Alkaline Phosphatase Predicts Survival in Patients with Metastatic Neuroendocrine Tumors

The clinical course of patients with metastatic neuroendocrine tumors is highly variable. While some patients experience an indolent clinical course over many years, other patients may rapidly succumb to their disease. Little is known about prognostic factors in these patients, making decisions regarding their management more difficult.We performed a retrospective analysis of 137 patients with metastatic neuroendocrine tumors referred to our institution for treatment. Potential prognostic factors were evaluated using multivariate survival analysis. The median overall survival of patients in our cohort was 6.0 years, although the range of survival times was broad (48 days to 23.4 years). Alkaline phosphatase levels above normal were predictive of shorter survival in both univariate and multivariate analysis. Elevated chromogranin A levels were also associated with shorter survival in univariate analysis; in a multivariate analysis, however, this correlation was no longer significant. There was no association between survival and gender, primary tumor site, or presence or absence of carcinoid syndrome. Elevated alkaline phosphatase is a robust adverse prognostic factor for survival in patients with metastatic neuroendocrine tumors and may be superior to chromogranin A in this setting. Close monitoring of alkaline phosphatase levels may be useful when considering initiation or changes of therapy in patients with metastatic neuroendocrine tumors.Matthew Kulke is supported in part by NIH grants K23 CA 093401, K30 HL04095, and gifts from Dr. Raymond and Beverly Sackler, the Caring for Carcinoid Foundation, and the Stephen and Caroline Kaufer Fund for Neuroendocrine Tumor Research.     

Clinical characteristics,treatment intent,and outcome in a consecutive 10-year cohort of oral cancer patients aged 75 years and older

The prevalence of oral squamous cell carcinoma (OSCC) in the elderly is expected to increase by nearly a third in the next decade. Its management in older patients is potentially more challenging due to their pre-existing medical comorbidities, frailty, reduced life expectancy, and social issues. The aim of this retrospective review was to report on treatment given to patients aged 75 years and over, case mix, and survival. All patients aged 75 years and over who were diagnosed with OSCC in Merseyside between 1 January 2007 and 31 December 2016, and treated with either curative or palliative intent, were included. Their hospital notes were reviewed. Fisher’s exact test and Kaplan-Meier analysis were used for data analysis. There were 236 patients (median (IQR) age 81 (78-86) years); 67% were treated curatively and 33% palliatively. Factors associated with palliation included older age, advanced tumour stage, cognitive impairment, and residence in a nursing or residential home. Of the 165 patients who were offered curative treatment, six (4%) declined due to personal or family reasons. Overall survival for palliative patients was 12% at one year and 7% at two years, whereas for patients treated curatively it was 74% at one year, 56% at two years, and 34% at five years. Patients over 85 years of age were less likely to have composite free flaps and postoperative radiotherapy. Perioperative mortality was 2.6%. Improvements in surgical techniques and perioperative management have enabled clinicians to offer treatment with curative intent to older frail patients, and with careful case selection outcomes can be very good.     

Infection of human T-cell leukemia virus type I and development of human T-cell leukemia lymphoma in patients with hematologic neoplasms: a possible linkage to blood transfusion

Among 354 adult patients with either hematological malignancy or aplastic anemia, eight were positive for anti-HTLV-I antibodies; six of eight had received multiple transfusions. There was an approximately 3.5-fold increase (P less than .001) of HTLV-I seropositivity in the patients with hematologic disease (8 of 354, 2.23%) compared to the healthy adults older than 20 years (34 of 5252, .65%). Two hematological patients, one with Hodgkin's disease and one with acute promyelocytic leukemia, were found to be positive for HTLV-I, and developed and died of adult T-cell leukemia/lymphoma (ATL) subsequently. Both were long-term survivors of the primary disease and had received multiple transfusions. The latent period from blood transfusion to onset of ATL was 6 months and 11 years, respectively. Immunocompromised patients, who were seropositive for HTLV-I, may be at increased risk for ATL compared to healthy carriers of HTLV-I, and the latent period may be shorter.     

Results of surgical treatment for hyperparathyroidism associated with renal disease

Recently, the role and timing of surgery for treating secondary and tertiary hyperparathyroidism (HPT) have been questioned. In order to delineate the indications for surgery in these patients, a retrospective analysis of 53 consecutive patients treated with parathyroidectomy was conducted. Subtotal thyroidectomy was done in 37 of 45 patients undergoing their initial operations for HPT. Eight additional patients were referred after failed operations. Of 33 patients with preoperative bone pain, 70% improved. Joint pain improved in 87% of 30 patients, pruritus improved in 81% of 27 patients, and preoperative malaise improved in 73% of 33 patients after parathyroidectomy. Abdominal pain and irritated eyes were unlikely to improve. The best predictors of a successful outcome were a markedly elevated preoperative immunoreactive parathyroid hormone (mid-region) level and an elevated alkaline phosphatase level. There were no perioperative deaths. One patient (1.6%) had a recurrent laryngeal nerve injury, and one patient required reoperation for a neck hematoma. No patient had permanent hypoparathyroidism, but transient hypocalcemia (less than 7 mg/dL) occurred in 22%. Postoperative hypocalcemia correlated with elevated preoperative alkaline phosphatase levels (r2 = 0.247).     

Characterization of murine sarcoma virus transformation of guinea pig cells and activation of an RNA tumor-like virus from nonproducer guinea pig cells.

Guinea pig embryo (GEP) cells were transformed in vitro by the Kirsten strain of mouse sarcoma virus (Ki-MSV). The transformed cells were found to release infectious virus continuously and produced high titers of group-specific (gs) complement-fixing (CF) antigen characteristics of the murine sarcoma-leukemia virus complex. Foci of transformed cells were similar in appearance to those obtained with Ki-MSV in mouse and rat cells. The transformed cells produced RNA dependent DNA polymerase and type C virus particles with a density of approximately 1.15 g/ml in sucrose gradients by 3H-uridine labeling. The transformed cells produced tumors when transplanted into newborn guinea pigs. A number of focus-derived clonal lines from Ki-MSV transformed cells were isolated and characterized. All the focus-derived lines were found to be either producers or nonproducers (NP). The NP guinea pig cells produced neither infectious virus nor viral antigens of the murine sarcoma-leukemia virus complex although they were morphologically indistinguishable from virus-releasing MSV transformed GPE lines and produced tumors when transplanted into newborn guinea pigs. However, the sarcoma virus genome could be rescued in these NP cells by cocultivation with "helper" murine leukemia virus (MuLV) releasing GPE cells. Particles resembling guinea pig leukemia virus were activated from guinea pig NP cells or cultured normal guinea pig cells following chemical treatment. These particles were approximately 100 nm in the mature form and had a density of 1.16-1.17 g/ml. They contained RNA dependent DNA polymerase activity.     

Technical quality of root canal treatment in Taiwan

AIM: To evaluate the current technical quality of root canal treatment (RCT) in Taiwan. METHODOLOGY: A total of 1085 RCT cases, randomly selected from a large sample and representative of the Taiwanese population from April to September 2000, were evaluated by eight endodontic specialists. The qualitative evaluation of RCT cases was based on two variables: length of the root filling and density of the obturation. A root canal with both adequate filling length (the apical termination of the root filling within 2 mm of the radiographic apex) and complete obturation (no lateral or apical canal lumen visible in the apical one-third of the root canal) was defined as having good-quality endodontic work (GQEW). A tooth was defined as having a GQEW when all its canals were categorized as GQEW. RESULTS: From a total of 1867 root canals, overfilling occurred in 235 (12.6%), adequate filling length in 1152 (61.7%), underfilling in 466 (25.0%) and no filling in 12 (0.6%). Of the 1867 root canals, 710 (38.0%) demonstrated complete obturation and 1157 (62%) demonstrated incomplete obturation. GQEW was found in 650 (34.8%) root canals and 329 (30.3%) teeth. The percentage of teeth with GQEW in hospital cases (38.1%) was significantly greater (P < 0.001) than that in private clinic cases (24.3%). In addition, the frequency of teeth with GQEW in the anterior teeth (40.4%) or in the premolars (33%) was significantly greater (P < 0.001) than that in the molars (18.4%). CONCLUSIONS: Approximately 70% of the teeth receiving RCT in Taiwan were either of inadequate filling length or sealing density.     

A randomized prospective comparison of oral versus intraperitoneal ofloxacin as the primary treatment of CAPD peritonitis

Summary: Oral ofloxacin has been successfully used in our centres for the primary treatment of peritonitis complicating continous ambulatory peritoneal dialysis (CAPD). In view of the progressive rise in the resistance rate to ofloxacin among peritoneal bacterial isolates, a study was conducted to determine if oral ofloxacin remains a viable first line treatment for CAPD peritonitis in our centres and if the result can be improved by changing from an oral to an intraperitoneal (i.p.) route. In patients on three 2 L daily CAPD exchanges, ofloxacin given at the i.p. dosage of 200 mg loading followed by 25 mg/L of peritoneal dialysate achieved overnight trough peritoneal levels which are at least four times the minimal 90% inhibitory concentration (MIC90) of most bacterial pathogens without significant accumulation in the systemic circulation. This i.p. dosage was therefore chosen for the clinical study and the result was compared to that using ofloxacin given in the oral dosage of 400 mg loading followed by 300 mg once daily as maintenance. of all the recruited episodes, 35 were eligible for analysis. the overall primary cure rate including primary failures and relapses was 55.6% (10/18) in the oral treatment group and 70.6% (12/17) in the i.p. treatment group. the corresponding figures for gram positive bacterial (g +) infections were 36.4% and 50%, for gram negative bacterial (g -) infections were 66.7 and 80% and for culture negative infections were 75 and 80%. In culture positive cases, all treatment failures were due to resistant infections which were observed in 42.3% of all bacterial isolates, 47.1% of g + isolates and 33.3% of g - isolates. Due to the high background level of bacterial resistance among our CAPD population, ofloxacin monotherapy given either by the oral or the i.p. route can no longer be recommended for the primary treatment of CAPD peritonitis.     

原代培养猪甲状腺细胞及甲状腺过氧化物酶活性与氟化钠的影响

目的:流行病学调查结果显示,地方性氟中毒与甲状腺肿的流行有很大的重叠性。探讨氟化钠对原代培养猪甲状腺细胞及甲状腺过氧化物酶活性的影响。方法:实验于2006-10/2007-05在辽宁医学院科学实验室中心完成。①实验方法:在猪死亡1h内取其甲状腺组织,去除甲状腺组织包膜及外层活性差的组织,选取中央活性高的部位,剪成1mm3组织块,用胰蛋白酶、胶原酶Ⅳ消化分离,得到含猪甲状腺细胞的消化液,沉淀悬于含体积分数为0.15的胎牛血清、1U/L牛促甲状腺素、80万U/L庆大霉素的F12培养基中,过滤,调整细胞浓度至5×105L-1,接种培养,每3d更换培养液。常规培养48h的猪甲状腺细胞接种于96孔培养板,按氟化钠终浓度不同分为0,40,80,160mg/L组。②实验评估:染毒48h后,采用噻唑蓝法测定细胞存活量,采用改良愈创木酚法测定甲状腺过氧化物酶活性。结果:①氟化钠对原代培养猪甲状腺细胞存活量的影响:与0mg/L氟化钠比较,40mg/L氟化钠染毒后猪甲状腺细胞的存活量基本相似;80,160mg/L氟化钠染毒后猪甲状腺细胞的存活量均明显下降(P<0.01)。②氟化钠对甲状腺过氧化物酶活性的影响:与0mg/L氟化钠比较,40,80,160mg/L氟化钠染毒后的甲状腺过氧化物酶活性均明显下降(P<0.01),呈剂量-效应关系。结论:氟化钠对原代培养的猪甲状腺细胞及甲状腺过氧化物酶活性均具有抑制作用。     

Determination of the falloff constant (k(f)) from modeling biochemical marker release: a new variable for discriminating therapies

A new variable termed the falloff constant (k(f)) was derived from the curve fitting of serial CK-MB measurements. k(f) represents the rate constant of maximal decline in serum CK-MB and is determined from the slope of the lognormal curve at the inflection point. Physiologically, kf's magnitude reflects the balance between CK-MB's rate of release from tissue and the rate of elimination. We examined k(f) in two myocardial infarction (MI) patient sets. The first set was homogeneous and taken from the TAMI 7 study (n = 147) and included 111 patients having TIMI 2-3 flow after thrombolytic therapy and 36 patients who initially had TIMI 0-1 flow. The TIMI 0-1 patients were opened to TIMI 3 by angioplasty within 3 h. The second set consisted of 196 patients enrolled in the IMPACT-AMI study that demonstrated the efficacy of the glycoprotein (GP) IIb/IIIa antagonist eptifibatide. This second set consisted of 93 patients in the GP IIb/IIIa treatment group and 103 in the placebo group. Log-normal curve-fitting parameters including peak maximum and curve area were also compared to k(f) in the GP IIb/IIIa versus placebo set. The Wilcoxon test showed no difference between the two groups of TAMI 7 patients (p = 0.22). However, there was a highly significant difference in kf between the GP IIb/IIIa treatment group versus the placebo group (p = 0.0014). Both k(f) and peak maximum from curve fitting showed significant differences between the GP IIb/IIIa treatment group and the placebo group; however, k(f) showed a substantially lower p-value (p = 0.0014 and p = 0.023, respectively). As expected, k(f) showed no difference between the TAMI 7 groups because this was a homogeneous patient set in that they all had TIMI 3 patency status within 3 h of treatment. However, in the patient set having very different treatments, GP IIb/IIIa versus placebo, there was a highly significant difference in the kf variable. These data suggest that differences in reperfusion are reflected by kf and that this variable may represent a valuable new nonmortality end point derived from curve fitting analysis.