Hyperparathyroidism in octogenarians: A plea for ambulatory minimally invasive surgery under local anesthesia.

BACKGROUND: With the current aging of the world's population, diagnosis of primary hyperparathyroidism is being reported in increasingly older patients, with the associated functional symptomatology exacerbating the vicissitudes of age. This retrospective study was designed to establish functional improvements in older patients following parathyroid adenomectomy under local anesthesia as outpatient surgery. MATERIALS AND METHODS: Data were collected from 53 patients aged 80 years or older who underwent a minimally invasive parathyroid adenomectomy. All patients underwent a preoperative ultrasound, scintigraphy, and were monitored for the effectiveness of the procedure according to intra- and postdosage of parathyroid hormone (PTH) at 5min, 2h and 4h. RESULTS: Mean preoperative serum calcium level was 2.8mmol/L (112mg/L) and mean PTH was 180pg/ml. Thirty-eight patients were operated under local anesthesia using minimally invasive surgery and 18 patients were operated under general anesthesia. In 26 cases, the procedure was planned on an outpatient basis but could only be carried out in 21 patients. Fifty-one patients had normal serum calcium and PTH levels during the immediate postoperative period. Two patients were reoperated under general anesthesia, since immediate postoperative PTH did not return to normal. Four patients died due to reasons unrelated to hyperparathyroidism. Five patients were lost to follow-up six months to two years postsurgery. Of the 44 patients (83%) with long-term monitoring for PTH, none had recurrence of biological hyperparathyroidism. Excluding the three asymptomatic patients, 38 of the 41 symptomatic patients (93%) with long-term follow-up were considering themselves as "improved" or "strongly improved" after the intervention, notably with respect to fatigue, muscle and bone pain. Two patients (4.9%) reported no difference and one patient (2.4%) said her condition had worsened and regretted having undergone surgery. CONCLUSION: In patients 80 years or older, minimally invasive surgery as an outpatient under local anesthesia offered an excellent risk/benefit ratio given its many advantages: simplicity, speed, absence of general anesthesia, ease of monitoring, direct voice control intraoperatively, very low morbidity, effectiveness in treating primary hyperparathyroidism in more than 95% of first intention patients, and the possibility of immediate or delayed recovery in the event of multiglandular disease going unnoticed.

Adenoma detection rate and risk of colorectal cancer and death.

BACKGROUND: The proportion of screening colonoscopic examinations performed by a physician that detect one or more adenomas (the adenoma detection rate) is a recommended quality measure. However, little is known about the association between this rate and patients' risks of a subsequent colorectal cancer (interval cancer) and death. METHODS: Using data from an integrated health care delivery organization, we evaluated the associations between the adenoma detection rate and the risks of colorectal cancer diagnosed 6 months to 10 years after colonoscopy and of cancer-related death. With the use of Cox regression, our estimates of attributable risk were adjusted for the demographic characteristics of the patients, indications for colonoscopy, and coexisting conditions. RESULTS: We evaluated 314,872 colonoscopies performed by 136 gastroenterologists; the adenoma detection rates ranged from 7.4 to 52.5%. During the follow-up period, we identified 712 interval colorectal adenocarcinomas, including 255 advanced-stage cancers, and 147 deaths from interval colorectal cancer. The unadjusted risks of interval cancer according to quintiles of adenoma detection rates, from lowest to highest, were 9.8, 8.6, 8.0, 7.0, and 4.8 cases per 10,000 person-years of follow-up, respectively. Among patients of physicians with adenoma detection rates in the highest quintile, as compared with patients of physicians with detection rates in the lowest quintile, the adjusted hazard ratio for any interval cancer was 0.52 (95% confidence interval [CI], 0.39 to 0.69), for advanced-stage interval cancer, 0.43 (95% CI, 0.29 to 0.64), and for fatal interval cancer, 0.38 (95% CI, 0.22 to 0.65). Each 1.0% increase in the adenoma detection rate was associated with a 3.0% decrease in the risk of cancer (hazard ratio, 0.97; 95% CI, 0.96 to 0.98). CONCLUSIONS: The adenoma detection rate was inversely associated with the risks of interval colorectal cancer, advanced-stage interval cancer, and fatal interval cancer. (Funded by the Kaiser Permanente Community Benefit program and the National Cancer Institute.).

Nuclear orphan receptor NR4A2 confers chemoresistance and predicts unfavorable prognosis of colorectal carcinoma patients who received postoperative chemotherapy.

BACKGROUND: NR4A2, an orphan nuclear receptor essential in neuron generation, has been recently linked to inflammatory and metabolic pathways of colorectal carcinoma (CRC). However, the effects of NR4A2 on chemo-resistance and postoperative prognosis of CRC remain unknown. METHODS: NR4A2 was transfected into CRC cells to investigate its effects on chemo-resistance to 5-fluorouracil and oxaliplatin and chemotherapeutics-induced apoptosis. We also investigated prostaglandin E2 (PGE2)-induced NR4A2 expression and its effect on chemo-resistance. Tissue microarrays including 51 adenoma, 14 familial adenomatous polyposis with CRC, 17 stage IV CRC with adjacent mucosa and 682 stage I-III CRC specimens were examined immunohistochemically for NR4A2 expression. Median follow-up time for stage I-III CRC patients was 53 months. RESULTS: Ectopic expression of NR4A2 increased the chemo-resistance, and attenuated the chemotherapeutics-induced apoptosis. Transient treatment of PGE2 significantly up-regulated NR4A2 expression via protein kinase A pathway and increased the chemo-resistance. NR4A2 expression in epithelials consecutively increased from adenoma, adjacent mucosa to CRC (P(trend)<0.001). In multivariate Cox regression analyses, high NR4A2 expression in cancer nuclei (immunoreactive score ≥ 4) significantly predicted a shorter disease-specific survival (DSS) of CRC patients (hazard ratio [HR]=1.88, P=0.024). High NR4A2 expression specifically predicted a shorter DSS of colon cancer patients (dichotomisation, HR=2.55, log-rank test P=0.011), especially for those who received postoperative 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX) chemotherapy (3-score range, HR=1.86, log-rank test P=0.020). CONCLUSION: High expression of NR4A2 in CRC cells confers chemo-resistance, attenuates chemotherapeutics-induced apoptosis, and predicts unfavorable prognosis of colon cancer patients, especially for those who received postoperative chemotherapy. NR4A2 may be prognostic and predictive for colon cancer.

Combination aspirin and/or calcium chemoprevention with colonoscopy in colorectal cancer prevention: cost-effectiveness analyses.

BACKGROUND: Clinical and cohort studies have shown that low-dose aspirin and calcium are effective low-risk strategies for primary prevention of colorectal cancer (CRC). We compared the cost-effectiveness of aspirin and calcium chemoprevention used with colonoscopy for primary prevention of CRCs. METHODS: Markov chain Monte Carlo simulations for a population of 100,000 persons, with a colonoscopy compliance rate of 50%, were used for the analysis. If adenomas were detected, colonoscopy was repeated every 4 years until no adenomas were evident. Data sources included adenoma transition rates, initial adenoma and CRC incidences, and treatment complication rates from existing literature. Age-adjusted U.S. standard population mortality rates were used and costs were from Medicare reimbursement data. The target population was U.S. adults, undergoing CRC screening from ages 50 to 75 years. RESULTS: Outcomes included incremental cost-effectiveness ratios (ICER), life-years saved (LYS), and cancer-free years saved (CFYS). The ICER per LYS for colonoscopy alone dominated compared with no screening. Compared with colonoscopy alone, colonoscopies with aspirin (ICER = $12,950/LYS) or calcium (ICER = $13,041/LYS) were the next most cost-effective strategies. ICERs per CFYS were $3,061 and $2,317 for aspirin and calcium, respectively, when added to colonoscopy. Sensitivity analyses indicated that initial prevalence of adenomas was a main determinant of prevention cost-effectiveness. CONCLUSION: Low-dose aspirin or calcium supplementation may be beneficial when added to colonoscopy, for optimum CRC prevention, at small incremental costs. IMPACT: Cost-effectiveness analyses suggest that aspirin and calcium in combination with colonoscopies are cost-effective for CRC prevention in average-risk populations.

Anti-cancer activity of nitrones in the Apc(Min/+) model of colorectal cancer.

Abstract The nitrones of alpha-phenyl-tert-butyl nitrone (PBN) and 4-hydroxyl-PBN (4-OH-PBN) that have anti-cancer activity in models of liver cancer and glioblastomas were tested in the ApcMin/+ mouse model. Mice were administered PBN and 4-OH-PBN in drinking water and intestinal tumour size and number assessed after 3-4 months. Throughout the experiment, contrast-enhanced magnetic resonance imaging (MRI) was used to monitor colon tumours. MRI data showed a time-dependent significant increase in total colonic signal intensity in sham-treated mice, but a significant decrease for PBN-treated mice and slight decrease for 4-OHPBN treated mice, probably due to the limited water solubility of 4-OH-PBN. Final pathological and percentage survival data agreed with the MRI data. PBN had little effect on oxaliplatin-mediated killing of HCT116 colon cancer cells and caused only a slight decrease in the amount of active fraction caspase 3 in oxaliplatin-treated cells. PBN has significant anti-cancer activity in this model of intestinal neoplasia.

Pituitary adenoma: a radiotherapeutic perspective.

Pituitary adenomas comprise approximately 10% to 20% of all central nervous system neoplasms whereas autopsy series have suggested that the incidence of pituitary adenoma in the general population may approach 25%. Several treatment modalities are used in the treatment of pituitary adenomas, including observation, surgery, medical intervention, and radiotherapy. The treatment modality employed depends greatly on the type of pituitary adenoma and presenting symptoms. This review will discuss the biology of pituitary adenomas and the current management principles for the treatment of prolactinomas, Cushing disease, acromegaly, and nonsecretory adenomas, with an emphasis on the published radiotherapeutic literature.

Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial.

OBJECTIVES: Dietary folate intake is inversely associated with the risk of colorectal cancer. This study investigated the effect of folate supplementation on genomic DNA methylation and DNA strand breaks in exons 5-8 of the p53 gene of the colonic mucosa, two provisional biomarkers of colon cancer. METHODS: Twenty subjects with adenomas were randomized to receive either folate (5 mg/day) or placebo for 1 yr after polypectomy. At baseline, 6 months and 1 yr, systemic and colonic measures of folate status were determined, as were the biomarkers mentioned earlier. RESULTS: Folate supplementation increased serum, red blood cell and colonic mucosal folate concentrations (p < 0.02). Folate supplementation also increased the extent of genomic DNA methylation at 6 months and 1 yr (p = 0.001), whereas placebo administration was associated with an increase in the extent of genomic DNA methylation only at 1 yr. Similarly, folate supplementation decreased the extent of p53 strand breaks in exons 5-8 at 6 months and 1 yr (p < 0.02), whereas placebo administration was associated with a decrease in the extent of p53 strand breaks only at 1 yr. CONCLUSIONS: Both of these provisional biomarkers of colon cancer underwent accelerated improvement at 6 months with folate supplementation. However, these markers also improved with placebo at 1 yr. Therefore, potential confounding factors that seem to modulate these biomarkers need to be identified and corrected in order for these markers to serve as suitable surrogate endpoints in folate chemoprevention trials.

The combined effects of dietary fat and estrogen on survival, 7,12-dimethylbenz(a)anthracene-induced breast cancer and prolactin metabolism in rats.

The relationships between dietary fat concentration (10 or 40% of energy), fat source (corn oil or beef tallow) and estrogen (control, ovariectomy or ovariectomy with estrogen replacement) to 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast carcinogenesis and survival in rats were studied in a 2 x 2 x 3 factorial experiment. Female Sprague-Dawley rats given DMBA (2.5 mg/100 g body wt, intragastric) at 55 d of age were randomly allocated to three groups 48 h later: sham ovariectomy (control), ovariectomy (OVX) or ovariectomy with a subcutaneous estrogen implant (OVX+E). Each group was subdivided into dietary groups fed 10 and 40% of energy as corn oil or beef tallow for 70 wk. OVX+E rats exhibited serum estrogen concentrations in excess of physiologic values. Survival at 70 wk for the 3 hormonal groups was control 51%, OVX 67% and OVX+E 13%. Mortality in controls was doubled by feeding a high fat diet; no diet effect was detected in OVX or OVX+E rats. Palpable tumors developed in 74, 14 and 60% of control, OVX and OVX+E rats, respectively. High fat diets approximately doubled the hazard of developing a palpable tumor. Adenocarcinoma prevalence was 58, 12 and 63% in control, OVX and OVX+E rats, respectively. The odds of having any tumor, an adenocarcinoma or an adenoma were multiplied by 3.6, 2.8 and 2.3, respectively, for rats fed high vs. low fat. Additional studies showed that diet had no effect on serum prolactin or estrogen concentrations or metabolism and clearance of intravenously administered radiolabeled prolactin. We demonstrated that high dietary fat concentration enhances breast carcinogenesis independently of cyclic ovarian function, although the presence of estrogen may be a prerequisite for significant dietary modulation. The effect of fat on breast cancer is not mediated by major changes in systemic prolactin metabolism.