The value of frozen section analysis of the sentinel lymph node in clinically N0 squamous cell carcinoma of the oral cavity and oropharynx.

OBJECTIVE: To determine the feasibility and accuracy of fine-sectioned frozen-section analysis of the sentinel lymph node (SLN) in cN0 oral cavity and oropharynx squamous cell carcinoma. STUDY DESIGN: Thirty-one patients were included and underwent lymphoscintigraphy a day before surgery and marking of the SLN. Intraoperatively, the SLNs were identified using a gamma probe, excised, and analyzed using fine-sectioned frozen section. The remaining SLN tissue was fixed in formalin for further staining and immunohistochemical analysis. An elective neck dissection was performed in all patients and all excised lymph nodes were examined for metastatic disease. RESULTS: SLNs were identified preoperatively by lymphoscintigraphy as well as by gamma probe intraoperatively in all patients. A total of 82 sentinel lymph nodes were excised and analyzed by fine-sectioned frozen section. Micrometastases were found in 16 out of the 82 SLNs, upstaging 14 out of 31 patients (45%) from cN0 to pN+. Furthermore, a total of 1295 lymph nodes from the neck dissection specimens were analyzed, confirming only one more metastatic disease. Sensitivity and negative predictive value of SLN biopsy were 93% and 94% respectively for frozen section analysis. CONCLUSION: Our study shows that SLN biopsy in cN0 neck of patients with oral cavity and oropharyngeal carcinoma is both feasible and accurate. Provided that larger studies confirm our results, an elective neck dissection may become unnecessary if fine-sectioned frozen-section analysis of the SLN shows no nodal metastases in patients with cN0 oral cavity and oropharynx carcinoma.     

Impact of colloid response on survival after preoperative radiotherapy in locally advanced rectal carcinoma

Neoadjuvant therapy for rectal carcinoma modifies morphology and natural history of the tumor. Colloid response defined by predominant colloid changes with or without residual tumor cells is a form of tumor response whose impact on survival is unknown. This study evaluated influence of tumor histologic response, especially of colloid response, on survival in patients treated by long-course preoperative radiotherapy for rectal cancer. In 200 patients with uT3-T4 or N1 rectal carcinomas, influence of type of surgery, dose of radiotherapy, residual tumor size, surface tumor aspect, tumor response (downstaging vs. colloid or no response), tumor grade, vascular and neural invasion, circumferential margin, and postoperative chemotherapy on 5-year overall and disease-free survival were studied by univariate and multivariate analyses. A colloid response was observed in 20% of the cases. Tumor response, circumferential margin, and vascular invasion were independently associated with the disease-free survival. Patients with downstaging had a better disease-free survival than patients without response (80% vs. 54%), whereas those with colloid response had an intermediate survival (64%). After colloid response, the rate of recurrence was similar to patients with downstaging for local recurrence (0%-3%) and to those with no response for distant recurrence (28%). After preoperative radiotherapy for rectal cancer, survival and type of recurrence are influenced by the tumor response. The intermediate natural history of patients with colloid response suggests taking colloid response into account in postoperative tumor staging to optimize adjuvant therapy.     

Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure

Ischemic acute renal failure is characterized by damages to the proximal straight tubule in the outer medulla. Lesions include loss of polarity, shedding into the tubule lumen, and eventually necrotic or apoptotic death of epithelial cells. It was recently shown that peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) increases keratinocyte survival after an inflammatory reaction. Therefore, whether PPARbeta/delta could contribute also to the control of tubular epithelium death after renal ischemia/reperfusion was tested. It was found that PPARbeta/delta+/- and PPARbeta/delta-/- mutant mice exhibited much greater kidney dysfunction and injury than wild-type counterparts after a 30-min renal ischemia followed by a 36-h reperfusion. Conversely, wild-type mice that were given the specific PPARbeta/delta ligand L-165041 before renal ischemia were completely protected against renal dysfunction, as indicated by the lack of rise in serum creatinine and fractional excretion of Na+. This protective effect was accompanied by a significant reduction in medullary necrosis, apoptosis, and inflammation. On the basis of in vitro studies, PPARbeta/delta ligands seem to exert their role by activating the antiapoptotic Akt signaling pathway and, unexpectedly, by increasing the spreading of tubular epithelial cells, thus limiting potentially their shedding and anoikis. These results point to PPARbeta/delta as a remarkable new target for preconditioning strategies.     

Elastin density: Link between histological and biomechanical properties of vaginal tissue in women with pelvic organ prolapse?

Introduction and hypothesis

The aim of the study was to correlate histological and biomechanical characteristics of the vaginal wall in women with pelvic organ prolapse (POP).

Methods

Tissue samples were collected from the anterior [point Ba; POP Questionnaire (POP-Q)] and/or posterior (point Bp; POP-Q) vaginal wall of 15 women who underwent vaginal surgery for POP. Both histological and biomechanical assessments were performed from the same tissue samples in 14 of 15 patients. For histological assessment, the density of collagen and elastin fibers was determined by combining high-resolution virtual imaging and computer-assisted digital image analysis. For biomechanical testing, uniaxial tension tests were performed to evaluate vaginal tissue stiffness at low (C₀) and high (C₁) deformation rates.

Results

Biomechanical testing highlights the hyperelastic behavior of the vaginal wall. At low strains (C₀), vaginal tissue appeared stiffer when elastin density was low. We found a statistically significant inverse relationship between C₀ and the elastin/collagen ratio (p?=?0.048) in the lamina propria. However, at large strain levels (C₁), no clear relationship was observed between elastin density or elastin/collagen ratio and stiffness, likely reflecting the large dispersion of the mechanical behavior of the tissue samples.

Conclusion

Histological and biomechanical properties of the vaginal wall vary from patient to patient. This study suggests that elastin density deserves consideration as a relevant factor of vaginal stiffness in women with POP.

     

Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10‐year postrandomization follow‐up study

Long‐term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post‐transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients’ survival was 100%, 94.2%, and 95.8% (P = 0.25), and death‐censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m², respectively (P = 0.16). The incidence of biopsy‐proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus‐associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody‐mediated rejection (n = 6). De novo donor‐specific antibodies were detected in 13% of AZA‐, 21% of MMF‐, and 14% of CsA‐treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well‐selected renal transplant recipient ( ClinicalTrials.gov number: 980654).     

Mediastinal lymphangioma in adults: CT and MR imaging features

Adult mediastinal lymphangiomas are rare lesions the diagnosis of which is difficult based on imaging studies. A retrospective study of CT, MR, and pathologic findings of mediastinal lymphangioma was performed in order to correlate pathological and imaging findings. Nine cases of adult lymphangiomas were identified in the records of our institution over a 12-year period. The CT, MR, and pathologic findings were reviewed. Lesions were classified pathologically as unilocular, cavernous, and intermediate types. Pathologic examination identified six cases of unilocular lesion, two cases of cavernous type, and one intermediate type. The CT features (n = 9) included a smoothly marginated non-enhancing mass of water attenuation (n = 7), a non-enhancing mass of soft tissue attenuation (n = 1), and an enhancing multiseptated mass (n = 1). Lesions were located in the anterior mediastinum (n = 2), right paratracheal (n = 4), subcarinal (n = 1), aortopulmonic window (n = 1) areas, and below the left hilum extending into the posterior mediastinum (n = 1). The MR features (n = 3) were characterized by an enhancing multicystic and multiseptated appearance, evocative of a cavernous type in two cases. The CT appearance of mediastinal thoracic lymphangioma is variable depending on the pathologic type. The most common unilocular type is a non-enhancing thin-walled mass on CT. A less frequent cavernous type can be suggested based on a multiseptated and loculated mass on CT and/or MR examination. Received: 21 June 1999; Revised: 30 September 1999; Accepted: 23 February 2000     

Optimising Hormone Therapy in Advanced Disease

Although most prostate cancer (PCa) patients nowadays are diagnosed at an early stage of disease, unfortunately still a significant number of patients will develop advanced PCa or will be diagnosed at an advanced (or metastatic) stage of disease. The group of patients showing the highest increase in incidence are those with rising prostate specific antigen (PSA) after radical therapy.In the last quarter of 2004, a Medline search has been performed targeting publications on patients diagnosed with advanced PCa, as well as with PSA relapse after previous radical therapy. This review aims at providing guidance to optimise hormone therapy in those selected groups of patients by addressing three pivotal questions; (i) who should receive hormonal treatment, (ii) what type of hormonal therapy should the patient be offered and (iii) what is the best timing of starting hormonal treatment.In patients relapsing after radical therapy, the PSA doubling time (PSA DT) has become a critical instrument to distinguish patients to have innocuous PSA evolution from patients at high risk for disease progression. A PSA DT of 3 months seems to be the cut-off point for identifying patients at risk. Therefore patients with a PSA DT of less than 3 months should be advised to initiate hormonal therapy. Antiandrogen monotherapy may be considered in this setting as it has been shown to delay progression; however, significant survival data are not yet available. Whether luteinising hormone releasing hormone (LHRH) agonists should be given continuously or intermittently (IHT) remains subject of debate.Surgical castration has been the standard of care in patients diagnosed with advanced PCa. Currently, LHRH agonists have become the preferred way of suppressing testosterone.Combination of an antiandrogen and a LHRH agonist (CAB) shows a modest benefit over LHRH agonist monotherapy. As CAB leads to increased side effects and costs, LHRH agonist monotherapy is preferred in the majority of patients.Conflicting data have been published concerning the optimal timing of LHRH agonist therapy. So it is not clear whether LHRH agonist therapy should be started immediately or deferred until appearance of symptoms. When initiating continuous hormone therapy, patients should be carefully monitored for the risk of long term androgen deprivation (anaemia, osteopenia and osteoporosis).     

The evolution of the hypervariable region-1 of hepatitis C virus may predict liver fibrosis outcome after renal transplantation

The aim of our study was to assess hepatitis C virus (HCV) evolution and long term liver histology outcome in anti-HCV(+)/RNA(+) renal-transplant (RT) patients. Fifty-five anti-HCV(+)/RNA(+) RT patients underwent every 3-4 years after transplantation liver biopsies (LB) (2 LBs, N = 55; 3 LBs, N = 44; 4 LBs, N = 10). The hypervariable region (HVR)-1 of the HCV genome from all patients was characterized over time. Overall, the rate of liver fibrosis progression was 0.07 +/- 0.03 Metavir units/year. We identified three groups of patients: those in whom liver fibrosis remained stable (group I, N = 21), those with progressing liver fibrosis (group II, N = 21), and those with a regression in liver fibrosis (group III, N = 13). Initial fibrosis stage and high diversification of the HVR-1 of HCV genome between the transplantation and the first liver biopsy were independent factors associated with liver fibrosis regression. In conclusion, in this study, after renal transplantation, HCV infection is not harmful upon liver histology in more than fifty percent of the patients. The diversification of the HVR-1 of the HCV genome might be used to predict liver fibrosis outcome.     

A critical assessment of the prognostic value of clear cell,papillary and chromophobe histological subtypes in renal cell carcinoma: a population‐based study

OBJECTIVE

To assess the magnitude of the effect of histological subtype (HS, the three most common being clear cell, papillary and chromophobe) on cause‐specific mortality (CSM) from renal cell carcinoma (RCC).

PATIENTS AND METHODS

Univariable and multivariable Cox regression models included data from 11 618 patients treated with nephrectomy between 1988 and 2004 in nine Surveillance Epidemiology and End Results registries. We tested whether HS represents an independent predictor of CSM, and whether HS adds to the ability of other variables to predict CSM. The covariates comprised age, year of surgery, T stage, nodal status, M stage and Fuhrman grade.

RESULTS

In a multivariable model predicting CSM, HS was an independent predictor (P = 0.03), but failed to improve the accuracy of the model (+0.1% gain when HS was included in the model).

CONCLUSION

Although we confirmed that HS is an independent predictor for CSM, there was no gain in accuracy when HS was added to standard predictors of CSM. From a practical perspective, this implies that patients with clear cell, papillary and chromophobe HS share similar natural histories after nephrectomy, provided that other cancer characteristics are accounted for. From a statistical perspective, in multivariable models of CSM, the clear cell, papillary and chromophobe HS might be included as a single entity.