Safety, feasibility, and short-term-outcome of anal endoscopic submucosal dissection for anal intraepithelial neoplasia: an option for focal lesions?

BACKGROUND: Anal intraepithelial neoplasia (AIN) appears in three different stages. AIN 1 and AIN 2 (p16 negative) are defined as low risk and unlikely to progress to invasive anal cancer. AIN 2 (p16 positive) and AIN 3 are of high risk and should be treated because progression rates to anal cancer are around 10% and treatment significantly reduces this risk. The correct treatment is still a matter of debate. Human papilloma virus (HPV) plays a role in the development of AIN. Our aim was to assess anal endoscopic dissection (aESD) as an intervention for AIN3. METHODS: We retrospectively evaluated patients who underwent aESD for AIN 3 between December 2017 and March 2023. The interventional technique itself (duration, complications, size of specimen) and patient outcomes (recurrence, progression to anal cancer, re-intervention) were analyzed. RESULTS: Fifteen patients with a median age of 52 years (23-78) underwent aESD for AIN 3. All tested specimens were positive for HPV. Median duration of intervention was 56.1 min, one delayed postinterventional bleeding occurred, and specimen size was 12.05 cm2. Median follow-up was 11.17 months. Three recurrences (20%) appeared: one was resected via biopsy and two were again treated with aESD. There was no progression to invasive anal cancer in the follow-up period. CONCLUSIONS: Anal endoscopic submucosal dissection seems to be a safe and feasible treatment for AIN. Recurrences are seldom and can be treated again with the same method. Nevertheless, indications for resection in comparison to radiofrequency ablation, pharmacological therapy, and watch-and-wait strategy are still unclear. TRIAL REGISTRATION: Ethics commission of Salzburg, Austria, EK-Nr. 1056/2023. Keywords: Endoscopic submucosal dissection, anal intraepithelial neoplasia, anal cancer.

[Polymyalgia rheumatica in 18-fluorodeoxyglucose-positron-emission-tomography/computed tomography : Improvement in diagnostic accuracy and differentiation from rheumatoid arthritis]. / Polymyalgia rheumatica in der 18-Fluordesoxyglukose-Positronenemissionstomographie/Computertomographie : Verbesserung diagnostischer Genauigkeit und Abgrenzung von rheumatoider Arthritis.

BACKGROUND: The diagnosis of patients with polymyalgia rheumatica (PMR) has relied upon the clinical examination of symptoms and laboratory parameters of inflammation until now. Currently, the use of different imaging modalities is being explored, including ultrasound, MRI and PET. OBJECTIVES: The aim was to evaluate the diagnostic value of 18-fluorodeoxyglucose-positron-emission-tomography/computed tomography (18F-FDG-PET/CT) for PMR, in order to improve the sensitivity and specificity of diagnosing PMR and to improve the differential diagnosis of rheumatoid arthritis (RA). MATERIALS AND METHODS: Examinations using 18F-FDG-PET/CT of 284 rheumatological patients, including 97 patients with PMR, were retrospectively evaluated over a 44-month period. Furthermore, 13 regions changed by inflammation were analysed via a three-dimensional region of interest (ROI) measurement with determination of maximum standardized uptake values (SUVmax), followed by statistical analyses. RESULTS AND DISCUSSION: Patients with PMR presented significantly elevated uptake in all regions examined (p < 0.001), compared with a control group treated for rheumatological diseases. The method with the highest diagnostic relevance was represented by the combination of four SUVmax values of both anterolateral hip capsules and both ischial tuberosities, reaching a sensitivity of 91.3% and a specificity of 97.6% with a cut-off of 11.0 SUV at the initial diagnosis of PMR patients who had not yet received any immunosuppressive therapy. Patients with RA could be significantly distinguished from those with PMR at initial diagnosis in the same anatomical regions (p < 0.001).

[Impact of anastomotic leakage on long-term survival in mid-to-low rectal cancer]. / Einfluss der Anastomoseninsuffizienz auf das Langzeitüberleben beim tiefen Rektumkarzinom.

BACKGROUND: The occurrence of anastomotic leakage (AL) after sphincter preserving anterior rectal resection in patients with rectal cancer is associated with increased morbidity and mortality. The impact of AL on long-term survival has, however, still not been sufficiently investigated and is currently the subject of controversial discussion. OBJECTIVES: The aim of this study was to investigate the impact of AL on long-term survival in patients with Union of International Cancer Control (UICC) (y)0-III stage mid-to-low rectal cancer who underwent sphincter preserving rectal resection. MATERIAL AND METHODS: A total of 108 patients with a mid-to-low rectal cancer (UICC stage (y)0-III) who underwent sphincter preserving surgery between January 2003 and October 2010 were identified within the institutional prospective colorectal cancer database. The impact of AL on 5-year overall (OS), cancer specific (CSS) and relapse-free survival (RFS) was investigated. RESULTS: The overall leakage rate was 17.6 % (grade A 4.6 %, grade B 4.6 % and grade C 8.3 %). After a median follow-up of 70 months (range 24-123 months), patients with an anastomotic leakage had a significantly decreased 5-year OS (63.6 % versus 87.8 %, p = 0.02), CSS (72.2 % versus 93.5 %, p = 0.02) and RFS rate (61.1 % versus 84.2 %, p = 0.01). In univariable Cox regression analysis AL was associated with an unfavorable OS (hazard ratio HR 3.05, 95 % CI: 1.11-8.39, p = 0.03), CSS (HR 4.21, 95 % CI: 1.13-15.70, p = 0.03) and RFS (HR 3.02, 95 % CI: 1.20-7.58, p = 0.02). CONCLUSION: In the study cohort anastomotic leakage after sphincter preserving anterior resection in patients with mid-to-low rectal cancer was associated with a significantly unfavorable impact on overall and oncological survival.

First Report of the Root-Knot Nematode Meloidogyne arenaria on Cheeseweed Mallow (Malva parviflora) in the United States.

During a 2010 field trial for examining alternatives to methyl bromide soil fumigation for the production of field-grown cut flowers, weeds were collected for identification and evaluated for their potential as hosts for plant pathogenic nematodes. In one cut flower field located in Martin County, FL, six cheeseweed mallow (Malva parviflora L.) plants were collected that had root-galling typical of infection by a root-knot nematode (Meloidogyne spp.). Field collected plants were used for species identification of the weed and maintained in the greenhouse for seed production. Several gravid female nematodes were extracted from field collected mallow roots and individually identified as Meloidogyne arenaria based on their esterase phenotype (PhastSystem, GE Healthcare) (1). A single egg mass was then extracted from the field collected mallow roots and inoculated onto a tomato plant (Solanum lycopersicum, 'Rutgers') grown in steamed builders sand in the greenhouse. The single egg mass culture was increased for 8 weeks, until galling was sufficient to produce adequate nematode inoculum to complete Koch's postulates on the original mallow host. Ten mallow plants were inoculated with single egg masses originally isolated from mallow and increased on tomato. Ten additional plants were maintained in the greenhouse as uninoculated controls. Inoculated and control mallow plants were grown in the greenhouse for 8 weeks, after which the roots were evaluated for galling, and root-knot nematode J2 were extracted from roots and soil and counted. All inoculated plants produced galled roots and control plants did not. Gravid females were extracted from mallow roots and identified as M. arenaria based on esterase phenotype as previously described. Ten gravid females for each DNA extraction were collected from mallow roots and DNA was isolated with the PowerSoil DNA Isolation Kit (MO BIO Laboratories, Inc., Carlsbad, CA). Identification of M. arenaria was confirmed by using species-specific primers F5'-TCGAGGGCATCTAATAAAGG-3' and R5'-GGGCTGAATAATCAAAGGAA-3' (2) and F5'-TCGGCGATAGAGGTAAATGAC-3' and R5'-TCGGCGATAGACACTACAACT-3' (4), which produced single amplicon bands of the expected size of 420 and 950 bp, respectively. This weed species has been reported as a host for M. javanica in Algeria and as an experimental host in Egypt (3), but this report, to our knowledge, constitutes the first documentation of Malva parviflora as a natural host of M. arenaria. The importance of weeds as hosts for plant parasitic nematodes cannot be over emphasized. As growers, particularly in Florida and California, continue to lose tools for broad-spectrum pest control, the ability of nematodes to reproduce on uncontrolled weeds will become increasingly important. References: (1) J. A. Brito et al. Nematology 10:757, 2008. (2) K. Dong et al. Nematropica 31:273, 2001. (3) M. Quader et al. Australas. Plant Pathol. 30:357, 2001. (4) C. Zijlstra et al. Nematology 2:847, 2000.

Cardiac re-synchronization therapy: effects on myocardial perfusion at rest, after vasodilation and oxygen consumption.

AIM: Cardiac resynchronization therapy (CRT) has been shown to improve haemodynamics and clinical symptoms in heart failure patients. The present study evaluated the effects of a 4-month CRT on myocardial blood flow (MBF) at rest, after vasodilation and on myocardial oxygen consumption (MVO(2)). PATIENTS, METHODS: We studied 16 patients with idiopathic dilated cardiomyopathy prior to and during CRT performed as biventricular pacing. Resting MBF and MVO(2) were determined from an (11)C-acetate PET study and vasodilator MBF from a (13)N-ammonia study. RESULTS: MBF at rest (0.55 +/- 0.10 ml/min/g), after vasodilation (1.20 +/- 0.45 ml/min/g), and MVO2 (0.082 +/- 0.014/min) did not change by mid-term CRT at a global level (0.57 +/- 0.11 ml/min/g; 1.32 +/- 0.49 ml/min/g; 0.085 +/- 0.018/min), whereas the rate pressure product (RPP) normalised MVO(2) decreased from 0.104 +/- 0.024 to 0.086 +/- 0.018/min (p = 0.02). At baseline, the regional analysis revealed significantly higher values for all parameters in the lateral wall than for those in the other walls. Under CRT the regional differences between the resting parameters equalized and all parameters showed significant lower coefficients of variation. CONCLUSION: Effects of mid-term CRT on resting MBF, vasodilator MBF and MVO(2) occur at a regional level. The resynchronization is associated with a more homogenous distribution pattern of these parameters among the myocardial walls. Substantial alterations to global MBF at rest, after vasodilation or to MVO(2) are not detectable. Regarding the RPP normalised MVO(2), there is evidence of improved ventricular efficiency through CRT.

ATP-induced structural change of the thermosome is temperature-dependent.

Protein folding by chaperonins is powered by ATP binding and hydrolysis. ATPase activity drives the folding machine through a series of conformational rearrangements, extensively described for the group I chaperonin GroEL from Escherichia coli but still poorly understood for the group II chaperonins. The latter--archaeal thermosome and eukaryotic TRiC/CCT--function independently of a GroES-like cochaperonin and are proposed to rely on protrusions of their own apical domains for opening and closure in an ATP-controlled fashion. Here we use small-angle neutron scattering to analyze structural changes of the recombinant alpha-only and the native alphabeta-thermosome from Thermoplasma acidophilum upon their ATPase cycling in solution. We show that specific high-salt conditions, but not the presence of MgATP alone, induce formation of higher order thermosome aggregates. The mechanism of the open-closed transition of the thermosome is strongly temperature-dependent. ATP binding to the chaperonin appears to be a two-step process: at lower temperatures an open state of the ATP-thermosome is predominant, whereas heating to physiological temperatures induces its switching to a closed state. Our data reveal an analogy between the ATPase cycles of the two groups of chaperonins and enable us to put forward a model of thermosome action.

Successful use of cardiac allograft from serotonin antagonist intoxication.

BACKGROUND: Compromised organ donors are generally not accepted for heart transplantation (HT) despite the increasing number of critically ill patients on the waiting lists. By extending the donor criteria to include certain cases of intoxication, the organ shortage may be reduced. METHODS: The case of a successful orthotopic HT with an allograft from a donor poisoned by antidepressant overdose is presented. RESULTS: Early graft function was satisfactory with anteroseptal dyskinesis and an ejection fraction of 75% on echocardiography. The cardiac allograft recipient suffered some postoperative complications including gastrointestinal problems. The following period was up to now uneventful. Discharge from the intensive care unit was after 4 days. In-hospital stay was prolonged at 26 days. CONCLUSIONS: Because of limited myocardial toxicity, donor hearts from certain victims of antidepressant intoxication may be safely used for HT. Existing cardiac organ donor criteria must be reevaluated to maximise the available organ pool.

Laparoscopic cholecystectomy and interventional endoscopy for gallstone complications during pregnancy.

BACKGROUND: Symptomatic or complicated gallstone disease is the most common reason for nongynecological operations during pregnancy. Gallstones are present in 12% of all pregnancies, and more than one-third of patients fail medical treatment and therefore require surgical endoscopy or laparoscopy. Gallstone pancreatitis and jaundice during pregnancy is associated with a high recurrence rate, exposing both fetus and mother to an increased risk of morbidity and mortality. METHODS: During a 4-year period, all pregnant patients (n = 37) with symptomatic or complicated gallstone disease were studied prospectively at the Landeskrankenhaus in Salzburg, Austria. Five patients had an endoscopic retrograde cholangiopancreatogram (ERCP) for biliary pancreatitis or jaundice; two of these underwent subsequent laparoscopic cholecystectomy. Another seven patients required laparoscopic cholecystectomy for severe pain or cholecystitis; all were in their 13th-32nd gestational week. Access was established by Veress needle in all cases. Insufflation pressure was 8-10 mm Hg, and mean operative time was 62 min. RESULTS: All patients delivered full-term, healthy babies. There were no postendoscopic or postoperative complications. All patients enjoyed full relief from their symptoms; there were no recurrences of pancreatitis or jaundice. CONCLUSIONS: The combination of ERCP and laparoscopic cholecystectomy offers a safe and effective option for the definitive treatment of complicated gallstone disease and intractable pain during pregnancy, and there is sufficient access for the combined treatment to be employed.

Conformational rearrangements of an archaeal chaperonin upon ATPase cycling.

Chaperonins are double-ring protein assemblies with a central cavity that provides a sequestered environment for in vivo protein folding. Their reaction cycle is thought to consist of a nucleotide-regulated alternation between an open substrate-acceptor state and a closed folding-active state. The cavity of ATP-charged group I chaperonins, typified by Escherichia coli GroEL [1], is sealed off by a co-chaperonin, whereas group II chaperonins--the archaeal thermosome and eukaryotic TRiC/CCT [2]--possess a built-in lid [3-5]. The mechanism of the lid's rearrangements requires clarification, as even in the absence of nucleotides, thermosomes of Thermoplama acidophilum appear open in vitrified ice [6] and closed in crystals [4]. Here we analyze the conformation of the thermosome at each step of the ATPase cycle by small-angle neutron scattering. The apo-chaperonin is open in solution, and ATP binding induces its further expansion. Closure seems to occur during ATP hydrolysis and before phosphate release, and represents the rate-limiting step of the cycle. The same closure can be triggered by the crystallization buffer. Thus, the allosteric regulation of group II chaperonins appears different from that of their group I counterparts.

Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol-lowering therapy in patients with early stages of coronary atherosclerosis.

BACKGROUND: Early stages of coronary atherosclerosis are characterized by a mainly functional impairment of coronary vasodilator capacity under the impact of such risk factors as hypercholesterolemia. The goal of this study was to determine whether 6-month cholesterol-lowering therapy improves coronary flow reserve in patients with angina, reduced flow reserve despite minimally diseased coronary vessels or even normal angiogram, and mild to moderately elevated LDL levels on average. METHODS AND RESULTS: We noninvasively investigated 23 consecutive patients (18 men, 5 women; mean age, 56+/-7.6 years) with a mean LDL level of 165+/-34 mg/dL at baseline by PET for myocardial blood flow measurement with [13N]ammonia at rest and under dipyridamole stress (0.56 mg/kg) before and after lipid-lowering therapy with simvastatin for 6 months. Between baseline and the 6-month follow-up, total cholesterol concentration fell from 241+/-44 to 168+/-34 mg/dL, and the LDL level decreased from 165+/-34 to 95+/-26 mg/dL (P<0.001). Overall, coronary flow reserve increased from 2.2+/-0.6 to 2.64+/-0.6 (P<0.01). Maximal coronary flow increased significantly from 182+/-36 to 238+/-58 mL/minx100 g (P<0.001) at follow-up. Minimum coronary resistance declined significantly from 0. 51+/-0.12 to 0.40+/-0.14 mm Hg. mL-1. minx100 g (P<0.001). Concomitantly, a regression of anginal symptoms was observed in most patients. CONCLUSIONS: Our results suggest that cholesterol-lowering therapy with simvastatin may improve overall coronary vasodilator capacity assessed noninvasively by PET in patients with mild to moderate hypercholesterolemia. Consequently, intensive lipid-lowering therapy is considered a vasoprotective treatment for selected patients in very early stages of coronary atherosclerosis with the potential of preventing further disease progression.

[Improved coronary vasodilator capacity by drug lipid lowering therapy in patients in the early stage of coronary atherosclerosis with reduced coronary reserves and moderate LDL hypercholesteremia]. / Verbesserung der koronaren Vasodilatationskapazität durch medikamentöse Lipidsenkung bei Patienten im Frühstadium der koronaren Atherosklerose mit eingeschränkter Koronarreserve und mässiggradiger LDL-Hypercholesterinämie.

BACKGROUND: An abnormal coronary flow reserve represents an early marker of impaired blood flow regulation in the natural history of coronary atherosclerosis under the impact of risk factors such as hypercholesterolemia. Our clinical investigation was aimed at assessing noninvasively the integrative coronary flow response to dipyridamole stress in 18 consecutive patients with microvascular angina, only moderately elevated LDL-cholesterol levels (168 +/- 33 mg/dl), and reduced vasodilator capacity despite normal (n = 9) or slightly abnormal (n = 9) coronary arteriograms (minimal disease with luminal irregularities and/or diameter reduction < or = 30%) before and after 6-month lipid-lowering therapy (simvastatin). METHODS: Regional and averaged myocardial blood flow were measured at rest and after dipyridamole induced vasodilation (0.56 mg/kg) using dynamic positron emission tomography (PET) and N-13 ammonia as flow tracer related to a 3-compartment kinetic model. Baseline data (mean +/- SD): 13 males, 5 females; mean age: 56 +/- 8 years; basal coronary flow: 90 +/- 22 ml/min x 100 g; after lipid intervention: 93 +/- 18 ml/min x 100 g (n.s.). Total cholesterol: 246 +/- 45 mg/dl. RESULTS AFTER 6-MONTH LIPID INTERVENTION: Total cholesterol decreased to 170 +/- 36 mg/dl (p < 0.001); mean LDL level: 97 +/- 26 mg/dl (p < 0.001). Coronary dilator capacity increased, assessed in terms of minimal coronary resistance: 0.38 +/- 0.08 vs 0.49 +/- 0.09 units at baseline (p < 0.01), myocardial blood flow under dipyridamole: 232 +/- 43 vs 186 +/- 37 ml/min x 100 g at baseline (p < 0.01), and instantaneous flow ratio: 2.6 +/- 0.7 vs 2.2 +/- 0.6 (p = 0.06). Concomitantly, a considerable regression of angina was noticed in the majority of patients. CONCLUSIONS: An improvement of the non-invasively determined integrative dipyridamole induced coronary vasodilator capacity may be achieved after 6 months by intensive lipid lowering at a very early stage of coronary atherosclerosis. Consequently, aggressive cholesterol-lowering therapy represents an antiischemic and antianginal approach suggesting, at least in part, functional reversal and probably prevention of further disease progression.

[Treatment of postoperative bile fistulas after laparoscopic cholecystectomy by ERCP, EPT and bile duct drainage]. / Die Behandlung postoperativer Gallefisteln nach laparoskopischer Cholezystektomie durch ERCP, EPT und Gallengangsdrainage.

BACKGROUND: Bile leakage as a complication following cholecystectomy can be found more frequently after laparoscopic cholecystectomy (LC) than after open cholecystectomy. The present study planned to find out the importance of ERCP, sphincterotomy and temporary drainage of the bile duct system in the treatment of bile leakage. PATIENTS AND METHODS: From July 1992 to October 1996 15 consecutive patients presenting with bile leakage following LC underwent endoscopic therapy by CBD-drainage with sphincterotomy (n = 11), CBD-drainage without sphincterotomy (n = 1) and sphincterotomy alone (n = 3). RESULTS: Closure of the bile leakage could be achieved in all cases, biliary secretion stopped after 2.1 days (1-7 days). One dislocation of the drainage into the CBD was found and could be treated endoscopically. Endoscopy-related mortality was 0%. CONCLUSIONS: Endoscopic therapy offers a safe, effective and minimal invasive method in the treatment of bile leakage following LC.

[Preoperative therapeutic splitting]. / Präoperatives therapeutisches Splitting.

INTRODUCTION: The best clinical strategy for using ERC combined with LC is still unknown. Based on a wide discussion of literature reports the aim of our study is to critically analyse laparoscopic bile duct exploration and to correlate these data to our prospective study of "therapeutical splitting". PATIENTS AND METHODS: In a prospective study 1645 consecutive patients with sympomatic gall stone disease were examined by ultrasound. 309 patients had open cholecystectomy because of previous gastric surgery or perforation. Patients with a high probability of harbouring stones in the common duct or having other related disorders like biliary pancreatitis had ERC, EPT and stone extraction. 1336 patients had attempted LC. RESULTS: At endoscopy 70% of the 260 patients required therapy like EPT and/or stone extraction, 95% consequently had their gallbladder removed laparoscopically. Including the patients with biliary pancreatitis morbidity amounted to 3% with no mortality. In the non-endoscopic group with 1076 patients conversion was 6.8%, morbidity was 4.3% and mortality 0.09%. Residual stones were found in 0.5% so far. CONCLUSION: If selection criteria for bile duct pathology have a high sensitivity and specificity and endoscopical stone clearance rate is high, at present "therapeutical splitting" still is the method of choice.

[Urgent ERCP and early elective laparoscopic cholecystectomy in biliary pancreatitis]. / Dringliche ERCP und früh-elektive laparoskopische Cholezystektomie bei biliärer Pankreatitis.

BACKGROUND: For many years the best algorithm of treatment for complicated gallstone disease has been intensively discussed. Gallstone pancreatitis with cholangitis still belongs to the most often identified causes of death of necrotizing pancreatitis. The reduction of complication and lethality rates was mainly achieved by urgent ERCP and sequential cholecystectomy. In a prospective study we have combined endoscopic therapy with laparoscopic cholecystectomy (LC) and are discussing the results. PATIENTS AND METHODS: Between May 1991 and December 1996 146 patients with biliary pancreatitis were subjected to ERCP after laboratory tests and ultrasound screening of the biliary system. If there were no contraindications and the gallbladder was still in situ, LC was attempted during the initial admission. RESULTS: Of the 70 patients with attempted LC 26 had common bile duct calculi, 23 had an impacted papillary stone and 10 had signs of a stone passage. 59 patients underwent LC successfully, a conversion to open surgery was necessary in 11 patients. The morbidity rate amounted to 7%, lethality to 0%. DISCUSSION: Since a more liberal indication for ERCP in the management of acute pancreatitis was introduced the number of biliary related cases of acute pancreatitis is increasing. In response to early endoscopic bile duct clearance the rates of morbidity and mortality can be significantly reduced. Early LC is the ideal complementary treatment option to absolutely prevent recurrencies.

[Potential for improvement of combined endoscopic-surgical treatment of bleeding gastroduodenal ulcer]. / Verbesserungspotentiale bei der kombiniert endoskopisch-chirurgischen Behandlung des blutenden gastroduodenalen Ulcus.

A total of 119 patients (January 1995-December 1996; 53 women, 66 men) with a medium age of 63.1 years were admitted to hospital with bleeding gastroduodenal ulcer. Emergency gastroduodenoscopy was performed immediately in all cases, sclerotherapy in 94 cases (78.9%). Control endoscopy was done routinely after 12-24 h; the recurrent bleeding rate amounted to 14.3%, mortality was 5%, and surgical intervention was necessary in 8.4% with a mortality of 40% (!).