Postoperative hyperamylasemia (POH) and acute pancreatitis after pancreatoduodenectomy (POAP): State of the art and systematic review

BackgroundPostoperative hyperamylasemia is a frequent finding after pancreatoduodenectomy, but its incidence and clinical implications have not yet been analyzed systematically. The aim of this review is to reappraise the concept of postoperative hyperamylasemia with postoperative acute pancreatitis, including its definition, interpretation, and correlation.MethodsOnline databases were used to search all available relevant literature published through June 2019. The following search terms were used: “pancreaticoduodenectomy,” “amylase,” and “pancreatitis.” Surgical series reporting data on postoperative hyperamylasemia or postoperative acute pancreatitis were selected and screened.ResultsAmong 379 screened studies, 39 papers were included and comprised data from a total of 9,220 patients. Postoperative hyperamylasemia was rarely defined in most of these series, and serum amylase values were measured at different cutoff levels and reported on different postoperative days. The actual levels of serum amylase activity and the representative cutoff levels required to reach a diagnosis of postoperative acute pancreatitis were markedly greater on the first postoperative days and tended to decrease over time. Most studies analyzing postoperative hyperamylasemia focused on its correlation with postoperative pancreatic fistula and other postoperative morbidities. The incidence of postoperative acute pancreatitis varied markedly between studies, with its definition completely lacking in 40% of the analyzed papers. A soft pancreatic parenchyma, a small pancreatic duct, and pathology differing from cancer or chronic pancreatitis were all predisposing factors to the development of postoperative hyperamylasemia.ConclusionPostoperative hyperamylasemia has been proposed as the biochemical expression of pancreatic parenchymal injury related to localized ischemia and inflammation of the pancreatic stump. Such phenomena, analogous to those associated with acute pancreatitis, could perhaps be renamed as postoperative acute pancreatitis from a clinical standpoint. Patients with postoperative acute pancreatitis experienced an increased rate of all postoperative complications, particularly postoperative pancreatic fistula. Taken together, the discrepancies among previous studies of postoperative hyperamylasemia and postoperative acute pancreatitis outlined in the present review may provide a basis for stronger evidence necessary for the development of universally accepted definitions for postoperative hyperamylasemia and postoperative acute pancreatitis.     

Does the false-negative rate for 1 or 2 negative sentinel nodes after neo-adjuvant chemotherapy translate into a high local recurrence rate?

Prospective trials demonstrate that sentinel node (SN) biopsy after neo-adjuvant chemotherapy (NACT) has a significant false-negative rate (FNR) when only 1 or 2 SNs are removed. It is unknown whether this increased FNR correlates with an elevated risk of recurrence. Tumor Registry data at an NCI-Designated Comprehensive Cancer Center were reviewed from 2004 to 2018 for patients having a negative SN biopsy after NACT. Among 190 patients with histologically negative nodes after NACT having 1 (n = 42), 2 (n = 46), and ≥3 (n = 102) SNs, axillary recurrences occurred in 7.14%, 0%, and 1.96% (p = 0.09), breast recurrences occurred in 2.38%, 6.52%, and 0.98% (p = 0.12), and distance recurrences occurred in 16.67%, 8.70%, and 7.84% (p = 0.27), respectively. Time to first recurrence did not differ by SN count (p = 0.41). After adjustment for age, race, clinical stage, and receptor status, there were no differences in the rates of axillary (p = 0.26), breast (p = 0.44), or distance recurrence (p = 0.24) by numbers of SNs harvested. Median follow-up was 46.8 months. Despite higher post-NACT FNRs reported in randomized trials for patients having <3 sentinel nodes, recurrence rates were not significantly different for 1 versus 2 versus ≥3 SNs. This suggests that patients having 1 or 2 post-NACT SNs identified may not necessitate axillary dissection.     

HbA1C is not directly associated with complications of bariatric surgery

IntroductionBariatric surgery is effective therapy for weight loss and diabetes control. While patients with poorly controlled type 2 diabetes (T2D) experience significant benefit from bariatric surgery, the impact of hyperglycemia on perioperative risks is unclear.ObjectiveThis study aims to investigate effect of elevated glycated hemoglobin (HbA1C) on perioperative risks for patients undergoing sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB).Settings117,644 patients undergoing RYGB or SG between the years of 2017 and 2018 in the United Stated were analyzed. Data was obtained using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database.MethodsThree commonly used cutoff levels of HbA1C were selected (6.5, 7.0, and 8.5). Complications were compared between groups of patients above and below each HbA1C level. Multivariable logistic regression models were used to account for confounders.ResultsWithout risk adjustment, HbA1C is indirectly associated with increased rates of surgical complications. However, after adjusting for underlying co-morbidities, HbA1C is not associated with overall complications, including 30 day readmissions, reoperations, reinterventions, or death at any HbA1C cutoff: 6.5 (odds ratio [OR] 1.041, P value = .219), 7.0 (OR 1.020, P value = .551), or 8.5 (OR 1.051, P value = .208).ConclusionThere is no direct relationship between HbA1C and early postoperative complications of SG and RYGB. Thus, optimizing preoperative HbA1C values alone, may not translate into decreased surgical complications of bariatric surgery. (Surg Obes Relat Dis 2020;17:271–275.) © 2020 American Society for Metabolic and Bariatric Surgery. All rights reserved.     

Endoscopic therapy of weight regain after bariatric surgery

Weight regain following primary bariatric surgery occurs in a significant proportion of patients and is attributed to epidemiological, anatomical and metabolic factors. Surgical revision of these patients has significant risks and limited benefits. Endoscopic revisions that reduce gastric pouch size and diameter of the gastrojejunal anastomosis may offer an effective, safe, less invasive and even reproducible treatment. We herein discuss the indication, selection and feasibility of different endoscopic techniques that could be used in the management of weight regain following primary bariatric surgery. Future research could optimize a personalized approach not only in the endoscopic management but also in combination with other therapeutic modalities for weight regain after bariatric surgery.     

A case-control study of risk factor for renal cell cancer in northern Italy

A hospital-based case-control study of renal cell cancer was conducted in northern Italy betwen 1986 and 1989, with 240 cases of renal cell cancer (150 males and 90 females), and 665 controls (445 males and 220 females) chosen on the basis of age, sex, and area of residence. No associations were found between renal cell cancer and: body mass index (BMI); number of cigarettes smoked; age at starting to smoke; years of smoking; consumption of wine, beer, spirits, coffee, decaffeinated coffee; tea; intake of animal protein, fruits, and vegetables; various resproductive factors; hormonal use; sexual habits; sexually transmitted diseases; or selected occupational exposures. The odds ratio (OR) was above unity in smokers (OR=1.34 for 15 cigarettes/day), but the trends in risk with dose or duration were not statistically significant. Significant positive associations were found between renal cell cancer and sources of fat intake, especially margarine (OR for highest vs lowest intake = 1.71), and oils (OR=1.89) whereas carrot intake showed a negative association (OR=0.62). Also, a history of nephrolithiasis and multiple episodes of cystitis showed weak positive associations (OR=2.00, 95 percent confidence interval (CI) 1.07–3.73; and OR=1.60, 95 percent CI 0.95–2.70, respectively).Address reprint requests to Dr Talamini. The work was conducted with the contribution of the Italian Association for Cancer Research, Milan, Italy and the CNR (Italian National Research Council) Applied Projects Oncology (Contract n. 85.02209.44).Drs Talamini, Barón, Barra, Bidoli, Serraino, and Franceschi are in the Epidemiology Unit, Aviano Cancer Center, Via Pedemontana Occ. 33081 Aviano (PN) Italy. At the time of this work, Dr Barón was a visiting biostatistician from the Department of Preventive Medicine and Biometrics, University of Colorado, Health Science Center, CO, funded by the National Cancer Institute (US) and the Italian National Research Council. Dr Franceschi is also chief of the Hormones and Sexual Factors and Cancer Working Group of the European Organization for Cooperation in Cancer Prevention Studies, Bruxelles, Belgium. Drs La Vecchia and Negri are in the Mario Negri Institute for Pharmacological Research, Milan, Italy. Dr La Vecchia is also in the Institute of Social and preventive Medicine, University of Lausanne, Switzerland.     

Prevalence of hepatitis C virus genotypes in southern Italy

HCV is ubiquitous. In 50% of all cases it causes chronic hepatitis that often evolves into liver cirrhosis and hepatocellular carcinoma. Recently HCV has been classified in 5 genotypes by Okamoto. The purpose of this study is to evaluate the prevalence of 5 genotypes in Campania, a region of Southern Italy, where the prevalence of anti-HCV antibodies ranges from 0.87 to 4%, and to evaluate the correlation between the HCV genotypes and the severity of histological damage. One hundred and thirty-five anti-HCV positive patients were enrolled and tested by PCR to identify HCV-RNA. One hundred and twenty-four patients resulted HCV-RNA positive. Genotyping was performed as described by Okamoto et al. with minor modifications of the specific primer to type III proposed by Silini et al. Eight patients were negative for all genotypes. Eight patients were positive for type I(1a), 61 for type II(1b), 39 for type III(2a), 11 for type IV(2b) and 1 for type V(3a). In 4 cases two different genotypes were present in the same sample [II(1b)-IV(2b), III(2a)-II(1b) twice, III(2a)-IV(2b)]. Histological evaluation of liver damage showed: CPH (22 cases), minimal CAH (56), severe CAH (31) and liver cirrhosis (15). There was no statistically significant correlation between the 5 genotypes and the severity of histological damage. Data on the prevalence of genotype II(1b) in Italy are similar to those reported for other European countries. The prevalence of genotypes in Southern Italy is similar to that reported in the population of Northern Italy.     

Role of nitric oxide in the contractile response to 5-hydroxytryptamine of the basilar artery from Wistar Kyoto and stroke-prone rats

1. Isolated basilar arteries from spontaneously hypertensive stroke-prone rats (SHRSP) are more sensitive to the contractile effect of 5-hydroxytryptamine (5-HT) than those from normotensive Wistar Kyoto rats (WKY). This has been attributed to a different proportion of 5-HT receptor subtypes mediating these responses. In the present study we have examined if differences in nitric oxide release could also contribute to this difference in sensitivity to 5-HT.
2. At rest, the normalized internal diameter was significantly smaller in SHRSP (297.4±3.5 μm, n=88) than in WKY (375.1±4.0 μm, n=62, P<0.01) arteries. The contractile response to 100 mM KCl was higher in WKY (3.57±0.15 mN mm⁻¹, n=22) than in SHRSP arteries (2.32±0.20 mN mm⁻¹, n=28, P<0.01).
3. When added on the plateau of contraction to 5-HT (1 μM), acetylcholine (ACh, 3 μM) evoked significant relaxation in all preparations from WKY (n=20), but only in 15 out of 26 preparations from SHRSP. The mean relaxations were 55.4±5.2% in WKY and 20.6±4.6% in SHRSP (as % of the contractile tone evoked by 5-HT; P<0.01).
4. The NO synthase inhibitor N^ω-nitro-L-arginine (L-NOARG, 0.1 mM) produced a similar increase in tone in both WKY and SHRSP. This tone was equal (in % of the contractile response to 100 mM KCl) to 70.8±4.4% in WKY (n=20) and 67.6±5.9% in SHRSP (n=26) and was reversed by L-arginine (1 mM) and by 1,4-dihydropyridine calcium channel blockers (10 nM nisoldipine, 10 nM lacidipine, 100 nM nifedipine). The L-NOARG-induced tone was absent when the arteries were bathed in phosphate-free Krebs (pH 7.4).
5. EC₅₀ values of 5-HT were about four fold smaller in SHRSP than in WKY arteries (P<0.01). The maximal response to 5-HT (E_max) was higher than 100 mM KCl-contraction in SHRSP but not in WKY arteries. Removal of endothelium produced a shift to the left of the 5-HT curve in WKY, but not in SHRSP arteries.
6. When evoked in phosphate-free Krebs, the contractile responses to 5-HT showed tachyphylaxis, but the responses were reproducible by adding the agonist at 30 min intervals. In such conditions, EC₅₀ values of 5-HT were about two fold smaller in SHRSP than in WKY arteries (P<0.01). In phosphate-free Krebs, the blockade of NO synthase did not change the contractile response to 100 mM KCl; it reduced EC₅₀ and increased E_max of 5-HT in WKY, but not in SHRSP.
7. These results confirm that the sensitivity to 5-HT is higher in basilar artery isolated from SHRSP than in those from WKY. They show that endothelium-dependent vasorelaxation to ACh is impaired in SHRSP. The finding that removal of endothelium or blockade of NO synthase augmented the contractile response to 5-HT in WKY, but not in SHRSP basilar arteries indicates that the difference in responsiveness to 5-HT observed between WKY and SHRSP basilar arteries might be, at least in part, related to dissimilarities in NO release. Furthermore, the L-NOARG-induced contraction sensitive to calcium channel blockers indicates that, in basilar arteries, NO production might lower L-type calcium channel opening and thereby control the tone of the vessels.

     

Immune response to specific molecules of the retina in proliferative vitreoretinal disorders

In recent years, several reports have contributed to a growing suspicion that there is immunologic involvement in proliferative intraocular disorders such as proliferative vitreoretinopathy and proliferative diabetic retinopathy. Immune privilege, as in the brain, ovary and testis, also exists in the eye. Therefore, immune responses to unique molecules of the eye, e.g. retinal S-antigen (S-Ag), which the immune system never learns to regard as self, are possible. This study describes the presence of S-Ag, a major soluble photoreceptor protein involved in the visual transduction cascade, in pathological vitreous. We employed indirect immunoblotting, with human retina as substrate, and demonstrated the occurrence of antiretinal antibodies in the sera of a series of patients with proliferative vitreoretinal disorders. Immunoblot analysis of physiological retina and lyophilized S-Ag, revealed this protein as a target molecule of the immunological involvement of the retina. Further immunochemical investigation, however, must clarify whether this autoimmune reaction is the cause, a consequence, or an aggravating factor of the disease. As we come to understand the cellular and molecular mechanism, a new generation of therapeutic strategies may be envisioned.Presented in part at the 18th Meeting of the Club Jules Gonin, Vienna, 1992     

A rise in the incidence of childhood cancer in the United States.

From the early 1980s to the early 1990s, the incidence of cancer in American children under 10 years of age rose 37 percent, or 3 percent annually. There is an inverse correlation between increases in cancer rates and age at diagnosis; the largest rise (54 percent) occurred in children diagnosed before their first birthday. Rates rose for all 11 states and cities included in the analysis. A jump in cancer rates for children born in 1982-83 was followed by a drop; but another abrupt rise for the 1986-87 birth cohort has been sustained thereafter. Results indicate that the rising childhood cancer rate represents a far more serious problem in the United States than previous reports have suggested. The methodology used here adds three additional states and cities, analyzes children under 10 rather than under 15, begins the analysis in 1980 rather than in 1973, and extends the study to 1993, which may partially account for the new findings. There are no apparent explanations for these trends, suggesting that researchers should analyze the data more fully and propose hypotheses on potential causes. One possible factor, fetal and infant exposure to low-dose radioactivity, is explored here.     

Zaleplon, A Novel Nonbenzodiazepine Hypnotic, Effectively Treats Insomnia in Elderly Patients Without Causing Rebound Effects

BACKGROUND: Insomnia is a very common symptom, particularly in the elderly. Thus, all hypnotic medications should be carefully evaluated in the elderly population. Zaleplon, a new nonbenzodiazepine hypnotic with a short elimination half-life (approximately 1 hour), was evaluated in the current study. METHOD: This multicenter, randomized, placebo-controlled outpatient study evaluated the efficacy and safety of zaleplon, 5 and 10 mg, in elderly patients with insomnia (as defined by DSM-IV); zolpidem, 5 mg, was the active comparator. Sleep was assessed in 549 elderly patients (>/= 65 years old) by using morning questionnaires completed after each of 7 baseline nights during which placebo was given, 14 nights of double-blind treatment, and 7 nights of placebo after discontinuation of active treatment. RESULTS: Zaleplon, 10 mg, and zolpidem, 5 mg, significantly reduced sleep latency during both weeks of the study. Zaleplon, 5 mg, reduced sleep latency only during week 2. Sleep duration was increased with zolpidem, 5 mg, during weeks 1 and 2 and with zaleplon, 10 mg, during week 1. No clinically significant rebound insomnia was observed after discontinuation of treatment with zaleplon, whereas evidence of rebound effects was seen with zolpidem. There was no significant difference between either zaleplon dose and placebo in the frequency of any central nervous system adverse events. CONCLUSION: Zaleplon is effective in reducing latency to sleep without evidence of undesired effects in elderly patients with insomnia.