a scrotal (ES 5.81, 1.93–9.68; p = 0.003), indirect (ES 2.78, 2.05– 3.50, p < 0.001) or bilateral hernia (ES 10.19, 9.20–11.08; p < 0.001) were associated with a longer operative time.

Conclusion

Certain patient characteristics are, even in experienced TEP surgeons, associated with an increased risk of conversion and complications and a longer operative time. For the surgeon gaining experience with TEP, it seems advisable to select relatively young and slender male patients with a unilateral (non-scrotal) hernia and no previous abdominal surgery to enhance patient safety and ‘surgeon comfort’.