Modified enhanced recovery after surgery protocol in patients with acute cholecystitis: efficacy, safety and feasibility. Multicenter randomized control study.

Laparoscopic cholecystectomy (LC) is a common surgical procedure in acute cholecystitis (AC). Patients often suffer from considerable postoperative pain and indigestion, which prolongs in-hospital stay. The enhanced recovery after surgery (ERAS) program has proven its efficacy in elective surgery and could hypothetically improve outcomes of emergency LC. Currently, there is no ERAS program for LC in patients with AC. A modified ERAS (mERAS) protocol was studied in a prospective, randomized non-blinded clinical trial (NCT03754751). The mERAS group consisted of 88 patients the control group of 101 patients. The modified protocol included a patient information brochure; minimizing drain use; local anesthesia; low-pressure pneumoperitoneum; PONV prophylaxis, early mobilization and oral diet. The primary outcome was postoperative length of stay (pLOS). The postoperative length of stay in the mERAS group was shorter (24 (21-45.5) h) than in the control (45 (41-68) h) (p < 0.0001). One re-admission in the mERAS group was reported (p = 0.466). There difference in complications was insignificant (mERAS 6.8% vs 5% p = 0.757). Post-operative pain intensity was significantly lower in the mERAS group immediately after awaking (3.7 ± 1.8 vs 5.4 ± 1.3 p < 0.0001), 2 h (3.3 ± 1.7 vs 4.9 ± 1.6 p = 0.0006), 6 h (2.9 ± 1.5 vs 4.2 ± 1.2 p < 0.0001), 12 h (2.7 ± 0.9 vs 4.1 ± 1.2 p = 0.0001) and 24 h after surgery (2.1 ± 1.2 vs 3 ± 1.2 p < 0.0001). The incidence of shoulder and neck pain was lower in mERAS group (13.6% vs 34.7% p = 0.0009). Peristalsis recovery was similar in both groups. The proposed protocol improved postoperative recovery and reduced hospital stay in patients with AC without increasing the rate of complications or re-admissions.

Thermal Processes in Bile Ducts During Laparoscopic Cholecystectomy with Monopolar Instruments. Experimental Study Using Real-Time Intraluminal and Surface Thermography.

Introduction. A significant rate of complications during laparoscopic cholecystectomy (LC) occurs due to thermal injury caused by monopolar electrosurgery (MES) equipment. Most of them manifest weeks and months after surgery with the common bile duct (CBD) and large duodenal papilla strictures, some in the early postoperative period with bile leaks. Objective. To study thermal processes occurring in the lumen and on the surface of the bile ducts during monopolar coagulation in a porcine model of LC. Methods. The temperature of the bile ducts was measured using instrumentation consisted of biliary stent with temperature sensors, which was inserted in the porcine CBD, signal amplifier, and current sense transformer. Surface temperature was measured with a scientific grade thermal camera. Cholecystectomy was performed using a standard "critical view of safety" (CVS) approach with 5 mm monopolar laparoscopic instruments. Results. Application of MES caused significant tissue heating. Lateral thermal spread and the rate of tissue heating depended on the duration of energy application and the initial tissue temperature. In 5 out of 6 experiments, the intraluminal temperature rose up to the critical threshold, and the exposure time ranged from 54 to 560 seconds. A sensor positioned at the papilla site was heated in all the experiments but still below the cell damage inducing threshold. The analysis of thermographic charts revealed the presence of the "current channeling" effect and the pedicle effect. Conclusion. There is a possibility of a direct and delayed thermal injury to the bile ducts during LC.

Evaluation of enhanced recovery after surgery program components implemented in laparoscopic appendectomy: prospective randomized clinical study.

BACKGROUND: Laparoscopic appendectomy (LA) is a widely used surgical procedure. Patients often suffer from considerable postoperative pain and indigestion, which prolongs their in-hospital stay. Almost 10% of patients develop postoperative complications. The enhanced recovery after surgery (ERAS) program has proven its efficacy in elective surgery and could hypothetically improve LA outcomes. Currently, there is no ERAS program for LA. METHODS: A modified ERAS (mERAS) protocol was studied in a prospective, randomized nonblinded clinical trial. The mERAS group consisted of 50 patients; the control group, of 54 patients. The mERAS protocol included a patient information brochure; minimizing drain use; local anesthesia; low-pressure pneumoperitoneum; early mobilization and oral diet. The primary outcome was postoperative length of stay (pLOS). RESULTS: Modified protocol reduced median pLOS to 1.25 days vs 2 days in the controls (p < 0.0001). Twenty-one (42%) mERAS patients and 4 (7.4%) controls were discharged within 24 h (p < 0.001) after surgery; 0 readmissions were reported. Postoperative pain intensity assessed on the visual analogue scale was significantly lower in the mERAS group [mERAS vs control 0 h, 2 h, 6 h, 12 h and 24 h after surgery: 2.33 ± 2.12 vs 4.19 ± 2.08 (p < 0.0001), 2.27 ± 1.91 vs 4.02 ± 1.89 (p < 0.0001), 2.28 ± 1.98 vs 3.70 ± 1.57 (p = 0.0001), 1.98 ± 1.72 vs 3.43 ± 1.54 (p < 0.0001) and 1.80 ± 1.74 vs 3.00 ± 1.27 (p = 0.032), respectively)]. The severity of shoulder and neck pain was lower but its incidence was similar. Peristalsis recovery was achieved earlier in the study group (median (min-max))-mERAS 7 (2-34) h vs control 11 (3-43) h; p = 0.009) but did not affect the time of the first flatus 23 (2-72) h vs 29 (6-70) h, respectively; p = 0.499). CONCLUSIONS: The modified ERAS program for LA has advantages over the traditional approach. REGISTRATION: This trial was registered at ClinicalTrials.gov as NCT03754777 (27/11/2018).

Thermal effects of monopolar electrosurgery detected by real-time infrared thermography: an experimental appendectomy study.

BACKGROUND: Monopolar energy (ME) is routinely used in appendectomy. This study aimed to investigate the degree of lateral thermal spread generated by ME and to evaluate the thermal injury sustained by the close-lying tissues. METHODS: Appendectomy with a monopolar Maryland dissector was performed in 8 rabbits (at 30 and 60 W power settings). A high-resolution infrared camera was used to record tissue heating during the intervention. After autopsy macroscopic changes were evaluated and tissue samples were subjected to myeloperoxidase (MPO) assay and histological examination. RESULTS: No significant differences in the extent of thermal spread, MPO activity and histological signs of inflammation were observed between groups. Regardless of the power settings, the heat spread exceeded 2 cm laterally along the mesoappendix when application time exceeded 3 s. The spread of heat through tubular structures in both groups caused a significant temperature rise in the nearby intestinal loop, resulting in perforation (n = 3) and necrosis (n = 1). CONCLUSIONS: Application time is critical in thermal spread during appendectomy aided by ME. Tubular anatomic structures can enhance thermal injury on distant tissues. The observed effects of ME bear clinical relevance that need further investigation.

Intraperitoneally applied gentamicin increases collagen content and mechanical stability of colon anastomosis in rats.

BACKGROUND: Anastomotic leakage remains a serious complication in colorectal surgery, and is being caused by a multitude of factors. Recent reports reveal changes of the extracellular matrix as risk factors as well as gentamicin as a potential agent to influence wound healing. This experimental study was initiated to investigate the influence of intraperitoneally applied gentamicin on colonic anastomotic wound healing and in particular on mechanical stability, overall collagen content and collagen type I/III ratio. MATERIALS AND METHODS: Sixty Sprague Dawley rats were randomized to one of two groups. In each animal, a standard transverse colonic end-to-end anastomosis was performed. Immediately postoperative, either 5 ml gentamicin (1 ml/kg bodyweight) or NaCl 0.9% was applied intraperitoneally. On postoperative days 3, 5, and 14, ten of the animals in each group were sacrificed. Measurements of the anastomosis bursting pressure were performed on postoperative days 3 and 5. At each explantation time, the collagen per protein ratio, the collagen types I/III ratio, and both the expression of MMP-2, -9, and Ki67 were analyzed. RESULTS: None of the animals died. None of the rats exhibited clinical evidence of anastomotic leakage. The bursting strength in the gentamicin group was significantly elevated on postoperative day 5. Both the overall collagen content and the collagen type I/III ratio in the gentamicin group were significantly increased 3, 5, and 14 days postoperatively compared to the control group. The expression of MMP-9 was significantly elevated in the gentamicin group both 3 and 5 days postoperatively. In contrast, there were no significant differences in the expression of MMP-9 14 days postoperatively. All investigated samples demonstrated positive staining for MMP-2 and Ki67 without statistically significant differences at any term, respectively. CONCLUSIONS: The present data confirm that intraperitoneally applied gentamicin is able to enhance healing and stability of colonic anastomosis due to an increase of both the overall collagen content and collagen type I/III ratio.

Different tissue reaction of oesophagus and diaphragm after mesh hiatoplasty. Results of an animal study.

BACKGROUND: Laparoscopic mesh-reinforcement of the hiatal region in the treatment of gastroesophageal reflux disease (GERD) and paraesophageal hernia (PEH) reduces the risk of recurrence. However, there are still controversies about the technique of mesh placement, shape, structure and material. We therefore compared tissue integration and scar formation after implantation of two different polypropylene-meshes in a rabbit model. METHODS: A total of 20 female chinchilla rabbits were included in this study. Two different meshes (Polypropylene PP, Polyglecaprone 25 Composite PP-PG) were implanted on the abdominal diaphragm around the oesophagus. After 3 months the implanted meshes were excised en-bloc. Histological and morphological analyses were carried out accordingly proliferation rate, apoptosis and collagen type I/III ratio. RESULTS: Regarding proliferation rate of oesophagus PP (9.31 +/- 3.4%) and PP-PG (13.26 +/- 2.54%) differ in a significant (p = 0.0097) way. In the diaphragm we found a significant (p = 0.00066) difference between PP (9.43 +/- 1.45%) and PP-PG (18.73 +/- 5.92%) respectively. Comparing oesophagus and diaphragm we could prove a significant difference within PP-PG-group (p = 0.0195). Within PP-group the difference reached no statistical significance (p = 0.88). We found analogous results regarding apoptosis.Furthermore, there is a significant (p = 0.00013) difference of collagen type I/III ratio in PP-PG (12.28 +/- 0.8) compared to PP (8.44 +/- 1,63) in case of oesophageal tissue. Concerning diaphragm we found a significant difference (p = 0.000099) between PP-PG (8.85 +/- 0.81) and PP (6.32 +/- 1.07) as well. CONCLUSION: The histologic and morphologic characteristics after prosthetic enforcement of the hiatus in this animal model show a more distinct tissue integration using PP-PG compared to PP. Additionally, different wound healing and remodelling capability influence tissue integration of the mesh in diaphragm and oesophagus.

The influence of blood on the efficacy of intraperitoneally applied phospholipids for prevention of adhesions.

BACKGROUND: The formation of adhesions following abdominal surgery is a well known problem. In previous studies we demonstrated the efficacy and safety of intraperitoneally applied phospholipids in order to prevent adhesion formation. This study evaluates the influence of blood on the efficacy of intraperitoneally applied phospholipids for prevention of adhesions. METHODS: In 40 Chinchilla rabbits adhesions were induced by median laparotomy, standardized abrasion of the visceral and parietal peritoneum in defined areas of the ventral abdominal wall and the caecum. The animals were randomly divided into four groups. They received either phospholipids 3.0% or normal saline (NaCl 0.9%) (5 ml/kg body weight). In 50% of the rabbits we simulated intraperitoneal bleeding by administration of blood (1.5 ml/kg body weight). The other half served as control group. Ten days following the operation the animals were sacrificed and adhesion formation was assessed by computer aided planimetry and histopathologic examination. RESULTS: The median adhesion surface area in the NaCl-group (n = 9) amounted to 68.72 mm2, in the NaCl+Blood-group (n = 10) 147.68 mm2. In the Phospholipid (PhL)-group (n = 9) the median adhesion surface area measured 9.35 mm2, in the PhL+Blood-group (n = 9) 11.95 mm2. The phospholipid groups had a significantly smaller adhesion surface area (p < 0.05). CONCLUSION: Again these results confirm the efficacy of phospholipids in the prevention of adhesions in comparison to NaCl (p = 0.04). We also demonstrated the adhesion preventing effect of phospholipids in the presence of intraperitoneal blood.

Surgical mesh as a scaffold for tissue regeneration in the esophagus.

BACKGROUND: Textiles in the form of surgical meshes are widely used in hernia surgery. Their porous structure allows tissue infiltration to incorporate the fabric for complete healing and device stabilization. This study was aimed to reconstitute the esophageal wall and to investigate the functional and histological consequences of a new, non-absorbable polyvinylidene fluoride (PVDF) mesh and an absorbable polyglactin 910 (Vicryl((R))) mesh. METHODS: Semicircular esophageal defects of 0.5 x 1 cm were created 2 cm proximal of the cardia in 10 rabbits. This gap was bridged using either polyglactin 910 or PVDF and additionally covered by omental wrapping. The clinical outcome was observed by clinical observation, regular esophagoscopies and X-ray contrast medium examinations. Local tissue regeneration was verified by light microscopy and immunohistochemistry. RESULTS: After an observation period of 3 months we found no anastomotic strictures, complete mucosal regeneration, minimal inflammation reaction and initial regeneration of the muscle layer for the PVDF group. Within the polyglactin 910 group, three patch failures with consecutive anastomotic leakage occurred. CONCLUSION: The results indicate that PVDF mesh structure gives the opportunity of local tissue regeneration in the esophagus. Though re-epithelialization and muscle cell ingrowth could be detected for absorbable polyglactin 910 mesh, this implant was accompanied by a high and early rate of anastomotic leakage.

Postoperative peridural analgesia increases the strength of colonic contractions without impairing anastomotic healing in rats.

BACKGROUND AND AIMS: Peridural analgesia (PDA) is a common treatment in postoperative management after abdominal surgery to shorten postoperative ileus and to permit early postoperative nutrition. There are conflicting opinions on the effect of early peristalsis on healing of colonic anastomoses. PATIENTS AND METHODS: A short segment of the distal colon was resected in 32 Wistar rats. Two strain gauge transducers were placed on the serosa proximal to the anastomosis to measure the strength and periodicity of bowel contractions. A peridural catheter was placed between lumbar vertebra 7 and the sacral crest. The animals received 4, 16, 20, and 24 h after operation an injection of either 0.03 ml ropivacaine 0.75%/kg body weight or the same amount of sodium chloride (controls). After 3 and 10 days the colonic anastomoses were resected to measure the bursting pressure. The anastomoses were prepared for histopathological examination and determination of relative collagen content. RESULTS: Postoperative PDA led to an increasing amplitude of phasic and tonic contractions while the frequency of contractions was not significantly affected. None of the groups presented with any anastomotic complications. The bursting pressure after 3 and 10 days was similar in the two groups. The relative amount of collagen I in the anastomotic area was significantly higher after treatment with peridural ropivacaine. CONCLUSION: Postoperative PDA with ropivacaine increases the strength of colonic contractions. The increase in phasic contractions suggests a better propulsive bowel function. The significantly higher amount of collagen I in the anastomosis of animals in the PDA group supports the idea that healing of colonic anastomoses is improved rather than diminished by PDA.

Tension banding closure of laparotomies: results of an experimental study in dogs.

BACKGROUND: Conventional laparotomy closure may cause ischemia, edema, and necrosis of the incisional edges, weakening of the tissue, and incisional hernia formation. Two experimental closure techniques were established to investigate laparotomy healing without suturing the incisional edges. METHODS AND MATERIALS: In 24 dogs median laparotomies were closed applying two techniques following the principle of tension banding. Investigations after 3, 9, and 15 months were laparoscopy, tensiometry, light and electron microscopy and measurement of collagen fibril diameters. RESULTS: Incisions healed without incisional hernias with only minimal adhesion formation. At all time points the tensile strength after the bridging technique (BT) did not differ significantly from that in the control group. Mean tensile strength after BT was higher than after the onlay technique (OT) at all time points but did not reach statistical significance. After 3 months the incisions after OT were significantly weaker than the control group. At all time points fibril diameters after OT were significantly smaller than in the control group. After 3 and 9 months the fibril diameters after OT were significantly smaller than after BT. Incisions healed with little scar formation in spite of a chronic inflammatory reaction. This reaction was more pronounced after OT and made access to the fascia difficult after 3 months. Both techniques led to early postoperative seroma formation. CONCLUSIONS: Applying the principle of tension banding, laparotomies healed without suturing the incisional edges. The effect of foreign material on the ultrastructure of regenerating tissue in direct contact to the incisional region was demonstrated by the OT, in which chronic inflammation disturbed the adequate formation of collagen. Further development of both techniques might allow laparotomy closure according to the physiological requirements of wound healing.

Influence of early drainage of intraperitoneal phospholipids on efficacy of adhesion prevention.

Postoperative peritoneal adhesions impose a long-term risk of morbidity and mortality. Adjunctive means are needed to prevent these complications. In previous studies we could demonstrate the efficacy and safety of intraperitoneally applied phospholipids with regard to adhesion prevention and wound healing, respectively. The assumption is that phospholipids rapidly adhere to the peritoneal surface and to the mesothelial lesions. This study was designed to evaluate the influence of early drainage of the administered fluid volume on the control of adhesion formation. Forty chinchilla rabbits underwent median laparotomy and standardized abrasion of circumscript areas of the ventral abdominal wall, the cecum, and the ileum. The animals randomly received either 75 mg/kg body weight of phospholipids in a volume of 5.0 mL/kg body weight (n = 20) or the same volume of Ringer's lactate solution (n = 20) prior to closing the laparotomy wounds. In 50% of the rabbits with either medication, 80% of the volume was recovered after 30 min before final closure of the abdominal wall ("drainage"). In the remaining animals the intraabdominal fluid load was not evacuated ("no drainage"). At day 10 after surgery all rabbits were sacrificed for evaluation of adhesion areas by computer-aided planimetry and histopathologic examination. The mean areas of adhesion in both Ringer's lactate groups were significantly larger than in the comparable phospholipid groups (p < .05). In the Ringer's lactate groups, adhesions averaged 341.7 (318.6) mm2 without and 263.3 (275.5) mm2 with drainage. In the phospholipid groups the respective mean areas reached only 24.6 (36.7) mm2 without drainage and 27.0 (49.7) mm2 following evacuation of the fluid 30 min after administration (median, mean in parentheses). These results prove the efficacy of phospholipids after a limited contact period of 30 min. The frequent use of drains in abdominal surgery will not impair the beneficial effect of phospholipids on prevention of adhesions.

Influence of postoperative epidural analgesia with bupivacaine on intestinal motility, transit time, and anastomotic healing.

Epidural application of bupivacaine has been suggested to have a sympatholytic effect on spinal reflex mechanisms that shortens postoperative paralysis and leads to an improved transit time. The influence on anastomitic healing remains controversial. Laparotomy was performed in eight dogs. A short segment of the distal colon was resected and five electrodes were fixed on the serosa to measure the myoelectric activity (e.g., Migrating Myoelectric Complex--MMC). After operation a peridural catheter was placed between L7 and the sacral crest. One milliliter of bupivacaine 0.25% for each 3 kg of body weight was injected every 4 hours. Barium pellets coated in wax were placed into the stomach to allow radiographic representation of transit time. After 5 days the colon anastomosis was resected to measure the bursting pressure. In the peridural analgesia group (PDA) we found one small bowel intussusception and one covered anastomotic leakage. Postoperative PDA led to early and severe myoelectric activity but did not influence the time until the first MMC occurred (44 +/- 0.8 h, PDA; 44.6 +/- 1.5 h,control). Neither the transit time to the colon (50.2 +/- 1.9h, PDA; 51.7 +/- 5.5 h, control) nor the anastomotic healing was influenced (bursting pressure: 176 +/- 21.1 mmHg, PDA; 152 +/- 27.7 mmHg, control). Postoperative epidural analgesia with bupivacaine shortens intestinal paralysis. Early myoelectric activity with a lack of propulsive activity can cause complications like small bowel intussusception. Hence early postoperative enteral nutrition after epidural analgesia is risky. Because the influence of epidural analgesia on propulsive motility remains unclear, it seems reasonable to recommend its limited use in colon surgery.