[The effects of cannabis and cannabinoids on anesthesia and analgesia during the perioperative period]. / Der Einfluss von Cannabis und Cannabinoiden auf Anästhesie und Analgesie in der perioperativen Phase.

Cannabis is the most frequently used recreational drug worldwide. Moreover, the use of cannabinoids for medical purposes is also constantly growing and medical cannabis products are legalised by an increasing number of countries. First clinical reports have shown enhanced requirements for propofol and analgesics used for general anesthesia and perioperative pain management in cannabis users. Therefore, this article discusses the potential impact of medical or recreational cannabis use on patients with regard to the recent literature. Besides the significantly increased requirement for propofol and fentanyl during anesthesia and for postoperative analgesia, a higher risk for tachycardia, pulmonary and cardiovascular complications was observed. With respect to these data, the authors recommend asking patients pre-operatively about recreational or medical cannabis use or cannabinoid-based medication.

What are the differences in the outcome of laparoscopic axial (I) versus paraesophageal (II-IV) hiatal hernia repair?

INTRODUCTION: Comparison of elective laparoscopic repair of axial vs paraesophageal hiatal hernias reveals relevant differences in both the patient collectives and the complexity of the procedures. MATERIALS AND METHODS: The present uni- and multivariable analysis of data from the Herniamed Registry compares the outcome for 2047 (67.3%) (type I) axial with 996 (32.7%) (types II-IV) paraesophageal primary hiatal hernias following laparoscopic repair. RESULTS: Compared with the patients with axial hiatal hernias, patients with paraesophageal hiatal hernia were nine years older, had a higher ASA score (ASA III/IV: 34.8 vs 13.7%; p < 0.001), and more often at least one risk factor (38.8 vs 21.4%; p < 0.001). This led in the univariable analysis to significantly more general postoperative complications (6.0 vs 3.0%; p < 0.001). Reflecting the greater complexity of the procedures used for laparoscopic repair of paraesophageal hiatal hernias, significantly higher intraoperative organ injury rates (3.7 vs 2.3%; p = 0.033) and higher postoperative complication-related reoperation rates (2.1 vs 1.1%; p = 0.032) were identified. Univariable analysis did not reveal any significant differences in the recurrence and pain rates on one-year follow-up. Multivariable analysis did not find any evidence that the use of a mesh had a significant influence on the recurrence rate. CONCLUSION: Surgical repair of paraesophageal hiatal hernia calls for an experienced surgeon as well as for corresponding intensive medicine competence because of the higher risks of general and surgical postoperative complications.

Does surgeon volume matter in the outcome of endoscopic inguinal hernia repair?

INTRODUCTION: For open and endoscopic inguinal hernia surgery, it has been demonstrated that low-volume surgeons with fewer than 25 and 30 procedures, respectively, per year are associated with significantly more recurrences than high-volume surgeons with 25 and 30 or more procedures, respectively, per year. This paper now explores the relationship between the caseload and the outcome based on the data from the Herniamed Registry. PATIENTS AND METHODS: The prospective data of patients in the Herniamed Registry were analyzed using the inclusion criteria minimum age of 16 years, male patient, primary unilateral inguinal hernia, TEP or TAPP techniques and availability of data on 1-year follow-up. In total, 16,290 patients were enrolled between September 1, 2009, and February 1, 2014. Of the participating surgeons, 466 (87.6 %) had carried out fewer than 25 endoscopic/laparoscopic operations (low-volume surgeons) and 66 (12.4 %) surgeons 25 or more operations (high-volume surgeons) per year. RESULTS: Univariable (1.03 vs. 0.73 %; p = 0.047) and multivariable analysis [OR 1.494 (1.065-2.115); p = 0.023] revealed that low-volume surgeons had a significantly higher recurrence rate compared with the high-volume surgeons, although that difference was small. Multivariable analysis also showed that pain on exertion was negatively affected by a lower caseload <25 [OR 1.191 (1.062-1.337); p = 0.003]. While here, too, the difference was small, the fact that in that group there was a greater proportion of patients with small hernia defect sizes may have also played a role since the risk in that group was higher. In this analysis, no evidence was found that pain at rest [OR 1.052 (0.903-1.226); p = 0.516] or chronic pain requiring treatment [OR 1.108 (0.903-1.361); p = 0.326] were influenced by the surgeon volume. As confirmed by previously published studies, the data in the Herniamed Registry also demonstrated that the endoscopic/laparoscopic inguinal hernia surgery caseload impacted the outcome. However, given the overall high-quality level the differences between a "low-volume" surgeon and a "high-volume" surgeon were small. That was due to the use of a standardized technique, structured training as well as continuous supervision of trainees and surgeons with low annual caseload.

TEP versus TAPP: comparison of the perioperative outcome in 17,587 patients with a primary unilateral inguinal hernia.

INTRODUCTION: More than 20 years since the introduction of TAPP and TEP into clinical routine, there is a lack of clarity due to conflicting comparative data. Therefore, more results from registries are needed. PATIENTS AND METHODS: A total of 17,587 patients were enrolled prospectively between September 1, 2009, and April 15, 2013, in the Herniamed registry. Of these patients, 10,887 (61.9%) had a TAPP and 6700 (38.1%) a TEP repair. The dependent variables were intra- and postoperative complication rates, number of reoperations as well as absolute and relative frequencies. The results of unadjusted analyses were verified via multivariable analyses. RESULTS: Multivariable analysis verified the results of unadjusted analysis, indicating that the surgical technique did not have any significant impact, also while taking account of other factors, on occurrence of intraoperative [p = 0.1648; OR = 1.214 (0.923; 1.596)] and general postoperative complications [p = 0.0738; OR = 1.315 (0.974; 1.775)]. Postoperative surgical complications [OR = 2.323 (1.882; 2.866); p < 0.0001] were noted more often after TAPP. Furthermore, the hernia defect size [p < 0.0001; I vs III: OR = 0.439 (0.313; 0.615), II vs III: OR = 0.712 (0.582; 0.872)] or scrotal [p < 0.0001; OR = 2.170 (1.501; 3.137)] hernia and age [p = 0.0002; 10-year OR = 1.135 (1.062; 1.213)] had a significant impact on the occurrence of postoperative complications. Complications were observed more commonly for larger hernia defects and a scrotal hernia. However, the difference in the postoperative complication rate between TEP and TAPP did not result in any difference in the reoperation rate (TEP 0.82% vs TAPP 0.90%; p = 0.6165). CONCLUSION: The intraoperative and general postoperative complication rates as well as the reoperation rate for complications show no significant difference between TEP and TAPP. The higher postoperative complication rate for TAPP, which could be managed conservatively, is partly explained by larger defect sizes, more scrotal hernias and older age.

Perioperative outcome of unilateral versus bilateral inguinal hernia repairs in TAPP technique: analysis of 15,176 cases from the Herniamed Registry.

INTRODUCTION: Following repair of a unilateral inguinal hernia, there is a risk of 1% per year of onset of an inguinal hernia on the other side. Comparison of bilateral with unilateral TAPP operation in a high-volume center found that morbidity and reoperation rates were only marginally higher for bilateral TAPP operation. Some authors are calling for prophylactic operation of the contralateral side. METHODS: Between September 2009 and April 2013, data were entered into the Herniamed Registry on 15,176 patients who had undergone TAPP operation. Of these patients, 10,887 had been operated on because of a unilateral (71.7%) and 4289 because of a bilateral (28.3%) inguinal hernia. RESULTS: A significant difference was noted in the rate of postoperative complications occurring within 30 days, which was 4.9% for bilateral compared with 3.9% for unilateral inguinal hernia (p = 0.009). The postoperative complications necessitated reoperation in 0.9% of patients after unilateral and in 1.9% of patients after bilateral inguinal hernia repair, thus attesting to the significantly higher risk presented by bilateral inguinal hernia repair (p = <0.001).Multivariate analysis confirmed the highly significant influence of bilateral TAPP on increased reoperation rates due to complications (p > 0.0001). The odds ratio was 2.13 (95% CI 1.58-2.86). Comparison of the results from a high-volume center with those from the Herniamed Registry showed that perioperative complication rates were markedly higher. CONCLUSION: Perioperative outcome of bilateral TAPP operation demonstrates significantly worse postoperative complication and reoperation rates compared with unilateral TAPP. Likewise, the results were markedly unfavorable compared with those of a high-volume center. If a bilateral hernia repair should be attempted in those patients with only a unilateral hernia, these data give the surgeon more information on how to better prepare a patient and obtain consent preoperatively.

Functional conservation of Nematostella Wnts in canonical and noncanonical Wnt-signaling.

Cnidarians surprise by the completeness of Wnt gene subfamilies (11) expressed in an overlapping pattern along the anterior-posterior axis. While the functional conservation of canonical Wnt-signaling components in cnidarian gastrulation and organizer formation is evident, a role of Nematostella Wnts in noncanonical Wnt-signaling has not been shown so far. In Xenopus, noncanonical Wnt-5a/Ror2 and Wnt-11 (PCP) signaling are distinguishable by different morphant phenotypes. They differ in PAPC regulation, cell polarization, cell protrusion formation, and the so far not reported reorientation of the microtubules. Based on these readouts, we investigated the evolutionary conservation of Wnt-11 and Wnt-5a function in rescue experiments with Nematostella orthologs and Xenopus morphants. Our results revealed that NvWnt-5 and -11 exhibited distinct noncanonical Wnt activities by disturbing convergent extension movements. However, NvWnt-5 rescued XWnt-11 and NvWnt-11 specifically XWnt-5a depleted embryos. This unexpected 'inverse' activity suggests that specific structures in Wnt ligands are important for receptor complex recognition in Wnt-signaling. Although we can only speculate on the identity of the underlying recognition motifs, it is likely that these crucial structural features have already been established in the common ancestor of cnidarians and vertebrates and were conserved throughout metazoan evolution.

One-year results of a prospective, randomised clinical trial comparing four meshes in laparoscopic inguinal hernia repair (TAPP).

BACKGROUND: A low rate of chronic pain and maximum postoperative comfort are the main goals today in inguinal hernia repair. This four-arm randomised trial compares these parameters after laparoscopic hernia repair (TAPP) with a standard heavyweight mesh (HW), a pure middleweight polypropylene mesh (MW), a lightweight composite polypropylene mesh (LW), or a titanised lightweight mesh (TLW). The primary endpoint of the study was the incidence of chronic pain of any severity at the site of hernia repair at 1 year. METHODS: A total of 600 patients with a laparoscopic inguinal hernia repair and a defect diameter of 3-5 cm were included in the trial. In all patients, a non-invasive mesh fixation technique was performed using fibrin glue. Patients were assessed for pain, foreign body sensation, and physical activities preoperatively, early postoperatively, at 4 weeks, at 6 months, and at 1 year by questionnaire, and were examined clinically. Postoperatively, seroma formation was measured by ultrasound. RESULTS: At 1 year after TAPP, frequency of pain did not differ statistically between the four groups (depending on type of activity: between 6-8% with HW mesh, 2-4% with middleweight mesh, and 2-4.7% with both lightweight meshes); average intensity of pain was very low, at between VAS 0.4 ± 3.1 and 1.5 ± 7.8 (MW, LW, TLW) and between 1.9 ± 8.6 and 2.3 ± 9.1 (HW) depending on activity (n.s.). Early postoperatively between 31.3% (LW) and 21.3% (TLW) of the patients needed pain medication (n.s.); at 1 year this percentage had dropped to 0.3% (one HW, one MW). Foreign body sensation did not differ but impairment of physical activities (P = 0.0437) was significantly less in the MW, LW, and TLW group (6-12.7%) compared to HW (15.3%) at 4 weeks; at 1 year this percentage was between 0 and 1.3% (n.s.). CONCLUSION: Compared to HW mesh, the use of MW, LW, and TLW meshes for laparoscopic hernia repair did not significantly affect rate of chronic pain, but seemed to improve early postoperative convalescence. No difference was found between middleweight pure polypropylene (MW), composite lightweight (LW), or titanised lightweight polypropylene (TLW) meshes.

Acute psychotropic effects of oral cannabis extract with a defined content of Delta9-tetrahydrocannabinol (THC) in healthy volunteers.

INTRODUCTION: The medical use of cannabinoids is limited mainly by their undesirable effects. With respect to acute psychotropic effects, the aim of this study is the comparison of an oral cannabis extract and low-dose diazepam in a cross-over experiment in drug-naïve healthy women. METHODS: Sixteen healthy females participated in this randomized, double-blind, active comparator-controlled, single-dose, balanced 2-way cross-over study. Cannabis extract with standardised Delta (9)-tetrahydrocannabinol (THC) content (20 mg) or active placebo (5 mg diazepam) was administered orally. Subjects were assessed by self- and observer-rated visual analogue scales (VAS), the BRIEF PSYCHIATRIC RATING SCALE (BPRS) and three psychomotor tests up to 6 h after administration. RESULTS: VAS showed significantly elevated fatigue, drowsiness, dizziness, and "feeling high" after cannabis as compared to baseline and diazepam. BPRS scores were significantly higher after cannabis intake. Only in one psychomotor test a decrease of psychomotor activity after cannabis was evident. One subject in the cannabis condition experienced severe transient psychotic symptoms. DISCUSSION: Orally administered cannabis produced significant central depressant side-effects compared to diazepam, mostly subjective effects (VAS) but marginal effects in psychomotor performance in 15 healthy females. Regarding the medical use of cannabis, a rigorous benefit-risk analysis and an exact psychiatric assessment before and during treatment are necessary.

[Analgesia in colon surgery. Can the use of NSAIDs reduce the opioid consumption following conventional and laparoscopic interventions?]. / Analgesie in der Kolonchirurgie. Kann die Verwendung von Nichtopoidanalgetika den Opioidbedarf nach konventioneller und laparoskopischer Kolonchirurgie senken?

BACKGROUND: The goal of our study was to evaluate the morphine-sparing effect of nonsteroidal anti-inflammatory drugs (NSAIDs) following both conventional and laparoscopic colon surgery. MATERIALS AND METHODS: In this prospective, randomized clinical trial, 180 patients were assigned to three groups. Two groups received either paracetamol or parecoxib/valdecoxib in addition to piritramid via patient-controlled or nurse-controlled analgesia pump. Patients in the control group received piritramid only. The total piritramid consumption during hospital stay was recorded. RESULTS: Total opioid consumption was significantly lower in the two groups who received NSAIDs. Comparing conventional and laparoscopic surgery, the latter group had much lower opioid consumption. CONCLUSION: The use of NSAIDs following colon surgery significantly reduces postoperative opioid consumption.

TAPP - Stuttgart technique and result of a large single center series.

UNLABELLED: Laparoscopic hernioplasty is assessed as a difficult operation. Operative technique determines the frequency of complications, the time of recovery and the rate of recurrences. A proper technique is absolutely necessary to achieve results that are superior to open hernia surgery. TECHNIQUE: The key points in our technique are 1) use of nondisposable instruments; 2) use of blunt trocars, consisting of expanding and non-incisive cone-shaped tips; 3) spacious and curved opening to the peritoneum, high above all possible hernia openings; 4) meticulous dissection of the entire pelvic floor; 5) complete reduction of the hernial sac; 6) wide parietalization of the peritoneal sac, at least down to the mid of psoas muscle; 7) implantation of a large mesh, at least 10 cm × 15 cm; 8) fixation of the mesh by clip to Cooper's ligament, to the rectus muscle and lateral to the epigastric vessels, high above the ileopubic tract; 9) the use of glue allows fixation also to the latero-caudial region; and 10) closure of the peritoneum by running suture. RESULTS: With this technique in 12,678 hernia repairs, the following results could be achieved: operating time - 40 min; morbidity - 2.9%; recurrence rate - 0.7%; disability of work - 14 days. In all types of hernias (recurrence after previous open surgery, recurrence after previous preperitoneal operation, scrotal hernia, hernia in patients after transabdominal prostate resection), similar results could be achieved. SUMMARY: Laparoscopic hernia repair can be performed successfully in clinical practice even by surgeons in training. Precondition for the success is a strictly standardized operative technique and a well-structured educational program.

Laparoscopic hernia repair--TAPP or/and TEP?

BACKGROUND: Of various endoscopic hernia repair procedures, TAPP and TEP have been selected for routine use. METHODS: Results from Medline research were analysed. RESULTS: There is a similar risk for postoperative morbidity for both techniques. The recurrence rate in large single-centre series is between 0% and 3.4%. There were numerous indications for both procedures, whereby a transperitoneal TAPP can also be applied in cases of previous preperitoneal operations. CONCLUSION: Randomised trials comparing both methods of hernia repair are lacking. Seven non-randomised studies showed no differences in recurrence rate and morbidity. In general the learning curve for is shorter in favour of TAPP repair.

Highly conserved gene expression profiles in humans with allergic rhinitis altered by immunotherapy.

BACKGROUND: Atopic diseases, resulting from hypersensitivity to a wide variety of allergens, affect 10-20% of the population. Immunotherapy is an effective treatment for atopic diseases, but its mechanisms are not fully understood. OBJECTIVE: We studied gene expression profiles in the peripheral blood mononuclear cells (PBMC) and examined whether the individuals with allergic rhinitis (AR) have a unique gene expression profile and how the immunotherapy affect the gene expression profiles. METHODS: We used cDNA microarray and 'expression analysis systemic explorer' to examine the gene expression profiles in the PBMC of atopic subjects and other groups. RESULTS: We identified a highly conserved gene expression profile in atopic subjects that permitted their accurate segregation from control or autoimmune subjects. A major feature of this profile was the under-expression of a variety of genes that encode proteins required for apoptosis and over-expression of genes that encode proteins critical for stress responses and signal transduction. We also identified 563 genes that can segregate individuals with AR based upon receipt of immunotherapy. CONCLUSION: There is a highly conserved gene expression profile in the PBMC of individuals with AR. This profile can be used to identify individuals with AR and to evaluate responses to immunotherapy. Quantitative endpoints, such as gene expression, may assist clinicians faced with clinical decisions in the diagnosis of patients and the evaluation of response to therapy. The knowledge of the possible genetic basis for immunotherapy efficacy may also lead to novel therapeutic approaches for atopic diseases.

A gene expression signature for recent onset rheumatoid arthritis in peripheral blood mononuclear cells.

BACKGROUND: In previous studies the presence of a distinct gene expression pattern has been shown in peripheral blood cells from patients with autoimmune disease. OBJECTIVE: To determine whether other specific signatures might be used to identify subsets of these autoimmune diseases and whether gene expression patterns in early disease might identify pathogenetic factors. METHODS: Peripheral blood mononuclear cells were acquired from patients with rheumatoid arthritis (RA) and analysed by microarrays containing over 4300 named human genes. Patients with RA for <2 years were compared with subjects with longstanding RA (average duration 10 years) and with patients with other immune or autoimmune diagnoses. RESULTS: Cluster analyses permitted separation of the patients with early RA (ERA) from those with longstanding disease. Comparison with other patient groups suggested that the ERA signature showed some overlap with that seen in the normal immune response to viral antigen as well as with a subset of patients with systemic lupus erythematosus. CONCLUSIONS: The ERA signature may reflect, in part, a response to an unknown infectious agent. Furthermore, shared features with some lupus patients suggest that common aetiological factors and pathogenetic pathways may be involved in these two autoimmune disorders.

The AESOP robot system in laparoscopic surgery: increased risk or advantage for surgeon and patient?

BACKGROUND: The aim of this study was to examine the advantages and risks of the Automated Endoscopic System for Optical Positioning (AESOP) 3000 robot system during uncomplicated laparoscopic cholecystectomies or laparoscopic hernioplasty. METHODS: In a randomized study, we examined two groups of 120 patients each with the diagnosis cholecystolithiasis respectively the unilateral inguinal hernia. We worked with the AESOP 3000, a robotic arm system that is voice-controlled by the surgeon. The subjective and objective comfort of the surgeon as well as the course and length of the operation were measured. RESULTS: The robot-assisted operations required significantly longer preparation and operation times. With regard to the necessary commands and manual camera corrections, the assistant group was favored. The same was true for the subjective evaluation of the surgical course by the surgeon. CONCLUSIONS: Our study showed that the use of AESOP during laparoscopic cholecystectomy and hernioplasty is possible in 94% of all cases. The surgeon must accept a definite loss of comfort as well as a certain loss of time against the advantage of saving on personnel.

[Cannabinoids and the immune system. Of men, mice and cells]. / Cannabinoide und Immunsystem. Menschen, Mäuse und Zellen.

The medical use of cannabis or cannabinoid compounds is controversial. Cannabinoids like the Delta(9)-THC (tetrahydrocannabinol) or the synthetic derivative Nabilone are available against cancer- and HIV-associated cachexia, nausea and vomiting. Over the last 20 years, the cannabinoid receptors CB(1) and CB(2) and their endogenous ligands have been found. The involvement of this endogenous cannabinoid signalling system in feeding, appetite, pain perception and immunomodulation could be demonstrated using animal and in vitro studies. Thus, the concern about immunosuppressive effects in humans using medical cannabinoid preparations grew. However, up to now most human studies have failed to demonstrate a well-defined and reproducible immunosuppressive cannabinoid-effect. Only the smoking of marijuana showed a significant local immunosuppression of the bactericidal activity of human alveolar macrophages. In animal studies, cannabinoids were identified as potent modulators of cytokine production, causing a shift from Th1 to Th2 cytokines. In consequence, a compromised cellular immunity was observed in these animals, resulting in enhanced tumor growth and reduced immunity to viral infections. In vitro, immunosuppressive effects were shown in all immune cells, but only at high micromolar cannabinoid concentrations not reached under normal clinical conditions. In conclusion, there is no evidence that cannabinoids induce a serious, relevant immunosuppression in humans, with the exception of marijuana-smoking which may affect local broncho-alveolar immunity.