[Clinical value of alternative technologies to standard laparoscopic cholecystectomy - single port, reduced port, robotics, NOTES]. / Klinischer Stellenwert alternativer Technologien zur standardmäßigen laparoskopischen Cholezystektomie ­ Single-Port, Reduced-Port, Roboter, NOTES.

Surgical interventions should ideally treat an existing disease curatively and achieve this with a low complication rate and minimal trauma. In this sense, laparoscopic cholecystectomy has become established as the recognized standard for the treatment of cholecystolithiasis. Newer procedures, such as single-port surgery or natural orifice transluminal endoscopic surgery (NOTES) have recently emerged to reduce the already low interventional trauma even further and to provide a better cosmetic outcome. With all new methods the main aim is the reduction of the transabdominal access points. Based on published results and diagnosis-related groups (DRG) data, this article examines whether this goal has been achieved, also with respect to the overall quality of treatment and the complication rates. In this context and in addition to the already mentioned approaches, robotic cholecystectomy and the reduced port approach are also considered.

Factors influencing the fascial closure rate after open abdomen treatment: Results from the European Hernia Society (EuraHS) Registry : Surgical technique matters.

PURPOSE: Definitive fascial closure is an essential treatment objective after open abdomen treatment and mitigates morbidity and mortality. There is a paucity of evidence on factors that promote or prevent definitive fascial closure. METHODS: A multi-center multivariable analysis of data from the Open Abdomen Route of the European Hernia Society included all cases between 1 May 2015 and 31 December 2019. Different treatment elements, i.e. the use of a visceral protective layer, negative-pressure wound therapy and dynamic closure techniques, as well as patient characteristics were included in the multivariable analysis. The study was registered in the International Clinical Trials Registry Platform via the German Registry for Clinical Trials (DRK00021719). RESULTS: Data were included from 630 patients from eleven surgical departments in six European countries. Indications for OAT were peritonitis (46%), abdominal compartment syndrome (20.5%), burst abdomen (11.3%), abdominal trauma (9%), and other conditions (13.2%). The overall definitive fascial closure rate was 57.5% in the intention-to-treat analysis and 71% in the per-protocol analysis. The multivariable analysis showed a positive correlation of negative-pressure wound therapy (odds ratio: 2.496, p < 0.001) and dynamic closure techniques (odds ratio: 2.687, p < 0.001) with fascial closure and a negative correlation of intra-abdominal contamination (odds ratio: 0.630, p = 0.029) and the number of surgical procedures before OAT (odds ratio: 0.740, p = 0.005) with DFC. CONCLUSION: The clinical course and prognosis of open abdomen treatment can significantly be improved by the use of treatment elements such as negative-pressure wound therapy and dynamic closure techniques, which are associated with definitive fascial closure.

Laparoscopic pectopexy: a follow-up cyclic biomechanical analysis determining time to functional stability.

INTRODUCTION: Pectopexy, a laparoscopic method for prolapse surgery, showed promising results in previous transient testing by this group. It was shown that a single suture, yielding an ultimate load of 35 N, was equivalent to continuous suturing. This was demonstrated in an in vitro cadaver study. This transient data were used to establish an elastic stress-strain envelope. It was now possible to proceed to dynamic in vitro analysis of this surgical method to establish time to functional stability. METHODS: Cyclic testing of this fixation method was performed on human female embalmed cadaver (cohort 1) and fresh, non-embalmed cadaver (cohort 2) pelvises. The testing envelope was 5-25 N at a speed of 1 mm/s. 100 load regulated cycles were applied. RESULTS: 100 cycles were completed with each model; no overall system failure occurred. Steady state, i.e., functional stability was reached after 14.5 (± 2.9) cycles for the embalmed group and after 19.1 (± 7.2) cycles for the non-embalmed group. This difference was statistically significant p = 0.00025. CONCLUSION: This trial showed in an in vitro cyclic testing of the pectopexy method that functional stability may be achieved after no more than 19.1 cycles of load exposure. When remaining within the established load envelope of below 25 N, patients do not need to fear global fixation failure. Testing did demonstrate differences in non-embalmed and embalmed cadaver testing. Embalmed cadaver testing tends to underestimate time to steady state by 26.3%.

[Natural orifice transluminal endoscopic surgery in Germany: Data from the German NOTES registry]. / "Natural orifice transluminal endoscopic surgery" in Deutschland : Daten aus dem deutschen NOTES-Register.

BACKGROUND: The German NOTES registry (GNR) was initiated by the German Society for General and Visceral Surgery (DGAV) as a treatment and outcome database for natural orifice transluminal endoscopic surgery (NOTES). AIM: The aim of this study was the descriptive analysis of all GNR data collected over a 5-year period since its start in 2008 with more than 3000 interventions. MATERIAL AND METHODS: The GNR is an online database with voluntary participation available to all German-speaking clinics. Demographic data, therapy details, complications and data on the postoperative course of patients are recorded. All cases in the GNR between March 2008 and November 2013 were included in the analysis. RESULTS: From a total of 3150 data sets 2992 (95 %) were valid and suited for the analysis. Hybrid transvaginal cholecystectomy was the most frequently used procedure (88.7 %), followed by hybrid transvaginal/transgastric appendectomy (6.1 %) and hybrid transvaginal/transrectal colon procedures (5.1 %). Intraoperative complications occurred in 1.6 %, postoperative complications in 3.7 % and conversions were reported in 1.5 %. Intraoperative bladder injuries and postoperative urinary tract infections were identified as method-specific complications of transvaginal procedures. Bowel injuries occurred as a rare (0.2 %) but potentially serious complication of transvaginal operations. CONCLUSION: The German surgical community ensures a safe and responsible introduction of the new NOTES operation techniques with its active participation in the GNR. Despite an overall low complication rate, the high number of procedures in the GNR permitted the identification of method-specific complications. This knowledge can be used to further increase the safety of NOTES in practice.

[Transvaginal/transumbilical hybrid NOTES appendicectomy : Comparison of techniques in uncomplicated and complicated appendicitis]. / Transvaginale/transumbilikale Hybrid-NOTES-Appendektomie : Vergleich der Technik bei unkomplizierter und komplizierter Appendizitis.

BACKGROUND: Appendicectomy (AE), the most frequent emergency surgical procedure, can be performed as a transvaginal hybrid natural orifice translumenal endoscopic surgery (NOTES) technique (TVAE). The question of feasibility also arises in cases of advanced inflammation with perforation. MATERIAL AND METHODS: Since May 2012 all female patients with suspected acute appendicitis were offered a TVAE as an alternative to the standard procedure. Preoperative, intraoperative and postoperative parameters were registered prospectively. RESULTS: Until October 2013 a total of 13 TVAEs had been performed. The median age of the patients was 41 years (range 20-76 years), median BMI was 23.1 (range 18.1-28.3 kg/m(2)) and the American Society of Anesthesiologists score (ASA) distribution (I/II/≥ III) was 8/5/0. Histology revealed three cases of perforated, one hemorrhagic necrotizing and seven phlegmonous appendicitis. Furthermore, there were two findings without inflammation, namely one neurogenic appendicopathy and one neuroendocrine tumor. For the three patients with perforated appendicitis, there was a trend for higher age (67.0 years versus 33.5 years, p=0.063) and a higher C-reactive protein (CRP) level on admission (134.4 mg/l versus 26.4 mg/l, p=0.043). Also, procedural time and hospital stay were longer (64 min versus 47 min, p=0.033 and 14 days versus 3 days, p=0.004, respectively). The former was mostly due to more extensive intraoperative flushing (volume 3000 ml versus 500 ml, p=0.013 and duration 13 min versus 2 min, p=0.011). None of the cases required conversion but two of the three postoperative complications occurred in patients with perforation, which also resulted in the longer hospital stay. CONCLUSION: Technically, TVAE seems feasible also in cases of perforated appendicitis. However, in these cases procedural time is prolonged due to more extensive flushing. Whether or not the longer hospital stay can be attributed to the perforation or if TVAE results in a higher rate of complications in cases of perforated appendicitis needs further evaluation.

Is the transnasal access for esophagogastroduodenoscopy in routine use equal to the transoral route? A prospective, randomized trial.

BACKGROUND AND STUDY AIMS: Routine esophagogastroduodenoscopy (EGD) is increasingly performed without sedation. Transoral (TO) and transnasal (TN) EGD offer different patient comfort and complications. PATIENTS AND METHODS: For a controlled, randomized, clinical trial comparing TN-EGD with TO-EGD without sedation, patients were assigned to TN-EGD using a thin endoscope (group 1, 93 patients), or TO-EGD using a standard endoscope (group 2, 90 patients). Physician-rated procedural time and complications as well as patient-rated side effects and preferences were compared. In group 3, patients (118) who had previously undergone TO-EGD, now underwent TN-EGD. RESULTS: Between group 1 and 2 there was no significant difference for procedural time. Nausea (p = 0.047) and epistaxis (p < 0.001) were significantly more frequent for TN-EGD. Conversion rate from TN- to TO-EGD was low with 4.3 %. For TN-EGD, patients' tolerance was better (p < 0.001), gagging was less (p < 0.001). In case of a future EGD, patients who know both procedures (group 3), strongly vote for TN-EGD (80 %). All groups vote against sedation for future procedures (90 %/90 %/89 %). CONCLUSIONS: Epistaxis can be relevant after TN-EGD, but can mostly be managed conservatively. TN-EGD is superior to TO-EGD regarding subjective and objective gagging as well as procedural tolerance. Patients who experienced both access routes, prefer TN-EGD. TN-EGD without sedation should be aspired for patient comfort and is recommended for routine use.

Lack of transmission of mouse minute virus (MMV) from in vitro-produced embryos to recipients and pups due to the presence of cumulus cells during the in vitro fertilization process.

The risk of transmission of mouse minute virus (MMV) to recipients of murine embryos arising from in vitro fertilization (IVF) of cumulus-enclosed oocytes (CEOs) or without cumulus cells (CDOs) in the presence of MMV-exposed (10(4) TCID(50) [mean tissue culture infective dose]/ml MMVp [prototype strain of MMV]) spermatozoa was evaluated. Also, the time after embryo transfer to detection of MMV antibody and the presence of MMV DNA in the mesenteric lymph nodes of recipients and pups were investigated. All mice were MMV free, but two seropositive recipients and four seropositive pups were found in the group with CDOs. With regard to the CEOs, two of 11 holding drops and five of 11 groups of embryos were MMV positive using PCR, while neither holding drops nor embryos carried infectious MMVp, as evidenced by the in vitro infectivity assay. From IVF with CDOs, five of 14 holding drops and four of nine groups of embryos were MMV positive, while one of 14 holding drops and no embryos carried infectious MMVp. When 10(5) cumulus cells were analyzed 5 h after exposure to 10(4) TCID(50)/ml MMVp, cells had an average titer of 10(4) TCID(50)/ml MMVp. The present data show that, in contrast to CDOs, 2-cell embryos from CEOs did not transmit infectious MMVp to the holding drops and to recipients. This observation is due to the presence of cumulus cells during the IVF process that reduce entry of MMV into the zona pellucida and absorb some of the virus. These data further confirm the efficacy of the IVF procedure in producing embryos that are free of infectious virus, leading to virus-free seronegative recipients and rederived pups.

Impairment of germline transmission after blastocyst injection with murine embryonic stem cells cultured with mouse hepatitis virus and mouse minute virus.

The aim of this study was to determine the susceptibility of murine embryonic stem (mESCs) to mouse hepatitis virus (MHV-A59) and mouse minute virus (MMVp) and the effect of these viruses on germline transmission (GLT) and the serological status of recipients and pups. When recipients received 10 blastocysts, each injected with 10(0) TCID(50) MHV-A59, three out of five recipients and four out of 14 pups from three litters became seropositive. When blastocysts were injected with 10(-5) TCID(50) MMVp, all four recipients and 14 pups from four litters remained seronegative. The mESCs replicated MHV-A59 but not MMVp, MHV-A59 being cytolytic for mESCs. Exposure of mESCs to the viruses over four to five passages but not for 6 h affected GLT. Recipients were seropositive for MHV-A59 but not for MMVp when mESCs were cultured with the virus over four or five passages. The data show that GLT is affected by virus-contaminated mESCs.

Production of virus-free seronegative pups from murine embryos arising from in vitro fertilization with mouse minute virus-exposed spermatozoa.

In the present study, the risk of transmission of mouse minute virus (MMV) to recipients of murine embryos arising from in vitro fertilization (IVF) of oocytes with MMV-exposed spermatozoa and to resulting pups was evaluated. Also, the time of seroconversion of recipients and pups was investigated. To achieve this goal, IVF of oocytes with cryopreserved spermatozoa from the inbred C3HeB/FeJ mouse strain was performed, and the resulting embryos were transferred to suitable Swiss recipients. Three groups were investigated: 1) oocytes or the developing embryos were continuously exposed to 10(4) TCID(50) MMVp per milliliter in the fertilization (human tubal fluid [HTF]), culture (KSOM), and embryo transfer (M2) media (positive control); 2) oocytes and spermatozoa were exposed to MMVp in the HTF medium only and transferred after a standard washing procedure with 10 washing steps in virus-free KSOM and M2; and 3) oocytes and spermatozoa were exposed to virus-free HTF, KSOM, and M2 (negative control). To detect antibodies to MMV in recipients and progeny, serological analyses were performed by ELISA on Days 14, 21, 28, and 42, and on Days 42 and 63, respectively, after embryo transfer. The presence of MMV in the washing drops was analyzed by PCR and an in vitro infectivity assay, while organs of some recipients and pups were analyzed by PCR. Using 10(4) of the tissue culture infective dose of MMVp per millilitre in the fertilization medium only, the present results demonstrate that 10 washing steps in the IVF-ET procedure are sufficient to remove the virus to a noninfectious dose, producing MMV-free seronegative recipients and pups. As such, there is minimal risk of transmission of MMV to recipients and pups if spermatozoa become contaminated with such viral loads.

Effects of melatonin in perimenopausal and menopausal women: a randomized and placebo controlled study.

In aging humans, night levels of melatonin (MEL) decline progressively. Also thyroid and gonadal functions decline during aging while gonadotropins (luteotropic hormone (LH) and follicle stimulating hormone (FSH)) steadily increase. A desynchronization of pineal circadian cyclicity as expressed by the progressive decrease of the MEL night peak may be permissively linked to the onset and progression of menopause. We studied the effects of exogenous, evening administration of MEL on the level of hormones which are known to be involved in the genesis and progression of menopause. Perimenopausal and menopausal women from 42 to 62years of age with no pathology or medication were selected. MEL was measured in saliva to divide them into low, medium and high-MEL patients. Half of them took 3mg MEL and half of them Placebo at bedtime (10-12p.m.) in a fully randomized and double-blind fashion. Three and six months later blood was taken for determination of pituitary (LH, FSH), ovarian, and thyroid hormones I(T3 and T4). All women taking MEL with low basal level of MEL and/or Placebo for three and six months showed a significant increase in levels of thyroid hormones. Before initiation of the study, a negative correlation was found in all women between LH, FSH and basal MEL levels. Within six months of treatment, MEL produced a significant diminution of LH in the younger women (43 to 49year-old), while no effect was seen in the older women (50-62years old). A decrement of FSH was observed in MEL-treated women with low basal MEL levels. In addition, most MEL-treated women reported a general improvement of mood and a significant mitigation of depression. MEL decline during aging may thus signal the derangement of pineal and pituitary-controlled ovarian cyclicity and the progressive quenching of fertility in women. These findings seem to show a recovery of pituitary and thyroid functions in MEL-treated women, towards a more juvenile pattern of regulation.

The pineal gland and cancer. I. Pinealectomy corrects congenital hormonal dysfunctions and prolongs life of cancer-prone C3H/He mice.

Hormonal derangements almost invariably anticipate and signal the onset of tumors. Chronic, nocturnal melatonin administration delays aging in normal strains of mice. On the contrary it promotes and accelerates the onset of tumors in the cancer-prone strain of C3H/He mice. Grafting of a young pineal gland into aging mice prolongs their longevity and maintains juvenile circadian hormonal functions while pinealectomy (Px) does the opposite. We investigated if Px in C3H/He mice would modify their congenitally deranged pituitary function and affect their longevity. It was found that contrarily to Px in normal mice, Px in C3H/He mice remarkably maintains juvenile night levels of thyroid hormones and lipids, preserves a cell-mediated immune response and significantly prolongs their life. The pineal gland and its pathology may be the key for understanding, not only the causes of metabolic aging, but also the origin of those congenital or progressive aging-related hormonal alterations preceding onset of all tumors and thus allow preventive corrective interventions with pineal-derived agents.

Transferrin treatment corrects aging-related immunologic and hormonal decay in old mice.

Experiments were conducted to study the effect of heterologous plasma transferrins separated and purified from human plasma pools on endocrine and immune functions of old, aging mice. Two similar experiments have shown that parenteral treatment with iron and zinc-free human transferrins produces a significant improvement of immunological and endocrine functions in the aging mice toward more juvenile values. Those changes occur in the thymus and its cell subsets, in peripheral blood lymphocytes, in the restoration of juvenile levels of thyroxine, in the increase of testis weight, and in the normalization of plasma zinc levels. These totally unsuspected effects of transferrin in aging mice suggest a most important role of endogenous transferrins in the maintenance of neuroendocrine and immune functions. The mechanism remains unexplained although the basic immunoenhancing and anti-apoptotic effect of transferrin-vehiculated zinc may be relevant.

Melatonin administration in tumor-bearing mice (intact and pinealectomized) in relation to stress, zinc, thymulin and IL-2.

Melatonin (MEL) may counteract tumors through a direct oncostatic role. MEL is also an antistress agent with immunoenhancing properties against tumors due to a suppressive role of MEL on corticosterone release. Rotational stress (RS) (spatial disorientation) facilitates metastasis progression in mice. Also, MEL counteracts tumors because of its influence on immune responses via the metabolic zinc pool, which, is reduced in tumors and stress. Zinc is required for normal thymic endocrine activity (i.e. thymulin) and interleukin-2 (IL-2) production. Because in vivo data is still controversial, exogenous MEL treatment (22 days in drinking water) in both intact and pinealectomized (px) mice bearing Lewis lung carcinoma leads to significant decrements of metastasis volume, restoration of the negative crude zinc balance, recovery of thymulin activity and increment of IL-2 exclusively in intact and px tumor bearing mice subjected to RS. Significant inverse correlations are found in both stressed intact and px tumor bearing mice after MEL treatment between zinc and corticosterone (r = 0.78, P < 0.01; r = 0.80, P < 0.01, respectively). Positive correlations between zinc and IL-2 (r = 0.75, P < 0.01; r = 0.73, P < 0.01, respectively) or thymulin (r = 0.75, P < 0.01; r = 0.82, P < 0.01, respectively) are observed in same models of mice. These findings suggest a MEL action to decrease metastasis mediated by a possible interplay between zinc and MEL, via corticosterone, with consequent restoration of thymic efficiency and IL-2 production. MEL as an antistress agent with immunoenhancing properties in cancer deserves further consideration.nuclear factor-kb; POMC, proopiomelanocortin; Px, pinealectomized mice; RIA, radioimmunoassay; RS, rotational stress; SDI, stressed intact mice; SDPx, stressed pinealectomized mice; TNF-alpha, tumor necrosis factor-alpha; ZnFTS, active zinc-bound thymulin; ZnFTS + FTS, total thymulin.

Presence of links between zinc and melatonin during the circadian cycle in old mice: effects on thymic endocrine activity and on the survival.

Links between zinc and melatonin in old melatonin treated mice with a reconstitution of thymic functions have been recently documented. Concomitant increments of the nocturnal peaks of zinc and melatonin, with a synchronization of their circadian patterns, are achieved in old mice after melatonin treatment. A recovery of the nocturnal peaks of thymulin plasma levels and of the number of thymulin-secreting cells with a synchronization of their circadian patterns are also achieved. The existence of significant positive correlations between melatonin and zinc and between melatonin and thymulin or the number of thymulin-secreting cells supports the presence of links between zinc and melatonin also during the circadian cycle with a beneficial effect on thymic functions. The altered circadian pattern of corticosteron in old mice is normalized by melatonin. The existence of inverse correlations between corticosteron and melatonin, between corticosteron and zinc and between corticosteron and thymulin or the number of thymulin-secreting cells during the whole circadian cycle, suggests the involvement of glucocorticoids pathway in the melatonin thymic reconstitution, via zinc. The presence of an interplay among zinc, melatonin, glucocorticoids and thymulin may be, therefore, supported during the circadian cycle. 'In vitro' experiments from old thymic explants show a direct action of zinc, rather than melatonin, on thymulin production, further suggesting that the action of melatonin on the thymic efficiency is mediated by the zinc bioavailability. The beneficial effect of the links between zinc and melatonin on thymic functions during the circadian cycle, may be extended to a prolonged survival in aging, where, however, zinc may be more involved.

Circadian melatonin and young-to-old pineal grafting postpone aging and maintain juvenile conditions of reproductive functions in mice and rats.

Chronic, night administration of melatonin to aging mice and transplantation of a young pineal gland into the thymic rudiment of older mice and rats have been studied with the aim of evaluating their effects on aging of gonadal, sexual, and reproductive functions. Both melatonin administration and young-to-old pineal grafting positively affect size and function of testes and maintenance of juvenile hippocampal and testicular LHRH-receptors and beta-adrenergic receptors in the tests of old rats and mice. These results demonstrate that a pineal-directed circadian function and cyclicity is fundamental for the regulation of sexual, reproductive physiology, and that proper intervention with melatonin may potentially postpone aging of both neural and gonadal sexual function.

Long-term melatonin supplementation does not recover the impairment of natural killer cell activity and lymphocyte proliferation in aging mice.

In this study we evaluated the effect of long-term melatonin (MEL) treatment on the cytotoxic activity and number of natural killer (NK) cells and the proliferative response of spleen lymphocytes to phytohemagglutinin (PHA) or interleukin-2 (IL-2) in old mice. Seventeen-eighteen month-old Balb/c mice were supplemented with MEL (40-50 microg/day/mouse) and sacrificed after eight months. The MEL supplementation was unable to recover the low levels of both endogenous and IL-2-induced NK cell activity found in old untreated mice. Also the NK cell number was unaffected by MEL treatment. The spleen lymphocyte proliferative response to both PHA and IL-2 was not different in old MEL-treated compared to old untreated mice. These results indicate that long-term MEL supplementation does not recover the age-related deterioration of NK cell activity and lymphocyte proliferative capacity.

Effect of melatonin and pineal grafting on thymocyte apoptosis in aging mice.

We have evaluated the effect of chronic melatonin (MEL) treatment or pineal grafting (PG) in old mice on the apoptosis of both thymocytes and spleen lymphocytes under conditions of either serum deprivation or glucocorticoid or zinc administration. The apoptosis was correlated with the modulation of thymus and adrenal weight and corticosterone and zinc plasma levels induced by MEL treatment or PG in old mice. Balb/c mice (17-18 months old) were given supplements of MEL (40-50 micrograms/day/mouse) or grafted with a young pineal gland and then sacrificed after 8 months. Both the MEL treatment and PG partially prevented thymic involution in very old mice. Both treatments protected the thymic and spleen lymphocytes in old mice from the apoptosis induced by serum deprivation and recovered the reduced thymocyte sensitivity to the apoptosis induced by dexamethasone (DEX), present in old untreated animals, to the values found in young mice. DEX caused a bigger loss of G D /G 1 phase cells in MEL treated mice than in old untreated mice. The protective action of MEL treatment or PG on serum deprivation induced apoptosis was correlated with increased thymus weight, reduced adrenal weight and corticosterone levels and increased zinc plasma levels. The greater DEX-induced apoptosis found in MEL treated and PG mice was correlated with reduced adrenal weight and function. In vitro MEL did not affect thymocyte apoptosis in young or old mice. These results suggest that MEL treatment or PG prevent age-related thymus involution through regulation of thymocyte apoptosis which, in turn, occurs through modulation of the pituitary-adrenal axis and zinc turnover determined by the pineal hormone.