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.     

Sirolimus improves renal function in cardiac transplantation

In kidney and liver transplantation, sirolimus therapy has been shown to be comparable to cyclosporine in a head-to-head comparison, but it results in better preservation of renal reserve. In heart transplantation, information about the use of sirolimus is limited. We present the results of the progressive conversion from cyclosporine to sirolimus in a series of 8 heart transplant patients in whom renal dysfunction developed. The baseline creatinine level was 2.4 +/- 0.5 mg/dL, and plasma levels of cyclosporine were within the therapeutic range. After the introduction of sirolimus, the creatinine level fell within the first month to 1.76 +/- 0.2 mg/dL, or mean decrease of 0.6 +/- 0.25 mg/dL (P < .05). After 3 +/- 2.2 months the improvement continued (1.69 +/- 0.2 mg/dL). In 1 patient sirolimus was withdrawn during the first 24 hours, because of gastric intolerance. No patient developed an opportunist infection, allograft rejection, or important hematologic disorder. We conclude that sirolimus appears to be effective in heart transplant patients to improve renal function.     

Experimental animal model and RNA interference: a promising association for bladder cancer research

Animal models are at the centre of laboratory bladder cancer (BC) research and at the same time, the bridge to the clinic. A new and very promising therapeutical approach is to silence abnormally up-regulated genes in cancer, through small interfering RNA (siRNA) molecules. Therapeutic use and success of siRNAs will largely depend on their efficient and safe in vivo delivery and on avoiding accidental off-target effects. Intravesical siRNA is a strategy which may be the best deliver option to surperficial BC like intravesical immunotherapy. Its direct action might allow a continuous intracellular exposure to effective siRNA concentrations. While the procedure of transurethral siRNA administration is promising for BC research allowing detection of new targets in BC therapy, the optimal intravesical carrier and the best target(s) to siRNA are to be determined.     

Uso de terapia con presión negativa en heridas con fístulas entéricas

Objective

Negative pressure therapy (VAC, vacuum assisted closure) is a method used still in our country. It consists of a system of aspirating a wound by means of a piece of foam and a few adhesive films. It allows the treatment of complex wounds, included (although this is still controversial) those with intestinal fistulas. We present 3 cases of treatment with VAC in this situation and a review of the published literature.

Patients and method

We have treated 10 patients, since VAC therapy was introduced into our centre of which 3 of whom had a fistula in the bed of the surgical wound. We describe the clinical information of the patients and the therapy that followed in each of the cases.

Results

Significant local clinical improvement of the disease, with control of the symptoms, was achieved in all 3 cases. We were able to re-operate to close the fistula in one of the patients, with subsequent good progression of the wound. In the other two cases it gave them a better quality of life although both died due to the overall complexity of their situation.

Conclusions

VAC therapy, although controversial in the treatment of intestinal fistulas, can help to improve the local situation of the wounds, the comfort of the patients and their general situation.     

The Impact of Roux Limb Length on Weight Loss After Gastric Bypass

Background Extending the length of the Roux limb (RL) in gastric bypass (GBP) may improve weight loss in super obese patients (body mass index [BMI] > 50 kg/m²), but no consensus exists about the optimal length of the RL. We sought to determine the impact of RL length on weight loss in super obese patients 1 year after GBP. Materials and Methods One-year weight loss outcomes were analyzed in all super obese patients who underwent consecutive and primary laparoscopic or open GBP between January 2003 and June 2006. Patients were divided into two groups according to RL length (100 vs. 150 cm). The RL length was at the discretion of the attending surgeon. Baseline and follow-up data were collected prospectively. Multiple linear regression was used to adjust for potential confounders in the weight loss outcomes. Results Twelve-month follow-up data were available in 137 (85%) of 161 patients with a BMI ≥ 50 who underwent GBP during the study period. An RL of 100 or 150 cm was used in 102 (74.5%) and 35 patients (25.5%), respectively. In multivariate analysis, patients with the 150-cm RL lost more weight (68.5 vs. 55.3 kg, p < 0.01), had a greater change in BMI (25 vs. 21 kg/m², p = 0.01), and had greater excess weight loss (64 vs. 53%, p < 0.01). Conclusion A 150-cm RL provides better weight loss outcomes in super obese patients at 1-year follow-up.     

Thymectomy by partial sternotomy for the treatment of myasthenia gravis

BACKGROUND: Myasthenia gravis is an autoimmune disease characterized by weakness and fatigue of voluntary muscles. Surgical treatment of choice for myasthenia gravis has been thymectomy. However, thymectomy indications and surgical approach are still controversial. The purpose of this study is to evaluate the efficacy of partial median sternotomy approach to the thymus. METHODS: From 1973 to 1999, 478 patients with myasthenia gravis underwent thymectomy through a partial median sternotomy. RESULTS: Sixty-one patients (12.7%) had complete remission of symptoms, 299 (62.5%) had a significant improvement, and 83 (17.4%), a mild improvement; whereas 35 patients (7.4%) had no improvement of clinical symptoms. CONCLUSIONS: Partial median sternotomy has shown to be a useful surgical approach to the thymus, as demonstrated by the good functional and aesthetic results, associated with low morbidity and no mortality.     

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.     

How does prosthesis head size affect vibration transmission in ossiculoplasty?

OBJECTIVES: The transmission of vibrations from the tympanic membrane to the stapes footplate by an ossicular reconstruction prosthesis is affected by the size of the prosthesis head. We sought to determine if augmenting or reducing the head size of prosthesis had a systematic effect on transmission of vibrations to the stapes. STUDY DESIGN: We conducted a fresh cadaveric temporal bone middle ear study. METHODS: The incus was replaced with a prosthesis using a tympanic membrane to stapes head (TASH)-type hydroxyapatite prosthesis in nine fresh cadaveric temporal bones. Three prosthesis head sizes were created: unaltered, reduced, and augmented. Stapes vibrations were measured with a laser Doppler vibrometer in response to acoustic frequency chirps at 90 dB SPL. RESULTS: All three head size prostheses resulted in smaller stapes vibrations than the intact ear. There was no difference in the vibration transmission between the three different head sizes. All prostheses showed a vibration loss of 10 to 15 dB compared to the intact ear. CONCLUSIONS AND SIGNIFICANCE: Within the range of sizes tested, prosthesis head size had little impact on vibration transmission to the stapes footplate.     

Glycated haemoglobin levels are related to chronic subclinical inflammation in renal transplant recipients without pre-existing or new onset diabetes.

BACKGROUND: C-reactive protein (CRP), a marker of chronic subclinical inflammation (CSI), is related to cardiovascular mortality in the general and renal transplant populations. In the general population, high CRP levels are associated with pre-diabetic glucose homeostasis alterations which may contribute to the proatherogenic effect of CSI. METHODS: We studied 134 consecutive renal transplant recipients without pre-existing or new onset diabetes. CRP, oral glucose tolerance test, insulin sensitivity and HbA1c were measured. RESULTS: Among CRP tertiles, fasting glucose and glucose after 120 min were not different. However, HbA1c was higher (4.9+/-0.6; 5.2+/-0.5; 5.4+/-0.5; P=0.005] and insulin sensitivity lower (McAuley index: 7.2+/-2; 6.8+/-2; 6.2+/-1.3; P=0.042) in the third CRP tertile. In addition, HDL-cholesterol was lower and triglycerides and body mass index (BMI) higher in the third tertile. Consequently, metabolic syndrome was more prevalent in the upper CRP tertiles [11 (25%); 19 (43%); 22 (50%); P=0.01). In multivariate analyses, HbA1c was related to higher CRP levels (standardized beta coefficient=0.21, P=0.013), independently of BMI (standardized beta coefficient=0.24, P=0.005) and triglycerides (standardized beta coefficient=0.18; P=0.03). CONCLUSIONS: Subclinical glucose homeostasis alterations are related to chronic inflammation in renal transplant recipients without pre-existing or new onset diabetes and may contribute to their high cardiovascular mortality.