George Kokosis

Wound contraction is attenuated by fasudil inhibition of Rho-associated kinase.

Background: Dermal scarring and scar contracture result in restriction of movement. There are no effective drugs to prevent scarring. RhoA and Rho-associated kinase have emerged as regulators of fibrosis and contracture. Fasudil, a Rho-associated kinase inhibitor, has been demonstrated to have antifibrotic effects in models of liver, renal, and cardiac fibrosis. The role of fasudil in preventing dermal scarring and contractures has not been studied. The authors used a rat model of dermal wound healing to assess the effects of fasudil with regard to the prevention of scarring. Methods: Human scar tissue and surrounding normal skin were immunostained for RhoA and Rho-associated kinase. Full-thickness wounds were created on Wistar-Han rats, and fasudil (30 mg/kg/day) or saline was continuously delivered subcutaneously. Wound contraction was measured by gravitational planimetry. After 21 days, tissue was harvested for Massons trichrome, hematoxylin and eosin, Ki-67, and CD31 staining. Fibroblast-populated collagen lattices were used to assess the mechanistic effects of fasudil on contractility. Myofibroblast formation was assessed in the presence of fasudil. Results: Human scar tissue in the remodeling phase of repair showed increased expression of RhoA and Rho-associated kinase in scar tissue compared with surrounding normal tissue. Fasudil inhibited wound contraction as compared with controls. Hematoxylin and eosin and Massons trichrome were similar between groups. Fasudil did not alter angiogenesis or proliferation. Fasudil inhibited fibroblast contractility and myofibroblast formation in vitro. Conclusions: There is growing evidence that the RhoA/Rho-associated kinase pathway plays an important role in wound healing and scar contracture. The authors present data showing that inhibition of Rho-associated kinase hinders fibroblast contractility and may be beneficial in preventing scar contracture.

Myofibroblasts contribute to but are not necessary for wound contraction.

Wound contraction facilitates tissue repair. The correct balance between too little contraction, which leads to non-healing wounds, and too much contraction, which leads to contractures, is important for optimal healing. Thus, understanding which cells cause wound contraction is necessary to optimize repair. Wound contraction is hypothesized to develop from myofibroblast (cells which express alpha-smooth muscle actin; ACTA2) contractility, while the role of fibroblast contractility is unknown. In this study, we utilized ACTA2 null mice to determine what role fibroblasts play in wound contraction. Human scar contractures were immunostained for ACTA2, beta-cytoplasmic actin (ACTB), and gamma-cytoplasmic actin (ACTG1). Full-thickness cutaneous wounds were created on dorsum of ACTA2+/+ mice and strain-matching ACTA2+/− and ACTA2−/− mice. Wound contraction was quantified. Tissue was harvested for histologic, immunohistochemical and protein analysis. Compared with surrounding unwounded skin, human scar tissue showed increased expression of ACTA2, ACTB, and ACTG1. ACTA2 was focally expressed in clusters. ACTB and ACTG1 were widely, highly expressed throughout scar tissue. Wound contraction was significantly retarded in ACTA2−/− mice, as compared to ACTA2+/+ controls. Control mice had increased epithelialization, cell proliferation, and neovascularization. ACTA2−/− mice had lower levels of apoptosis, and fewer total numbers of cells. Smaller amount of collagen deposition and immature collagen organization in ACTA2−/− mice demonstrate that wounds were more immature. These data demonstrate that myofibroblasts contribute to but are not necessary for wound contraction. Mechanisms by which fibroblasts promote wound contraction may include activation of contractile signaling pathways, which promote interaction between non-muscle myosin II and ACTB and ACTG1.

Surgical management of necrotizing pancreatitis: An overview

Necrotizing pancreatitis is an uncommon yet serious complication of acute pancreatitis with mortality rates reported up to 15% that reach 30% in case of infection. Traditionally open surgical debridement was the only tool in our disposal to manage this serious clinical entity. This approach is however associated with poor outcomes. Management has now shifted away from open surgical debridement to a more conservative management and minimally invasive approaches. Contemporary approach to patients with necrotizing pancreatitis and/or infectious pancreatitis is summarized in the 3Ds: Delay, Drain and Debride. Patients can be managed in the intensive care unit and any intervention should be delayed. Percutaneous drainage can be utilized first and early in the course of the disease, followed by endoscopic drainage or video assisted retroperitoneoscopic drainage if necrosectomy is deemed necessary. Open surgery is now less frequently performed and should be reserved for cases refractory to any other approach. The management of necrotizing pancreatitis therefore requires a multidisciplinary dynamic model of approach rather than being a surgical disease.

Erratum to: angiotensin II stimulates canonical TGF-β signaling pathway through angiotensin type 1 receptor to induce granulation tissue contraction.

Hypertrophic scar contraction (HSc) is caused by granulation tissue contraction propagated by myofibroblast and fibroblast migration and contractility. Identifying the stimulants that promote migration and contractility is key to mitigating HSc. Angiotensin II (AngII) promotes migration and contractility of heart, liver, and lung fibroblasts; thus, we investigated the mechanisms of AngII in HSc. Human scar and unwounded dermis were immunostained for AngII receptors angiotensin type 1 receptor (AT1 receptor) and angiotensin type 2 receptor (AT2 receptor) and analyzed for AT1 receptor expression using Western blot. In vitro assays of fibroblast contraction and migration under AngII stimulation were conducted with AT1 receptor, AT2 receptor, p38, Jun N-terminal kinase (JNK), MEK, and activin receptor-like kinase 5 (ALK5) antagonism. Excisional wounds were created on AT1 receptor KO and wild-type (WT) mice treated with AngII ± losartan and ALK5 and JNK inhibitors SB-431542 and SP-600125, respectively. Granulation tissue contraction was quantified, and wounds were analyzed by immunohistochemistry. AT1 receptor expression was increased in scar, but not unwounded tissue. AngII induced fibroblast contraction and migration through AT1 receptor. Cell migration was inhibited by ALK5 and JNK, but not p38 or MEK blockade. In vivo experiments determined that absence of AT1 receptor and chemical AT1 receptor antagonism diminished granulation tissue contraction while AngII stimulated wound contraction. AngII granulation tissue contraction was diminished by ALK5 inhibition, but not JNK. AngII promotes granulation tissue contraction through AT1 receptor and downstream canonical transforming growth factor (TGF)-β signaling pathway, ALK5. Further understanding the pathogenesis of HSc as an integrated signaling mechanism could improve our approach to establishing effective therapeutic interventions.Key messageAT1 receptor expression is increased in scar tissue compared to unwounded tissue.AngII stimulates expression of proteins that confer cell migration and contraction.AngII stimulates fibroblast migration and contraction through AT1 receptor, ALK5, and JNK.AngII-stimulated in vivo granulation tissue contraction is AT1 receptor and ALK5 dependent.

Acute carpal tunnel syndrome secondary to iatrogenic hemorrhage. A case report.

Carpal tunnel syndrome is a common compression neuropathy of the median nerve. Acute carpal tunnel syndrome (aCTS) is rare, associated with a variety of conditions. In this case report we present a patient who developed aCTS and volar forearm compartment syndrome after a radial artery line placement, while receiving intravenous heparin. The patient underwent immediate forearm fasciotomy and surgical release for restoration of nerve function, which resulted in improved hand function and mild residual median nerve neuropathy. There is controversy whether to discontinue or not anticoagulation in a patient with aCTS. In our patient, heparin therapy was restarted on the second postoperative day.

Laparoscopic duodenectomy for benign nonampullary duodenal neoplasms.

Background: The aim of this study was to review our experience with laparoscopic duodenectomy for benign duodenal neoplasms and compare with a contemporary cohort of open duodenectomy. Methods: Twelve cases of laparoscopic duodenectomy for benign duodenal tumors not amenable to endoscopic resection and away from the ampulla performed from 2009 to 2011 at our institution were retrospectively reviewed. Demographic information, patient comorbidities, procedural data, and postoperative outcomes were analyzed. These data were compared with the data derived from 6 patients who underwent open duodenectomy for benign duodenal tumors. Results: Comparison of the laparoscopic to open duodenectomy data demonstrated that the length of stay was similar between the 2 groups (6.1±0.72 vs. 7±2.1, respectively, P>0.05), but the laparoscopic group was associated with a lower combined short-term and long-term complication rate. Statistically significant difference in patients’ body mass index (31±10 for the laparoscopic group vs. 22±4 for the open group, P<0.05) was yielded. The remainder of the preoperative, intraoperative, and postoperative variables were similar or not statistically different. The mean follow-up for the laparoscopic group was 12±3months. There were no recurrences in either group. Conclusions: Laparoscopic partial duodenal resection is a safe and effective alternative approach to managing patients with benign nonampullary duodenal neoplasms that are not amenable to endoscopic resection and had similar outcomes compared with the traditional open resection with the added benefit of less postoperative incisional hernias, also suited for patients with higher body mass index.

Review of complications associated with endoscopic pancreatic cyst-gastrostomy: a single-institution experience.

Background: Pancreatic fluid collections can form after episodes of pancreatitis, either acute or chronic. The majority will resolve spontaneously but when decompression is mandated, endoscopic drainage is the method of choice. However, it is not void of complications. Methods: We retrospectively reviewed the charts of 65 patients who underwent endoscopic drainage of pancreatic fluid collections in our institution. The primary outcomes examined included the incidence and type of complications associated with the endoscopic approach. Results: Endoscopic ultrasound was utilized in 86.2% and transgastric approach was used in 81.5% of the cases. The complication rate was 17%. Specifically, complications recorded were infection (6%), perforation and acute abdomen necessitating surgical intervention (4.6%), pneumoperitoneum that was managed nonoperatively (3%), upper gastrointestinal bleed in the knife puncture site that resolved spontaneously (1.5%), and stent migration (1.5%). One patient died remotely to the endoscopic drainage after paracentesis of ascites that resulted in hemorrhagic shock. Conclusions: This study is one of the largest studies reporting the associated morbidity and mortality after endoscopic cyst-gastrostomy. Major and minor complications occurred at a rate of 17% in our study. Endoscopic approach is a safe draining method and should remain the approach of choice for pancreatic fluid collection decompression.

Current evidence on the role of smoking in plastic surgery elective procedures: A systematic review and meta-analysis

BACKGROUND Smoking is considered to be a significant risk factor for the development of postoperative complications after various surgical procedures, mainly by limiting oxygen delivery to tissues. Evidence on the collective impact of smoking in aesthetic procedure outcomes is scarce. The aim of this study is to evaluate the current evidence on the association between smoking and postoperative outcomes in patients who underwent common elective procedures in plastic surgery. METHODS PubMed and Cochrane bibliographical databases were searched from January 1950 to October 2016 for studies reporting on patients who underwent facelift, abdominoplasty, breast reduction and breast reconstruction and for studies with included data on smoking history of treated patients. RESULTS Fifty-three studies reporting on postoperative complications in tobacco users undergoing facelift, abdominoplasty, breast reduction and reconstruction were identified. Tobacco use is found to significantly increase the total number of postoperative complications as far as abdominoplasty (OR: 5.43; 95% CI = 2.92-10.10), breast reduction (OR: 2.36; 95% CI = 1.64-3.39) and breast reconstruction (OR: 1.91; 95% CI = 1.69-2.17) are concerned. Smoking history does not significantly affect total postoperative complications after facelift procedures (OR: 3.36; 95% CI = 0.92-12.30). CONCLUSIONS Smoking predisposes to surgical site infections, delayed wound healing and skin necrosis in patients undergoing the most common aesthetic procedures in plastic surgery. More rigorous and detailed reporting on the history of tobacco use and surgical outcomes following plastic surgery procedures is needed to better quantify the impact of smoking on the overall postoperative care for this patient population.

Pulmonary toxicity after intraperitoneal mitomycin C: a case report of a rare complication of HIPEC

BackgroundCytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has become a common treatment approach for disseminated appendiceal neoplasms. Systemic absorption of intraperitoneal chemotherapeutics may lead to drug-induced toxicity, most commonly neutropenia. Mitomycin C has been the most commonly used chemotherapeutic in HIPEC for the past several decades.Case presentationHere, we describe a rare pulmonary complication secondary to intraperitoneal administration of mitomycin C.ConclusionsWhile rare, intraperitoneal mitomycin C has the potential to cause serious pulmonary toxicity that should be considered with administration. To our knowledge, this report represents only the second case described in the literature.

Femur reconstruction using combined autologous fibula transfer and humeral allograft

ZusammenfassungZur Behandlung von kindlichen Knochenmalignomen im Bereich des Femurschaftes ist nicht selten eine Resektion bis in den Metaphysenbereich erforderlich. In diesem Zusammenhang ist die biologische Rekonstruktion mit vaskularisierter, autologer Fibula eine etablierte Operationstechnik. Ein kurzer Femurmarkkanal und ein relativ geringer Fibuladurchmesser können die suffiziente Fixierung des vaskularisierten Knochentransplantats erschweren. Eine hohe Primärstabilität und eine kurze knöcherne Konsolidierungszeit werden mit der Verwendung eines zusätzlichen diapysären Humerus-Allografts in Kombination mit einer winkelstabilen Plattenosteosynthese erreicht.AbstractWide resection far into the femoral metaphysis may be required to treat malignant bone tumors in the pediatric and adolescent patient population. Biological reconstruction using a free, vascularized fibular graft is a well-established surgical technique. A short remaining femoral medullary canal and a relatively small fibula diameter can make fixation of the vascularized bone transfer difficult. Stable fixation and short fusion times, however, can be achieved with the use of an additional humeral allograft and plate osteosynthesis.