Imaging and video of late preterm delivery by midline laparotomy due to incarcerated uterus: A case report and literature review of a rare but morbid condition.

Incarcerated gravid uterus (IGU) is a rare and serious obstetric complication. IGU is defined as the entrapment of the gravid uterus between the pubic symphysis and the sacral promontory. The incidence of IGU is 1 in 3000-10 000 cases. IGU is associated with significant obstetric complications, including preterm labor, intrauterine fetal death, growth restriction, renal failure, uterine ischemia/rupture and thrombosis. Here, we present the case of a primigravida with urinary retention at 14 weeks. On transabdominal ultrasound at 19+5/7 weeks the cervix was difficult to visualize, and the anterior uterine wall appeared thickened. The bladder was elongated superior to the uterus and the placenta was low-lying. Initially the patient was managed with intermittent self-catheterization, and subsequently indwelling catheterization was required from 22 weeks. At 30 weeks, the patient was transferred to a tertiary center and magnetic resonance imaging (MRI) was preformed due to challenging visualization of the cervix on ultrasound and the patient's continued symptoms of constipation and recurrent urinary infections. The MRI found a retroflexed gravid uterus, with vagina and endocervix displaced anteriorly and compressed by the gravid uterus. The findings were consistent with an incarcerated uterus. The patient subsequently had positive urinary cultures for Pseudomonas and rising creatinine. Given the obstructive uropathy and associated morbidity and mortality, a plan for elective pre-term delivery at 33+6/7 weeks was made. Delivery was by midline laparotomy, normal anatomy was restored after manual evacuation of the fundus from below the sacral promontory, and an uncomplicated lower segment transverse uterine cesarean section was performed.

Association between maternal blood lipids during pregnancy and offspring growth trajectories in a predominantly macrosomic cohort: findings from the ROLO longitudinal birth cohort study.

The purpose of this study is to examine associations between maternal lipid profiles in pregnancy and offspring growth trajectories in a largely macrosomic cohort. This is a secondary analysis of the ROLO birth cohort (n = 293), which took place in the National Maternity Hospital, Dublin, Ireland. Infants were mostly macrosomic, with 55% having a birthweight > 4 kg. Maternal mean age was 32.4 years (SD 3.9 years), mean BMI was 26.1 kg/m2 (SD 4.4 kg/m2) and 48% of children born were males. Total cholesterol, high density lipoprotein cholesterol (HDL-cholesterol), low density lipoprotein cholesterol (LDL-cholesterol) and triglycerides were measured from fasting blood samples of mothers at 14 and 28 week gestation. The change in maternal lipid levels from early to late pregnancy was also examined. Offspring abdominal circumference and weight were measured at 20- and 34-week gestation, birth, 6 months, 2 years and 5 years postnatal. Linear spline multilevel models examined associations between maternal blood lipid profiles and offspring growth. We found some weak, significant associations between maternal blood lipids and trajectories of offspring growth. Significant findings were close to the null, providing limited evidence. For instance, 1 mmol/L increase in maternal triglycerides was associated with faster infant weight growth from 20- to 34-week gestation (0.01 kg/week, 95% CI - 0.02, - 0.001) and slower abdominal circumference from 2 to 5 years (0.01 cm/week, 95% CI - 0.02, - 0.001). These findings do not provide evidence of a clinically meaningful effect.    Conclusion: These findings raise questions about the efficacy of interventions targeting maternal blood lipid profiles in pregnancies at risk of macrosomia. New studies on this topic are needed. What is Known: • Maternal fat accumulation during early pregnancy may potentially support fetal growth in the third trimester by providing a reserve of lipids that are broken down and transferred to the infant across the placental barrier. • There are limited studies exploring the impact of maternal lipid profiles on infant and child health using growth trajectories spanning prenatal to postnatal life. What is New: • Maternal blood lipid profiles were not associated with offspring growth trajectories of weight and abdominal circumference during pregnancy up to 5 years of age in a largely macrosomic cohort, as significant findings were close to the null, providing limited evidence for a clinically meaningful relationship. • Strengths of this work include the use of infant growth trajectories that span prenatal to postnatal life and inclusion of analyses of the change of maternal lipid levels from early to late pregnancy and their associations with offspring growth trajectories from 20-week gestation to 5 years of age.

Fetal Growth Trajectories and Their Association with Maternal, Cord Blood, and 5-year Child Adipokines.

BACKGROUND: The growth of the fetus is a complex process influenced by multiple factors. Studies have highlighted the important role of biochemical growth markers such as leptin and adiponectin on fetal growth. OBJECTIVE: To compare fetal growth trajectories with biochemical growth markers from maternal blood samples at 28 weeks' gestation, cord blood samples at birth, and in child blood samples at 5 years of age from mother-infant pairs who were part of the longitudinal ROLO study. METHODS: 781 mother-infant pairs from the ROLO and ROLO Kids study were included. Ultrasound measurements and birth weight were used to develop fetal growth trajectory groups for estimated abdominal circumference and estimated weight. Blood serum levels of leptin, adiponectin, insulin, TNF-alpha, and IL-6 from maternal, cord, and 5-year child samples were recorded. ANOVA and chi-square tests were applied to test the associations between fetal growth trajectory membership and maternal and child biochemical growth indicators. The influence of child sex was also investigated. RESULTS: Male sex was associated with a faster weight trajectory compared to females (p=0.001). At 28 weeks' gestation, maternal leptin levels were significantly higher in mothers with a fetus on a slower estimated abdominal circumference trajectory compared to fast (25616 [IQR: 11656.0 to 35341.0] vs. 14753.8 [IQR: 8565.4 to 24308.1], p < 0.001) and maternal adiponectin levels were lower in fetuses on a slower estimated abdominal circumference trajectory compared to a fast trajectory (22.4 [IQR: 13.6 to 35.9] vs. 27.6 [IQR: 17.6 to 46.3], p=0.027). No associations were noted with inflammatory markers. No associations were identified between fetal growth trajectories and growth markers at 5 years of age. CONCLUSIONS: This study shows that male sex is associated with an accelerated estimated weight trajectory. Furthermore, high leptin and low adiponectin in maternal serum in late gestation are associated with a slower fetal growth trajectory. No associations were identified with blood growth markers after pregnancy.

Genetic ablation of carbonic anhydrase IX disrupts gastric barrier function via claudin-18 downregulation and acid backflux.

AIM: This study aimed to explore the molecular mechanisms for the parietal cell loss and fundic hyperplasia observed in gastric mucosa of mice lacking the carbonic anhydrase 9 (CAIX). METHODS: We assessed the ability of CAIX-knockout and WT gastric surface epithelial cells to withstand a luminal acid load by measuring the pHi of exteriorized gastric mucosa in vivo using two-photon confocal laser scanning microscopy. Cytokines and claudin-18A2 expression was analysed by RT-PCR. RESULTS: CAIX-knockout gastric surface epithelial cells showed significantly faster pHi decline after luminal acid load compared to WT. Increased gastric mucosal IL-1ß and iNOS, but decreased claudin-18A2 expression (which confer acid resistance) was observed shortly after weaning, prior to the loss of parietal and chief cells. At birth, neither inflammatory cytokines nor claudin-18 expression were altered between CAIX and WT gastric mucosa. The gradual loss of acid secretory capacity was paralleled by an increase in serum gastrin, IL-11 and foveolar hyperplasia. Mild chronic proton pump inhibition from the time of weaning did not prevent the claudin-18 decrease nor the increase in inflammatory markers at 1 month of age, except for IL-1ß. However, the treatment reduced the parietal cell loss in CAIX-KO mice in the subsequent months. CONCLUSIONS: We propose that CAIX converts protons that either backflux or are extruded from the cells rapidly to CO2 and H2 O, contributing to tight junction protection and gastric epithelial pHi regulation. Lack of CAIX results in persistent acid backflux via claudin-18 downregulation, causing loss of parietal cells, hypergastrinaemia and foveolar hyperplasia.

Identification of a novel aviadenovirus, designated pigeon adenovirus 2 in domestic pigeons (Columba livia).

The young pigeon disease syndrome (YPDS) affects mainly young pigeons of less than one year of age and leads to crop stasis, vomitus, diarrhea, anorexia and occasionally death. This disease is internationally a major health problem because of its seasonal appearance during competitions such as homing pigeon races or exhibitions of ornamental birds. While the etiology of YPDS is still unclear, adenoviruses are frequently discussed as potential causative agents. Electron microscopy of feces from a YPDS outbreak revealed massive shedding of adenovirus-like particles. Whole genome sequencing of this sample identified a novel adenovirus tentatively named pigeon adenovirus 2 (PiAdV-2). Phylogenetic and comparative genome analysis suggest PiAdV-2 to belong to a new species within the genus Aviadenovirus, for which we propose the name Pigeon aviadenovirus B. The PiAdV-2 genome shares 54.9% nucleotide sequence identity with pigeon adenovirus 1 (PiAdV-1). In a screening of further YPDS-affected flocks two variants of PiAdV-2 (variant A and B) were detected which shared 97.6% nucleotide identity of partial polymerase sequences, but only 79.7% nucleotide identity of partial hexon sequences. The distribution of both PiAdV-2 variants was further investigated in fecal samples collected between 2008 and 2015 from healthy or YPDS-affected racing pigeons of different lofts. Independent of their health status, approximately 20% of young and 13% of adult pigeon flocks harbored PiAdV-2 variants. Birds were free of PiAdV-1 or other aviadenoviruses as determined by PCRs targeting the aviadenovirus polymerase or the PiAdV-1 fiber gene, respectively. In conclusion, there is no indication of a correlation between YPDS outbreaks and the presence of PiAdV-2 or other aviadenoviruses, arguing against an causative role in this disease complex.

Variations in the presence of chloride cells in the gills of lampreys (Petromyzontiformes) and their evolutionary implications.

Although confined to fresh water, non-parasitic species of lampreys and the landlocked parasitic sea lamprey, all of which were derived relatively recently from an adromous ancestors, still develop chloride cells, whose function in their ancestors was for osmoregulation in marine waters during the adult parasitic phase. In contrast, such cells are not developed by the non-parasitic least brook lamprey Lampetra aepyptera, which has been separated from its ancestor for >2 million years, nor by the freshwater parasitic species of the genus Ichthyomyzon. The length of time that a non-parasitic species or landlocked parasitic form or species has spent in fresh water is thus considered the overriding factor determining whether chloride cells are developed by those lampreys.

Relevance of UDP-glucuronosyltransferase polymorphisms for drug dosing: A quantitative systematic review.

UDP-glucuronosyltransferases (UGT) catalyze the biotransformation of many endobiotics and xenobiotics, and are coded by polymorphic genes. However, knowledge about the effects of these polymorphisms is rarely used for the individualization of drug therapy. Here, we present a quantitative systematic review of clinical studies on the impact of UGT variants on drug metabolism to clarify the potential for genotype-adjusted therapy recommendations. Data on UGT polymorphisms and dose-related pharmacokinetic parameters in man were retrieved by a systematic search in public databases. Mean estimates of pharmacokinetic parameters were extracted for each group of carriers of UGT variants to assess their effect size. Pooled estimates and relative confidence bounds were computed with a random-effects meta-analytic approach whenever multiple studies on the same variant, ethnic group, and substrate were available. Information was retrieved on 30 polymorphic metabolic pathways involving 10 UGT enzymes. For irinotecan and mycophenolic acid a wealth of data was available for assessing the impact of genetic polymorphisms on pharmacokinetics under different dosages, between ethnicities, under comedication, and under toxicity. Evidence for effects of potential clinical relevance exists for 19 drugs, but the data are not sufficient to assess effect size with the precision required to issue dose recommendations. In conclusion, compared to other drug metabolizing enzymes much less systematic research has been conducted on the polymorphisms of UGT enzymes. However, there is evidence of the existence of large monogenetic functional polymorphisms affecting pharmacokinetics and suggesting a potential use of UGT polymorphisms for the individualization of drug therapy.

Global acetylation and methylation changes predict papillary urothelial neoplasia of low malignant potential recurrence: a quantitative analysis.

Papillary urothelial neoplasia of low malignant potential (PUNLMP) recurs in approximately 35% of patients. Conventional histopathological assessment does not distinguish non-recurrent from recurrent PUNLMP. The aim of this study is to explore the differences in global histone acetylation and global DNA methylation between non-recurrent and recurrent PUNLMP. Acetylated histone H3 lysine 9 (AcH3K9) and 5-methylcytosine (5MeC) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). The total optical density of the nuclear staining was measured photometrically in at least 40 nuclei separately for the basal, intermediate and luminal positions in each case. Concerning the total optical density values for both acetylation and methylation, a decrease in staining is observed from non-recurrent PUNLMP to recurrent PUNLMP, at all nuclear locations. For acetylation the mean value in non-recurrent PUNLMP, intermediate between NU and UC, is closer to the former than to latter. The mean value in recurrent PUNLMP is closer to UC than to NU. In NU, non-recurrent and recurrent PUNLMP, the acetylation to methylation ratio decreased from the nuclei in basal position to those in the surface, the average for the above groups being 1.491, 1.611 and 1.746, respectively. Setting the observed values for NU at each sampling location to unity, acetylation shows a steady decrease, the percentages of changes in this nuclear location compared to NU being -5% in non-recurrent PUNLMP, -15% in recurrent PUNLMP and -24% in UC. Concerning methylation, there is a slight increase in non-recurrent PUNLMP (+5%), a decrease in recurrent PUNLMP (-19%) followed by a sharp rise for the UC (+61%). In conclusion, there are differences in global histone acetylation and DNA methylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed to elucidate the complex interplay between chromatin structure, its modifications and recurrence of PUNLMP.

[Special aspects of postoperative complications following visceral surgery]. / Spezielle Gesichtspunkte postoperativer Komplikationen in der Viszeralchirurgie.

Postoperative complications occur in 10% of patients following major visceral surgery. Of these more than 80% are surgical complications, more than 70% are septic complications and more than 60% are related to anastomotic leakage which accounts for the majority of postoperative deaths. To achieve successful management, early diagnosis is mandatory in cases of deviations from the normal postoperative course. Sufficient external drainage of the leakage and prevention of further contamination across the leakage by gastrointestinal contents are the primary therapeutic goals. The spectrum of therapeutic options is different and depends on the location of the leakage in the gastrointestinal tract. In the surgical treatment of peritonitis, the fundamental requirements for successful management are early detection of persistent abdominal sepsis and of newly developing abdominal complications during the treatment. Furthermore early initiation of effective antibiotic concepts is mandatory.

Limited resection and free jejunal graft interposition for squamous cell carcinoma of the cervical oesophagus.

BACKGROUND: Therapeutic strategies for cervical oesophageal squamous cell carcinoma (SCC) are controversial. Treatment options range from definitive radiotherapy to multimodal treatment. Outcome after limited resection and reconstruction with a free jejunal graft interposition was evaluated retrospectively. METHODS: Patients with clinical T1-4 Nx M0 tumours treated between 1986 and 2006 were included. RESULTS: Of 109 patients, 94 underwent preoperative chemoradiotherapy and 15 had a primary resection. Complete or partial preservation of the larynx was achieved in 93 patients (85.3 per cent). Minor and major complications occurred in 74.3 per cent, with 44.0 per cent of all patients having more than one complication. Reoperation was necessary in 29.4 per cent. The 30-day mortality rate was 1.8 per cent, and the in-hospital mortality rate 2.8 per cent. The complete R0 resection rate was 72.5 per cent. Median overall survival was 34.3 months; 1-, 3- and 5-year survival rates were 83.8, 47.0 and 47.0 per cent respectively. Survival was not influenced by complications (P = 0.401) or reoperation (P = 0.428). CONCLUSION: Despite high complication and reoperation rates, the mortality rate was low, even after preoperative chemoradiation. This complex surgical strategy is a treatment option for cervical SCC in oncological centres with an infrastructure providing multidisciplinary management.

The additive effect of co-occurring anxiety and depression on health status, quality of life and coping strategies in help-seeking tinnitus sufferers.

OBJECTIVE: Evaluating the effect of anxiety and depression on clinical measures of general health, tinnitus-specific quality of life, and coping abilities. DESIGN: Two hundred sixty-five chronic, subjective tinnitus sufferers were divided into four psychological symptom groups according to cut-off scores on anxiety and depression subscales of the Hospital Anxiety and Depression Scale: (1) no-symptoms, (2) anxiety-only, (3) depression-only, and (4) anxiety-plus-depression. General health-related quality of life (SF-36), tinnitus-specific quality of life (tinnitus reaction questionnaire and tinnitus handicap inventory), and coping abilities (tinnitus coping style questionnaire) were assessed and analyzed across these four psychological symptom groups, which did not differ on age, gender, marital, and working status. RESULTS: Statistically significant and clinically relevant differences on general health-related and tinnitus-specific quality of life and coping abilities were identified when comparing anxiety-plus-depression subgroup with the subgroups anxiety-only, depression-only, or no-symptoms. Highest associations were seen between the anxiety-plus-depression subgroup and impaired quality of life and maladaptive coping. CONCLUSIONS: Our results demonstrate the additive effect of both anxiety and depression in impairing general health-related and tinnitus-specific quality of life and application of coping strategies, and reiterate the need for investigating both symptoms in the clinical evaluation of tinnitus patients.

Functional imaging of unilateral tinnitus using fMRI.

CONCLUSIONS: This article shows that the inferior colliculus plays a key role in unilateral subjective tinnitus. OBJECTIVES: The major aim of this study was to determine tinnitus-related neural activity in the central auditory system of unilateral tinnitus subjects and compare this to control subjects without tinnitus. SUBJECTS AND METHODS: Functional MRI (fMRI) was performed in 10 patients (5 males) with unilateral tinnitus (5 left-sided, 5 right-sided) and 12 healthy subjects (6 males); both groups had normal hearing or mild hearing loss. fMRI experiments were performed using a 3T Philips Intera Scanner. Auditory stimuli were presented left or right and consisted of dynamically rippled broadband noise with a sound pressure level of 40 or 70 dB SPL. The responses of the inferior colliculus and the auditory cortex to the stimuli were measured. RESULTS: The response to sound in the inferior colliculus was elevated in tinnitus patients compared with controls without tinnitus.

[Therapy of mediastinitis in patients with esophageal cancer]. / Therapie der Mediastinitis am Beispiel des Osophaguskarzinoms.

Mediastinitis caused by anastomotic leaks is the most severe complication after esophagectomy and the major source of morbidity and mortality. It is characterized by local intrathoracic reactions (mediastinitis) and systemic extrathoracic reactions (sepsis). Consequently the therapeutic concepts are clearly defined. To achieve successful management, early diagnostic work-up is mandatory in every disturbance of the normal postoperative course. This includes direct endoscopic inspection of the anastomosis to evaluate the vitality of the anastomosed organs and the size of the leak. According to location and clinical classifications of the leak, the spectrum of therapeutic options ranges from simple drainage procedures, endoscopic interventions, and stent implantation to reoperation or discontinuity resection. In any case the treatment goals must be immediate and sufficient drainage of the leakage and hindrance of further contamination across the leakage by gastrointestinal content. Also mandatory is the early initiation of supportive systemic strategies according to pathophysiologic principles of sepsis. The fundamental requirements for successful management are therefore aggressive local intervention and application of new concepts in sepsis therapy.

Long-term evaluation of treatment of chronic, therapeutically refractory tinnitus by neurostimulation.

OBJECTIVE: Long-term evaluation of treatment of chronic, therapeutically refractory tinnitus by means of chronic electrical stimulation of the vestibulocochlear nerve. PATIENTS: Inclusion criteria were severe, chronic, therapeutically refractory, unilateral tinnitus and severe hearing loss at the ipsilateral site. Out of 6 patients, 4 patients were selected for long-term evaluation. Two patients were not evaluated because of premature dropout. MATERIAL AND METHODS: A stimulation electrode was placed around the vestibulocochlear nerve through a retrosigmoid approach and connected to a subcutaneously positioned pulse generator via an extension cable. Follow-up was performed 3 months and 42.5 months after implantation. Three measures for treatment outcome were used. First, effect sizes were determined by means of the total Tinnitus Handicap Inventory (THI) score using Cohen's formula. Second, general and tinnitus-specific audiometric tests were performed in on and off conditions of the neurostimulation system. Third, recordings were noted for tinnitus severity and treatment success on a visual analogue scale. RESULTS: All 4 patients reported successful treatment with neurostimulation. The effect size after 3 months was 0.7, indicating an average effect, while the effect size measured during long-term follow-up was 1.75, indicating a substantial effect with major clinical implications. No changes in hearing level for both ears were measured. The neurostimulation system did not change the tinnitus pitch in any of the patients, and resulted in a minimal reduction of tinnitus loudness in only 2 patients. In all 4 patients the original tinnitus sound was replaced by another, pleasantly perceived sound. The average VAS score of perceived tinnitus severity was reduced from 8 to 3.25. The average VAS score for treatment success was 7.25. CONCLUSIONS: The long-term follow-up of neurostimulation treatment for chronic tinnitus shows promising results. Long-term results were better than those determined after a 3-month follow-up. In all patients the tinnitus was replaced by another sound, which was perceived as pleasant. Further studies are needed before accepting neurostimulation as a treatment modality for chronic, therapeutically refractory tinnitus.

Blood interleukin 12 as preoperative predictor of fatal postoperative sepsis after neoadjuvant radiochemotherapy.

INTRODUCTION: The value of preoperative whole-blood interleukin (IL) 12 levels in predicting death from postoperative sepsis was evaluated, in patients stratified by underlying malignancy, neoadjuvant tumour treatment and surgical procedure. METHODS: Blood samples were collected from 1444 patients before major surgery. Whole blood was incubated with Escherichia coli lipopolysaccharide (LPS) and IL-12 production in supernatants was assessed by enzyme-linked immunosorbent assay. The prognostic impact of ability to synthesize IL-12 before surgery was investigated in patient subgroups with respect to sepsis-related mortality using multivariate binary logistic regression analysis. RESULTS: IL-12 synthesizing capability in patients who survived sepsis was significantly higher than that in patients who developed fatal sepsis (P = 0.006). In multivariate analysis only IL-12 was associated with a lethal outcome from postoperative sepsis (P = 0.006). The prognostic impact of IL-12 was evident in patients with underlying malignancy (P = 0.011) and in those who had undergone neoadjuvant tumour treatment (P = 0.008). When patients were analysed according to the type of neoadjuvant therapy, preoperative ability to synthesize IL-12 had a significant prognostic impact in patients who had neoadjuvant radiochemotherapy (P = 0.026), but not in those who had neoadjuvant chemotherapy. CONCLUSION: IL-12 production after stimulation of whole blood with LPS appears to be useful for the preoperative assessment of risk of sepsis-related death after operation in patients who have undergone neoadjuvant radiochemotherapy.

The "stamp method": a new treatment for perforated peptic ulcer?

BACKGROUND: The aim of this study was to develop a simple method for closure of a perforated peptic ulcer, making it more accessible for laparoscopic surgery. METHODS: An experimental pilot study was performed using five male Wistar rats. The perforation was closed by a bioabsorbable patch made of lactide-glycolid-caprolactone fixed with glue onto the outside of the stomach. RESULTS: Postoperatively, there were no signs of leakage or other complications. Histologically, there were no signs of inflammation on the inside of the stomach, and there was a 50% reduction of the perforation each successive postoperative week. No adverse reactions because of the degradable material or glue were observed. CONCLUSIONS: Treatment of a perforated peptic ulcer by placing a patch of biodegradable material like a "stamp" on the outside of the stomach is a feasible option.

[Indicators for early prediction of outcome in sepsis]. / Parameter der frühen Prädiktion des Sepsisverlaufs.

Sepsis is still a major cause of postoperative morbidity and mortality. Numerous biochemical indicators have been evaluated regarding their potential in predicting prognosis in sepsis. Generally, one must differentiate between indicators: those for preoperative detection of patients at risk for lethal sepsis and those for early prediction of lethal outcome of septic complications. The first include the analysis of mononuclear phagocyte interleukin (IL)-12-synthesizing capability. Reduced IL-12 levels were associated with higher lethality. Cytokine-associated gene polymorphisms such as the loss of monocyte HLA-DR expression and homozygotism for the tumor necrosis factor B2 allele have a place in preoperative risk evaluation, as they were associated with worse prognosis in sepsis. Among the most important biochemical indicators for early prediction of lethal outcome in sepsis are decreased L-selectin and elevated IL-18, IL-6, and PCT plasma concentrations. Increased nuclear factor kappaB activity in mononuclear phagocytes and elevated calcitonin gene-related protein plasma concentrations were associated with unfavourable prognosis.

Karyometry in the early detection and chemoprevention of intraepithelial lesions.

The ideal chemopreventive agent targets pre-neoplastic changes and intraepithelial neoplasia, preventing progression over time without notable side effects. Assessment of success of chemopreventive intervention in the short and medium term remains a challenge, and in this review the suggestion is investigated that karyometric measurements constitute suitable markers of chemopreventive efficacy. Karyometry provides the sensitivity required to detect small differences amidst relatively high biological variability. It can help establish progression curves of intraepithelial neoplasia (IEN) to invasive cancer, and thus detect chemopreventive effects. Such effects can be observed in two ways, at the group level (intervention vs. placebo), and at the case (or patient) level. The latter is more difficult to establish, necessitating the development of specialised statistical methods. Analysis of between-case and within-case heterogeneity can reveal useful information about cancer progression and prevention. We suggest that karyometry can objectively quantify IEN progression, providing a framework for statistically securing chemopreventive effects. It can act as an integrating biomarker by detecting chemopreventive activity even when the mechanism for a given progression pathway is unknown, or when multiple pathways exist. The sensitivity of karyometric detection can help optimise the design of clinical trials of novel chemopreventive agents by decreasing trial duration and/or sample size.

[Abdomino-right-thoracic esophagectomy with intrathoracic anastomosis in Barrett's cancer]. / Abdomino-rechts-thorakale Osophagusresektion mit intrathorakaler Anastomose beim Barrett-Karzinom.

The modified technique of abdomino-right-thoracic esophagectomy (the Lewis-Tanner approach) is increasingly being favoured as the surgical procedure of choice in patients with resectable adenocarcinoma of the distal esophagus, so-called Barrett's cancer. The technical details of this procedure and the reconstruction of gastrointestinal continuity using a gastric tube with high intrathoracic anastomosis are illustrated, as they have proved useful in our own practice during recent years.