Impaired calcitonin secretion following stimulation in spasmophilic women

Calcitonin (CT) secretion following stimulation was studied in 9 young women suffering from spasmophilia, this having been diagnosed by clinical and electromyographic criteria. The controls were 9 women, matched by age, who responded negatively to the diagnostic tests. After rapid intravenous infusion (60 sec) of 4 mg/kg/lean body mass of calcium (as gluconate), CT concentration increased measurably (p less than 0.0001) in the controls, while remaining unchanged in the spasmophilic. The average increase per cent vs. the baseline values was 225% in the controls and 34% in those with spasmophilia (p less than 0.005). 5 out of 9 of the patients showed a completely flat curve. This finding, due to a diminished CT reserve in spasmophilia, may be considered a possible diagnostic feature as well as a fundamental pathological element in the reduction of the intracellular calcium pool responsible for the neuromuscular hyperexcitability. Moreover, the therapeutic use of the hormone in this condition is to be encouraged.     

Clinical value of cervical mediastinoscopy in the staging of bronchial carcinoma

Whether mediastinoscopy is indicated in the preoperative staging of bronchogenic carcinoma is still a controversial issue. It may be performed routinely (to exclude locally inoperable patients from surgery), selectively, or it may be regarded as superfluous (in centers which prefer an extended lympho adenectomy at the time of thoracotomy). We regard mediastinoscopy as indicated for the following purposes: 1) staging of NSCLC and SCLC; 2) diagnostic (mediastinal masses or lung tumors without previous histology); 3) restaging after primary chemotherapy; 4) assessment of prognosis in patients with borderline operability. The indication for 224 mediastinoscopies performed at our institution in the period from September 1991 through March 1999 was mainly for staging (59.2%) or diagnostic (30.6%). Eight (5.4%) patients underwent mediastinoscopy for the assessment of operability, and 7 (4.8%) after primary chemotherapy for the restaging of loco-regionally advanced lung cancer. Sensitivity and specificity rates were 87% and 100%, respectively, with an accuracy of 93% for the mediastinoscopy performed for the staging of lung cancer at all stages. If we consider the N2 tumors (42 cases) alone, the sensitivity was 76.7% and the specificity 100%, with an accuracy of 83.3%. Overall positive and negative predictive value resulted 100% and 87%, respectively, according to the data reported in literature. Our data confirm the role of mediastinoscopy as the gold standard for regional staging of lung cancer.     

Further evidence that insulin metabolism is a major determinant of peripheral insulin response to oral glucose in subjects with mild glucose intolerance

In mild glucose intolerance plasma concentration of C-peptide seems to give an estimate of pancreatic B cell secretion more reliable than plasma insulin itself. In the present study we measured the plasma levels of insulin and C-peptide after oral glucose load in 100 mildly glucose intolerant subjects, focusing our attention on high and low insulin responders. According to an insulin incremental area after oral glucose higher or lower than the mean +/- SD of the mean, 16 subjects were classified as "high insulin responders", and 17 as "low insulin responders". The two groups were similar for sex, age and bw. Mean insulin incremental area was almost 9-fold greater in high insulin responders than in low insulin responders (0.88 +/- 0.03 vs 0.10 +/- 0.01 pmol/ml min, p less than 0.001). Also mean C-peptide incremental area was significantly greater in high insulin responders than in low insulin responders, but the differences between the two groups were smaller. Indeed, mean C-peptide area was approximately 2.5-fold greater in high insulin responders than in low insulin responders (1.58 +/- 0.12 vs 0.66 +/- 0.07 pmol/ml min, p less than 0.001). These results give further support to the concept that in mild glucose intolerance insulin metabolism is a major determinant of peripheral insulin response to oral glucose load.     

Assessment and treatment of severe pancreatitis. Protease inhibitor

From the theoretical point of view, antiproteolytic therapy would seem to be the rationale for acute pancreatitis management. Unfortunately, clinical human trials studying the role of antiproteases in the treatment of acute pancreatitis differ in several respects in terms of their basic design. As a consequence, any form of homogeneous analysis of the reported data as a whole is impossible. Considering the data emerging from a meta-analysis of five trials a rational use of antiproteases may result in a reduction of complications requiring surgery and of patient management costs only in selected cases, meaning by that severe and necrotic forms. As regards presumptive applications, over 400 patients were prospectively tested versus placebo in a double-blind trial with the aim of preventing acute pancreatitis after ERCP. The complication incidence was significantly lower among the pretreated patients; anyway, also in this field of protease inhibitor clinical application it is necessary to identify the patients with the greatest risk to develop post-ERCP acute pancreatitis. In conclusion, antiproteases can still play a role when given prophylactically or when used in the very early phases of the disease; moreover a 'multiple drugs approach' (including, for example, suitable antibiotics) seems to represent nowadays the most modern and rational treatment of acute pancreatitis.     

Diminished pituitary responsiveness to growth hormone-releasing factor in aging male rats

The pattern of GH secretion undergoes substantial changes in the aging rat, resulting in decreased daily secretion of GH. In this study, the pituitary responsiveness to GH-releasing factor (GRF) was examined in young (2- to 5-month old) and aging (14- to 18-month old) male rats. In vivo studies were performed under sodium pentobarbital anesthesia. After injection of 250 ng GRF/100 g BW, young rats experienced more GH secretion [peak level, 544.5 +/- 209.5 (+/- SEM) ng/ml] than did 18-month-old rats (89.3 +/- 13.7 ng/ml). To investigate the locus of this insensitivity to GRF, anterior pituitary cells from young and aging rats were dispersed and placed in primary culture. While basal GH secretion from the cultured pituitary cells was similar in the two groups (49.7 +/- 3.5 vs. 47.8 +/- 2.7 ng/ml X 4 h for the 2- and 18-month old rats, respectively), the GH-releasing ability of GRF was partially but significantly impaired in cells derived from both 14- and 18-month old rats; 100 nM GRF stimulated the release of 96.7 +/- 1.8 ng/ml X 4 h in the 18-month old rats as opposed to 115.0 +/- 6.0 (P less than 0.05) ng/ml X 4 h in the 2-month-old rats. Since GRF stimulates GH release through the activation of adenylate cyclase, intracellular cAMP levels were measured in the cultured pituitary cells. GRF stimulated 65% less intracellular cAMP accumulation in the 18-month-old rats. In 14-month-old rats, the ability of forskolin and (Bu)2 cAMP to release GH was impaired, while phorbol ester-elicited GH secretion was unchanged. In conclusion, the GH response to GRF is blunted in aging rats. While much of the insensitivity to GRF may be mediated by the increased somatostatin tone reported in aging rats, a diminished pituitary cAMP response to GRF may also be an important etiological factor in the hyposomatotropinemia of the aging male rat.     

Decreased hepatic insulin extraction in subjects with mild glucose intolerance

The fact that hyperinsulinemia occurs in simple obesity and mild glucose intolerance has been well established. Altered hepatic insulin extraction may influence the levels of circulating hormone. The simultaneous measurement of insulin and C-peptide concentrations in peripheral blood enables an in vivo estimation of hepatic insulin removal. To evaluate hepatic insulin extraction, insulin and C-peptide responses to oral glucose were studied in 176 obese and nonobese subjects with normal, impaired, or diabetic glucose tolerance. Insulin levels as well as insulin incremental areas in glucose intolerant subjects were significantly higher than in weight-matched controls. The levels of C-peptide as well as C-peptide incremental areas were only slightly enhanced in subjects with impaired glucose tolerance, whereas they were reduced in subjects with diabetic tolerance. The molar ratios of C-peptide to insulin, both in the fasting state and after ingestion of glucose, as well as the relationship between the incremental areas of the two peptides were used as measures of hepatic insulin extraction. They were significantly reduced in glucose intolerant subjects and, to a lesser extent, in nondiabetic obese subjects. These results indicate that peripheral hyperinsulinemia in subjects with simple obesity or impaired glucose tolerance is a result of both pancreatic hypersecretion and diminished hepatic insulin extraction. In subjects with a more severe degree of glucose intolerance, decreased hepatic insulin removal is the primary cause of hyperinsulinemia.     

Diagnosis and management of postoperative pancreatic fistula

Background

Postoperative pancreatic fistula (POPF) is the leading complication after partial pancreatic resection and is associated with increased length of hospital stay and resource utilization. The introduction of a common definition in 2005 by the International Study Group of Pancreatic Surgery (ISGPS), which has been since employed in the vast majority of reports, has allowed a reliable comparison of surgical results. Despite the systematic investigation of risk factors and of surgical techniques, the incidence of POPF did not change in recent years, whereas the associated mortality has decreased.

Purpose

The purposes of this review article were to summarize the current evidence on the diagnosis and management strategies of POPF and to provide a concise reference for the practicing surgeons and physicians.

Conclusion

The high incidence of POPF was accompanied by a shift from operative to non-operative management. However, the current management strategy is driven by the patient’s condition and local expertise and is generally based on poor evidence. A randomized trial showed that enteral nutrition is superior to total parenteral nutrition, and pooled data of randomized trials failed to show any advantage of somatostatin analogs for accelerating fistula closure. The choice of percutaneous versus endoscopic drainage of peripancreatic collections remains arbitrary, and—when re-operation is needed—there are very few comparative data regarding local drainage with or without main pancreatic stenting as opposed to anastomotic revision or salvage re-anastomosis. The continuous development of specialist, high-volume units with appropriate resources and multidisciplinary experience in complication management might further improve the evidence and the outcomes.     

Pancreatic fistula rate after pancreatic resection. The importance of definitions

BACKGROUND: Pancreatic fistula (PF) is still regarded as a serious complication both in terms of frequency and sequelae. The incidence varies greatly in different reports because of the different definitions used. The aim of this study was to compare several definitions of PF encountered in the current literature and to demonstrate that the PF rate in the same group of patients treated in a high volume center is dependent upon the definition applied. METHODS: A Medline search of the last 10 years was performed as regards the definition of PF. A score was assigned to the reproducible definitions based upon two basic parameters: daily output (cm3) and duration of the fistula represented by the number of days between the postoperative day of onset and the duration of the complication. Four definitions were formulated and were then applied to a group of 242 patients that underwent pancreatic head or intermediate resections with pancreatico-jejunal anastomosis in our Pancreatic Unit between November 1996 and December 2000. Statistical analysis was carried out using the Yates correct chi2 test with statistical significance set at p < 0.05. RESULTS: Among 26 different definitions identified, 14 were found suitable for the applied score. We formulated four final definitions summarizing the current concepts of PF. The incidence of PF ranged between 9.9 and 28.5% according to the different definitions applied with highly statistical differences between them. CONCLUSIONS: The PF rate after pancreatic resections is strictly dependent upon the definition used. An overall general agreement for an internationally accepted definition is urgently needed to correctly compare different experiences.     

Duct-to-mucosa versus end-to-side pancreaticojejunostomy reconstruction after pancreaticoduodenectomy: results of a prospective randomized trial

BACKGROUND: Anastomotic failure is still a significant problem that affects the outcome of pancreaticoduodenectomy. There have been many techniques proposed for the reconstruction of pancreatic digestive continuity, but there have been few prospective and randomized studies that compare their efficacy. METHODS: In the current work, 144 patients who underwent a pancreaticoduodenectomy with soft residual tissue were assigned randomly to receive either a duct-to-mucosa anastomosis (group A) or a 1-layer end-to-side pancreaticojejunostomy (group B). RESULTS: The 2 treatment groups were found not to have any differences in regards to vital statistics, underlying disease, or operative techniques. The postoperative course was complicated in 54% of the 144 patients, with a comprehensive incidence of abdominal complications in 36% (group A, 35%; group B, 38%; P=not significant). The principal complication was pancreatic fistulas, which occurred in 14% of patients (group A, 13%; group B, 15%; P=not significant). Two patients (2%) required reoperation; the postoperative mortality rate was 1%. CONCLUSION: The 2 methods that were studied revealed no significant difference the rate of complications.     

Modeling minimal residual disease (MRD)-testing

There is considerable effort to develop more sensitive methods to detect minimal residual disease (MRD) in bone marrow and blood samples of persons with cancer. Results of MRD-testing are used to predict clinical outcome and determine if more anti-cancer therapy is needed.Mathematical models were developed to assess factors affecting sensitivity and specificity of MRD-testing at diverse cancer cell prevalences. Modeling results and predictions were compared to results of large published studies.Accuracy of MRD-testing depends on cancer cell prevalence and distribution in the blood or bone marrow of the subject, sensitivity and specificity of the MRD-test and sample size. In subjects with low cancer cell prevalences (< or = 10(-4)) results of MRD testing are likely inaccurate. Increasingly sensitive MRD-tests are only marginally useful; the major obstacle to accuracy is inadequate sampling.Increasing sensitivity of methods to detect MRD is unlikely sufficient to increase accuracy of MRD-testing. In contrast, increased sampling (size and frequency) and assigning a high cut-off value (for example, > or = 10(-3)) to declare a MRD-test positive will increase sensitivity and specificity, respectively.