Quality of life after Nissen fundoplication in patients with gastroesophageal reflux disease: Comparison between long- and short-term follow-up.

INTRODUCTION:: Nissen fundoplication is the golden standard for surgical treatment of gastroesophageal reflux disease (GERD). Numerous studies report excellent short-term results. However, data regarding long-term quality of life are lacking. The aim of this study is to investigate the long-term quality of life after Nissen fundoplication in patients with GERD and to compare this with the short-term results. PATIENTS AND METHODS: We retrospectively analysed all patients who underwent laparoscopic Nissen fundoplication for GERD between January 2004 and January 2016. All patients received a validated GERD-Health-Related Quality of Life questionnaire by mail to assess post-operative quality of life. Maximum quality of life is represented by a score of 75. Secondary outcome measures were complications and recurrence rate. RESULTS:: One hundred and seventy-five (77.1%) of the 227 operated patients returned the questionnaire. The median follow-up was 3.7 (0.1-10.3) years. Mean age was 51.6 (range 15-85) and 72 patients were male. We report an excellent quality of life with a median total score of 70 (range 2-75). Re-operation rate was 13.6% (23/169); the re-operation was due to recurrent reflux in 12 patients and due to persistent dysphagia in 11 patients. 91.3% of the re-operations were performed within the first 5 years after surgery. Mortality rate was zero. CONCLUSION:: We report a large series of single-centre, single-surgeon laparoscopic Nissen fundoplication. Despite the re-operation rate of 13.6%, we found excellent long-term symptomatic outcome. There was no difference between short- and long-term results.

A collective review of biological versus synthetic mesh-reinforced cruroplasty during laparoscopic Nissen fundoplication.

BACKGROUND: Laparoscopic cruroplasty and fundoplication have become the gold standard in the treatment of hiatal hernia and gastro-oesophageal reflux disease (GERD). The use of a mesh-reinforcement of the cruroplasty has been proven effective; although, there is a lack of evidence considering which type of mesh is superior. The aim of this study was to compare recurrence rates after mesh reinforced cruroplasty using biological versus synthetic meshes. METHODS: We performed a systematic review of all clinical trials published between January 2004 and September 2015 describing the application of a mesh in the hiatal hernia repair during Nissen fundoplication for both GERD and hiatal hernia. The primary outcome was the recurrence rate, and secondary outcomes were complication rate, mortality and symptomatic outcome. RESULTS: We included 16 studies and extracted data regarding 1089 mesh operated patients of whom 385 received a biological mesh and 704 a synthetic mesh. The mean follow-up was 53.4 months. The recurrence rate in the synthetic mesh group was 6.8% compared to 16.1% in the biological mesh group (P < 0.05). The complication rate was 5.1% and 4.6% (P = 0.694), respectively, and there were 12 mesh-related complications. No mesh-related mortality was reported. CONCLUSION: Mesh reinforcement of hiatal hernia repair seems safe in the short-term follow-up. The available literature suggests no clear advantage of biological over synthetic meshes. Regarding cost-efficiency and short-term results, the use of synthetic nonabsorbable meshes might be advocated.

Mesh Versus Patch Repair for Epigastric and Umbilical Hernia (MORPHEUS Trial); One-Year Results of a Randomized Controlled Trial.

DESIGN: This trial is a randomized controlled, patient-blinded, multicentre, superiority trial. METHODS: All patients ≥18 years with a single, symptomatic and primary umbilical or epigastric hernia (<2 fingers) qualified for participation in the study. Flat polypropylene mesh repair was compared to patch repair (PROCEED® Ventral Patch) (PVP). The objective of this trial was to identify a superior method for umbilical and epigastric hernia repair in terms of complication rates. RESULTS: A total of 352 patients were randomized in this trial; 348 patients received the intervention (n = 177 PVP vs. n = 171 mesh). No peri-operative complications occurred. PVP placement was significantly faster compared to mesh placement (30 min, SD 11 vs. 35 min, SD 11) and was scored as an easier procedure. At 1-month follow-up, 76 patients suffered any kind of complication. There was no significant difference in the proportion of complications (24.9% for PVP and 18.7% for mesh, p = 0.195). A significant difference was seen in re-operation rate within 1 month, significantly less early re-operations in the mesh group (0.0 vs. 2.8%, p = 0.027). After 1-year follow-up, no significant differences are seen in recurrence rates (n = 13, 7.8% PVP vs. n = 5, 3.3% mesh, p = 0.08). CONCLUSIONS: Both mesh and PVP had a comparable amount of reported complications. There was a significantly higher incidence of early re-operations due to early complications in the PVP group. No differences were seen in infection rates and the need for antibiotic treatment. No significant difference was seen in the recurrence rates. REGISTRATION: This trial was registered in the Dutch Trail Registry (NTR) NTR2514NL33995.060.10. [12].

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).

Subjective outcome after laparoscopic hiatal hernia repair for intrathoracic stomach.

PURPOSE: For decades, an intrathoracic stomach (ITS) has been a definite indication for surgery due to the perceived risk of an acute volvulus with perforation, gangrene, or hemorrhage. At the present time, elective laparoscopic repair is the first choice for treatment of ITS. There is a lack of evidence in the long-term quality of life after a hiatal hernia repair for an intrathoracic stomach. METHODS: A retrospective analysis was performed on all patients undergoing a hiatal hernia repair for an intrathoracic stomach between January 2004 and January 2015. Additionally, to a hiatal closure, the patients received an antireflux procedure. Outcome measures included patient characteristics, operative details, complications, and postoperative morbidity and mortality. All patients were sent a quality of life questionnaire to assess long-term quality of life and patient satisfaction. A higher quality of life score represents a better quality of life. RESULTS: Eighty-six patients underwent laparoscopic repair for ITS, from which, one patient died during surgery. Eighty-five patients were contacted and 81 completed the questionnaire, resulting in a response rate of 95.3 %. At a median follow-up of 2.7 years (range 0.1-9.6), the mean quality of life score was 13.5 (standard deviation 2.8). The mean overall satisfaction was 8.4. There were four recurrences: three in the first 12 days after surgery and one in 2.4 years. CONCLUSIONS: Very good results in patient satisfaction and symptom reduction were achieved after a median follow-up of 2.7 years in this laparoscopic repair of the intrathoracic stomach single center experience study. The symptomatic recurrence rate was very low.

An umbilical surprise: a collective review on umbilical pilonidal sinus : An uncommon alternative diagnosis in common umbilical symptoms.

PURPOSE: Umbilical pilonidal sinus (UPS) has an atypical clinical presentation and is therefore not well recognized. The aim of this case series and review of the literature, is to provide more insight in the underlying pathology and a guidance for the treatment of this condition. METHODS: Three recent clinical cases are described that made us perform a multi-database research was to reveal relevant literature. RESULTS: Three relevant clinical cases from our clinic are described. Thirth three studies, describing 463 patients were included. Most studies were case reports or series; few were case series or cohort studies. UPS develops by loose hairs getting caught in the umbilical pit and subsequently penetrate the umbilical cicatrix by friction. In this way an inflammatory response is triggered, resulting in oedema that further narrows the umbilical orifice, hence forming a sinus. Several risk factors are identified. There is no particular consensus on the treatment of this disease. Although older literature advocates immediate umbilical excision without exception, recent studies provide evidence that supports multiple courses of conservative treatment. Several cases were described in which surgery consisted of excision of the sinus and hair tufts in contrast to excision of the entire umbilicus. CONCLUSIONS: Umbilical pilonidal disease has an atypical presentation and might mimic conditions such as incarcerated hernia, Anterior Cutaneous Nerve Entrapment Syndrome or urachal cyst. Risk factors that can bring physicians closer to a reliable diagnosis are identified. An example of a treatment algorithm is provided, suggesting surgery should only be considered when conservative treatment fails.

A consecutive series of 235 epigastric hernias.

BACKGROUND: Epigastric herniation is a common, though not always symptomatic condition. It is likely, that in accordance to the tension-free principles for other hernias, epigastric hernia repair should be mesh based. METHODS: Patients from two large hospitals were investigated retrospectively if they were operated on an epigastric hernia for the past 6 years. Follow-up was completed with a postal questionnaire. RESULTS: A total of 235 patients (50 % male) were operated. Sixty-eight patients were operated with mesh and 167 patients with suture repair. Forty-six patients were loss-to follow-up (19.6 %). In the mesh operated patients the recurrence rate was 10.9 % (n = 6) compared to 14.9 % (n = 20) in the suture repair group. Cox-regression analysis showed an increased risk for recurrence in the suture repair group (odds ratio 1.43; 95 % CI 0.56-3.57; p = 0.44). Operation time for mesh repair (47 min) was significantly longer compared to suture repair (29 min) (p < 0.0001). Thirty-seven patients had previous or other anterior wall hernias. A total of 51 patients smoked and 14 patients had diabetes mellitus. Fourteen patients used steroids and 22 patients suffered from a chronic lung disease. Subgroup analysis showed a significant difference for pain in patients in which re-operation for a recurrence occurred (p = 0.004). CONCLUSIONS: This is one of the largest reported series on solely epigastric hernias. A recurrence occurred more often after sutured repair compared to mesh repair. No differences in chronic pain was seen between mesh and suture repaired patients. Male:female ratio of 1:1, which is different from the 3:1 ratio found in previous older smaller studies, could be more reliable.

Ultrasound-guided ilioinguinal/iliohypogastric nerve blocks for chronic pain after inguinal hernia repair.

PURPOSE: The aim of this study was to evaluate the outcome of ilioinguinal and iliohypogastric nerve blocks in patients with chronic pain after herniorrhaphy, by comparing nerve stimulator and ultrasound guidance to administer the block. METHODS: A total of 43 patients who received nerve blocks for chronic inguinal post-herniorrhaphy pain received standardized questionnaires. Nerve stimulator-guided blocks were performed prior to January 2009, and thereafter, ultrasound-guided blocks were performed using a local anaesthetic solution and a corticosteroid. RESULTS: The questionnaire was completed by 38 patients (88 %). The inguinal hernia repair was performed for a median 16 months (range 3-219) ahead of the nerve blocks. A median of 2 pain treatments (range 1-7) was calculated. Median follow-up was 21 months (range 3-68). According to the DN4, 21 patients (55.3 %) no longer reported neuropathic pain. Subjectively, 32 % no longer reported moderate-to-severe pain. After ultrasound-guided blocks, a higher VAS score (at rest and during activities), a higher proportion of daily pain and more anxiety and depression are reported compared to blocks performed after nerve stimulator guidance. CONCLUSIONS: Ilioinguinal/iliohypogastric nerve blocks can be effective to treat chronic inguinal pain following surgery of the groin. The use of ultrasound was not superior to nerve stimulator-guided blocks. These blocks could be considered prior to more invasive procedures such as neurectomy.

Pathogenesis of the epigastric hernia.

PURPOSE: Epigastric herniation is a rather common condition with a reported prevalence up to 10 %. Only a minority is symptomatic, presumably the reason for the scarce literature on this subject. Epigastric hernias have specific characteristics for which several anatomical theories have been developed. Whether these descriptions of pathological mechanisms still hold with regard to the characteristics of epigastric hernia is the subject of this review. METHODS: A multi-database research was performed to reveal relevant literature by free text word and subject headings 'epigastric hernia', 'linea alba', 'midline' and 'abdominal wall'. Reviewed were studies on anatomical theories describing the pathological mechanism of epigastric herniation, incidence, prevalence and female-to-male ratio and possible explanatory factors. RESULTS: Three different theories have been described of which two have not been confirmed by other studies. The attachment of the diaphragm causing extra tension in the epigastric region is the one still standing. Around 1.6-3.6 % of all abdominal hernias and 0.5-5 % of all operated abdominal hernias is an epigastric hernia. Epigastric hernias are 2-3 times more common in men, with a higher incidence in patients from 20 to 50 years. Some cadaver studies show an epigastric hernia rate of 0.5-10 %. These specific features of the epigastric hernias (the large asymptomatic proportion, male predominance, only above umbilical level) are discussed with regard to the general theories. CONCLUSIONS: The epigastric hernia is a very common condition, mostly asymptomatic. Together with general factors for hernia formation, the theory of extra tension in the epigastric region by the diaphragm is the most likely theory of epigastric hernia formation.

The region ion sensitive field effect transistor, a novel bioelectronic nanosensor.

A novel type of bioelectronic region ion sensitive field effect transistor (RISFET) nanosensor was constructed and demonstrated on two different sensor chips that could measure glucose with good linearity in the range of 0-0.6mM and 0-0.3mM with a limit of detection of 0.1 and 0.04 mM, respectively. The sensor is based on the principle of focusing charged reaction products with an electrical field in a region between the sensing electrodes. For glucose measurements, negatively charged gluconate ions were gathered between the sensing electrodes. The signal current response was measured using a low-noise pico ammeter (pA). Two different sizes of the RISFET sensor chips were constructed using conventional electron beam lithography. The measurements are done in partial volumes mainly restricted by the working distance between the sensing electrodes (790 and 2500 nm, respectively) and the influence of electrical fields that are concentrating the ions. The sensitivity was 28 pA/mM (2500 nm) and 830 pA/mM (790 nm), respectively. That is an increase in field strength by five times between the sensing electrodes increased the sensitivity by 30 times. The volumes expressed in this way are in low or sub femtoliter range. Preliminary studies revealed that with suitable modification and control of parameters such as the electric control signals and the chip electrode dimensions this sensor could also be used as a nanobiosensor by applying single enzyme molecule trapping. Hypotheses are given for impedance factors of the RISFET conducting channel.

[Cervical carcinoma progression-associated genetic alterations on chromosome 6]. / Geneticheskie izmeneniia na khromosome 6, assotsiirovannye s progressiei raka sheiki matki.

To identify the loci associated with progression of cervical carcinoma, chromosome 6 regions were tested for loss of heterozygosity. Detailed analysis with 28 microsatellite markers revealed a high frequency of allelic deletions for several loci of the short (6p25, 6p22, 6p21.3) and long (6q14, 6q16-21, 6q23-24, 6q25, 6q27) arms of chromosome 6. Examination of 37 microdissected carcinoma and 22 cervical dysplasia specimens revealed allelic deletions from the HLA class I-III genes (6p22-21.3) and subtelomeric locus 6p25 were found in more than 40% dysplasia specimens. With multiple microdissection of cryosections, genetic heterogeneity of squamous cervical carcinoma was analyzed, and clonal and subclonal allelic deletions from chromosome 6 were identified. Half of the tumors had clonal allelic deletion of D6S273 (6p21.3), which is in a Ly6G6D (MEGT1) intron in the HLA class III gene locus. The frequency of allelic deletions from the chromosome 6 long arm was no more than 20% in dysplasias. Allelic deletions from two loci, 6q14 and 6q16-21, were for the first time associated with invasion and metastasis in cervical carcinoma.

Preload changes by positive pressure ventilation can be used for assessment of left ventricular systolic function.

BACKGROUND: Assessment of preload independent left ventricular function with conductance volumetry is traditionally accomplished by inflating a balloon in the inferior caval vein. Our aim was to investigate if a similar change in preload could be achieved by positive pressure ventilation with large tidal volume. METHODS: Conductance volumetry generating left ventricular pressure-volume loops was used in seven pentobarbital-anesthetized pigs. Changes in preload recruitable stroke work were studied, comparing the effects of inferior vena cava occlusion (IVCO) or large tidal volume (LTV). Cardiodepression was induced by halothane anesthesia and halothane + phenylephrine, and stimulation by epinephrine infusion. RESULTS: Although the decreasis in left ventricular end diastolic volume was slightly less with LTV (16.5 +/- 1.7 ml, mean +/- SEM) than with IVCO (22.4 +/- 1.7 ml) (P < 0.0001) the PRSW-slopes showed a high degree of correlation (r=0.80, P < 0.0001). Although peak tracheal pressures increased significantly to 27.8 +/- 0.9 mmHg during LTV, esophageal pressures (used as an indicator of pericardial pressure) were unchanged. CONCLUSIONS: Positive pressure ventilation with LTV is similar to IVCO in creating transient changes in preload, necessary for assessment of left ventricular systolic function. This observation was valid also during drug-induced cardiac depression and stimulation. The preload recruitable stroke work used for this validation was shown to be a reliable and stable method.

Interpretation of radial pulse contour during fentanyl/nitrous oxide anesthesia and mechanical ventilation.

BACKGROUND: Peripheral arterial blood pressure is not a reliable substitute for proximal aortic pressure. Recognition of this phenomenon is important for correct appreciation of cardiac afterload. Our aim was to evaluate the utility of the radial pulse wave to better understand ventriculo-vascular coupling during anesthesia. METHODS: We observed the differences between aortic systolic pressure (AoSAP, tipmanometry) and radial systolic pressure in 15 patients, (including two women) aged 53-78 years, before coronary artery bypass surgery. We studied the induction of anesthesia with fentanyl (20 microg kg-1), moderate volume loading, and thereafter the addition of 70% nitrous oxide. The circulatory effects of mechanical ventilation were studied by doubling the tidal volumes. Pulse wave contours were assessed by calculation of radical and aortic augmentation indices (AI), which measure the second systolic pressure peak. RESULTS: Radial systolic pressure was higher than AoSAP in the control situation (8+/-2 mmHg), and this SAP gradient increased further with fentanyl (12+/-2 mmHg). The gradient persisted throughout the study, but was partially reduced by volume loading and nitrous oxide, respectively. Radial augmentation index was the only parameter remaining in a stepwise multivariate model to explain the variance in the SAP gradient (r2=0.48). Radial augmentation index also correlated with aortic pulse pressure (r2=0.71). Mechanical ventilation had significant and similar effects on pulse wave augmentation both in the aorta and in the radial artery, and did not affect the radial to aortic SAP gradient. CONCLUSION: These elderly coronary patients had stiff vasculature (high aortic AI) and considerable pulse wave reflection, which was beneficially delayed by fentanyl. Changes in the radial pulse wave augmentation during mechanical ventilation were mainly a result of cyclic changes in the stroke volume, and were seldom associated with an increased systolic pressure gradient from the aorta to the radial artery.

Can a clinically useful aortic pressure wave be derived from a radial pressure wave?

BACKGROUND: The information contained in arterial pressure waveforms is probably underused by most clinicians who manage critically ill patients. It is not generally known that an aortic pressure wave can be synthesized by applying a generalized transfer function to the radial arterial pressure wave. We validated a commercially available system, SphygmoCo (PWV Medical, Sydney). METHODS: Ascending aortic pressure waves were synthesized and comparisons were made between the synthesized aortic waveforms, the measured aortic and radial arterial waveforms. Ascending aortic pressure waves (catheter-tip manometer) and radial artery pressure waves (short fluid-filled catheter) were recorded simultaneously in 12 patients with angina pectoris (age 62-76 years) undergoing cardiac catheterization. Patients were studied at rest, following midazolam, sublingual nitroglycerin and during Valsalva manoeuvres. RESULTS: Both midazolam and nitroglycerin lowered mean arterial pressure but nitroglycerin caused a more selective decrease in the measured and synthesized aortic systolic pressures than in the radial artery pressure. The synthesized aortic systolic pressure was less, by 6-8 mm Hg (SD 2-3) and the synthesized aortic diastolic pressure greater, by 4 mm Hg (SD 2). Despite these differences in pulse pressure, the synthesized waveform tracked the measured waveform before and during interventions. CONCLUSIONS: By deriving an aortic waveform from the radial pulse, monitoring of left ventricular afterload can improve without more invasive means.

Sequence variations of the late upstream region of HPV16 in cervical intraepithelial neoplasm and invasive carcinoma.

HPV16 is the most common type of human papillomavirus (HPV) seen in cervical squamous cell carcinoma. A 78-bp promotor element at nt 4118-4196 called late upstream region (LUR), critical for the expression of late genes, has been identified recently. Late genes encode viral capsid proteins that coat viral DNA to form particles and serve as antigen. To elucidate whether there are any sequence variations within LUR of HPV16 and any difference of these sequence variations between cervical invasive squamous cell carcinoma (CIC) and cervical intraepithelial neoplasia (CIN), we sequenced HPV16 LUR from 50 cases of HPV16-positive CIC and CIN. We found that variation frequency in the late upstream region ranged from 0 to 4.2 except for two cases in which variation frequency was as high as 22.8%. Eight of 24 CINs and 17 of 26 CICs contained two or more variations (33% vs. 65%, P < 0.025). The results suggested that the sequence variations occurred more often in LUR of HPV16 than in other regions of HPV16 and the variations in HPV16 LUR might play a role in the process of carcinogenesis of cervical carcinoma.

Cell biology of precancer.

This article explores the possibilities of understanding the natural history of human cancers. In particular it attempts to understand precancer in cell biological or molecular rather than clinical or pathological terms. The questions discussed on the relevance of precancer in the neoplastic development are: are all cancers preceded by precancer? Is a precancer in the cell lineage characterised by hypermutability? Is there a direct DNA lineage from precancer to cancer? How many mutations have been added as a function of a number of DNA generations in the process to neoplastic transformation? Is precancer reversible? Can analysis of precancer provide a short cut to assessment of carcinogenic risk? The present data addressing these questions are discussed and the still unexplained phenomena are highlighted.

Oncogene lineages of human papillomavirus type 16 E6, E7 and E5 in preinvasive and invasive cervical squamous cell carcinoma.

Human papillomavirus (HPV)16 accounts for about 60% of the HPV infections in invasive cervical cancer (ICC). There are many sequence variations within HPV16, some of which have been associated with different biological properties, although no definite correlations have yet been established. However, the definition 'variant' has been a source of confusion in research and diagnosis, since it is based on all sequence deviations from a randomly selected prototype. This study has sequenced the HPV16 oncogenes E6, E7 and E5 from 61 Swedish cases with cervical intraepithelial neoplasia grade III (CIN III) or ICC. Clustering the sequence variations at the three common sites of variation (nucleotide 350 in E6, which has previously been associated with the progression from CIN III to ICC, and nucleotides 3979 and 4042 in E5) resulted in the distinction of three major oncogene lineages encompassing more than 95% of the cases, and two minor oncogene lineages. Simple comparison of the distribution of the individual variations or oncogene lineages between CIN III and ICC showed no significant difference, but the number of variations in addition to the three common ones was significantly higher in ICC. This novel classification scheme, based on the variations in the E6, E7 and E5 region, is considered to be a major improvement over the classical 'prototype-variant' classification, and can help to clarify the interpretation of HPV sequence data in relation to the progression of cervical cancer.