Causes of death among cancer patients.

Background: The purpose of our study was to characterize the causes of death among cancer patients as a function of objectives: (i) calendar year, (ii) patient age, and (iii) time after diagnosis. Patients and methods: US death certificate data in Surveillance, Epidemiology, and End Results Stat 8.2.1 were used to categorize cancer patient death as being due to index-cancer, nonindex-cancer, and noncancer cause from 1973 to 2012. In addition, data were characterized with standardized mortality ratios (SMRs), which provide the relative risk of death compared with all persons. Results: The greatest relative decrease in index-cancer death (generally from > 60% to < 30%) was among those with cancers of the testis, kidney, bladder, endometrium, breast, cervix, prostate, ovary, anus, colorectum, melanoma, and lymphoma. Index-cancer deaths were stable (typically >40%) among patients with cancers of the liver, pancreas, esophagus, and lung, and brain. Noncancer causes of death were highest in patients with cancers of the colorectum, bladder, kidney, endometrium, breast, prostate, testis; >40% of deaths from heart disease. The highest SMRs were from nonbacterial infections, particularly among <50-year olds (e.g. SMR >1,000 for lymphomas, P < 0.001). The highest SMRs were typically within the first year after cancer diagnosis (SMRs 10-10,000, P < 0.001). Prostate cancer patients had increasing SMRs from Alzheimer's disease, as did testicular patients from suicide. Conclusion: The risk of death from index- and nonindex-cancers varies widely among primary sites. Risk of noncancer deaths now surpasses that of cancer deaths, particularly for young patients in the year after diagnosis.

Risk of cardiovascular disease in HIV, hepatitis C, or HIV/hepatitis C patients compared to the general population.

BACKGROUND: As a result of effective antiretroviral therapy HIV patients are living longer, and their risk of cardiovascular disease (CVD) is a growing concern. It remains unknown whether coinfection with hepatitis C (HCV) changes an HIV person's CVD risk, and how the risks compare to the general population. The objective of this study was to compare the Framingham Risk Score (FRS) and vascular age differences in persons with HIV, HCV or HIV/HCV disease to the general population. METHODS: HIV, HCV, and HIV/HCV patients with clinic visits between 2004 and 2009 were sampled from medical clinics in Rochester, NY. Uninfected persons were randomly selected from the National Health and Nutrition Examination Survey (NHANES), and individually matched on gender, race, and age. We stratified by infection group and conducted separate multivariable linear regression analyses between each infection group and the gender, race, and age matched participants from NHANES. RESULTS: Rochester patients (HIV = 239, HCV = 167, HIV/HCV = 182) were compared 3 : 1 with the NHANES participants. After controlling for weight, marital status, current pharmacotherapies and the matching variables of gender, race, and age, HIV/HCV patients had a 2% higher general FRS compared with the general population (p = 0.03), and vascular age differences that were 4.1 years greater (p = .01). HCV patients had a 2.4% higher general FRS than the general population (p < .001), and vascular age differences that were 4.4 years greater (p < .001). CVD risk was elevated but not significantly different between HIV patients and the general population. CONCLUSION: Cardiovascular disease risk is elevated among HIV/HCV and HCV infected persons compared with the general population.

Antibodies to HSP-70 in normal donors and autoimmune hearing loss patients.

OBJECTIVE: To evaluate serum antibody to heat shock protein (HSP) 70 as a marker for autoimmune sensorineural hearing loss (AISNHL). DESIGN: Sera from 20 patients with rapidly progressive sensorineural HL and 20 control volunteers without HL were tested for antibody reactivity against multiple HSP 70 substrates. Substrates included recombinant human HSP (rHuHSP) 72, purified bovine brain heat shock cognate (HSC) 73 and HSP 72, as well as heat-shocked and non-heat-shocked protein extracts from bovine kidney (MDBK) cells. All serum donors were previously tested for antibody to guinea pig inner ear supporting cells; 17 of 20 patients but none (0 of 20) of the controls were positive. METHODS: Sera were tested using Western blots. RESULTS: Reactivity with rHuHSP 70 was observed in 16 patients and 17 controls. Similarly, 15 of 20 patients and 17 of 20 controls stained for both HSP 72 and HSC 73 from the bovine brain. When tested against the heat-shock-induced and control MDBK extracts, six patients and nine controls had greater reactivity with the induced HSP 72. CONCLUSION: The frequency of antibodies to HSP substrates did not differ in patients and controls. Prior studies reported that HSP 72 is the 68 kD antigen commonly detected by AISNHL sera. However, we show that HSP 72 antibodies are no more prevalent in patients than in normal controls. Thus, it is unlikely that the 68 kD protein is HSP 72. Therefore, HSPs are not appropriate substrates for serodiagnosis of AISNHL.

Survival after HLA-identical allogeneic peripheral blood stem cell and bone marrow transplantation for hematologic malignancies: meta-analysis of randomized controlled trials.

The impact of peripheral blood stem cell transplantation (PBSCT) on survival relative to bone marrow transplantation (BMT) remains poorly defined. Several randomized controlled trials (RCTs) comparing HLA-matched related PBSC- and BMT for patients with hematologic malignancies have been published, yielding differing results. We conducted a meta-analysis of published RCTs to more precisely estimate the effect of PBSCT on survival. Seven trials that assessed survival were identified and included in our analysis. Using a fixed effects model, and combining the results of all seven trials, the summary odds ratio for mortality after PBSCT was 0.81 (95% CI, 0.62-1.05) when compared to BMT. Subgroup analysis revealed no association between the median PBSCT 34+ cell dose and relative risk for morality after PBSCT. However, there was an association between the proportion of patients enrolled with advanced-stage disease and the summary odds ratio for mortality. The pooled estimate was 0.64 for studies where patients with intermediate/advanced disease comprised at least 25% of enrollment, and was 1.07 for the studies enrolling a smaller proportion. This finding substantiates results from previously published studies that have demonstrated a survival advantage with PBSCT limited to patients with advanced disease.

A multi-institutional phase II trial of a novel inpatient schedule of continuous interleukin-2 with interferon alpha-2b in advanced renal cell carcinoma: major durable responses in a less highly selected patient population.

BACKGROUND: A prospective multi-institutional phase II trial was undertaken to define the activity and toxicity of a unique decrescendo infusion of interleukin-2 (IL-2) in combination with interferon (IFN) in patients with metastatic renal cell carcinoma. The identical regimen has shown promise in advanced melanoma. PATIENTS AND METHODS: Between February 1997 and March 1999, 47 patients with metastatic renal cell carcinoma, from five institutions, were treated with outpatient s.c. IFN (10 mU/m2/day) on days 1-5, followed by inpatient IL-2 via continuous i.v. decrescendo infusion [18 million International Units (MIU) (I mg)/m2/6 h, followed by 18 MIU/m2/12 h, then 18 MIU/m2/24 h and 4.5 MIU/m2/24 h for the following 3 days] on days 8-12, in a hospital ward without intensive care unit (ICU)-type monitoring. Treatment was repeated every 4 weeks. In contrast to high dose IL-2 protocols, patient eligibility did not require pulmonary function tests and allowed serum creatinine up to 2 mg/dl. RESULTS: Among 44 eligible patients, 57% (25) had their primary in place, 57% (25) had bone or visceral involvement, and only 4% (2) had lung as their only site of disease. The overall response rate in 43 response-evaluable patients was 16.3% [95% confidence interval (CI) 5.3 to 27.3], with three complete responses and four partial responses observed. The median survival was 13 months; nine patients remain alive at >23 months. The median duration of response is 36 months (range 11.5 to 48+ months). Toxicity was modest, consisting of typical cytokine-induced systemic symptoms and rare organ dysfunction. Severe grade 4 toxicity occurred in only 13% of the 130 cycles. CONCLUSIONS: This unique, reasonably well tolerated IL-2/IFN combination induced a modest response rate with a number of durable remissions. While the optimal IL-2-based regimen for the treatment of advanced renal cell carcinoma remains elusive, the present regimen should attract considerable interest. This is based on tumor activity very similar to high dose IL-2 in a patient population not as carefully selected for optimal organ function.

The effect of nonsteroidal anti-inflammatory drugs on ovulation: a prospective, randomized clinical trial.

OBJECTIVE: To assess the effect of ibuprofen, a nonspecific inhibitor of prostaglandin synthesis, on ovulation. DESIGN: Prospective, randomized, double-blind, placebo-controlled cross-over study. SETTING: University Medical Center. PATIENT(S): Twelve normally cycling women between ages 20 and 40. INTERVENTION(S): Subjects were randomized to either oral ibuprofen (800 mg) or placebo three times per day, beginning when the maximum diameter of the leading follicle reached 16 mm by ultrasound, and continuing for 10 days total. The second cycle was a washout period, and in the third cycle, the subjects were crossed over to the alternate regimen from the first cycle. The probability of delayed follicular collapse was determined using the binomial distribution, and changes in P levels were compared using the paired t test. MAIN OUTCOME MEASURE(S): Urinary LH surge, follicular collapse by serial transvaginal ultrasonography, and serum midluteal P levels. RESULT(S): Eleven of 12 subjects detected an LH surge with both ibuprofen and placebo. Five of 11 women demonstrated a >or=2-day increase in time interval from detection of the LH surge to follicular collapse, and 3 of those 5 had been randomized to ibuprofen. This represents a 27% (3 of 11; 95% confidence limits: 1%, 53%) rate of delay for follicular collapse for ibuprofen. There was no difference in average midluteal P levels for ibuprofen or placebo. CONCLUSION(S): If ibuprofen inhibits follicular collapse, this effect is seen in a small group of study subjects, and this information should be clinically reassuring to patients who take nonsteroidal anti-inflammatory drugs. Serum midluteal P levels were unaffected by administration of ibuprofen.

Outpatient care and morbidity reduction in diabetic foot ulcers associated with chronic pressure callus.

In a retrospective review of 233 cases of diabetic foot ulceration preceded by minor trauma, 192 ulcerations exhibited focal pressure keratosis as the preceding traumatic event. The frequency of outpatient visits and other foot care interventions were correlated with the occurrence and severity of ulceration. Patients seen more frequently in an outpatient foot clinic had less severe ulcers and were less likely to undergo surgical treatment than those with less frequent visits.

A murine model for the effects of pelvic radiation and cisplatin chemotherapy on human papillomavirus vaccine efficacy.

Therapeutic human papillomavirus (HPV) vaccines for cervical cancer depend on a competent immune system to be effective. However, cancer patients are often found to be immunosuppressed, which could be attributable to prior radiation, chemotherapy, or the tumor burden itself. This study investigated whether pelvic radiation or cisplatin treatment affected the efficacy of an HPV vaccine and how long these effects lasted. Mice were given pelvic radiation, 2 Gy/day to a total dose of 45 Gy, or 5 mg/kg/week of cisplatin for 3 weeks. Mice were then immunized with an HPV-16 peptide vaccine between 0 and 16 weeks after their treatment. An ELISPOT analysis revealed that a reduced level of peptide-specific, IFNgamma-producing spleen cells was present in immunized mice treated previously with pelvic radiation or cisplatin compared with immunized mice that had not been treated. However, when mice were challenged with HPV-16-expressing tumor cells, immunized mice developed no tumors, regardless of prior treatment, whereas nonimmunized mice did develop tumors. Our results suggest that pretreatment with pelvic radiation or cisplatin alone does not prevent the induction of an effective immune response by a peptide vaccine. These data will have important implications for immunotherapeutic treatment of pretreated cancer patients, especially in the adjuvant setting when immunosuppression by tumor burden would be low.

Double-blind comparative trial of oral ondansetron versus oral granisetron versus IV ondansetron in the prevention of nausea and vomiting associated with highly emetogenic preparative regimens prior to stem cell transplantation.

The optimal management of transplantation preparative regimen-induced nausea and vomiting remains unknown. We conducted a Phase III double-blind study to determine the efficacy and costs of oral ondansetron versus oral granisetron versus IV ondansetron and PRN rescue antiemetics for the prevention/control of nausea and vomiting associated with high-dose chemotherapy or chemoradiotherapy prior to stem cell transplantation. One hundred two patients were randomized to receive either 8 mg PO ondansetron every 8 hours, 1 mg PO granisetron every 12 hours, or 32 mg IV ondansetron every 24 hours plus 10 mg IV dexamethasone daily during and 1 day after the various preparative regimens. Study arms were compared in terms of emetic episodes, subjective nausea, amount and cost of rescue antiemetics used, and total costs. Response was defined as complete response (CR), no emesis with no or mild nausea and no rescue antiemetics; major response (MR), 1 episode of emesis or moderate nausea with or without rescue antiemetics; and major efficacy (ME), CR + MR. Subjective nausea was assessed using a 100-mm visual analog scale (VAS) with 0 = no nausea. Ninety-six patients completed the study; the trial was analyzed according to intention-to-treat. Overall CR rates were: 48% for oral ondansetron, 47% for oral granisetron, and 49% for IV ondansetron. Overall ME rates were 82% for oral ondansetron, 84% for oral granisetron, and 81% for IV ondansetron. Mean VAS scores were 32 for oral ondansetron, 32 for oral granisetron, and 27 for IV ondansetron. None of the differences were statistically significant. A cost analysis revealed significant differences among all arms (P = .0001, all comparisons). All 3 regimens had similar efficacy in this BMT population; oral ondansetron was the most cost-effective.

Recurrent basal cell carcinoma after incomplete resection.

BACKGROUND: Because the probability of basal cell carcinoma (BCC) recurrence was thought to be 30% to 50%, surgical tradition became not to perform additional resection when the margin was positive. OBJECTIVE: To determine whether there is an association among age or sex of the patient, anatomic location, histologic type, or reconstructive procedures and the signs and symptoms of the recurrence, interval between incomplete resection and Mohs micrographic surgery (MMS), or extent of MMS resection. DESIGN: During 20 years, all patients with incompletely excised BCC of the head referred for MMS were sequentially prospectively accrued into the cohort. SETTING: An outpatient MMS practice. PATIENTS: Nine hundred ninety-four patients. MAIN OUTCOME MEASURES: Interval to tumor recurrence, interval to MMS, and extent of MMS as determined by mean surface area resected, depth of resection, and number of tumor nests. RESULTS: The interval to signs or symptoms of recurrence and to MMS from incomplete resection was greater for men, patients older than 65 years, those having a tumor on the nose or cheek, those with aggressive or fibrosing BCC, and those who underwent flap reconstruction (P =.001). The extent of MMS resection was greater for those with flap and split-thickness skin graft repairs. The number of tumor nests identified by MMS was significantly greater in those treated with split-thickness skin graft and flap (P =.001). CONCLUSION: Because it is more difficult to control recurrent BCC, treating tumor remaining at the margin of resection in the immediate postoperative period could result in less extensive surgery.

Identification of new minimally lost regions on 18q in head and neck squamous cell carcinoma.

Loss of heterozygosity (LOH) on 18q predicts poor survival in head and neck squamous cell carcinomas (HNSCCs). Several putative tumor suppressor genes, such as DCC, DPC4/Smad4, and MADR2/Smad2, are mapped to 18q, but thus far, the important gene locus in HNSCC is not known. To identify possible gene loci on 18q, we performed LOH studies using tumor DNA from 57 HNSCC primary tumor cell lines and DNA isolated from fibroblasts or lymphoblastoid cells from the same patients. Forty-two highly polymorphic microsatellite markers spaced not more than 5 cM apart (mean distance, 1.82 cM) spanning the region from D18S44 in 18q11.1 to D18S1141 in 18q23 were used. D18S71 in 18p11.21 on 18p was also used to determine whether the short arm was retained. Forty-three of 57 (75%) HNSCC lines showed LOH or isolated allelic imbalance (AI) for at least one locus on 18q. Although many of the cell lines had large distal 18q deletions with a breakpoint between 18q11.1 and 18q12.2 to qter, three loci were identified that were lost in 70% or more of the cases. The minimally lost regions (MLRs) range in size from 1.5-15.79 cM. The most proximal is centered on D18S39 (1.56 cM) in band 18q21.1, with LOH or isolated AI in 28 of 38 (74%) of informative cases. The largest (15.8 cM) begins at D18S61 (28 of 40; 70%) in band 18q22.2 and extends through D18S50 in 18q23. The third is centered on D18S70 (30 of 40; 75%) in band 18q23 (3.67 cM). Of these MLRs, only the one centered on D18S39 has been implicated previously in HNSCC. D18S70, the most frequently lost marker, was the only marker consistently lost in three tumor cell lines with very minimal losses, UM-SCC-19, UM-SCC-67, and UM-SCC-73A. In addition, UM-SCC-91 exhibited AI only at this locus, and UT-SCC-4 had AI at D18S70 and D18S39 only. Close physical mapping of these three regions may pinpoint one or more previously unidentified tumor suppressor genes.

How well do third-year medical students learn key objectives in a case-based surgical lecture series?

Faculty members were asked to list major and minor concepts of their case-based session presented during the 12-week 3rd-year surgical clerkship. After each session, students were queried to list the key concepts presented. Data were collected from two groups: one at the end of an academic year and a second at the beginning of the next academic year. Faculty members listed a median of 10 major and 15 minor concepts. The mean number of matched major concepts ranged from 0.2 to 4, and from 0.2 to 3.4 for minor concepts. In a comparative analysis, the end-of-the-year students listed a higher number of matched concepts for 17 of the 20 sessions than the beginning of the year students (8 sessions reached statistical significance, P < 0.05). The current case-based teaching method is not effective in emphasizing key concepts to students. Reformatting cases to better align with key concepts may be one solution to enhance a student's ability to grasp key concepts. Students at the end of the academic year outperformed those at the beginning of the year. This additional variable needs to be considered by faculty and incorporated into their teaching techniques.

P53 overexpression is associated with bulky tumor and poor local control in T1 glottic cancer.

PURPOSE: To study the role of two possible prognostic factors, p53 and tumor bulk, and their interaction with other tumor and treatment variables in early-stage laryngeal cancer patients treated with curative radiotherapy. METHODS: One hundred two patients with T1N0M0 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy were analyzed. p53 status in pretreatment biopsy specimens was assessed by immunohistochemistry (IHC) using mouse monoclonal antibody DO-7. Tumors were classified as small surface lesions or bulky tumors. All tumor-related and treatment-related variables which might influence the outcome were analyzed. Local control after definitive radiotherapy was the end point of the study. RESULTS: The local control at 5 years for the entire group of patients was 78% (80/102) and 91% (93/102) after surgical salvage. p53 overexpression by IHC was seen in 37% (38/102) of patients. Tumors were classified as small volume in 69 (68%) and bulky in 33 (32%) patients. Five-year local control was 48% for p53-positive patients as compared to 94% for p53-negative patients (p = 0.0001). Tumor bulk was the other important prognostic factor, with 5-year local control of 91% for small tumors and 48% for bulky tumors (p = 0.0001). Patients who had both p53 positivity and bulky tumors did worse, with a 5-year local control of 23% as compared to 92% for all other groups combined (p = 0.0001). Among other variables, only the length of radiation time was of borderline significance. CONCLUSION: Both p53 overexpression and tumor bulk are independent prognostic factors for local control in early-stage glottic cancer treated with curative radiotherapy. The precise relationship between a genetic event, the p53 mutation, and an observable phenotype expression such as tumor bulk needs to be further defined.

Changes in thyroid nodule volume caused by fine-needle aspiration: a factor complicating the interpretation of the effect of thyrotropin suppression on nodule size.

The effectiveness of TSH suppression therapy for thyroid nodules remains controversial. Prior studies have assumed that the fine-needle aspiration biopsy (FNAB), used to confirm a benign condition before the establishment of control and treatment groups, has no effect on nodule volume. Seventeen untreated euthyroid patients with clinical solitary thyroid nodules that were solid (on high-resolution ultrasound) and a colloid goiter (on cytologic examination) had ultrasound measurements of nodule volume before a FNAB, immediately thereafter, and 1 month and 6 months later. Size differences and individual variability at each time period were analyzed. No significant difference in mean thyroid nodule volume was present at any point after the FNAB; however, the changes in nodule volume were quite marked and bidirectional among patients masking the cumulative effect. The variability of the change in individual nodule volume was statistically significant when comparisons were made across time (P = 0.0032). FNAB of thyroid nodules results in significant individual changes in volume after the procedure. Studies, such as the effect of TSH suppression on thyroid nodule volume, that incorporate the FNAB in both control and treatment arms of the experimental design, need to take these changes into account, less erroneous conclusions result.

Predictive markers for response to chemotherapy, organ preservation, and survival in patients with advanced laryngeal carcinoma.

OBJECTIVE: A systematic retrospective study of the largest randomized trial of induction chemotherapy and radiation for advanced laryngeal cancer was undertaken to determine whether specific tumor or biologic factors were predictive of chemotherapy response, organ preservation, or survival. METHODS: The variables analyzed included clinical and histologic factors, immunohistochemical expression of proliferating cell nuclear antigen and p53, and adjusted DNA index measurements. Variables were evaluated for correlation with outcomes of tumor response, organ preservation, and survival. RESULTS: Multivariate analysis revealed that the best predictor of complete response to induction chemotherapy was low T class. The full multivariate model for predicting larynx preservation in patients treated with induction chemotherapy plus radiation shows that T class, p53 overexpression, and elevated proliferating cell nuclear antigen index were independent predictors of successful organ preservation. CONCLUSIONS: These predictive markers should be included in future clinical trials of advanced laryngeal cancer to determine their usefulness prospectively.

Higher prevalence of abdominal aortic aneurysms in patients with carotid stenosis but without diabetes.

BACKGROUND: We compared abdominal aortic aneurysm (AAA) prevalence in 3 groups of patients at the Hines Veterans Affairs Medical Center: (1) patients with 50% or more carotid stenosis, (2) patients with less than 50% stenosis, and (3) patients screened for the Aneurysm Detection and Management (ADAM) study. METHODS: Of all the patients referred to the vascular laboratory for carotid duplex examination during a 12-month period, patients with 50% or more carotid stenosis underwent ultrasonography of the abdominal aorta unless they had a previous scan or previous aortic surgery (group 1, n = 374). Patients with less than 50% carotid stenosis who had been screened for ADAM comprised group 2 (n = 139). They were compared with all patients screened for ADAM at our center during the same time period (group 3, n = 2477). RESULTS: AAA of 3.0 cm or more were present in 18.2%, 12.2%, and 7.2% of groups 1, 2, and 3, respectively; AAA of 4.0 cm or more were present in 8.3%, 5.8%, and 2.1% of groups 1, 2, and 3, respectively. Among patients with carotid stenosis, those patients without diabetes accounted for the observed increase in prevalence (21.9 % > or = 3.0 cm and 10.2% > or = 4.0 cm vs 9.2% and 2.8% in patients with diabetes). CONCLUSIONS: The relative risk of AAA is 2 to 3 times greater in patients with carotid stenosis compared with patients undergoing routine screening. However, only patients without diabetes account for the increased prevalence. Selective AAA screening of patients who are not diabetic with carotid stenosis is recommended.

Cancer risk associated with simian virus 40 contaminated polio vaccine.

BACKGROUND: The presence of SV40 in monkey cell cultures used in the preparation of the polio vaccine from 1955 through 1961 is well documented. Investigations have consistently demonstrated the oncogenic behavior of SV40 in animal models. Early epidemiologic studies were inadequate in demonstrating an increase in cancer incidence associated with contaminated vaccine. Recently, investigators have provided persuasive evidence that SV40 is present in human ependymomas, choroid plexus tumors, bone tumors, and mesotheliomas, however, the etiologic role of the virus in tumorigenesis has not been established. MATERIALS AND METHODS: Using data from SEER, we analyzed the incidence of brain tumors, bone tumors, and mesotheliomas from 1973-1993 and the possible relationship of these tumors with the administration of the SV40 contaminated vaccine. RESULTS: Our analysis indicates increased rates of ependymomas (37%), osteogenic sarcomas (26%), other bone tumors (34%) and mesothelioma (90%) among those in the exposed as compared to the unexposed birth cohort. CONCLUSIONS: These data suggest that there may be an increased incidence of certain cancers among the 98 million persons exposed to contaminated polio vaccine in the U.S.; further investigations are clearly justified.

Calciuria in symptom-free primigravid women remote from term: is the response to an oral calcium challenge predictable?

OBJECTIVE: This study was undertaken to compare the calciuric response in symptom-free primigravid women to an oral calcium load between those with normal urinary calcium excretions and those with relatively low urinary calcium excretions. STUDY DESIGN: This was a prospective clinical trial. Eligible primigravid women between 16 and 20 weeks' gestation provided a 24-hour urine sample for determination of urinary calcium/urinary creatinine ratio. On the basis of these results the patients were divided into 2 groups: a relatively hypocalciuric group, in which the urinary calcium excretion was 3.4 mg. kg-1. 24 h-1. All participants undertook a 3-day low calcium dietary regimen. On the fourth day women underwent an oral calcium challenge. A 2-hour urine sample was collected before ingestion of 1 g calcium carbonate (preload). One hour after ingestion the women again collected a 2-hour urine sample (postload). The urinary calcium/urinary creatinine ratios in the preload and postload samples were determined and compared within and between the groups. RESULTS: The mean change (+/-SD) between the preload and postload urinary calcium/urinary creatinine ratios in the relatively hypocalciuric group was 0.60 +/- 1.44 (P =.04); that in the normocalciuric group was 3.09 +/- 2.26 (P =.11 ). There was a 5-fold difference in the response to calcium load between the hypocalciuric women and the normocalciuric women (0.60 vs 3.09), although this difference was not statistically significant (P =.20). CONCLUSIONS: Both hypocalciuric and normocalciuric women responded to an oral calcium challenge by an increase in the calcium excretion. The cause of the hypocalciuria in women at increased risk for preeclampsia is therefore not simply poor absorption of calcium.

The failed gastrointestinal anastomosis: an inevitable catastrophe?

BACKGROUND: There is a great deal of conflicting data regarding risk factors for anastomotic leakage, with most studies being small and looking only at anastomoses performed at one level of the gastrointestinal (GI) tract. Surgeons have looked at patient and technical variables with inconsistent findings. The purpose of this study was to evaluate the incidence, possible predictive factors, and results of treatment of anastomotic dehiscence in patients undergoing operations at all levels of the GI tract. STUDY DESIGN: We evaluated the records of 2,842 patients undergoing esophagogastrectomy, total or partial gastrectomy, enterectomy, and partial or subtotal colectomy over a 12-year period. Complete demographic data, comorbidity, and details regarding anastomotic technique were collected on all patients sustaining leaks along with diagnostic methods used, treatment modalities, and outcomes data. Using age and gender-matched case control methodology, we compared patients sustaining an anastomotic leak to those undergoing successful anastomoses. RESULTS: Fifty-one of 2,842 patients (1.8%), ranging from 1.1% of enterectomy patients to 4.8% of total gastrectomy patients, sustained an anastomotic dehiscence. Foregut procedures were accompanied by a significantly increased rate of leakage, and depending on location, diagnosis was made between the 6th and 9th postoperative day. For each procedure, deaths from factors other than leakage far exceeded deaths from leaks. Standard risk stratifiers did not predict occurrence of leakage. Overall, 24% of patients sustaining a leak died, and this complication necessitated multiple reoperations and significantly increased length of hospital stay. CONCLUSIONS: In view of these findings, standard preoperative strategies to prepare these patients for operation may prove unsuccessful, because minimizing the incidence of anastomotic leaks will have little overall impact on survival. In addition, efforts to accomplish early hospital discharge may prove hazardous, because many of these patients manifest their leaks later in the postoperative period than is generally assumed. Improved management of GI tract disruption, including aggressive attempts at diagnosis, ICU care, antibiotics, and nutritional support may further increase survival in these patients.

Effects of amiodarone on tumor necrosis factor-alpha levels in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of congestive heart failure and may be associated with an increase in mortality. A recent in vitro study showed that amiodarone decreases TNF-alpha production by human blood mononuclear cells in response to lipopolysaccharide. However, no previous clinical studies have determined the effect of chronic amiodarone therapy on TNF-alpha levels. Thus, the purpose of this study was to determine whether amiodarone affects TNF-alpha levels in patients with ischemic and nonischemic cardiomyopathy. TNF-alpha levels were analyzed by an enzyme-linked immunoassay using plasma samples at baseline, 1, and 2 years of follow-up in New York Heart Association class III patients (n = 40 in each of the placebo and amiodarone groups, mean ejection fraction 0.25+/-0.09) who were randomized in the Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy, a multicenter, double-blind, placebo-controlled study in which the effect of amiodarone on survival was investigated. TNF-alpha levels were elevated in both groups of patients at baseline, 6.6+/-3.1 and 7.7+/-5.3 pg/ml in the amiodarone and placebo groups, respectively (p = 0.3). There were no significant differences in demographic or clinical variables between the 2 groups. Amiodarone treatment was associated with a significant increase in TNF-alpha levels in patients with ischemic cardiomyopathy, 12.7+/-12.5 and 6.8+/-3.7 pg/ml in the amiodarone and placebo groups, respectively (p = 0.03) at 1 year. No change in TNF-alpha levels was observed in patients with nonischemic cardiomyopathy. In contrast to the in vitro data, amiodarone treatment is associated with an increase in TNF-alpha levels in patients with ischemic cardiomyopathy. This increase is not associated with an adverse effect on survival.