Continuous local analgesic therapy reduces pain after radical inguinal/iliacal lymph node dissection.

BACKGROUND: To optimize postoperative pain therapy after a radical inguinal/iliacal lymph node dissection (RILND), we investigated the influence of a continuous application of a local anaesthetic via a subfascial wound catheter in the abdominal wall in addition to a standardized systemic analgesia. MATERIALS AND METHODS: Between July 2007 and December 2009, 50 patients with stage III/IV of melanoma disease received, in an observational study, a systemic analgesic therapy. Of these patients, 30 were additionally treated with a subfascial catheter. Main outcome criterion was the pain under mobilisation at the first postoperative morning registered via a visual analogue score. Minor criteria were the analgesic requirement, the specific (surgical) complications and the day of discharge. RESULTS: Patients treated with the subfascial catheter had significant less pain at the first postoperative morning in rest (p = 0.02) and after mobilisation (p = 0.03) without increased morbidity (p = 0.45). Less patients of the treatment group needed a supplementary analgesic medication (p = 0.01) and were able to leave hospital earlier than patients of the control group (p = 0.01). CONCLUSIONS: A subfascially placed pain catheter enhances postoperative pain therapy after RILND.

Postoperative surgical complications after radical axillary lymph node dissection in melanoma disease result in increased pain.

Postoperative pain is one of the major problems caused by the operative trauma. We recorded the postoperative pain of patients who underwent a radical axillary lymph node dissection (RALND) to evaluate the quality of our standardized perioperative pain management program and the influence of surgical complications. Between August 2003 and December 2007, we registered the postoperative level of pain of 111 patients who underwent a therapeutic RALND, using a visual analog scale (VAS). Patients received standardized perioperative pain therapy according to level I of the World Health Organization (WHO) ladder of pain. We registered a VAS score of 10 in patients at rest during the first 3 postoperative days, but after mobilization of the arm, patients had significantly more pain (P < 0.0001). Patients with a postoperative surgical complication needed significantly more central analgesia to reach the same level of pain (P = 0.04) as patients without complication. Level I of the WHO ladder of pain is not enough for patients after an RALND. Patients with a postoperative complication do have increased pain, and use of only peripheral analgesia is insufficient.

Preemptive analgesia reduces pain after radical axillary lymph node dissection.

BACKGROUND: Analyzing prospective data of our melanoma patients, we registered a suboptimal pain score under mobilization after radical axillary lymph node dissection (RALND). We performed a randomized, double blinded clinical trial to investigate the effects of a preemptive Parecoxib analgesic during the perioperative course. MATERIALS AND METHODS: Between October 2006 and December 2007, 32 patients with stage III/IV melanoma underwent therapeutic RALND and were randomized into two groups. Patients received intravenously 40 mg Parecoxib or 0.9% normal saline solution 2 h before RALND. The postoperative treatment and analgetic regime was defined in the study protocol. Main outcome criterion was the pain under mobilization at the first postoperative morning registered via a visual analogue score. Minor criteria were the postoperative complications, fatigue, amount of analgesics, and the day of discharge. RESULTS: Patients receiving a preemptive analgesic had a better outcome after RALND. The pain after mobilization was significantly decreased at the first postoperative morning (P = 0.04). Patients had less fatigue as well (P = 0.05) and the amount of pain medication in the treatment group was reduced (P = 0.04). CONCLUSIONS: Preemptive application of Parecoxib enhances outcome after RALND. A preemptive analgesic with Parecoxib in the perioperative management after RALND of melanoma patients can be recommended.

Effects of cyclooxygenase inhibition on anastomotic healing following large bowel resection in a rabbit model--a randomized, blinded, placebo-controlled trial.

PURPOSE: We performed an experimental study in a rabbit model to investigate the effects of a selective Cox-2 inhibitor (Valdecoxib) on anastomotic healing following large bowel resection after 1 week. MATERIALS AND METHODS: Eighty New Zealand white rabbits were randomized into four groups and underwent a colon resection with end-to-end anastomosis. Group 1 (n = 20) was treated with Valdecoxib, group 2 with Metamizole (Novalgin), group 3 with Resveratrol (specific Cox-1 inhibitor), or a placebo vehicle with similar volume (group 4). Anastomotic healing was tested at the seventh postoperative day by measurement of the bursting pressure in vitro. Immunohistochemical staining of the anastomotic site was performed with polyclonal antibodies (CD31). RESULTS: There were no significant differences in anastomotic dehiscence, bursting pressure, or vessel density between the treatment and control groups. CONCLUSION: The application of Valdecoxib does not influence anastomotic healing or new vessel formation in the anastomotic region following large bowel resection.

Intraoperative application of fibrin sealant does not reduce the duration of closed suction drainage following radical axillary lymph node dissection in melanoma patients: a prospective randomized trial in 58 patients.

BACKGROUND: Patients suffering from malignant melanoma often require radical lymph node dissection of the axillary nodal basin. The effects of intraoperative application of fibrin sealant following radical axillary lymph node dissection (RALND) on the incidence of postoperative lymphatic secretion are discussed. To study the effect of intraoperatively applied fibrin sealant following RALND a randomized patient-blinded trial was carried out. METHODS: Fifty-eight patients with axillary lymph node metastases of malignant melanoma underwent therapeutic RALND and were randomized into two groups: 29 patients received 2 cc of fibrin glue intraoperatively and 29 patients were only irrigated with 0.9% saline. The amount of drainage was recorded every 24 h. The main outcome criterion was the duration of drain placement in the wound. Minor criteria were the total amount of fluid and the length of hospital stay. Statistical analysis was performed using Spearman's log-rank correlation and paired t-test. RESULTS: There was no significant difference between the nonfibrin group 5 days (range = 3.6-5.7 days) and the fibrin group 5 days (range = 4.1-8.5 days) (p = 0.701). The total amount of fluid for the nonfibrin group (410 cc, range = 362-727 cc) and that for the fibrin group (503 cc, range = 369-1098 cc) (p = 0.605) and the length of postoperative hospital stay of 6 days (range = 5.4-7) vs. 7 days (range = 5.9-10.7), respectively, were not different between both groups (p = 0.387). CONCLUSION: Considering our study results, we cannot recommend the use of 2 cc of fibrin glue intraoperatively in the prevention of lymphatic secretion in patients undergoing RALND for metastatic melanoma.

The ubiquitin- and proteasome-dependent degradation of COX-2 is regulated by the COP9 signalosome and differentially influenced by coxibs.

The cyclooxygenase-2 (COX-2) enzyme is induced upon inflammation and in neoplastic tissues. It produces prostaglandins that stimulate tumor angiogenesis and tumor growth. Therefore, destruction and/or specific inhibition of COX-2 should be an important aspect of future tumor therapy. Recently, clinical application of specific COX-2 inhibitors called coxibs became doubtfully because they produce serious renal and cardiovascular complications under long term application. The exact underlying mechanisms are poorly understood and the different effects of diverse coxibs are not explained. It has been demonstrated before that COX-2 is degraded by the ubiquitin (Ub) proteasome system (UPS). However, how ubiquitination is accomplished and regulated was unclear. An important regulator of the UPS is the COP9 signalosome (CSN), which controls the stability of many proteins. Here we show that the proteasome-dependent degradation of COX-2 in HeLa cell lysate and in HeLa cells was stimulated by curcumin, an inhibitor of CSN-associated kinases. These data suggest a function of the CSN in the degradation of COX-2. In addition, proteolysis of COX-2 was significantly accelerated by parecoxib, but not by celecoxib or rofecoxib. By density gradient centrifugation and immunoprecipitation we demonstrate that COX-2 physically interacts with the CSN. Moreover, COX-2 is associated with large complexes consisting of the CSN, cullin-RING Ub ligases and the 26S proteasome. Pulldown experiments with Flag-COX-2 revealed cullin 1 and cullin 4 as components of the large super-complexes. Cullin 1 and 4 are scaffolding proteins of Ub ligases that presumably ubiquitinate COX-2. Treatment of HeLa cells with parecoxib results in an accelerated degradation of endogenous COX-2 accompanied by an increase of COX-2-Ub conjugates. In HeLa cells parecoxib is converted to the selective COX-2 inhibitor valdecoxib. Addition of valdecoxib also stimulates COX-2 degradation in HeLa cells. We therefore conclude that valdecoxib specifically interacts with COX-2 and induces a conformation accessible for ubiquitination and degradation.

Hypovolemia after traditional preoperative care in patients undergoing colonic surgery is underrepresented in conventional hemodynamic monitoring.

BACKGROUND AND AIMS: Hypovolemia after bowel preparation as well as capnoperitoneum (CP) may compromise hemodynamic function during laparoscopic colonic surgery. A fall in arterial pressure after induction of anesthesia is often answered by generous fluid administration, which might impair "fast-track" rehabilitation. Intraoperative assessment of the needed infusion volume is difficult because of a lack of data regarding the volume status in these patients. PATIENTS AND METHODS: Nineteen patients scheduled for laparoscopic colonic surgery after bowel preparation were prospectively monitored using the PULSION COLD Z-021 system and central venous catheter. Intrathoracic blood volume index (ITBVI), mean arterial pressure (MAP), cardiac index (CI), central venous pressure (CVP), and heart rate (HR) were measured after induction of anesthesia (M1), during CP in head-down position with an intraabdominal pressure (IAP) of 20 mmHg (M2) and 12 mmHg (M3). RESULTS: Although MAP (87 mmHg), HR (64 min(-1)), and CVP (8 mmHg) were within normal ranges at the induction of surgery, ITBVI (834 ml m(-2)), and CI (2.66 l m(-2)) were decreased, indicating a relative hypovolemia. CP with 12 mmHg increased ITBVI (p<0.05) and CI (p<0.01), while an IAP of 20 mmHg reduced CI (p<0.05) compared to 12 mmHg (M3). Mean infusion during the measurements was 1,355 ml. CONCLUSION: Combination of CP with 12 mmHg, head-down position, and infusion of 1,500 ml fluids compensated relative hypovolemia during colonic surgery. With conventional monitoring, intravascular volume status might be underestimated after traditional preoperative care.

Introduction of polyethylene terephthalate mesh (KoSa hochfest) for abdominal hernia repair: an animal experimental study.

BACKGROUND: Nowadays the surgical treatment of abdominal hernias includes the use of synthetic meshes in most cases. Due to chronic foreign body reactions, however, the most commonly used polypropylene meshes can lead to material hardening and recurrent hernias. As a proven cruciate ligament replacement polyethylene terephthalate (KoSa hochfest showed only little foreign body reactions and provided excellent clinical outcomes. In an animal trial it was therefore tested as mesh implant for hernia treatment and compared with Prolene. MATERIAL AND METHOD: The study was carried out in 12 mini-pigs. 10 x 10 cm of the musculofascial abdominal layer was resected, the peritoneum was preserved. A 15 x 15 cm synthetic mesh was implanted in sublay-technique (either KoSa hochfest, Telos GmbH, Marburg, Germany or Prolene, Ethicon, Norderstedt, Germany), mainly to test for chronic foreign body reactions. An independent pathologist tested the mesh size and foreign body reaction at 2 and 6 months, analysing the number of foreign body giant cells. RESULTS: No significant differences in mesh size were observed, neither between the compared groups nor with respect to the time periods. Compared to KoSa hochfest the foreign body reaction was significantly stronger in the Prolene implants, both at 2 and at 6 months (number of foreign body giant cells at 2 months: Prolene/KoSa hochfest: 2.2 +/- 0.4/0.8 +/- 0.2, at 6 months: 4.6 +/- 1.3/1.1 +/- 0.5). In contrast to KoSa hochfest, Prolene still showed significant foreign body reactions at 6 months as well as calcifications of all samples. CONCLUSION: The animal trials revealed that due to its high biocompatibility and little foreign body reaction KoSa hochfest is a promising implant for the treatment of hernias.

Inguinal hernia: obligatory indication for elective surgery? A prospective assessment of quality of life before and after plug and patch inguinal hernia repair.

BACKGROUND: Incarcerated inguinal hernia may be treated effectively by recent surgical techniques with a low rate of complications, but it is unclear whether quality of life is improved by elective inguinal hernia repair. Therefore we investigated the quality of life before and after inguinal hernia repair using plug and patch technique. PATIENTS AND METHODS: Quality of life was prospectively assessed in 123 patients before and 3 months after plug and patch inguinal hernia repair using the Short Form 36 questionaire and a visual analog scale. All patients complained preoperatively of pain associated with the clinical findings of inguinal hernia (visual analog scale: reduced quality of life 6.8+/-2.7; reduced daily activity: 5.5+/-2.6). Clinical characteristics (operation times, in-hospital stay, complications, need for pain medication) were documented. Inclusion criteria were patients with symptomatic inguinal hernia, scheduled for elective unilateral inguinal hernia repair by plug and patch technique. RESULTS: There were no major in-hospital complications. At 3 months no recurrences of inguinal hernia or late onset complications were observed; seven patients complained of dumbness, and eight felt pressure at the operation site with a tendency for resolving pain within this time. At 3 months patients had a significantly improved quality of life regarding freedom from pain, vitality, and physical activity compared to preoperatively. CONCLUSIONS: Plug and patch repair of unilateral inguinal hernia improves quality of life with a very low rate of procedural complications. Regarding freedom from pain, vitality, and physical activity there is significant improvement as compared to preoperatively. Therefore inguinal hernia repair should be intended in all elective cases and plug and patch repair appears as an excellent technique to improve quality of life.

Adhesions after intraperitoneal mesh repair in pigs: Prolene" vs. Vypro".

BACKGROUND: Newly developed meshes with low weight and large pores such as Vypro (Ethicon, Norderstedt) were exactly adapted to the physiology of the human abdominal wall and proved to reduce chronic inflammatory processes. It was hypothesized that the reduced inflammatory response to a Vypro mesh would lead to reduced adhesion formation following intraperitoneal implantation in comparison with a Prolene mesh (Ethicon). MATERIALS AND METHODS: To test this hypothesis, 20 25-kg pigs underwent resection of a 10 x 10-cm section of the full-thickness anterior abdominal wall, excluding subcutaneous and cutaneous surface. The fascial defect was repaired using a 20 x 20-cm piece of either Vypro or Prolene mesh, which was sutured in inlay position with 4-0 Prolene single sutures at the edges. The main endpoint was the presence and degree of intra-abdominal adhesions to the mesh after 3 months. The amount of adhesions was calculated as a percentage of the mesh square and classified into four grades. RESULTS: There were no significant differences in the amount and grade of adhesions between the groups. Adhesions were less intensive in the Vypro group, but this difference was not significant. Dense adhesions between the liver and the mesh and small-bowel obstruction were observed only in the Prolene group. CONCLUSIONS: From the results of this study, Prolene and Vypro meshes cannot be recommended for intraperitoneal placement in hernia surgery because of their adhesion potential and risk of bowel obstruction.

Trevira mesh: a promising new implant for the treatment of abdominal hernias.

BACKGROUND: Trevira (polyethylene terephthalate) has been in clinical use for more than 20 years, serving as implant material with minimal foreign body reaction for the replacement of the cruciate ligaments of the knee. An animal (pig) trial was performed to ascertain whether a Trevira mesh offers any advantages over currently employed meshes like Prolene for abdominal hernia repair. METHODS: In 12 mini-pigs 10 x 10 cm of the musculofascial abdominal layer was resected preserving the peritoneum. Subsequently, a 15 x 15 cm synthetic mesh was implanted (Prolene, Ethicon, Norderstedt, Germany, or Trevira, Telos GmbH, Marburg, Germany, in six animals each) using sublay technique. The main focus was on the extent of the chronic foreign body reaction. This was assessed by a pathologist who paid special attention to the presence of foreign body giant cells after 2 and 6 months. A further assessment was made of shrinkage of the implant as a result of foreign body reaction. RESULTS: The number of giant cells after two months was significantly higher with the Prolene implant than with the Trevira implant (Prolene 2.2+/-0.4, Trevira 0.8+/-0.2, per fixed microscopic field; P<0.05). After 6 months the number of giant cells associated with the Prolene implants rose further, while it remained relatively constant for those of Trevira (Prolene 4.6+/-1.3, Trevira 1.1+/-0.5; P<0.05). No significant difference was noted over time between the two types of implant with regard to shrinkage (2 months: Prolene 0.8+/-0.3 cm(2), Trevira 0.6+/-0.4 cm(2); 6 months: Prolene 1.3+/-0.6 cm(2), Trevira 1.1+/-0.5 cm(2)). CONCLUSION: In this animal study Trevira mesh demonstrated a high biocompatibility with a low foreign body reaction; it appears to be a promising new implant for the treatment of hernias.

Postoperative comfort after plug-and-patch repair of recurrent inguinal hernia.

OBJECTIVE: To evaluate postoperative comfort after the plug-and-patch repair. DESIGN: Prospective observational study. SETTING: University hospital, Germany. SUBJECTS: From July 1995 until August 2000, 93 consecutive patients with recurrent inguinal hernia were operated on using the plug-and-patch technique. MAIN OUTCOME MEASURES: Postoperative comfort assessed by pain (visual analogue score), analgesic requirements, duration of hospital stay, and restriction of daily activities. RESULTS: Postoperative pain decreased continuously from the morning of the first postoperative day (median VAS: 5.4; range 1.2-6.9) until day 13 (VAS <1). The median amount of analgesics given to the patients for 4 days was dipyrone 5.2 g (range 2.1-8.4). Median duration of hospital stay was 5 (2-14) days, limitation of daily activities 6 days (range 3-17) and 34 patients who were employed had returned to work after 21 days (range 8-42). CONCLUSIONS: Plug-and-patch repair offers a high degree of comfort to patients with recurrent inguinal hernia.