"Locus minoris resistentiae" and connective tissue weakness in older women: a case report and literature review on pelvic organ prolapse with inguinal bladder hernia.

BACKGROUND: Conditions such as genital prolapse and hernia are known to be related to connective tissue dysfunction. In this report on cases of the rare simultaneous finding of large genital prolapse and post-prolapse repair female inguinal bladder hernia, we aim to contribute to the discussion of a possible clinical definition of connective tissue weakness, for its clinical assessment and preoperative patient counselling. CASE PRESENTATION: Three cases of medial third-grade (MIII, Aachen classification) inguinal bladder hernia developing or enlarging after successful stage-IV pelvic organ prolapse (POP) repair at a university pelvic floor centre are presented. All patients were aged ≥ 80 years with long-standing postmenopausal status. One patient was followed for 5 years and two patients were followed for 6 months. In all patients, ultrasound revealed that the hernia sac contained the urinary bladder, which had herniated through the inguinal hernia orifice. A literature search revealed only one case report of direct female inguinal bladder hernia and few investigations of the simultaneous occurrence of POP and hernia in general. CONCLUSION: The simultaneous occurrence of inguinal hernia and female POP can lead to bladder herniation following prolapse surgery in the sense of a "locus minoris resistentiae". Clinical examination for simultaneous signs of connective tissue weakness and counselling prior to pelvic reconstructive surgery could help to increase patients' compliance with further surgical treatment for hernia.

Inverse correlation between urethral length and continence before and after native tissue pelvic floor reconstruction.

Urethral length was evaluated retrospectively in patients with prolapse undergoing anterior native-tissue repair. Effects of age, prolapse stage, defect pattern, urodynamic and clinical stress test findings, and tension-free vaginal tape (TVT) surgery indication were analyzed using Mann-Whitney and Wilcoxon tests and linear and logistic regression. Of 394 patients, 61% had stage II/III and 39% had stage IV prolapse; 90% of defects were central (10% were lateral). Median pre- and postoperative urethral lengths were 14 and 22 mm (p < 0.01). Preoperative urethral length was greater with lateral defects [p < 0.01, B 6.38, 95% confidence interval (CI) 4.67-8.08] and increased stress incontinence risk (p < 0.01, odds ratio 1.07, 95% CI 1.03-1.12). Postoperative urethral length depended on prolapse stage (p < 0.01, B 1.61, 95% CI 0.85-2.38) and defect type (p = 0.02, B - 1.42, 95% CI - 2.65 to - 0.2). Postoperatively, TVT surgery was indicated in 5.1% of patients (median 9 months), who had longer urethras than those without this indication (p = 0.043). Native-tissue prolapse repair including Kelly plication increased urethral length, reflecting re-urethralization, particularly with central defects. The functional impact of urethral length in the context of connective tissue aging should be examined further.

[Surgical treatment of peritoneal metastases of colorectal cancer]. / Chirurgische Therapie der Peritonealkarzinose kolorektaler Karzinome.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may significantly improve overall survival in selected patients with peritoneal metastases of colorectal cancer. For good oncological results complete macroscopic cytoreduction is crucial; furthermore, a linear correlation between peritoneal tumor load, as determined by the peritoneal cancer index (PCI) and overall survival has been demonstrated; therefore, surgical treatment should be initiated as early as possible. Synchronous resection of up to three liver metastases may be performed safely and with good results and no influence on the morbidity. With respect to intraperitoneal chemotherapy, mitomycin C and oxaliplatin are most commonly used and may be regarded as equal; however, for perioperative chemotherapy study results are so far inconclusive with some trials hinting at decreased overall survival following neoadjuvant chemotherapy. Adjuvant therapy is likely to improve overall survival if at least 6 cycles are applied. Early detection of peritoneal metastases is difficult at present but might be facilitated in the future by the use of liquid biopsies, which may detect circulating free tumor-specific DNA or RNA. In the meantime, planned second-look laparotomy should be considered for patients at high risk of peritoneal recurrence. In addition, several international studies are currently evaluating the concept of adjuvant or prophylactic HIPEC. The CRS and HIPEC may be repeated in cases of recurrence and should be considered in suitable patients, applying the same criteria as for primary CRS and HIPEC. A recurrence-free interval of >2 years is associated with a significantly better prognosis.

[Global Health Care]. / Global Health Care.

Global health data are changing rapidly and they show large regional differences. The incidence and mortality of infectious diseases can be reduced by successes in medical research, national health plans and large financial expenditure. In contrast, illnesses that are caused by unhealthy and changing environmental and living conditions are on the rise. The Global Health Care concept is a cross-sectoral master plan taking into account that worldwide health cannot be established by healthcare workers alone. It was designed to have a lasting impact on the cause of disease through global health programs, of which improved medical services, including essential surgical treatment need to play a key role.

Partial liver resection results in a significantly better long-term survival than locally ablative procedures even in elderly patients.

PURPOSE: The number of elderly patients with HCC will increase worldwide in the next years. Therefore, surgeons need to reassess clinical algorithms for the treatment of patients with HCC. We reevaluated a cohort of patients treated in the last 10 years at our hospital, with emphasis on long-term results and age. METHOD: A prospectively recorded consecutive series of all patients treated in between January 1995 and December 2014 with curative intent either by partial liver resection or by ablative therapy was analysed. RESULTS: At the time of diagnosis, 232 patients were younger than 70 years and 127 patients were aged 70 years and over. In the latter group, solitary tumours, absence of liver cirrhosis and resection therapy were more frequent compared to younger patients. Charlson index, AFP-negative tumours and CLIP score were equally distributed in both groups. Observed survival of older and younger patients was similar but after partial liver resection, younger patients had a better survival than elderly patients, whereas survival in patients treated with ablation was similar in both groups. In the univariate analysis, long-term survival of patients aged 70 years and over was influenced by treatment procedure, number of lesions, liver cirrhosis, Child's stage and CLIP score. In the multivariate analysis, only treatment procedure and CLIP score were identified as independent predictors of observed survival, and comorbidity was not. CONCLUSION: In patients aged 70 years and over, long-term prognosis is independently influenced by CLIP score and treatment procedure and other findings have only minor influence on long-term survival.

Acute mesenteric ischemia following cardiovascular surgery--A nested case-control study.

INTRODUCTION: Acute mesenteric ischemia is a rare but often fatal complication following cardiovascular surgery. Early suspicion may reduce overall mortality. This retrospective study aims to identify predictors and risk factors that may determine the onset and evolution of acute mesenteric ischemia. METHODS: In a retrospective case-control study, we compared co-morbidities and peri-operative risk factors of patients with or without mesenteric ischemia following cardiac surgery using univariate and logistic regression analyses. RESULTS: Of 9385 patients, 108 (1.15%) were diagnosed with acute mesenteric ischemia within two weeks after cardiac surgery. In-hospital mortality was 68% for this group. Patients with ischemia and controls were matched in regard to patient's age and type of surgical intervention and showed similar pre-operative parameters. Only liver cirrhosis (OR 13.3, CI95% 3.6-49.3), and emergency operation (OR 2.6, CI95% 1.3-5.2) remained independent pre-operative predictors for acute mesenteric ischemia in multivariate analysis. In contrast, early postoperative parameters revealed a higher correlation with the occurrence of mesenteric ischemia including the use of norepinephrine (OR 3.5 CI95% 1.6-7.8), epinephrine (OR 2.0, CI95% 1.1-3.7), and serum lactate levels >3 mmol/L (OR 2.9, CI95% 1.5-5.6). A set of key markers of regression analysis was evaluated in a ROC curve analysis. The area under curve was 0.835, which indicates moderate to good prognostic accuracy. CONCLUSION: Early identification of pre- and post-operative predictors including liver cirrhosis, emergency operation, serum lactate >3 mmol/L, and the use of norepinephrine and epinephrine may help facilitate early diagnosis of acute mesenteric ischemia following cardiac surgery, and thus may allow immediate adequate treatment, leading to a reduction in mortality rates.

Culturing explanted colon crypts highly improves viability of primary non-transformed human colon epithelial cells.

Chemoprotective effects of nutritional compounds are usually studied in cell lines. Studies using primary human colon cells have been limited due to the lack of established methods regarding their culture. We therefore optimized isolation and culture of non-transformed human epithelial cells from individual donors to enrich viable cells and sufficient amounts of intact RNA. Isolated epithelial cells were seeded in different coated cell culture dishes combined with several media (2-24h). To avoid cells from anoikis, also intact colon crypts were isolated to maintain cell interactions. These crypts were incubated with gut fermentation products (24h) derived from indigestible carbohydrates. In none of the coated (fibronectin, laminin) cell culture dishes isolated epithelial cells did attach. The number of these cells remaining in suspension, decreased already after 2h to 20%. Intact colon crypts cultured as pellets showed a stable viability up to 24h (91±4%) and were suitable to gain a sufficient quantity of RNA. The use of colon crypts with an appropriate cell culture medium could double the lifespan of intestinal epithelial cells from 12 up to 24h and represents a promising approach to study early events in carcinogenesis and chemoprevention as well as other diseases of the colon.

Gastrointestinal endoscopy in a low budget context: delegating EGD to non-physician clinicians in Malawi can be feasible and safe.

Gastrointestinal endoscopy is rarely performed in low-income countries in sub-Saharan Africa. One reason is the lack of available medical doctors and specialists in these countries. At Zomba Central Hospital in Malawi, clinical officers (non-physician clinicians with 4 years of formal training) were trained in upper gastrointestinal endoscopy. Prospectively recorded details of 1732 consecutive esophagogastroduodenoscopies (EGDs) performed between September 2001 and August 2010 were analyzed to evaluate whether upper gastrointestinal endoscopy can be performed safely and accurately by clinical officers. A total of 1059 (61.1%) EGDs were performed by clinical officers alone and 673 (38.9%) were carried out with a medical doctor present who performed or assisted in the procedure. Failure and complication rates were similar in both groups (P=0.105). Endoscopic diagnoses for frequent indications were generally evenly distributed across the two groups. The main difference was a higher proportion of normal findings and a lower proportion of esophagitis in the group with a doctor present, although this was significant only in patients who had presented with epigastric/abdominal pain (P<0.001). In conclusion, delegating upper gastrointestinal endoscopy to clinical officers can be feasible and safe in a setting with a shortage of medical doctors when adequate training and supervision are provided.

Butyrate suppresses mRNA increase of osteopontin and cyclooxygenase-2 in human colon tumor tissue.

The short chain fatty acid (SCFA) butyrate, a product of fermentation of dietary fiber in the human colon, is found to exert multiple regulatory processes in colon carcinogenesis. The aim of this study was to find out whether butyrate affects the tumor-promoting genes osteopontin (OPN) and cyclooxygenase (COX)-2, their respective proteins and/or their functional activity in matched normal, adenoma and tumor colon tissues obtained from 20 individuals at colon cancer surgery. Quantitative real-time polymerase chain reaction experiments showed increased levels of OPN and COX-2 messenger RNA in tumor tissues when compared with the adjacent normal samples (P < 0.001). The addition of butyrate reduced OPN and COX-2 mRNA expression in all tissue types compared with the related medium controls (tumor: P < 0.05). In tumor samples, a downregulation of up to median 35% (COX-2) and 50% (OPN) was observed, respectively. Thereby, tumors with lower levels of OPN basal expression were more sensitive to inhibition and vice versa for COX-2 in normal tissue. At the protein and enzyme level, which were determined by using western blot and enzyme immunometric assays, the impact of the SCFA was not clearly visible anymore. The active proteins of OPN and COX-2 (determined by prostaglandin E(2)) were found to correlate with their respective mRNA expression only in 50-63% of analyzed donors. For the first time, our data reveal new insights into the chemoprotective potential of butyrate by showing the suppression of OPN and COX-2 mRNA in primary human colon tissue with the strongest effects observed in tumors.

Outcome prediction in microsurgery by quantitative evaluation of perfusion using ICG fluorescence angiography.

The purpose of this prospective study was to evaluate the clinical efficacy of laser-induced fluorescence angiography with indocyanine green (ICG-FA) for perioperative monitoring of tissue perfusion in hand surgery. Different quantitative parameters of the uptake, distribution and clearance of dye-marked blood were evaluated for their sensitivity and prognostic value in comparison to each other and to clinical parameters. One hundred and fifty-five measurements were performed prior to, or following, surgery for severe hand injuries. All quantitative parameters of ICG-FA detected intraoperatively were found to be of significant predictive value for outcome, but clinical parameters were not. For the dye uptake, a minimum slope value of 0.01 was significantly related to sufficient perfusion and good prognosis. There was no correlation between the quantitative ICG-FA results or any of the clinical parameters. Since clinical evaluation of perfusion in this surgery remains difficult, the additional use of ICG-FA may improve surgical decision making and, thereby, lead to better clinical results.

The database dbEST correctly predicts gene expression in colon cancer patients.

This study aims to test the predictive power of gene expression data derived from NIH's database dbEST, which collects gene expression results from a large number and variety of DNA array experiments. The motivation of this study is to make comparable experimental studies, which are usually performed only for one or a few tissues or organs, with a wide variety of other tissues. Confirmation of a good predictive power of dbEST would put a number of interesting and partially surprising recent findings, solely based on data mining, on a more solid basis than available so far. The expression of nine genes (eIF4E, DDX6, HAT1, USP28, HSP90(beta, PKM2, PLK1, COX2 and OPN) plus two calibration genes in paired normal and cancer colon tissues of eight individual patients was investigated by quantitative RT-PCR and compared with the predictions made by the data-base. GUS and beta-actin reveal only little variation among different patients, making them good internal calibration standards. In normal colon tissue, data mining correctly predicts the expression of all nine genes, which covers two orders of magnitude. In cancer, dbEST is somewhat less precise, but still valuable for the comparison with clinical results.

Association of p53 mutations, microvessel density and neoangiogenesis in pairs of colorectal cancers and corresponding liver metastases.

p53 suppressor gene mutations are a well known step which occurs in the late stages of the complex tumourigenesis of colorectal cancer. A deregulation of p53 protein function may be associated with increased neovascularization and aggressive tumour growth. In vitro studies have shown that these genetic alterations cause a loss of wild-type p53-induced anti-angiogenetic control and could possibly induce expression of the neoangiogenic vascular endothelial growth factor (VEGF). Therefore, this in vivo study was performed to assess p53 mutations, i.e. hot spots in exons 4-9, in primary colorectal cancers and in corresponding liver metastases in order to test whether there is an association between p53 mutated tumours with increased microvessel density (MVD) and VEGF overexpression. Twenty-two tissue samples taken from primary colorectal cancers and the corresponding liver metastases were immediately snap-frozen in liquid nitrogen and fixed in formaldehyde. After DNA extraction exons 4-9 were amplified and directly sequenced. Cryostat sections were stained immunohistochemically using antibodies against VEGF, CD34, and p53 protein. A modified semiquantitative Weidner score and interactive computerized image analysis was used to assess MVD. Overexpression of immunohistochemically detected p53 protein was found in 7 of the 11 primary tumours and liver metastases (64%). Sequencing showed 3 out of 11 primary tumours (27%) and 5 out of 11 liver metastases (46%) to have p53 point or frameshift mutations; these samples tested immunohistochemically positive for p53 protein. Two p53 mutations in samples of liver metastases were not detectable in the corresponding primaries. We detected one frameshift mutation in exon 4 that has not yet been described in the literature. Tumour samples with p53 mutations and increased VEGF immunoreactivity were associated with higher MVD (p<0.01 and p<0.05, respectively). However, there was no association detected immunohistochemically between p53 and MVD as well as p53 mutations and VEGF overexpression. Our data demonstrate specific genetic alterations in the coding regions of p53 suppressor gene in both primary colorectal cancers and corresponding liver metastases, these alterations are associated with an increase in MVD, but not in VEGF overexpression. In addition, a novel frameshift mutation in both colorectal cancer and metastasis is described.

Preweaning experience as a modifier of prenatal drug effects in rats and mice--a review.

The effects of preweaning experience in rats and mice on neuroendocrine and behavioral end points and their implications for prenatal drug effects are reviewed. The hypothalamo-pituitary-adrenal axis and the dopaminergic system were shown to be affected. Behavior related to hippocampal, adrenocortical functions and to the benzodiazepine receptor system was also modified. Other paradigms (nociception, conditioned taste aversion) exhibited susceptibility to such preweaning manipulations also. The effects of these early experiences seem to be mediated through complex factors including neuroendocrine responses of the pup to hypothermia and a permanent alteration of mother-infant interactions, with subsequent effects on neuroendocrine functions that are important for postnatal brain organization. Studies of interactions between prenatal drug effects and preweaning manipulations have been performed only with ethanol. When extending this work to other compounds, the systems and functions described above may provide some guidance in looking for possible interactions. In most cases the preweaning manipulations alleviated the effects of prenatal ethanol exposure. These findings may have important implications regarding the controversy about environmental influences affecting the outcome of exposure to neurobehavioral teratogens.

[Reversal of therapy of postoperative complications by measuring lung water]. / Postoperative Komplikationen Therapieumkehr durch Lungenwassermessung.

Our data suggest that the indicator dilution technique allows differentiated and early prediction of cardiopulmonary complications during the postoperative period. This leads to significant changes in fluid therapy to prevent organ failure.

Effects of prenatal ethanol exposure and early experience on radial maze performance and conditioned taste aversion in mice.

C57BL/6 mice were intubated on gestational days 14-18 twice daily with 1.58 g/kg ethanol, 4.2 g/kg sucrose, or remained untreated. Offspring of ethanol-treated or lab chow control groups were raised either by group-housed dams and weaned on postnatal day (PND) 28 (enriched condition), or by individually housed dams and weaned on PND 21 (standard condition). Offspring of the sucrose control group were raised by individually housed dams and weaned on PND 21. Groups did not differ in pup weight or litter size. Male and female offspring were assessed for performance in an unbaited radial maze (PND 45-52) and male offspring only were tested for conditioned taste aversion (PND 54-59). As hypothesized, mice prenatally exposed to ethanol and raised under standard conditions failed to develop the conditioned taste aversion response. In contrast, subjects with in utero ethanol exposure that were raised under enriched preweaning conditions developed the taste aversion response. Maze performance improved significantly over days, but no significant effects were detected for either prenatal treatment or preweaning rearing conditions. In conclusion, enriched preweaning rearing conditions abolished the detrimental effects of prenatal ethanol exposure on conditioned taste aversion, but radial maze performance remained unaffected by any treatment in this study.

Differential effects of communal rearing and preweaning handling on open-field behavior and hot-plate latencies in mice.

On day 2 after delivery, dams of the DBA/1 mouse inbred strain (n = 20/group) with their litter were allocated to one of the following groups: NH21, nonhandling, housed 1 litter/cage, weaned on postnatal day (PND) 21;H21, handling, housed 1 litter/cage, weaned on PND 21; NH30, nonhandling, group-housed (5 litters/cage), weaned on PND 30; H30, handling, group-housed (5 litters/cage), weaned on PND 30. Two male pups of each litter were color marked on PND 2. From PND 8-21 they were removed from their cage, gently held in the experimenter's hand for 5 min/day. The two marked males of each litter were housed together after weaning, and tested in the open-field on PNDs 51-53, and one of each of these siblings was tested for hot-plate latencies on PND 54. Being raised in group-housing and weaned on PND 30 resulted in offspring exhibiting shorter latencies to initiate behavior and higher percentages of centerfield entries in the open field, hot-plate latencies, however, remained unaffected. Preweaning handling increased hot-plate latencies and the number of grooming episodes in the open field, and it decreased defecation, percent centerfield entries and open-field activity in general. It is concluded that the two forms of early experience have different effects on neurobehavioral endpoints 8 weeks after birth.

Effects of prenatal ethanol exposure and early experience on home-cage and open-field activity in mice.

-C57BL/6 mice were intubated from gestational day 14-18 twice daily with 1.58 g/kg ethanol, 4.2 g/kg sucrose, or remained untreated. Offspring of ethanol treated or lab chow control groups were raised either by group-housed dams and weaned on postnatal day (PND) 28 or by individually housed dams and weaned on PND 21. Offspring of the sucrose control group were raised by individually housed dams and weaned on PND 21. Groups did not differ in pup weight or litter size. Offspring were assessed for home-cage activity (PND 36-38) and open-field behavior (PND 40-42). Mice prenatally exposed to ethanol showed increased activity in their home cages, whereas open-field behavior was generally not different from that of control groups. Conversely, different preweaning rearing conditions had affected open-field behavior, but not home-cage activity. In conclusion, home-cage behavior was a sensitive paradigm for detecting hyperactivity subsequent to a relatively low dose of prenatal ethanol in mice, and communal nesting/late weaning vs. individual nesting/ standard weaning may be a useful preweaning environmental manipulation to study possible modifications of prenatal neurobehavioral effects.

[Net K+(86Rb+) uptake of human lymphocytes following phytohemagglutinin stimulation]. / Netto-K+(86Rb+)-Aufnahme menschlicher Lymphozyten nach Phytohämagglutinin-Stimulation.

We tried to develop a short-time incubation method for the early detection of lymphocyte stimulation due to lectins and antigens. For this purpose the netto-K+(86Rb+)- uptake of (1) nonstimulated, (2) phytohaemagglutinin (PHA) activated and (3) potassium dichromate (K2Cr2O7) activated human lymphocytes was examined by means of 86Rb+ as a marker. The relative netto-K+-uptake was reduced by 38 per cent (p less than or equal to 0.01) on average after the incubation with PHA. After the incubation with K2Cr2O7 the 86Rb+-values differed, however, only unessentially from the nonstimulated controls in one patient sensibilized by K2Cr2O7. We concluded from our results that this method is not suitable for the early detection of cell mediated immune reactions.