The effect of surgical strategy in difficult cholecystectomy cases on postoperative complications outcome: a value-based healthcare comparative study.

BACKGROUND: In patients undergoing laparoscopic cholecystectomy (LC) for complicated biliary disease, complication rates increase up to 30%. The aim of this study is to assess the effect of differences in surgical strategy comparing outcome data of two large volume hospitals. METHODS: A prospective database was created for all the patients who underwent a LC in two large volume hospitals between January 2017 and December 2018. In cases of difficult cholecystectomy in clinic A, regular LC or conversion were surgical strategies. In clinic B, laparoscopic subtotal cholecystectomy was performed as an alternative in difficult cases. The difficulty of the cholecystectomy (score 1-4) and surgical strategy (regular LC, subtotal cholecystectomy, conversion) were scored. Postoperative complications, reinterventions, and ICU admission were assessed. For predicting adverse postoperative complication outcomes, uni- and multivariable analyses were used. RESULTS: A total of 2104 patients underwent a LC in the study period of which 974 were from clinic A and 1130 were from clinic B. In total, 368 procedures (17%) were scored as a difficult cholecystectomy. In clinic A, more conversions were performed (4.4%) compared to clinic B (1.0%; p < 0.001). In clinic B, more subtotal laparoscopic cholecystectomies were performed (1.8%) compared to clinic A (0%; p = < 0.001). Overall complication rate was 8.2% for clinic A and 10.2% for clinic B (p = 0.121). Postoperative complication rates per group for regular LC, conversion, and subtotal cholecystectomy in difficult cholecystectomies were 45 (15%), 12 (24%), and 7 (35%; p = 0.035), respectively. The strongest predictor for Clavien-Dindo grade 3-5 complication was subtotal cholecystectomy. CONCLUSION: Surgical strategy in case of a difficult cholecystectomy seems to have an important impact on postoperative complication outcome. The effect of a subtotal cholecystectomy on complications is of great concern.

MSTO1 mutations cause mtDNA depletion, manifesting as muscular dystrophy with cerebellar involvement.

MSTO1 encodes a cytosolic mitochondrial fusion protein, misato homolog 1 or MSTO1. While the full genotype-phenotype spectrum remains to be explored, pathogenic variants in MSTO1 have recently been reported in a small number of patients presenting with a phenotype of cerebellar ataxia, congenital muscle involvement with histologic findings ranging from myopathic to dystrophic and pigmentary retinopathy. The proposed underlying pathogenic mechanism of MSTO1-related disease is suggestive of impaired mitochondrial fusion secondary to a loss of function of MSTO1. Disorders of mitochondrial fusion and fission have been shown to also lead to mitochondrial DNA (mtDNA) depletion, linking them to the mtDNA depletion syndromes, a clinically and genetically diverse class of mitochondrial diseases characterized by a reduction of cellular mtDNA content. However, the consequences of pathogenic variants in MSTO1 on mtDNA maintenance remain poorly understood. We present extensive phenotypic and genetic data from 12 independent families, including 15 new patients harbouring a broad array of bi-allelic MSTO1 pathogenic variants, and we provide functional characterization from seven MSTO1-related disease patient fibroblasts. Bi-allelic loss-of-function variants in MSTO1 manifest clinically with a remarkably consistent phenotype of childhood-onset muscular dystrophy, corticospinal tract dysfunction and early-onset non-progressive cerebellar atrophy. MSTO1 protein was not detectable in the cultured fibroblasts of all seven patients evaluated, suggesting that pathogenic variants result in a loss of protein expression and/or affect protein stability. Consistent with impaired mitochondrial fusion, mitochondrial networks in fibroblasts were found to be fragmented. Furthermore, all fibroblasts were found to have depletion of mtDNA ranging from 30 to 70% along with alterations to mtDNA nucleoids. Our data corroborate the role of MSTO1 as a mitochondrial fusion protein and highlight a previously unrecognized link to mtDNA regulation. As impaired mitochondrial fusion is a recognized cause of mtDNA depletion syndromes, this novel link to mtDNA depletion in patient fibroblasts suggests that MSTO1-deficiency should also be considered a mtDNA depletion syndrome. Thus, we provide mechanistic insight into the disease pathogenesis associated with MSTO1 mutations and further define the clinical spectrum and the natural history of MSTO1-related disease.

Colorectal cancer patients' preferences for type of caregiver during survivorship care.

PURPOSE: Colorectal cancer (CRC) survivors are currently included in a secondary care-led survivorship care programme. Efforts are underway to transfer this survivorship care to primary care, but met with some reluctance by patients and caregivers. This study assesses (1) what caregiver patients prefer to contact for symptoms during survivorship care, (2) what patient factors are associated with a preferred caregiver, and (3) whether the type of symptom is associated with a preferred caregiver. METHODS: A cross-sectional study of CRC survivors at different time points. For 14 different symptoms, patients reported if they would consult a caregiver, and who they would contact if so. Patient and disease characteristics were retrieved from hospital and general practice records. RESULTS: Two hundred and sixty patients participated (response rate 54%) of whom the average age was 67, 54% were male. The median time after surgery was seven months (range 0-60 months). Patients were divided fairly evenly between tumour stages 1-3, 33% had received chemotherapy. Men, patients older than 65 years, and patients with chronic comorbid conditions preferred to consult their general practitioner (GP). Women, patients with stage 3 disease, and patients that had received chemotherapy preferred to consult their secondary care provider. For all symptoms, patients were more likely to consult their GP, except for (1) rectal blood loss, (2) weight loss, and (3) fear that cancer had recurred, in which case they would consult both their primary and secondary care providers. Patients appreciated all caregivers involved in survivorship care highly; with 8 out of 10 points. CONCLUSIONS: CRC survivors frequently consult their GP in the current situation, and for symptoms that could alarm them to a possible recurrent disease consult both their GP and secondary care provider. Patient and tumour characteristics influence patients' preferred caregiver.

Randomized clinical trial of extended versus single-dose perioperative antibiotic prophylaxis for acute calculous cholecystitis.

BACKGROUND: Many patients who have surgery for acute cholecystitis receive postoperative antibiotic prophylaxis, with the intent to reduce infectious complications. There is, however, no evidence that extending antibiotics beyond a single perioperative dose is advantageous. This study aimed to determine the effect of extended antibiotic prophylaxis on infectious complications in patients with mild acute cholecystitis undergoing cholecystectomy. METHODS: For this randomized controlled non-inferiority trial, adult patients with mild acute calculous cholecystitis undergoing cholecystectomy at six major teaching hospitals in the Netherlands, between April 2012 and September 2014, were assessed for eligibility. Patients were randomized to either a single preoperative dose of cefazolin (2000 mg), or antibiotic prophylaxis for 3 days after surgery (intravenous cefuroxime 750 mg plus metronidazole 500 mg, three times daily), in addition to the single dose. The primary endpoint was rate of infectious complications within 30 days after operation. RESULTS: In the intention-to-treat analysis, three of 77 patients (4 per cent) in the extended antibiotic group and three of 73 (4 per cent) in the standard prophylaxis group developed postoperative infectious complications (absolute difference 0·2 (95 per cent c.i. -8·2 to 8·9) per cent). Based on a margin of 5 per cent, non-inferiority of standard prophylaxis compared with extended prophylaxis was not proven. Median length of hospital stay was 3 days in the extended antibiotic group and 1 day in the standard prophylaxis group. CONCLUSION: Standard single-dose antibiotic prophylaxis did not lead to an increase in postoperative infectious complications in patients with mild acute cholecystitis undergoing cholecystectomy. Registration number: NTR3089 (www.trialregister.nl).

A randomized controlled trial to compare a restrictive strategy to usual care for the effectiveness of cholecystectomy in patients with symptomatic gallstones (SECURE trial protocol).

BACKGROUND: Five to 22 % of the adult Western population has gallstones. Among them, 13 to 22 % become symptomatic during their lifetime. Cholecystectomy is the preferred treatment for symptomatic cholecystolithiasis. Remarkably, cholecystectomy provides symptom relief in only 60-70 % of patients. The objective of this trial is to compare the effectiveness of usual (operative) care with a restrictive strategy using a standardized work-up with stepwise selection for cholecystectomy in patients with gallstones and abdominal complaints. DESIGN AND METHODS: The SECURE-trial is designed as a multicenter, randomized, parallel-arm, non-inferiority trial in patients with abdominal symptoms and ultrasound proven gallstones or sludge. If patients meet the inclusion criteria they will be randomized to either usual care or the restrictive strategy. Patients in the usual care group will be treated according to the physician's knowledge and preference. Patients in the restrictive care group will be treated with interval evaluation and stepwise selection for laparoscopic cholecystectomy. In this stepwise selection, patients strictly meeting the preselected criteria for symptomatic cholecystolithiasis will be offered a cholecystectomy. Patients not meeting these criteria will be assessed for other diagnoses and re-evaluated at 3-monthly intervals. Follow-up consists of web-based questionnaires at 3, 6, 9 and 12 months. The main end point of this trial is defined as the proportion of patients being pain-free at 12 months follow-up. Pain will be assessed with the Izbicki Pain Score and Gallstone Symptom Score. Secondary endpoints will be the proportion of patients with complications due to gallstones or cholecystectomy, the association between the patients' symptoms and treatment and work performance, and ultimately, cost-effectiveness. DISCUSSION: The SECURE trial is the first randomized controlled trial examining the effectiveness of usual care versus restrictive care in patients with symptomatic gallstones. The outcome of this trial will inform clinicians whether a more restrictive strategy can minimize persistent pain in post-operative patients at least as good as usual care does, but at a lower cholecystectomy rate. (The Netherlands National Trial Register NTR4022, 17th December 2012) TRIAL REGISTRATION: The Netherlands National Trial Register NTR4022 http://www.zonmw.nl/nl/projecten/project-detail/scrutinizing-inefficient-use-of-cholecystectomy-a-randomized-trial-concerning-variation-in-practi/samenvatting/.

Anticipation of complications after laparoscopic cholecystectomy: prediction of individual outcome.

BACKGROUND: Complication rates after a laparoscopic cholecystectomy are still up to 10 %. Knowledge of individual patient risk profiles could help to reduce morbidity. AIM: The aim of this study is to create risk profiles for specific complications to anticipate on individual outcome. PATIENTS AND METHODS: Individual patient outcome for a specific post-operative complication was assessed from a retrospective database of two major teaching hospitals, using uni- and multivariable analyses. RESULTS: A total of 4359 patients were included of which 346 developed one or more complications (8 %). Five risk profiles were found to predict specific complications: older patients (>65 year) are at risk for pneumonia (OR 7.0, 95 % CI 3.3-15.0, p < 0.001) and bleeding (OR 2.2, 95 % CI 1.2-3.9, p = 0.014), patients with acute cholecystitis are at risk for intra-abdominal abscess (OR 5.9, 95 % CI 3.4-10.1, p < 0.001), bile leakage (OR 3.6, 95 % CI 2.0-6.6, p < 0.001) and pneumonia (OR 3.5, 95 % CI 1.6-7.6, p < 0.002), previous history of cholecystitis is predictive for wound infection (OR 5.1, 95 % CI, (2.7-9.7), p < 0.001), intra-abdominal abscess (OR 6.1, 95 % CI 2.8-13.8, p < 0.001), post-operative bleeding (OR 4.8, 95 % CI 2.1-11.1, p < 0.001), bile leakage (OR 7.2, 95 % CI 3.4-15.4, p < 0.001) and pneumonia (OR 3.9, 95 % CI 1.3-11.9, p = 0.018), pre-operative ERCP is predictive for intra-abdominal abscess (OR 3.3, 95 % CI 2.0-5.7, p < 0.001), post-operative bleeding (OR 2.1, 95 % CI 1.2-3.9, p = 0.058) and pneumonia (OR 3.8, 95 % CI 1.9-7.8, p = 0.001), and converted patients are at risk for wound infection (OR 4.0, 95 % CI 2.1-7.7, p < 0.001) and intra-abdominal abscess (OR 3.5, 95 % CI 1.6-7.7, p = 0.002). CONCLUSION: Individual risk prediction of outcome after laparoscopic cholecystectomy is feasible. This facilitates individual pre-operative doctor-patient communication and may tailor surgical strategies.

TPM3 deletions cause a hypercontractile congenital muscle stiffness phenotype.

OBJECTIVE: Mutations in TPM3, encoding Tpm3.12, cause a clinically and histopathologically diverse group of myopathies characterized by muscle weakness. We report two patients with novel de novo Tpm3.12 single glutamic acid deletions at positions ΔE218 and ΔE224, resulting in a significant hypercontractile phenotype with congenital muscle stiffness, rather than weakness, and respiratory failure in one patient. METHODS: The effect of the Tpm3.12 deletions on the contractile properties in dissected patient myofibers was measured. We used quantitative in vitro motility assay to measure Ca(2+) sensitivity of thin filaments reconstituted with recombinant Tpm3.12 ΔE218 and ΔE224. RESULTS: Contractility studies on permeabilized myofibers demonstrated reduced maximal active tension from both patients with increased Ca(2+) sensitivity and altered cross-bridge cycling kinetics in ΔE224 fibers. In vitro motility studies showed a two-fold increase in Ca(2+) sensitivity of the fraction of filaments motile and the filament sliding velocity concentrations for both mutations. INTERPRETATION: These data indicate that Tpm3.12 deletions ΔE218 and ΔE224 result in increased Ca(2+) sensitivity of the troponin-tropomyosin complex, resulting in abnormally active interaction of the actin and myosin complex. Both mutations are located in the charged motifs of the actin-binding residues of tropomyosin 3, thus disrupting the electrostatic interactions that facilitate accurate tropomyosin binding with actin necessary to prevent the on-state. The mutations destabilize the off-state and result in excessively sensitized excitation-contraction coupling of the contractile apparatus. This work expands the phenotypic spectrum of TPM3-related disease and provides insights into the pathophysiological mechanisms of the actin-tropomyosin complex.

The neuromuscular differential diagnosis of joint hypermobility.

Joint hypermobility is the defining feature of various inherited connective tissue disorders such as Marfan syndrome and various types of Ehlers-Danlos syndrome and these will generally be the first conditions to be considered by geneticists and pediatricians in the differential diagnosis of a patient presenting with such findings. However, several congenital and adult-onset inherited myopathies also present with joint hypermobility in the context of often only mild-to-moderate muscle weakness and should, therefore, be included in the differential diagnosis of joint hypermobility. In fact, on the molecular level disorders within both groups represent different ends of the same spectrum of inherited extracellular matrix (ECM) disorders. In this review we will summarize the measures of joint hypermobility, illustrate molecular mechanisms these groups of disorders have in common, and subsequently discuss the clinical features of: 1) the most common connective tissue disorders with myopathic or other neuromuscular features: Ehlers-Danlos syndrome, Marfan syndrome and Loeys-Dietz syndrome; 2) myopathy and connective tissue overlap disorders (muscle extracellular matrix (ECM) disorders), including collagen VI related dystrophies and FKBP14 related kyphoscoliotic type of Ehlers-Danlos syndrome; and 3) various (congenital) myopathies with prominent joint hypermobility including RYR1- and SEPN1-related myopathy. The aim of this review is to assist clinical geneticists and other clinicians with recognition of these disorders.

Genotype-phenotype studies of VCP-associated inclusion body myopathy with Paget disease of bone and/or frontotemporal dementia.

Valosin containing protein (VCP) disease associated with inclusion body myopathy, Paget disease of the bone and frontotemporal dementia is a progressive autosomal dominant disorder caused by mutations in Valosin containing protein gene. To establish genotype-phenotype correlations we analyzed clinical and biochemical markers from a database of 190 members in 27 families harboring 10 missense mutations. Individuals were grouped into three categories: symptomatic, presymptomatic carriers and noncarriers. The symptomatic families were further divided into ten groups based on their VCP mutations. There was marked intra and inter-familial variation; and significant genotype-phenotype correlations were difficult to establish because of small numbers. Nevertheless when comparing the two most common mutations, R155C mutation was found to be more severe, with an earlier onset of myopathy and Paget (p = 0.03). Survival analysis of all subjects revealed an average life span after diagnosis of myopathy and Paget of 18 and 19 years respectively, and after dementia only 6 years. R155C had a reduced survival compared to the R155H mutation (p = 0.03).We identified amyotrophic lateral sclerosis (ALS) was diagnosed in 13 individuals (8.9%) and Parkinson's disease in five individuals (3%); however, there was no genotypic correlation. This study represents the largest dataset of patients with VCP disease and expands our understanding of the natural history and provides genotype-phenotype correlations in this unique disease.

Suspicion of acute appendicitis in the third trimester of pregnancy: pros and cons of a laparoscopic procedure.

The presentation of acute appendicitis during pregnancy may cause diagnostic and therapeutic difficulty. Delay in diagnosis may lead to increased maternal and fetal risk. Therefore, an aggressive surgical approach is mandatory, even though this may result in an increased number of appendectomies for normal appendices. Diagnostic laparoscopy, followed by laparoscopic appendectomy in case of inflammation, seems a logical strategy. We present the case of a 36-week pregnant woman who presented with suspicion of acute appendicitis. The pro and cons of a laparoscopic approach in the third trimester of pregnancy are discussed as is its safety by reviewing the literature.

Safety and outcome of general surgical open and laparoscopic procedures during pregnancy.

BACKGROUND: Surgical procedures during pregnancy carry the risk of adverse fetal outcome. We analyzed outcomes of open and laparoscopic approaches in patients treated for symptomatic cholelithiasis and suspected appendicitis. We reviewed the literature for evidence on the safety of both procedures. METHODS: We retrospectively reviewed the data of all patients who underwent surgery for symptomatic cholelithiasis and suspicion of appendicitis during pregnancy between January 2004 and March 2009. Fetal loss, preterm delivery, maternal outcome, and surgical complications were assessed. RESULTS: Twenty patients were operated on during pregnancy: 5 of 652 (0.8%) patients with symptomatic cholelithiasis and 15 (4.5%) of 331 for suspected appendicitis. All cholecystectomies were performed by laparoscopic procedure; no premature deliveries or fetal death occurred. In patients with suspicion of appendicitis, three appendices sana were diagnosed laparoscopically, and nine laparoscopic appendectomies and three open appendectomies were performed. The outcome was two preterm deliveries and one fetal death. CONCLUSION: Reviewing our results and the available literature, we believe that the outcome of surgery during pregnancy is not dictated by the type of procedure but by the type of disease. The gain for fetal outcome in the future most likely lies in the diagnostic pathway rather than the type of surgery.

Frameshift and novel mutations in FUS in familial amyotrophic lateral sclerosis and ALS/dementia.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive paralytic disorder caused by degeneration of motor neurons. Mutations in the FUS gene were identified in patients with familial ALS (FALS) and patients with sporadic ALS (SALS) from a variety of genetic backgrounds. This work further explores the spectrum of FUS mutations in patients with FALS and patients with FALS with features of frontotemporal dementia (FALS/FTD) or parkinsonism and dementia (FALS/PD/DE). METHODS: All exons of the FUS gene were sequenced in 476 FALS index cases negative for mutations in SOD1 and TARDBP. A total of 561-726 controls were analyzed for genetic variants observed. Clinical data from patients with FUS mutations were compared to those of patients with known SOD1 and TARDBP mutations. RESULTS: We identified 17 FUS mutations in 22 FALS families, 2 FALS/FTD families, and 1 FALS/PD/DE family from diverse genetic backgrounds; 11 mutations were novel. There were 4 frameshift, 1 nonsense, and 1 possible alternate splicing mutation. Patients with FUS mutations appeared to have earlier symptom onset, a higher rate of bulbar onset, and shorter duration of symptoms than those with SOD1 mutations. CONCLUSIONS: FUS gene mutations are not an uncommon cause in patients with FALS from diverse genetic backgrounds, and have a prevalence of 5.6% in non-SOD1 and non-TARDBP FALS, and approximately 4.79% in all FALS. The pathogenicity of some of these novel mutations awaits further studies. Patients with FUS mutations manifest earlier symptom onset, a higher rate of bulbar onset, and shorter duration of symptoms.

Identification of risk factors for an unfavorable laparoscopic cholecystectomy course after endoscopic retrograde cholangiography in the treatment of choledocholithiasis.

BACKGROUND: Laparoscopic cholecystectomy (LC) after an endoscopic retrograde cholangiography (ERC) has higher rates for complications and conversion caused by unpredictable adhesions. The risk factors for an adverse outcome of LC after an ERC were analyzed. METHODS: Variables from patients treated by LC after ERC for cholelithiasis in two clinics from 1996 to 2003 were retrospectively stored in a database. Complications and conversions were recorded. RESULTS: A total of 140 patients underwent LC after ERC (83 from clinic A and 57 from clinic B), 31% (44/140) of whom were men. Peri- or postoperative complications occurred for 28 patients (20%). For 19 patients (14%), a conversion was necessary. Significant variables associated with complications and conversions were an elevated level of C-reactive protein (CRP) at the time of LC (odds ratio [OR], 10.2; 95% confidence interval [CI], 1.1-91, P = 0.037 for both) and severe adhesions during laparoscopy (OR, 3.6; 95% CI, 1.5-8.6; P = 0.003 and OR, 5.2; 95% CI, 1.9-14.4; P = 0.002, respectively). Male gender (OR, 2.8; 95% CI, 1.1-7.6; P = 0.037) and serum bilirubin level at the time of ERC (OR, 3.7; 95% CI, 1.24-11; P = 0.014) were associated with conversion only. Time after ERC (LC within 1 week vs. >1 week or < or = 2 weeks vs. 2-6 weeks vs. >6 weeks or < or = 6 weeks vs. >6 weeks) was not associated with complications or conversion. Multivariate regression analysis showed a pre-LC CRP exceeding 6 to be predictive of complications (OR, 10.5; 95% CI, 1.1-95; P = 0.040) and conversion (OR, 10.6; 95% CI, 1.1-99; P = 0.034). CONCLUSION: Male gender, bilirubin levels during ERC, severe adhesions during LC, and pre-LC CRP levels were associated with an adverse outcome for an LC after endoscopic cholangiography. The time between LC and ERC failed to be a significant risk factor in this larger series.

Laparoscopic resection of a symptomatic gastric diverticulum: a minimally invasive solution.

Gastric diverticula are rare and occasionally symptomatic. A sensation of fullness in the upper abdomen immediately after meals is the most common symptom. Dyspepsia and vomiting are less common. Ulceration with hemorrhage or perforation has been reported. If it is thought that complaints can be ascribed to the diverticulum and if proton pump inhibitors do not relieve symptoms, surgical resection is an option. Knowledge of the pitfalls in diagnosis and treatment of a gastric diverticulum are essential for successful and complete relief of symptoms. We report a successful laparoscopic approach as a minimally invasive solution to a symptomatic gastric diverticulum.

Conversion rate of laparoscopic cholecystectomy after endoscopic retrograde cholangiography in the treatment of choledocholithiasis: does the time interval matter?

BACKGROUND: Preceding endoscopic retrograde cholangiography (ERC) in patients with choledochocystolithiasis impedes laparoscopic cholecystectomy (LC) and increases risk of conversion. We studied the influence of time interval between ERC and LC on the course of LC. METHODS: All patients treated for choledochocystolithiasis with ERC and LC during 1996-2001 were studied retrospectively, comparing the course of LC in three time interval groups; LC < 2, 2-6, and > 6 weeks after ERC. PRIMARY OUTCOMES: adhesions, bile duct injury, operating time, and conversion-rate. RESULTS: Eighty-three patients were studied (group 1, n = 23; group 2, n = 15; group 3, n = 45). Adhesions, operation time, and bile duct damage did not significantly differ between the groups. The conversion rate in group 2 is significantly higher compared to group 1 (p = 0.027, OR 11 (1.13-106.8)) CONCLUSIONS: A higher conversion rate of LC is found 2-6 weeks after ERC compared to LC within 2 weeks. However, further research is needed to gain more reliable data on whether this is caused by timing.

Impact of anatomical wrap position on the outcome of Nissen fundoplication.

BACKGROUND: The importance of anatomical reposition and fixation of the type I hiatal hernia during antireflux surgery has often been emphasized. It is not known whether the initial anatomical repair withstands the test of time and whether this repair is necessary for a successful outcome. METHODS: The relationship between the objective anatomical and subjective symptomatic outcome of Nissen fundoplication was investigated prospectively in 57 patients. Findings of herniation, telescoping and obstruction at the level of the lower oesophageal sphincter on barium swallow were scored 2 years after operation by investigators who were unaware of the symptoms, and were related to symptoms and patient satisfaction evaluated by a standard questionnaire. RESULTS: According to strict criteria, some 55 per cent of patients had some degree of anatomical failure; if only complete herniation, significant telescoping and signs of obstruction were scored as abnormal, 27 per cent had anatomical failure. There was no relation to subjective outcome; relief was reported by 48 of 49 patients, 25 of whom were cured and 23 significantly improved. CONCLUSION: Anatomical repair during antireflux surgery does not stand the test of time. Although this has no demonstrable influence on the subjective outcome, the authors do not recommend deviating from well designed surgical guidelines. Current theories on the mechanism of antireflux surgery require further evaluation.

New method for faecal fat determination by mid-infrared spectroscopy, using a transmission cell: an improvement in standardization.

Current techniques used in clinical laboratories for faecal fat determination, such as the Van de Kamer method, are not very accurate or precise. This became apparent when results obtained by different laboratories were compared, and could explain the disappointing performance of near-infrared and mid-infrared spectroscopy since the accuracy of these techniques depends upon the accuracy of the calibration used (i.e. inaccurate wet chemical analysis). In order to improve standardization, we developed and tested a new quantitative method in three laboratories, based on Fourier transform infrared (FT-IR) spectroscopy. Fatty acids were extracted from faecal samples with acidified petroleum ether-ethanol and the extracts were dried and dissolved in chloroform. An infrared spectrum of the extracts was recorded in the range 4000-650 cm(-1), using an infrared transmission cell. Standard mixtures of stearic and palmitic acids (65:35) were used for calibration. Quantification was based on the absorbance band of the CH2 group (2855 cm(-1)) of free fatty acids and fatty acid glycerol esters. The calibration curve showed excellent linearity. The correlation coefficient between the titrimetric Van de Kamer and FT-IR methods was 0.96 (y = 1.12x-0.02, standard error of prediction = 0.89 g% fat). No significant difference was found when the FT-IR results of 28 faecal samples from patients were compared between two different university hospital laboratories. The new FT-IR method, using primary standards, is simple and rapid, and provides satisfactory intra- and inter-laboratory precision for the diagnosis and monitoring of steatorrhoea.