On the need for biopsy confirmation at suspected first recurrence of cancer

At the time of suspected first recurrence of cancer, it is unclear whether biopsy confirmation is routinely performed, although this is a very common clinical situation. First, 20 oncologists were surveyed to ascertain the pattern of practice in our community. A questionnaire with hypothetical typical cases suspected of having recurrent cancer was distributed. Second, eligibility criteria were reviewed from investigational protocols from the National Cancer Institute (NCI) and the Eastern Cooperative Oncology Group to see whether confirmation of recurrence was specifically required in these research studies. Third, 64 cases from our own practice were reviewed retrospectively to determine our patterns and results in performing biopsies to document suspected recurrence. Finally, criteria were developed that might suggest the need for biopsy confirmation of recurrence and then retrospectively tested against our cases. There was no clear consensus among oncologists regarding the need for tissue confirmation in patients with solid tumor with suspected recurrences, although rebiopsy was routinely requested for recurrent lymphoma. Published Eastern Cooperative Oncology Group and NCI protocols reviewed did not require biopsy proof specifically of recurrence. Retrospective review of our own cases suggested that, in the absence of one of the proposed indicators, the risk of making an erroneous diagnosis without biopsy confirmation is low. It is suggested that biopsy is not routinely necessary for confirmation of recurrence in all cases of suspected recurrent solid tumors, but criteria are proposed that would help to reduce the possibility of misdiagnosis when biopsy of suspected recurrence is not performed.     

Psychosis in elderly patients: classification and pharmacotherapy

Psychosis in elderly patients is a growing clinical concern because psychotic symptoms most frequently occur as noncognitive manifestations of Alzheimer's disease, as side effects of drug therapy for Parkinson's disease, or as the primary abnormalities in schizophrenia, and the clinical characteristics of psychosis are distinct for each. In planning antipsychotic pharmacotherapy for elderly patients, age-related pharmacokinetic changes, polypharmacy for comorbid diseases, and concerns about the underlying conditions responsible for the psychotic symptoms must be considered. Traditional antipsychotic agents bind to dopamine receptors and effectively relieve positive schizophrenic symptoms but frequently cause tardive dyskinesia and other extrapyramidal symptoms, a problem for elderly patients, particularly for those with Parkinson's disease. Atypical antipsychotics bind to dopamine and serotonin receptors, relieving both positive and negative symptoms, and are less likely to cause extrapyramidal symptoms. The authors review common diagnostics associated with psychosis in the elderly and clinical guidelines to selecting antipsychotic pharmacotherapy.     

A double-blind placebo-controlled case study of the use of donepezil to improve cognition in a schizoaffective disorder patient: functional MRI correlates

Cognitive impairment in multiple domains is common in patients with schizophrenia and may be a powerful determinant of poor functional ability and quality of life. We report a double-blind, placebo-controlled, cross-over study of donepezil augmentation in a schizoaffective disorder patient stabilized on olanzapine pharmacotherapy. The patient showed significant improvements in several cognitive measures and increased activation of prefrontal cortex and basal ganglia on functional MRI during the donepezil augmentation. In addition, the donepezil augmentation resulted in a reduction of depressive symptoms and in significant improvements in functional abilities and quality of life. Further studies of donepezil augmentation of neuroleptics in schizophrenia are warranted.     

The effect of the quality of Papanicolaou smears on the detection of cytologic abnormalities.

BACKGROUND: Controversy continues regarding the relation between the quality of Papanicolaou (Pap) smears, especially the presence of endocervical cells (ECC), with the finding of cytologic abnormalities. METHODS: As part of a study regarding performance feedback on the quality of Pap smears, data from 56,475 Pap smears obtained by 176 participating clinicians over a 20-month period were analyzed to assess the relation between the presence of ECC, the categorization of global specimen adequacy as "satisfactory" or "satisfactory with limitations," and the prevalence of atypia and squamous intraepithelial lesions (SILs). RESULTS: Atypia was less likely to be found in "satisfactory" Pap smears than in "satisfactory with limitations" quality Pap smears (odds ratio [OR], 0.6; 95% confidence interval [CI], 0.5-0.6; P < 0.001), even though the latter could contain ECC. No association was found between satisfactory Pap smears and cytologic abnormalities. Compared with specimens with no ECC, an ECC count of > or = 50 on a slide was associated positively with the detection of atypia (OR, 2.1; 95% CI, 1.8-2.4; P < 0.001) or SILs (OR, 1.7; 95% CI, 1.3-2.2; P < 0.001). A similar relation existed between ECC counts of 25-50 (OR, 1.9; 95% CI, 1.1-2.2; P = 0.01) and the detection of SILs. No relation was found between specimens with < 25 ECC and the presence of atypia or abnormalities. CONCLUSIONS: The global adequacy criterion of "satisfactory" assigned to a Pap smear does not indicate that there is a greater likelihood of detecting cytologic abnormalities compared with lower quality Pap smears. To the authors' knowledge, previous studies regarding the link between ECC in the Pap smear and cytologic abnormalities have not addressed the relevance of how many ECC are needed to maximize the identification of abnormalities. The data from the current study support the value of obtaining at least 25 ECC as a quality indicator of sampling.     

Variants in genes of innate immunity,appetite control and energy metabolism are associated with host cardiometabolic health and gut microbiota composition

ABSTRACT

Identifying the genetic and non-genetic determinants of obesity and related cardiometabolic dysfunctions is cornerstone for their prevention, treatment, and control. While genetic variants contribute to the cardiometabolic syndrome (CMS), non-genetic factors, such as the gut microbiota, also play key roles. Gut microbiota is intimately associated with CMS and its composition is heritable. However, associations between this microbial community and host genetics are understudied. We contribute filling this gap by genotyping 60 variants in 39 genes of three modules involved in CMS risk, measuring cardiometabolic risk factors, and characterizing gut microbiota in a cohort of 441 Colombians. We hypothesized that CMS risk variants were correlated with detrimental levels of clinical parameters and with the abundance of disease-associated microbes. We found several polymorphisms in genes of innate immunity, appetite control, and energy metabolism that were associated with metabolic dysregulation and microbiota composition; the associations between host genetics and cardiometabolic health were independent of the participants’ gut microbiota, and those between polymorphisms and gut microbes were independent of the CMS risk. Associations were also independent of the host genetic ancestry, diet and lifestyle. Most microbes explaining genetic-microbiota associations belonged to the families Lachnospiraceae and Ruminococcaceae. Multiple CMS risk alleles were correlated with increased abundance of beneficial microbiota, suggesting that the phenotypic outcome of the evaluated variants might depend upon the genetic background of the studied population and its environmental context. Our results provide additional evidence that the gut microbiota is under the host genetic control and present pathways of host–microbe interactions.     

High-dose human lymphoblastoid interferon in metastatic colorectal cancer: clinical results and modification of biological responses

A total of 22 patients with advanced measurable colorectal carcinoma were treated with human lymphoblastoid interferon, 15 X 10(6) U/m2 im 3 times a week, in a trial designed to evaluate therapeutic activity, toxic effects, and biological response modification. One partial response (4.5% response rate) was observed which lasted 4 months. Sixty-eight percent of the patients required dose reduction for excessive toxicity, primarily constitutional symptoms. One patient developed phenobarbital toxicity, a previously undescribed side effect thought to be related to interferon-induced depression of hepatic microsomal enzymes required for drug metabolism. Treatment was associated with an increase in peripheral blood natural killer (NK) cell activity and the activity of an interferon-induced enzyme, 2'-5' oligoadenylate synthetase. The increase in NK cell activity was observed only in patients whose pretreatment NK cell activity was below normal. No induction of serum factors inducing differentiation of myeloid leukemic cell lines was documented. We conclude that human lymphoblastoid interferon, at the dose and schedule tested, has minimal antitumor activity as a single agent in advanced colorectal cancer and induces unacceptable toxicity in the majority of such patients. Recent literature suggesting a possible role for interferon alpha in combination with other drugs in the treatment of colorectal cancer is discussed.     

Implantación de prótesis aórticas vía transapical. Experiencia inicial

We report our initial experience with transapical aortic valve implantation. All six of our patients were octogenarians, all had significant associated comorbid conditions and, according to the logistic EuroSCORE, their mortality was expected to be 22%. All procedures were performed successfully and there were no intraoperative or postoperative complications. Five patients were discharged between postoperative days 5 and 7 with normally functioning prostheses.