Current role of scapulectomy

Tumors of the scapula are an unusual clinical challenge. Partial or complete resection of the scapula, with its attached musculoaponeurotic tissue, is a seldom used technique for the treatment of primary bone and soft tissue tumors, as well as selected metastatic involvement of the scapula. Scapulectomy may allow wide margins of resection without amputation. The purpose of this study is to review our recent experience with scapulectomy. This study describes the recent experience with scapulectomy by the Section of Surgical Oncology and the Department of Orthopedics at Louisiana State Medical Center (New Orleans, LA). Between 1994 and 1998, 12 patients (between 16 and 79 years of age) underwent a resection of the scapula. Eleven of these patients had soft tissue tumors; one had a metastasis from a thyroid carcinoma. Six of these patients underwent a scapulectomy as a primary treatment, five for recurrence. Six patients also received postoperative radiation and/or chemotherapy. The follow-up ranged from 6 months to 4 years. There was no mortality or wound infection associated with scapulectomy. All patients had normal hand and wrist function after surgery. Three distant recurrences occurred, with no local or regional failures encountered during the follow-up period. Scapulectomy can result in excellent local tumor control. Whereas some loss of active shoulder motion may occur, hand, wrist and elbow function is preserved. Although maintenance of shoulder function should not take precedence over adequacy of resection, scapulectomy remains an excellent procedure for malignant disease that preserves hand, wrist, and elbow function.     

Effect of a long-term low tryptophan diet on the prolactin responses to the 5-HT1A and 5-HT2C agonists, 8-OH-DPAT and mCPP in the male rat

The study was undertaken to assess the long term effects of tryptophan (TRP) depletion through diet on the prolactin (PRL) responses to the serotonin (5-hydroxytryptophan, 5-HT) agonists m-chlorophenyl-piperazine (mCPP) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in the male rat. The low TRP diet caused significant reductions in both plasma total TRP and brain cortical 5-HT content together with a significant increase in the PRL responses to mCPP. In contrast the PRL responses to 8-OH-DPAT in animals on the low TRP diet for 1 week and 6 weeks were similar to control rats. However, a small but significant increase in PRL was observed at 2 min after dosing in the 1-week group. At the same time the 3H-8-OH-DPAT binding parameters, Kd and Bmax, were similar in both control and TRP depleted animals. The results confirm that long-term TRP depletion causes a deficiency of brain TRP and a subsequent reduction of brain 5-HT. This is associated with an enhanced PRL response to mCPP probably resulting from a functional up-regulation of post-synaptic 5-HT2C receptors. The small or transient changes brought about by long-term TRP depletion on post-synaptic 5-HT1A receptors, suggests that these receptors may be less susceptible to 5-HT depleting effects than the 5-HT2C subtype.     

Management of ischemic nephropathy: dialysis-free survival after surgical repair

PURPOSE: This retrospective review describes the surgical management of consecutive patients with severe hypertension and ischemic nephropathy due to atherosclerotic renovascular disease. METHODS: From January 1987 through December 1998, a total of 590 patients underwent operative renal artery repair at our center. A subgroup of 232 hypertensive patients (97 women, 135 men; mean age, 66 +/- 8 years) with atherosclerotic renovascular disease and preoperative serum creatinine levels of 1.8 mg/dL or more forms the basis of this report. Change in renal function was determined from glomerular filtration rates estimated from preoperative and postoperative serum creatinine. The influence of selected preoperative parameters and renal function response on time to dialysis and dialysis-free survival was determined by a proportional hazards regression model. RESULTS: In all, 83 patients underwent unilateral renal artery repair and 149 patients underwent bilateral repair, including repair to a solitary kidney in 17 cases. A total of 332 renal arteries were reconstructed, and 32 nephrectomies were performed in these patients. After surgery, there were 17 deaths (7.3%) in the hospital or within 30 days of surgery. Advanced patient age (P =.001; hazard ratio, 1.1; 95% CI [1.1, 1.2]) and congestive heart failure (P =.04; hazard ratio, 2.9 CI [1.0, 8.6]) demonstrated significant and independent associations with perioperative mortality. With a change of 20% or more in EGFR being considered significant, 58% of patients had improved renal function, including 27 patients removed from dialysis dependence; function was unchanged in 35% and worsened in 7%. Follow-up death from all causes or progression to dialysis dependence demonstrated a significant and independent association with early renal function response. Both patients whose function was unchanged (P =.005; hazard ratio, 6.0; CI [2.2, 16.6]) and patients whose function was worsened (P =.03; hazard ratio, 2.2; CI [1.1, 4. 5]) remained at increased risk of death or dialysis dependence. For patients with unchanged renal function after operation, risk of death or dialysis demonstrated a significant interaction with preoperative renal function. In addition to severe preoperative renal dysfunction, diabetes mellitus demonstrated a significant and independent association with follow-up death or dialysis. CONCLUSION: Surgical correction of atherosclerotic renovascular disease can retrieve excretory renal function in selected hypertensive patients with ischemic nephropathy. Patients with improved renal function had a significant and independent increase in dialysis-free survival in comparison with patients whose function was unchanged and patients whose function was worsened after operation. These results add further evidence in support of a prospective, randomized trial designed to define the value of renal artery intervention in patients with ischemic nephropathy.     

Overexpression of the receptor tyrosine kinase Tie-1 intracellular domain in breast cancer.

OBJECTIVE: Tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Tie-1) is a receptor tyrosine kinase that regulates angiogenesis and antiapoptotic survival signaling. Tie-1 expression is generally associated with endothelial cells and neovascularization. We previously identified Tie-1 in human breast tumor samples using a PCR-based screen for protein kinases expressed in breast tumors. The purpose of this study was to determine the cell types expressing Tie-1, whether Tie-1 is expressed in tumor cells, and to examine the regulation of Tie-1 in breast cancer. METHODS: Tie-1 expression was analyzed by Western blot and immunohistochemistry using an antibody to the carboxy terminus of Tie-1. Tie-1 expression was determined in a variety of cancer cell lines, clinical breast and colon tumor samples, and in corresponding benign tissue from the same patient. Tie-1 expression and distribution in breast tumors was scored by immunohistochemistry. RESULTS: Tie-1 was overexpressed in 14/23 breast tumors compared with 0/9 corresponding normal tissues from the same patients. Immunohistochemistry revealed that Tie-1 was overexpressed in epithelial breast cancer cells and ductal carcinoma in situ. In all breast tumor samples, Tie-1 was expressed as a truncated 40- to 43-kD doublet consisting of the intracellular portion of the protein, which contains the tyrosine kinase catalytic domain. The 40- to 43-kD Tie-1 doublet was expressed in a broad variety of cell lines. CONCLUSIONS: We have shown that breast cancer cells overexpress a cleaved form of the Tie-1 protein. Our results implicate the intracellular domain of Tie-1, which includes the catalytic kinase domain, in breast cancer progression.     

Exploring the decision-making preferences of people with colorectal cancer

OBJECTIVES: To explore patient views on participation in treatment, physical care and psychological care decisions and factors that facilitate and hinder patients from making decisions. DESIGN: Qualitative study using semi-structured interviews with patients. SETTING AND PARTICIPANTS: Three NHS Trusts in the north-west of England. Theoretical sampling including 41 patients who had been treated for colorectal cancer. RESULTS: For patients, participation in the decision-making process was about being informed and feeling involved in the consultation process, whether patients actually made decisions or not. The perceived availability of treatment choices (surgery, radiotherapy, chemotherapy) was related to type of treatment. Factors that impacted on whether patients wanted to make decisions included a lack of information, a lack of medical knowledge and trust in medical expertise. Patients perceived that they could have a more participatory role in decisions related to physical and psychological care. CONCLUSION: This study has implications for health professionals aiming to implement policy guidelines that promote patient participation and shared partnerships. Patients in this study wanted to be well informed and involved in the consultation process but did not necessarily want to use the information they received to make decisions. The presentation of choices and preferences for participation may be context specific and it cannot be assumed that patients who do not want to make decisions about one aspect of their care and treatment do not want to make decisions about other aspects of their care and treatment.     

Overexpression of the cytochrome p450 activator hpr6 (heme-1 domain protein/human progesterone receptor) in tumors.

OBJECTIVE: Hpr6 (heme-1 domain protein/human progesterone receptor) is one of a family of proteins that are implicated in progesterone metabolism, resistance to genotoxic agents and steroid biosynthesis. Because these processes are frequently misregulated in tumors, we have examined the expression of Hpr6 in a group of clinical tumor samples and cancer cell lines. METHODS: Hpr6 expression was analyzed by Western blot in extracts from breast, cervix, colon and thyroid cell lines and in nonmalignant and adjacent tumor tissue from breast, colon and thyroid. Hpr6 localization was determined by immunofluorescence. RESULTS: Hpr6 expression is significantly elevated in breast tumors in comparison with matched nonmalignant tissue and demonstrated limited overexpression in colon and thyroid tumors. Hpr6 is strongly expressed in a panel of tumor cell lines originating from breast, thyroid and colon. Hpr6 localizes to the perinuclear region of the cell, consistent with a role in cell detoxification, signaling and/or sterol synthesis. CONCLUSIONS: Hpr6 homologues regulate cytochrome P450 proteins implicated in hormone, steroid and xenobiotic chemical metabolism. These are the first studies linking Hpr6 expression to cancer progression and cellular survival. Our results suggest that Hpr6 is an important marker for cancer progression and a potential anticancer therapeutic target.     

Magnetic Resonance Imaging Biomarkers in Patients with Progressive Ataxia: Current Status and Future Direction

A diagnostic challenge commonly encountered in neurology is that of an adult patient presenting with ataxia. The differential is vast and clinical assessment alone may not be sufficient due to considerable overlap between different causes of ataxia. Magnetic resonance (MR)-based biomarkers such as voxel-based morphometry, MR spectroscopy, diffusion-weighted and diffusion-tensor imaging and functional MR imaging are gaining great attention for their potential as indicators of disease. A number of studies have reported correlation with clinical severity and underlying pathophysiology, and in some cases, MR imaging has been shown to allow differentiation of conditions causing ataxia. However, despite recent advances, their sensitivity and specificity vary. In addition, questions remain over their validity and reproducibility, especially when applied in routine clinical practice. This article extensively reviews the current literature regarding MR-based biomarkers for the patient with predominantly adult-onset ataxia. Imaging features characteristic of a particular ataxia are provided and features differentiating ataxia groups and subgroups are discussed. Finally, discussion will turn to the feasibility of applying these biomarkers in routine clinical practice.     

Diagnosis and Treatment of Mitochondrial Myopathies

Mitochondrial myopathies are progressive muscle conditions caused primarily by the impairment of oxidative phosphorylation (OXPHOS) in the mitochondria. This causes a deficit in energy production in the form of adenosine triphosphate (ATP), particularly in skeletal muscle. The diagnosis of mitochondrial myopathy is reliant on the combination of numerous techniques including traditional histochemical, immunohistochemical, and biochemical testing combined with the fast-emerging molecular genetic techniques, namely next-generation sequencing (NGS). This has allowed for the diagnosis to become more effective in terms of determining causative or novel genes. However, there are currently no effective or disease-modifying treatments available for the vast majority of patients with mitochondrial myopathies. Existing therapeutic options focus on the symptomatic management of disease manifestations. An increasing number of clinical trials have investigated the therapeutic effects of various vitamins, cofactors, and small molecules, though these trials have failed to show definitive outcome measures for clinical practice thus far. In addition, new molecular strategies, specifically mtZFNs and mtTALENs, that cause beneficial heteroplasmic shifts in cell lines harboring varying pathogenic mtDNA mutations offer hope for the future. Moreover, recent developments in the reproductive options for patients with mitochondrial myopathies mean that for some families, the possibility of preventing transmission of the mutation to the next generation is now possible.     

Left ventricular pseudoaneurysm after mitral valve replacement

Development of left ventricular pseudoaneurysm is a rare complication of mitral valve surgery and requires urgent surgical intervention. We describe a case of pseudoaneurysm of membranous septum following repeat mitral valve replacement with the use of multimodality imaging.