Long-term Survival After An Aggressive Surgical Approach in Patients With Breast Cancer Hepatic Metastases

Background: Metastatic breast cancer is generally believed to be associated with a poor prognosis. Therapeutic advances over the past two decades, however, have resulted in improved outcomes for selected patients with limited metastatic disease. Methods: Between March 1991 and October 2002, 31 patients had hepatic resection for breast cancer metastases limited to the liver. Clinical and pathologic data were collected prospectively from breast and hepatobiliary databases. Results: Median age of patients was 46 years (range, 31 to 70). Liver metastases were solitary in 20 patients and multiple in 11 patients. Median size of the largest liver metastasis was 2.9 cm (range, 1 to 8). Major liver resections (three or more segments resected) were performed in 14 patients, whereas minor resections (fewer than three segments resected) with or without radiofrequency ablation (RFA) were performed in 17 patients. No postoperative mortality occurred. Of the 31 patients, 27 (87%) received either preoperative or postoperative systemic therapy as treatment for metastatic disease. The median survival was 63 months; a single patient died within 12 months of hepatic resection. The overall 2- and 5-year survival rates were 86% and 61%, respectively, whereas the 2- and 5-year disease-free survival rates were 39% and 31%, respectively. No treatment- or patient-specific variables were found to correlate with survival rates. Conclusions: In selected patients with liver metastases from breast cancer, an aggressive surgical approach is associated with favorable long-term survival. Hepatic resection should be considered a component of multimodality treatment of breast cancer in these patients.     

Using a Theory-Guided Learning Collaborative Model to Improve Implementation of EBPs in a State Children’s Mental Health System: A Pilot Study

Learning collaboratives (LCs) are used widely to promote implementation of evidence-based practices. However, there has been limited research on the effectiveness of LCs and models vary widely in their structure, focus and components. The goal of the present study was to develop and field test a theory-based LC model to augment a state-led, evidence-based training program for clinicians providing mental health services to children. Analysis of implementation outcomes contrasted LC sites to matched comparison sites that participated in the clinical training program alone. Results suggested that clinicians from sites participating in the LC were more highly engaged in the state-led clinical training program and were more likely to complete program requirements.     

Caspase-3 gene deletion prolongs survival in polycystic kidney disease

Pan-caspase inhibition reduces tubular apoptosis and proliferation and slows progression of disease in a rat model of polycystic kidney disease (PKD). It is unknown, however, which specific caspases are involved in PKD progression. Because caspase-3 is a major mediator of apoptosis, its role in autosomal recessive PKD was determined. Mice with caspase-3 gene deletion were crossed with mice harboring the congenital polycystic kidney (cpk) mutation to generate double-mutant mice. cpk;casp3^−/− mice lived nearly 4 times longer than littermate control cpk mice (mean survival of 117 d versus 32 d, P < 0.01), and cpk;casp3^+/− mice lived slightly longer than controls (mean survival of 56 d). In addition, the kidney weight, relative to body weight, was significantly lower in the cpk;casp3^−/− mice than in the cpk and cpk;casp3^+/− mice. Despite deletion of caspase-3, however, apoptosis occurred and cysts formed; therefore, the alternative pathways of apoptosis in cystic kidneys were investigated. Caspase-7 was up-regulated and the anti-apoptotic protein Bcl-2 was down-regulated in cpk, cpk;casp3^+/−, and cpk;casp3^−/− mice compared with wild-type controls. In summary, homozygous deletion of caspase-3 markedly prolongs survival of cpk mice, but a caspase-7-mediated pathway may compensate for the deficiency of functional caspase-3. These findings suggest that pan-caspase inhibition may have a greater therapeutic effect than selective caspase inhibition in PKD.Inherited polycystic kidney disease (PKD) is one of the leading causes of end-stage kidney disease requiring dialysis and kidney transplantation in children and adults.¹ Inherited PKD includes both autosomal dominant and autosomal recessive forms. Autosomal dominant polycystic kidney disease (ADPKD) results from mutations in one of two genes, PKD1 or PKD2. The prevalence of ADPKD varies between 1 in 400 and 1 in 1000, thus making it one of the most common hereditary diseases in the United States. ADPKD progresses to end-stage renal disease (ESRD) over a period of decades in 50% to 75% of affected people. Autosomal recessive polycystic kidney disease (ARPKD) results from a mutation in a single gene, PKHD1. ARPKD is less common, affecting about 1 in 20,000 live births and results in ESRD in childhood.²The congenital polycystic kidney (cpk) mouse is the most extensively characterized mouse model of PKD.² The inheritance, cyst localization in the kidney, and severity of kidney disease in the cpk mouse resembles ARPKD. Cys1, the cpk gene, encodes a cilia-associated protein called cystin that is disrupted in the cpk mouse.³ Increased apoptosis in polycystic kidneys has been described in cpk mice^4–8 as well as in human and other rat and mouse models of PKD.⁹ In support of a deleterious effect of apoptosis in PKD, we have recently demonstrated that pan-caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in the Han:SPRD rat model of PKD.¹⁰ The effect of caspase or apoptosis inhibition in other rat and mouse models of PKD is not known. Caspase-3 is the major mediator of apoptosis (i.e., the so-called “executioner” caspase) and caspase-1 is a pro-inflammatory caspase. However, the effect of inhibition of a specific caspase on PKD is not known. We tested the hypothesis that specific inhibition of caspase-3 would prolong life and reduce cyst formation in PKD.In the present study, we developed cpk mice that were either heterozygous or homozygous for caspase-3 deletion to determine the effect of specific caspase-3 deletion on the development of PKD.     

Long-term outcomes in patients with mucinous, medullary, tubular, and invasive ductal carcinomas after lumpectomy

BACKGROUND: Mucinous, medullary, and tubular carcinomas are uncommon types of breast cancer whose rarity does not permit large single-institution studies or randomized trials to define optimal treatments. In this study, we evaluated the long-term outcomes of breast-conserving therapy (BCT) for these subtypes of breast cancer and compared them with those for invasive ductal carcinoma. METHODS: In our institutional database of patients who received BCT from 1965 to 1999, 1,643 patients with stage I to II mucinous (61), medullary (37), tubular (60), and invasive ductal (1,485) histologies were identified. The clinical and pathologic features of the 4 groups were evaluated and compared with respect to local-regional recurrence rates, disease-free survival, and overall survival (OS). RESULTS: No statistically significant differences were found in the local-regional failure rate among the 4 groups (10.6-year median follow-up). Only patients with tubular carcinoma had better 5- and 10-year OS rates (P = .013). In multivariable analysis, factors associated with improved OS included age at or below 50 years, negative nodal status, use of chemotherapy or hormonal therapy, and tubular histology. CONCLUSIONS: BCT for mucinous, medullary, or tubular carcinoma resulted in similar local-regional failure rates to that for invasive ductal carcinoma. Tubular carcinoma patients had the most favorable OS. BCT is an appropriate treatment strategy for early-stage mucinous, medullary, and tubular carcinomas.     

Post streptococcal acute glomerulonephritis secondary to sporadic <Emphasis Type="Italic">Streptococcus equi</Emphasis> infection

Streptococcus equi subspecies zooepidemicus infection is rare in humans, but a well-known cause of pyogenic disease in cows and horses. S. zooepidemicus uncommonly causes post-strep glomerulonephritis (PSGN) in humans via epidemic outbreaks. We present a sporadic case of post S. zooepidemicus glomerulonephritis in a child most probably contracted from a horse. The 14-year-old girl presented with the typical signs of PSGN, with S. equi zooepidemicus isolated from a blood culture, together with a low C3 and raised anti-DNAse B. This is the first known report of a sporadic case of PSGN in a child caused by this organism.     

Predictors of locoregional recurrence among patients with early-stage breast cancer treated with breast-conserving therapy

Background Our aim was to identify predictors of locoregional recurrence (LRR) in patients with early-stage breast cancer treated with breast-conserving therapy (BCT) and long-term follow-up. Methods From 1970 to 1994, 1153 patients with stage I to II breast cancer underwent BCT and radiotherapy at our institution. Patients with prior breast cancer or other primary malignancies were excluded. Clinical and pathologic characteristics evaluated were age, race, tumor size, stage, pathologic tumor margins, axillary nodal involvement, estrogen and progesterone receptor status, Black's nuclear grade, type of surgery, and use of adjuvant therapy. Results Of 1083 patients, 54% presented with stage I disease and 46% with stage II disease. Median age was 50 years, and median follow-up was 9 years. Axillary nodes were positive in 31% of the patients who underwent axillary dissection. LRR developed in 6%, LRR followed by systemic recurrence in 5%, and systemic recurrence alone in 13%, 76% had no evidence of recurrence at last follow-up. Age, tumor size, positive lymph nodes, and not receiving chemotherapy or hormonal therapy were independent predictors of LRR. Disease-specific survival among patients with LRR was similar to that among patients with no recurrence. Conclusions Multidisciplinary treatment strategies should be used to accomplish durable locoregional control after BCT. Presented at the 54th Annual Cancer Symposium of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.     

Long-term complications associated with breast-conservation surgery and radiotherapy

Background Breast-conservation surgery plus radiotherapy has become the standard of care for early-stage breast cancer; we evaluated its long-term complications. Methods We selected patients treated with surgery and radiotherapy between January 1990 and December 1992 (an era in which standard radiation dosages were used) with follow-up for at least 1 year. Patients were prospectively monitored for treatment-related complications. Median follow-up time was 89 months. Results A total of 294 patients met the selection criteria. Grade 2 or higher late complications were identified in 29 patients and included arm edema in 13 patients, breast skin fibrosis in 12, decreased range of motion in 4, pneumonitis in 2, neuropathy in 2, fat necrosis in 1, and rib fracture in 1. Arm edema was more common after lumpectomy plus axillary node dissection than after lumpectomy alone. Arm edema occurred in 18% of patients who underwent surgery plus irradiation of the lymph nodes and 10% who underwent surgery without nodal irradiation. Conclusions Breast-conservation surgery plus radiotherapy was associated with grade 2 or higher complications in only 9.9% of patients. Half of these complications were attributable to axillary dissection, it is hoped that lower complication rates can be achieved with sentinel lymph node biopsy.     

The combination of purified recombinant human platelet-derived growth factor-BB and equine particulate bone graft for periodontal regeneration

Background: The objective of this study is to evaluate the potential for periodontal regeneration of a critical‐sized defect with the application of recombinant human platelet‐derived growth factor (rhPDGF‐BB) combined with either a particulate equine or a β‐tricalcium phosphate (β‐TCP) matrix. Methods: Critical‐sized intrabony 2‐wall defects were created bilaterally on the distal surface of the second premolar and the mesial surface of the first molar in nine hounds. Twelve defects received rhPDGF‐BB/equine treatment, 12 defects received rhPDGF‐BB/β‐TCP treatment, and the remaining 12 sites served as sham‐surgery controls. The animals were sacrificed after a 10‐week healing period. Results: Clinical healing was uneventful without obvious signs of overt gingival inflammation. Histologic and histomorphometric analyses revealed statistically that there were differences among the three groups in terms of new bone formation (P <0.001). The amount of test material for both rhPDGF‐BB/equine and rhPDGF‐BB/β‐TCP groups was comparable, but the amount of newly formed bone was significantly higher (P <0.01) in favor of the rhPDGF‐BB/equine group. The amount of new cementum formed for the rhPDGF‐BB/equine group (4.8 ± 1.3 mm) was significantly higher (P =0.001) than the sham‐surgery control group (1.7 ± 1.9 mm). Conclusion: Both rhPDGF‐BB/equine and rhPDGF‐BB/β‐TCP have the potential to support the regeneration of the periodontal attachment apparatus.