Immunomagnetic enrichment and detection of isolated tumor cells in bone marrow of patients with epithelial malignancies

The detection of isolated tumor cells (ITC) in the bone marrow of patients with epithelial malignancies is an independant prognostic factor for several entities as breast cancer, colorectal cancer or non-small lung cancer. However, with conventional immunocytology using Ficoll density gradient and APAAP staining, only a small proportion of the bone marrow samples can be scanned for cytokeratin-positive (CK+) cells. To improve detection rates, we evaluated the enrichment of ITC by magnetic activated cell sorting (MACS) compared to regularly stained cytospins. Recovery experiments with a CK+ breast cancer cell line (SKBR3) were performed to calculate the MACS enrichment rate. Bone marrow was obtained by aspiration from 20 patients with carcinomas of epithelial origin and from 17 controls. ITC were enriched and stained with magnetically labeled CAM 5.2 antibodies directed to cytokeratin 7 and 8. MACS of SKBR3 seeded in peripheral blood revealed average recovery rates of 62% and 48% and average enrichment factors of 104-fold and 8139-fold of the CK+ cells after one and after two separations, respectively. After immunomagnetic enrichment, CK+ cells were detected in 16 of 20 (80%) cancer patients, whereas only 7 (35%) patients showed CK+ cells without magnetic enrichment (P=0.002). Ten of twelve (83%) patients with metastatic disease (stage M₁) and six of eight (75%) patients without any overt metastases (M₀) had CK+ cells in their bone marrow. None of the negative controls showed any CK+ cells. Enrichment with magnetically labeled anti cytokeratin antibodies increases the detection rate of epithelial cells in bone marrow of cancer patients compared to immunocytology. This revised version was published online in July 2006 with corrections to the Cover Date.     

Pigmented adrenocortical carcinoma: Case report and review

Darkly pigmented adrenocortical neoplasms are rare tumors that are often referred to as “black adenomas,” indicative of both their pigmented nature and their invariably benign clinical behavior in previously reported cases. We herein describe an exceptional case of a malignant pigmented adrenocortical neoplasm, with late recurrence and metastasis. At age 53, this female patient was diagnosed with Cushing's syndrome and underwent a laparoscopic right adrenalectomy, revealing a 3 cm well-circumscribed, darkly pigmented adrenocortical tumor. The tumor exhibited several atypical histologic features and was diagnosed as an atypical pigmented adrenal cortical neoplasm of uncertain malignant potential. Eight years later, the patient developed clinical and biochemical evidence of recurrent Cushing's syndrome, and imaging studies revealed the presence of several masses in the right retroperitoneum. At subsequent exploratory laparotomy, three separate tumor nodules exhibiting varying degrees of pigmentation and ranging from 2.2 to 3.3 cm maximum dimension were excised. Histologically, the tumor nodules were consistent with local recurrence/metastasis of the patient's previously excised pigmented adrenocortical neoplasm.     

What do clinicians derive from partnering with their patients?: A reliable and valid measure of “personal meaning in patient care”

Objective

Burnout is high among clinicians and may relate to loss of “meaning” in patient care. We sought to develop and validate a measure of “personal meaning” that practitioners derive from patient care.

Methods

As part of a larger study of well-being among genetics professionals, we conducted three focus groups of clinical genetics professionals: physicians, nurses and genetic counselors (N = 29). Participants were asked: “What gives you meaning in patient care?” Eight themes were identified, converted into Likert items, and included in a questionnaire. Next, we mailed the questionnaire to clinical geneticists, genetic counselors and genetic nurses (N = 480) randomly selected from mailing lists of their professional associations. Results were subjected to exploratory factor analysis. The survey also included validated scales of burnout and professional satisfaction, and a 1-item measure of gratitude, to assess predictive validity.

Results

214 eligible providers completed the survey out of an estimated 348 eligible (61% response rate). Factor analysis resulted in a unidimensional scale consisting of 6-items with an alpha of 0.82 and an eigen value of 3.2. Factor loadings ranged from 0.69–0.77. The mean total score was 18.1 (S.D. 3.7) out of a possible high score of 24. Higher meaning scores were associated with being female (p = 0.044), a nurse (p < 0.001), and in practice longer (p = 0.006). Meaning scores were inversely correlated with burnout (p < 0.001), and positively correlated with gratitude (p < 0.001) and professional satisfaction (p < 0.022).

Conclusion

The 6-item “personal meaning in patient care” scale demonstrates high reliability and predictive validity in a select group of health professionals. Future research should validate this scale in a broader population of clinicians.

Practice implications

The scale could be useful in identifying providers at risk of burnout, and in evaluating interventions designed to counteract burnout, enhance meaning and improve communication and partnership between providers and patients.     

Effect of finasteride, a 5 alpha-reductase inhibitor on prostate tissue androgens and prostate-specific antigen.

Whole tissue dihydrotestosterone (DHT) and testosterone (T) concentrations have been measured after finasteride, a 5 alpha-reductase inhibitor, and this was compared to other methods of androgen inhibition. In 10 patients treated for 1 week with finasteride, whole tissue DHT decreased to a mean of 0.302 ng/g. This value was significantly less than DHT values in control patients (mean, 4.5 ng/g) and patients treated with either surgical castration (mean, 1.14 ng/g), megestrol (160 mg/day) plus diethylstilbestrol (0.1 mg), or megestrol plus ketoconazole (1200 mg/day; mean, 0.609). Tissue T levels were significantly increased in finasteride-treated patients (1.18 ng/g) compared to a mean of 0.171 ng/g in controls and 0.105 ng/g in megestrol-treated patients. Part of the prostate tissue obtained at surgery was mechanically separated into epithelium and stroma. The epithelial cells were homogenized, the supernate was assayed for prostate-specific antigen (PSA), an androgen-dependent protein, and the pellet was assayed for DHT and DNA. Epithelial cell PSA and DHT values significantly decreased in finasteride- and megestrol- plus estrogen-treated patients compared to controls. However, the slope and position of the regression lines for DHT vs. PSA in patients treated with megestrol plus low dose estrogen (r = 0.79) differed significantly (P less than 0.05) from the regression line relating epithelial DHT to PSA in patients treated with finasteride (r = 0.82). Since the regression slope for finasteride described a greater increase in PSA per unit change in DHT compared to the slope for megestrol plus estrogen, which lowers both DHT and T, finasteride, despite its drastic lowering of DHT, may have a modest residual androgenic effect related to its effect on tissue T.     

The National Polyp Study. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas

The National Polyp Study (NPS), a randomized clinical trial to evaluate effective surveillance of patients discovered to have one or more colorectal adenomas, was the framework for this statistical analysis which used a multiple logistic model to assess the independent risk factors of patient and polyp characteristics associated with high-grade dysplasia in adenomas. The database included 3371 adenomas from 1867 patients. Adenoma size and the extent of the villous component were found to be the major independent polyp risk factors associated with high-grade dysplasia (p less than 0.0001). The adjusted odds ratios were 3.3 for medium-sized adenomas and 7.7 for large adenomas relative to small adenomas and 2.7 for villous A adenomas, 3.4 for villous B adenomas, and 8.1 for villous C and D adenomas relative to tubular adenomas. Increased frequency of high-grade dysplasia in adenomas located distal to the splenic flexure was attributable mainly to increased size and villous component rather than to location per se. The adjusted odds ratio was 1.4 (p less than 0.11) for left-sided location. Multiplicity of adenomas affected the risk for high-grade dysplasia in patients but was dependent on adenoma size and villous component and was not an independent factor. The adjusted odds ratio was 1.3 (p less than 0.17) for multiplicity. Increasing age was associated with risk for high-grade dysplasia in patients, and this effect was independent of the effect of adenoma size and histological type. The adjusted odds ratio was 1.8 (p less than 0.0016) for age greater than or equal to 60 yr. Gender was not associated with high-grade dysplasia. The adjusted odds ratio was 1.0 (p less than 0.95) for men. The size of the patient series, the prospective nature of the data collection, the completeness of information on all patients, the requirements of complete examination of the entire colon and pathological examination of all lesions encountered, and the exclusion of patients with previously diagnosed adenomas are, collectively, features unique to this study. The detailed model provided by the analysis integrates multiple patient and adenoma factors associated with high-grade dysplasia in colorectal adenomas.     

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis

Lymphoblasts in bone marrow samples, obtained from 43 children with acute lymphoblastic leukemia at diagnosis, were incubated with 1.0 mumols/L [3H] methotrexate for 24 hours in vitro. Nonexchangeable methotrexate and methotrexate polyglutamates were separated and quantitated. Event-free survival at 5 years was 38% +/- 9% for all 43 patients (27 failures), and 44% +/- 10% for the 35 with non-T, non-B- cell acute lymphoblastic leukemia (20 failures). Of these 35 children, those whose lymphoblasts accumulated more than 100 pmol methotrexate and 500 pmol methotrexate polyglutamates per billion cells experienced better 5-year event-free survival than those whose lymphoblasts did not (65% +/- 12% v 22% +/- 9%, P = .010). This difference characterized "good-risk" patients who were female (P = .014), less than age 7 at diagnosis (P = .005), or had low initial white blood cell counts (less than 20 X 10(9)/L, P = .018). Findings were similar for the 43 children with acute lymphoblastic leukemia and for the "good-risk" children in this total group. Thus, the ability of lymphoblasts to accumulate methotrexate and form methotrexate polyglutamates may be important to the curative properties of current therapy of acute lymphoblastic leukemia in children, particularly for "good-risk" patients. In such patients, inherent rather than acquired drug resistance may be the initial event leading to treatment failure.     

Aggressively recurrent infantile myofibroma of the axilla and shoulder girdle

Infantile myofibroma is the most common fibrous tumor of infancy, typically affecting neonates and children under 2 years of age. Though the multicentric variant portends a grave prognosis, solitary lesions have an excellent prognosis and frequently undergo spontaneous regression. Surgical excision of solitary lesions is usually curative. In this report, we describe a pediatric patient with an unusually aggressive solitary myofibroma of the axilla who ultimately required a forequarter amputation as a lifesaving measure following multiple tumor recurrences and progressive tumor growth. The clinical course, radiographic findings, histology, and management rationale are presented.     

Recovery Services and Outcomes in a State Psychiatric Hospital

Recovery has emerged as a focus of mental health rehabilitation in the past decade. Many have suggested that various domains of recovery-orientated services are integrated to an efficacious mental health care system. In this study we examined the association of domains of recovery-oriented services with recovery outcomes among inpatients in a state psychiatric hospital. A convenience sample of 36 hospital patients participated in a survey that included two standardized scales, with one measuring 6 domains of recovery-orientation of hospital-based services and one measuring 5 aspects of patients’ recovery outcomes. We used regression analysis to estimate the association between recovery-oriented services and recovery outcomes adjusting for gender, race, and education. Nearly 90% of patients had lengths of stay of more than 3 months. On average, patients reported receiving moderate levels of recovery-oriented services. Nevertheless those who reported receiving higher levels of recovery-oriented services also reported better recovery outcomes. Specifically three domains of recovery-oriented services, i.e., life goal vs. symptom management, individual tailored, and diversity of treatment options, are associated with better overall recovery and 3 specific aspects of recovery, namely willingness to ask for help, goal and success orientation, and reliance on others. The data from a small sample of patients at a state psychiatric hospital suggest that self-reported recovery-oriented services received are associated with better recovery outcomes. Future larger studies are warranted to confirm the study findings, and to examine whether a contemporary recovery-focused care model can facilitate even greater recovery outcomes.