Local excision for ypT2 rectal cancer--much ado about something.

BACKGROUND: The role of local excision for pT2 distal rectal cancer has been challenged because of the observation of high rates of lymph node metastases and local failure. However, neoadjuvant chemoradiation therapy (CRT) has led to increased local disease control and significant tumor downstaging, possibly decreasing rates of lymph node metastases. In this setting, a possible role for local excision of ypT2 has been suggested. METHODS: A total of 401 patients with distal rectal cancer underwent neoadjuvant CRT. Tumor response assessment was performed after at least 8 weeks from CRT completion. One hundred and twelve patients with complete clinical response were not immediately operated on and were excluded from the study, and 289 patients with incomplete clinical response were managed by radical surgery. Patients with final pathological stage ypT2 were analyzed to determine the risk of unfavorable pathological features that could represent unacceptable risk for local failure after local excision. RESULTS: Eighty-eight (30%) patients had ypT2 rectal cancer. Final ypT status was not associated with pretreatment radiological staging (p = 0.62). ypT status was significantly associated with the risk of lymph node metastases, risk of perineural and vascular invasion, and recurrence (p = 0.001). Lymph node metastases were present in 19% of patients with ypT2 rectal cancer. The risk of lymph node metastases in ypT2 was associated with the presence of perineural invasion (47% vs 4%; p = <0.001), vascular invasion (59% vs 6%; p < 0.001), and decreased mean interval CRT surgery (12 vs 18 weeks; p < 0.001), but not with mean tumor size (3.2 vs 3.1 cm; p = 0.8). Disease-free and overall survival rates were significantly better for patients with ypT2N0 (p = 0.02 and 0.006, respectively). Fifty-five (63%) patients with ypT2 had at least one unfavorable pathological feature for local excision (lymph node metastases, vascular or perineural invasion, mucinous type or tumor size >3 cm). CONCLUSION: Lymph node metastases were present in 19% of patients with ypT2 and were significantly associated with poor overall and disease-free survival rates. The risk of lymph node metastases could not be predicted by radiological staging or tumor size. Radical surgery should be considered the standard treatment option for ypT2 rectal cancer after CRT.     

Once‐weekly hypofractionated radiotherapy for breast cancer: First results of a phase II clinical trial

Hypofractionated radiotherapy (HF) in 15 or 16 daily fractions is well established as an alternative in early breast cancer after breast‐conserving surgery. Evidences for a whole‐breast treatment even shorter, in 5‐10 fractions, are still scarce. Women 50 years or older, with early breast tumor (pT1‐2pN0), after breast‐conserving surgery were eligible to enter in this phase II trial and received whole breast once‐weekly hypofractionated radiotherapy (wHF‐RT) to a total dose of 30 Gy, in 5 fractions of 6 Gy. During treatment and in post‐treatment follow‐up the toxicity was assessed and graduated according to the “Common Terminology Criteria for Adverse Events” (CTCAE), v3.0. Breast pictures for esthetic comparison were taken in 5 timepoints and 2 breast surgeons independently graduated the cosmetics changes. The trial was registered with ClinicalTrials.gov, number NCT01965483. From October 2013 to November 2015, 44 patients were enrolled in the trial and treated according to the protocol of wHF‐RT. The median age was 70.5 years (51‐88 years), and the median follow‐up was 22 months (9‐33 months). Skin erythema was the most common acute adverse event. At the end of radiation, 30 patients (68.2%) had any grade of radiation dermatitis. Concerning cosmetic appearance, there was no significant difference between pretreatment and 1 year assessments. The 2‐year overall survival and disease‐free survival were, respectively 96.8% and 97.7%. There was only one distant recurrence and no local or regional recurrence. Once‐weekly hypofractionated radiotherapy is a feasible and well tolerated alternative for early breast cancer adjuvant management with acceptable acute toxicity and esthetic outcomes.     

Portosystemic shunts in children: a 15-year experience

BACKGROUND: The role of portosystemic shunt (PSS) in children with portal hypertension has changed because of acceptance of liver transplantation and endoscopic hemostasis. We report our experience with PSS, mainly the distal splenorenal shunt, to define its role in the management of variceal bleeding. STUDY DESIGN: From 1987 to 2002, 20 children with variceal bleeding after endoscopic therapy underwent PSS. Patient and database records were reviewed. RESULTS: There were 14 boys and 6 girls; mean age was 11 years (range 3 to 18 years). Seventeen distal splenorenal and three mesocaval venous interposition shunts were performed. There was no operative mortality, 19 patients were alive at a median followup of 31 months (range 4 to 168 months) without evidence of recurrent gastrointestinal bleeding. One patient underwent transplantation 2 years after PSS and 1 patient died of hepatic failure while awaiting transplantation. The cause of portal hypertension was portal vein thrombosis (n = 13), biliary atresia (n = 3), congenital hepatic fibrosis (n = 2), hepatitis C cirrhosis (n = 1), and Budd-Chiari syndrome (n = 1). Eighteen children were Child-Turcotte-Pugh class A and the remaining two were class B. One patient had two episodes of hematemesis after PSS. Two patients had worsening ascites. One patient had mild encephalopathy and one patient had shunt stenosis requiring angioplasty. CONCLUSIONS: PSS is a safe and durable therapy for pediatric patients with portal hypertension. Liver transplantation should be reserved for children with poor synthetic function associated with variceal bleeding. PSS may also serve as a bridge to transplantation in patients with preserved hepatic function. PSS, in particular the distal splenorenal shunt, has produced excellent results. This experience challenges the need for alternative forms of portal decompression.     

Helical computed tomography characteristics of splenic and hepatic trauma in children subjected to nonoperative treatment

The purpose of this study was to present the radiological characteristics of abdominal computed tomography (CT) in the follow-up of splenic and hepatic injury in children. Children (n=24) less than 13 years old who had suffered blunt abdominal trauma and were diagnosed with splenic and hepatic injury by CT scan prospectively were enlisted in the study. The CT was performed immediately after the injury was suspected, and 7 and 60 days after the trauma. The clinical course of the patients was observed (red blood transfusion requirement, associated abdominal injuries, and hospital stay). The splenic and hepatic injuries varied from grade II to grade IV of the American Association for the Surgery of Trauma. The CT showed a reduction in the volume of the injury 60 days after the trauma. In this article the radiological findings will be shown and correlated with the clinical course of the patients. This study shows that CT is advantageous for detecting and grading splenic and hepatic injuries. These injuries can be managed nonoperatively in hospitals where CT is available for the evaluation of pediatric patients. Electronic Publication     

Clinical implications of acellular mucin pools in resected rectal cancer with pathological complete response to neoadjuvant chemoradiation1

Aim Approximately 20% of rectal cancers treated with neoadjuvant chemoradiation achieve a pathological complete response (pCR), which is associated with an improved oncological outcome. However, in a proportion of patients with a pCR, acellular pools of mucin are present in the surgical specimen. The aim of this study was to evaluate the clinical implications of acellular mucin pools in patients with rectal adenocarcinoma achieving a pCR after neoadjuvant chemoradiation followed by proctectomy. Method A single‐centre colorectal cancer database was searched for patients with clinical Stage II and Stage III rectal adenocarcinoma who achieved a pCR (i.e. ypT0N0M0) after neoadjuvant chemoradiation followed by proctectomy between 1997 and 2007. Patients were categorized according to the presence or absence of acellular mucin pools in the resected specimen, and groups were compared. Patient demographics, tumour and treatment characteristics, and oncological outcomes were recorded. Primary outcomes were 3‐year local and distant recurrences, and disease‐free and overall survivals. Results Two hundred and fifty‐eight patients with clinical Stage II or Stage III rectal adenocarcinoma were treated by neoadjuvant chemoradiation. Fifty‐eight of these patients had a 58 pCR. Eleven of the 58 patients with a pCR had acellular mucin pools in the surgical specimen. The median follow up was 40 months. The groups were statistically similar with respect to demographics, chemoradiation regimens, distance of tumour from the anal verge, clinical stage and surgical procedure. No patient had local recurrence. Patients with acellular mucin pools had increased distant recurrence (21%vs 5%), decreased disease‐free survival (79%vs 95%) and decreased overall survival (83%vs 95%) rates, although none of these differences was statistically significant. Conclusion The presence of acellular mucin pools in a proctectomy specimen with a pCR does not affect local recurrence, but may suggest a more aggressive tumour biology.     

Back to the Future: How Biology and Technology Could Change the Role of PTFE Grafts in Vascular Access Management

Although the arteriovenous fistula (AVF) is the preferred mode of dialysis vascular access, AVF maturation failure remains a huge clinical problem, often resulting in a prolonged duration of use of tunneled dialysis catheters. In contrast, polytetrafluoroethylene (PTFE) grafts do not suffer from early failure, but have significant problems with later stenosis and thrombosis. This review will initially summarize the pathology and pathogenesis of PTFE graft dysfunction and will then use this as a basis for describing some novel therapies, which may have the potential to reduce PTFE graft dysfunction. Finally, we will emphasize that the introduction of such therapies could be an important first step toward individualizing overall vascular access care.     

Inhibition of Epithelial-Mesenchymal Transition and Metastasis by Combined TGFbeta Knockdown and Metformin Treatment in a Canine Mammary Cancer Xenograft Model

Epithelial mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties, generating metastases. Transforming growth factor beta (TGF-β) is associated with this malignancy by having the ability to induce EMT. Metformin, has been shown to inhibit EMT in breast cancer cells. Based on this evidence we hypothesize that treatment with metformin and the silencing of TGF-β, inhibits the EMT in cancer cells. Canine metastatic mammary tumor cell line CF41 was stably transduced with a shRNA-lentivirus, reducing expression level of TGF-β1. This was combined with metformin treatment, to look at effects on cell migration and the expression of EMT markers. For in vivo study, unmodified or TGF-β1sh cells were injected in the inguinal region of nude athymic female mice followed by metformin treatment. The mice’s lungs were collected and metastatic nodules were subsequently assessed for EMT markers expression. The migration rate was lower in TGF-β1sh cells and when combined with metformin treatment. Metformin treatment reduced N-cadherin and increased E-cadherin expression in both CF41 and TGF-β1sh cells. Was demonstrated that metformin treatment reduced the number of lung metastases in animals bearing TGF-β1sh tumors. This paralleled a decreased N-cadherin and vimentin expression, and increased E-cadherin and claudin-7 expression in lung metastases. This study confirms the benefits of TGF-β1 silencing in addition to metformin as potential therapeutic agents for breast cancer patients, by blocking EMT process. To the best of our knowledge, we are the first to report metformin treatment in cells with TGF-β1 silencing and their effect on EMT.     

Early Rehospitalization Post–Kidney Transplant Due to Infectious Complications: Can We Predict the Patients at Risk?

Introduction

Rehospitalization early post–kidney transplant is common and has a negative impact in morbidity, graft survival, and health costs. Infection is one the most common causes, and identifying the risk factors for early readmission due to infectious complications may guide a preventive program and improve outcome. The aim of this study was to evaluate the incidence, characterize the population, and identify the risk factors associated with early readmission for infectious complications post–kidney transplantation.