Feasibility study: watchful waiting for localized low to intermediate grade prostate carcinoma with selective delayed intervention based on prostate specific antigen, histological and/or clinical progression

PURPOSE: We assessed the feasibility of a watchful waiting protocol with selective delayed intervention using clinical, prostate specific antigen (PSA) or histological progression as treatment indications for clinically localized prostate cancer. MATERIALS AND METHODS: In this prospective, single arm cohort study patients with favorable clinical parameters (stage T1b to T2b N0M0, Gleason score 7 or less and PSA 15 ng./ml. or less) are conservatively treated with watchful waiting. When a patient meets disease progression criteria, arbitrarily defined by the 3 parameters of the rate of PSA increase, clinical progression or histological upgrade on repeat prostate biopsy, appropriate treatment is implemented. Patients are followed every 3 months for the first 2 years and every 6 months thereafter. Serum PSA measurement and digital rectal examination are done at each visit and repeat prostate biopsy is performed 18 months after study enrollment. RESULTS: Since November 1995, the study has accrued 206 patients with a median followup of 29 months (range 2 to 66). Of these men 137 remain on the surveillance protocol with no disease progression, while 69 were withdrawn from study for various reasons. There was clinical, PSA and histological progression in 16, 15 and 5 cases, respectively. The estimated actuarial probability of remaining on the surveillance protocol was 67% at 2 years and 48% at 4. The probability of remaining progression-free was 81% and 67% at 2 and 4 years, respectively. CONCLUSIONS: A policy of watchful waiting with selectively delayed intervention based on predefined criteria of disease progression is feasible. This strategy offers the benefit of an individualized approach based on the demonstrated risk of clinical or biochemical progression with time and, thus, it may decrease the burden of therapy in patients with indolent disease, while providing definitive therapy for those with biologically active disease.     

Positive predictive value of maximal posterior joint-line tenderness in diagnosing meniscal pathology: a pilot study

OBJECTIVE: The purpose of this prospective study was to determine the positive predictive value (PPV) of the point of maximal posterior joint line tenderness (JLT), as a clinical sign, to diagnose underlying meniscal tears. METHODS: We conducted a prospective study of patients requiring arthroscopic surgery, who consecutively presented to the University of Calgary's Sport Medicine Centre. The femurotibial joint line was palpated for the point of maximal tenderness. We recorded the data on the arthroscopy report. A second examiner (orthopedic sport medicine surgical fellow or sport medicine physician) performed the same protocol. An arthroscopist documented the site of pathology as detected by arthroscopy. RESULTS: We found a PPV of 60.0% and a negative predictive value of 62.5%, suggesting that maximal posterior JLT may be predictive of meniscal pathology. The sensitivity and specificity were 84.6% and 31.2%, respectively (p = 0.155), with Fisher's exact test. The kappa score assessed interobserver reliability and was good at 0.48. Patients with maximal posterior JLT but no meniscal pathology did have other confounding pathology and patients with no maximal posterior JLT who had meniscal pathology usually had confounding knee pathology. CONCLUSIONS: We found a PPV of 60.0% of maximal posterior JLT and meniscal pathology located at the same anatomical site on arthroscopic examination.     

Prognostic Index for Extremity Soft Tissue Sarcomas With Isolated Local Recurrence

Background: Local recurrence occurs in 10% to 20% of patients with extremity soft tissue sarcomas despite optimal treatment. The association of local recurrence with subsequent survival is controversial and conflicting. There is a need for a staging system to predict outcome in this subset of patients and also to plan optimal treatment, including adjuvant systemic therapy.Methods:Data collected from 110 patients with locally recurrent extremity soft tissue sarcomas were studied. The influence of clinical and pathologic factors on local recurrence, distant metastasis, and disease-specific survival were analyzed by univariate and multivariate techniques.Results: Of the 110 patients who presented with local recurrence, 92 had an isolated local recurrence and 18 had prior or concomitant distant metastases. The 5-year disease-specific survival for all patients was 63% and for those with isolated local recurrence, it was 69%. Histologic grade, malignant fibrous histiocytoma histology, pathologic margins, previous local recurrence, and prior radiotherapy were independent prognostic factors for subsequent local recurrence. Tumor size, histologic grade, and time to local recurrence were independent prognostic factors for distant metastasis and disease-specific survival. A prognostic index was calculated by assigning a score of 1 to 3 for each of the three independent prognostic factors for survival and added to give the prognostic index for each patient. As the prognostic index increased from 3 to 9, there was a progressive increase in the hazard ratios and a corresponding deterioration in survival. The patients were then categorized into three prognostic groups based on the hazard ratios for disease specific survival. The differences in the survival curves were highly statistically significant (P < .0001).Conclusions: Tumor size, histologic grade, and time to local recurrence are the primary determinants of distant metastases and survival in locally recurrent extremity soft tissue sarcomas. The impact of local recurrence on survival varies considerably. The nature of the local recurrence, rather than its presence per se, is a more useful guide to prognosis. We propose a simple staging system based on size, grade, and time to recurrence that correlates extremely well with prognosis and may serve as a guide to make therapeutic decisions in patients with locally recurrent extremity soft tissue sarcomas.     

Safe surgical technique: reconstruction of the sternoclavicular joint for posttraumatic arthritis after posterior sternoclavicular dislocation

Posttraumatic sternoclavicular arthritis related to chronic ligamentous instability after posterior sternoclavicular dislocation represents a rare but challenging problem. The current article in the Journal’s “Safe Surgical Technique” series describes a successful salvage procedure by partial resection of the medial clavicle and ligamentous reconstruction of the sternoclavicular joint with a figure-of-eight semitendinosus allograft interposition arthroplasty.     

‘Aggressive papillary’ thyroid microcarcinoma

The objective of this study is to highlight the fact that papillary thyroid microcarcinoma can be aggressive, requiring therapeutic management similar to that of other differentiated thyroid cancers. This 8-year retrospective study concerned 187 surgical patients managed in an ENT and Head and Neck surgery department for thyroid cancer. 65 patients were found to have papillary microcarcinoma. 41 microcarcinomas were considered to be aggressive because of the presence of several risk factors such as larger than 5 mm, multifocal microcarcinomas, capsular effraction, vascular embolus, tumour extension beyond the thyroid parenchyma and metastatic lymphadenopathy. All patients with aggressive papillary microcarcinoma were treated by total thyroidectomy and ¹³¹I. Ipsilateral recurrent laryngeal and lateral cervical lymph node dissections were performed in ten patients, ipsilateral cervical lymph node dissection was performed in six patients and bilateral recurrent laryngeal and lateral cervical lymph node dissections were performed in three patients. No recurrence or metastasis was observed (follow-up ranging from 6 months to 8 years). The optimal management of thyroid papillary microcarcinoma is still controversial. “Aggressive” papillary thyroid microcarcinoma is not rare and may justify aggressive treatment depending on the presence or absence of prognostic risk factors.     

Successful heart transplantation following melphalan plus dexamethasone therapy in systemic AL amyloidosis

Recurrence in the allograft and progression in other organs increase mortality after cardiac transplantation in AL amyloidosis. Survival may be improved after suppression of monoclonal light chain (LC) production following high dose melphalan and autologous stem cell transplantation (HDM/ASCT). However, because of high treatment related mortality, this tandem approach is restricted to few patients without significant extra-cardiac involvement. A diagnosis of systemic AL amyloidosis was established in a 45-year old patient with congestive heart failure related to restrictive cardiomyopathy, nephrotic syndrome, peripheral neuropathy, postural hypotension, macroglossia, and lambda LC monoclonal gammopathy. After melphalan and dexamethasone (M-Dex) therapy, which resulted in 80% reduction of serum free lambda LC, he underwent orthotopic cardiac transplantation. Two years later, he remains in a sustained hematologic remission, with no evidence of allograft or extra-cardiac amyloid accumulation. M-Dex should be considered as an alternative therapy in AL amyloid heart transplant recipients ineligible for HDM/ASCT.     

Influence of data filtering on reliability of respiratory impedance and derived parameters in children

Forced oscillation impedance (Zrs) measurements are frequently corrupted by noisy data in children. Our aim was to improve the reliability of respiratory resistance (Rrs) and routine identification of its flow (V') and volume (V) dependence during tidal breathing, according to Rrs = K1 + K2 x /V'/ + K3 x V. Zrs was measured at 12 Hz, using a head generator in 23 children aged 4-13 years undergoing methacholine (Mch) challenge. Rrs, K1, K2, K3, and residual mean square error (RMSD), as well as reproducibility of the parameters, were obtained. Calculations were performed separately in inspiration and expiration on the raw data, and after eliminating values lying outside confidence intervals ranging from 99% (F3SD) to 95% (F2SD) of the mean Zrs. Filtering decreased RMSD and Rrs, F3SD improved reproducibility of Rrs in expiration compared to raw data. F2SD increased K1 and decreased the amplitude of K2 and K3 before and after Mch compared to F3SD. Rrs and K2 were significantly larger and K3 significantly more negative in expiration than in inspiration at all levels of filtering, probably because of the upper airways. F3SD appeared efficient in eliminating aberrant data, while allowing the identification of physiological variations of Rrs.     

Low-grade Sarcomas with CD34-Positive Fibroblasts and Low-Grade Myofibroblastic Sarcomas

A subset of low-grade fibrosarcomas is composed of CD34-positive spindle cells. These include dermatofibrosarcoma, its morphologic variants, and its associated fibrosarcoma, solitary fibrous tumor, hemangiopericytoma and their malignant counterparts, and some cases of myxoinflammatory fibroblastic sarcoma. Dermatofibrosarcoma and related lesions are characterized by a t(17;22)(q22;q13) rearrangement resulting in fusion of the genes COL1A (17q21-22) and PDGFB1 (22q13). Solitary fibrous tumor displays varying cellularity and fibrosis and a peripheral hemangiopericytomatous pattern; most tumors formerly called hemangiopericytoma are now subsumed into the category of solitary fibrous tumor, although a few strictly defined examples are recognized; however, these are probably not composed of pericytes. Myofibroblastic malignancies are best identified by electron microscopy, with which varying degrees of differentiation, including the presence of fibronexus junctions, can be identified. Low-grade sarcomas showing myofibroblastic differentiation include myofibrosarcomas and inflammatory myofibroblastic tumors. Myofibrosarcomas are spindle cell neoplasms that occur in children or adults in the head and neck, trunk, and extremities as infiltrative neoplasms and that display a fascicular or fasciitis-like pattern with focal nuclear atypia and variable expression of myoid antigens. These sarcomas are prone to recurrence and a small number metastasize. Inflammatory myofibroblastic tumor (synonymous with inflammatory fibrosarcoma) is a neoplasm arising predominantly in childhood, and frequently in intraabdominal locations. It has spindle cells in fascicular, fasciitis-like and sclerosing patterns, with heavy chronic inflammation including abundant plasma cells. Many IMT have clonal chromosomal abnormalities involving 2p22-24, and fusion of the ALK gene with tropomyosin 3 (TPM3-ALK) or tropomyosin 4 (TPM4-ALK) is found in a subset.