Surgical drain placement in distal pancreatectomy is associated with an increased incidence of postoperative pancreatic fistula and higher readmission rates.

BACKGROUND: Postoperative pancreatic fistula (POPF) can result in significant morbidity after distal pancreatectomy (DP). It is common practice to place prophylactic surgical drains during DP to monitor and minimize POPF complications; however, their use is controversial. OBJECTIVE: The aim of this study is to determine if drainage helps to prevent adverse outcomes and decrease the need for additional interventions after DP. METHODS: All patients who underwent DP without vascular resection were identified in the 2014 Targeted Pancreatectomy American College of Surgeons National Surgery Quality Improvement Program Participant Use File. Patients undergoing emergency procedures, American Society of Anesthesiology (ASA) 5, or diagnosed with preoperative sepsis were excluded. Univariate and multiple variable analyses were performed to evaluate postoperative outcomes based on use of surgical drain. RESULTS: A total of 1158 patients (age median: 62; interquartile range: 16; female 58.6%) underwent elective DP with 85.1% (n = 985) having drain placed at time of operation. Laparoscopic technique was used in the majority of patients (54.1%, n = 619). POPF occurred in 201 patients (17.5%). Additional percutaneous drain was required in 106 patients (9.2%). POPF was higher in surgical drain group, 19.4% vs 6.9% (P < .001). Need for percutaneous drain was similar between drain and no drain groups, 9.3% vs 8.1% (P = .600). Postoperative sepsis, shock, major complication, reoperation, and 30-day mortality was similar between drain and no drain groups (all P > .05). However, readmission was higher in the surgical drain group, 17.8% vs 10.4% (odds ratio [OR]: 1.9; 95% confidence interval [CI]: 1.1-3.1; P = .018). After adjusting for age, ASA, and operative time, readmission remained higher in the surgical drain group (OR: 1.9; 95% CI: 1.1-3.2; P = .016). CONCLUSION: The use of surgical drainage during DP was associated with increased incidence of readmission and POPF. Drainage showed no effect on outcomes of postoperative sepsis, shock, major complications, reoperation, and 30-day mortality. Based on these results, routine prophylactic drainage should be reconsidered for patients undergoing DP.

The Role of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Appendiceal Tumors and Colorectal Adenocarcinomas.

Peritoneal surface disease (PSD) has historically been used interchangeably with the term peritoneal carcinomatosis (PC) and has a dismal natural history. A variety of malignant pathologies, including colorectal and appendiceal primary tumors, can disseminate throughout the peritoneal cavity, leading to bowel obstruction and death. In general, peritoneal spread from high-grade appendiceal and colorectal primaries has the potential of hepatic and distant spread and best classified as PC. Low-grade appendiceal tumors are better categorized as PSD, due to low cellularity, high mucin production, and lack of potential spread outside the peritoneal cavity. Growing international experience with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) over the past 30 years has presented a therapeutic option to patients with PSD from colorectal and appendiceal tumors that can provide significant disease control, as well as potential for previously unattainable long-term survival. The proliferation of HIPEC centers and ongoing prospective trials are helping to standardize HIPEC techniques and patient selection.

WHIPPLE PROCEDURE: PANCREATICOGASTROSTOMY VERSUS PANCREATICOJEJUNOSTOMY: A LITERATURE REVIEW.

Pancreatic cancer is one of the leading causes of oncologic morbidity and mortality worldwide. The definitive surgical management for pancreatic cancer includes pancreaticoduodenectomy with either anastomosis to, or implantation of remnant pancreas to the stomach (pancreaticogastrostomy) or the jejunum (pancreaticojejunostomy). Operative morbidity and mortality following pancreaticoduodenectomy frequently results from complications associated with a pancreaticojejunal anastomotic leak. Pancreaticogastrostomy is an alternative method of restoring pancreatic continuity with the gut, which has been employed by a number of institutions showing some benefit in operative mortality.

Novel resveratrol analogues attenuate renal ischemic injury in rats.

BACKGROUND: Renal ischemia-reperfusion (I/R) is a severe clinical complication with no specific treatment. Resveratrol has been shown as a promising experimental agent in renal I/R due to its effect on cellular energy metabolism, oxidative stress, and inflammation. Recently, we identified two biologically active resveratrol analogues (RSVAs), RSVA405 and RSVA314. We hypothesized that both RSAVs would attenuate I/R-induced renal injury. METHODS: Adult male rats were subjected to renal I/R through bilateral renal pedicle clamping for 60 min, followed by reperfusion. RSVA405 (3 mg/kg Body Weight), RSVA314 (3 mg/kg Body Weight), or vehicle (10% dimethyl sulfoxide and 33% Solutol in phosphate buffered saline) were administered by intraperitoneal injection 1 h before ischemia. Blood and renal tissues were collected 24 h after I/R for evaluation. RESULTS: Administration of RSVA405 and RSVA314 significantly reduced the serum levels of renal dysfunction and injury markers, including creatinine, blood urea nitrogen, aspartate aminotransferase, and lactate dehydrogenase, compared with vehicle. The protective effect of RSVA405 and RSVA314 was also reflected on histologic evaluation. Both RSVAs reduced the number of apoptotic cells by more than 60% as determined by transferase dUTP nick end labeling assay, compared with vehicle. The renal adenosine triphosphate levels of the vehicle group was decreased to 52.4% of control, whereas those of the RSVA405 and RSVA314 groups were restored to 72.3% and 79.6% of control, respectively. Both RSVAs significantly reduced the protein expression of inducible nitric oxide synthase and nitrotyrosine and the messenger RNA levels of tumor necrosis factor-α, interleukin-6, and interleukin-1ß. CONCLUSIONS: RSVA405 and RSVA314 attenuate I/R-induced renal injury through the modulation of energy metabolism, oxidative stress, and inflammation.

Growth arrest-specific protein 6 protects against renal ischemia-reperfusion injury.

BACKGROUND: Renal injury caused by ischemia-reperfusion (I/R) often occurs after shock or transplantation. Growth arrest-specific protein 6 (Gas6) is a secreted protein that binds to the TAM-Tyro3, Axl, Mer-family tyrosine kinase receptors, which modulate the inflammatory response and activate cell survival pathways. We hypothesized that Gas6 could have a protective role in attenuating the severity of renal injury after I/R. MATERIALS AND METHODS: Adult mice were subjected to 45 min of bilateral renal ischemia. Recombinant mouse Gas6 (rmGas6, 5 µg per mouse) or normal saline (vehicle) was administered intraperitoneally 1 h before ischemia and all subjects were sacrificed at 23 h after I/R for blood and tissue analysis. The expression of protein and messenger RNA (mRNA) was assessed by Western blotting and quantitative polymerase chain reaction, respectively. RESULTS: Treatment with rmGas6 significantly decreased serum levels of creatinine and blood urea nitrogen by 29% and 27%, respectively, improved the renal histologic injury index, and reduced the apoptosis in the kidneys, compared with the vehicle. Renal mRNA levels of interleukin 1ß, interleukin 6, tumor necrosis factor α, keratinocyte-derived chemokine and macrophage inflammatory protein 2 were decreased significantly by 99%, 60%, 53%, 58%, and 43%, with rmGas6 treatment, respectively. After I/R, renal I-kappa-B α levels were reduced by 40%, whereas they returned to sham levels with rmGas6 treatment. The mRNA levels of inducible nitric oxide synthase and cyclooxygenase 2 were reduced by 79% and 70%, respectively, whereas the expression of cyclin D1 was increased by 2.1-fold in the rmGas6-treated group, compared with the vehicle. CONCLUSIONS: Gas6 suppresses the nuclear factor κB pathway and promotes cell proliferation, leading to the reduction of inflammation and protection of renal injury induced by I/R.

Significance of elevated transplant renal artery velocities in the postoperative renal transplant patient.

INTRODUCTION: Non-invasive imaging studies can provide visualization of allograft perfusion in the postoperative evaluation of newly transplanted renal allografts. AIM: The purpose of our study was to evaluate the significance of elevated renal artery velocities in the immediate postoperative period. METHODS: Peak systolic velocities (PSVs) were obtained in the transplanted renal artery of 128 patients immediately after transplantation. Repeat allograft Doppler ultrasonography was performed on patients with elevated values. RESULTS: Of the 128 patients, 57 (44.5%) had severely elevated Doppler velocities >400 cm/s on the initial studies. Three patients within this category had persistently elevated values of >400 cm/s, warranting angiographic visualization of the renal vessels. Stent placement within the transplanted renal artery was required in two of these patients. There was normalization of the PSV in the remaining patients. CONCLUSIONS: Routine allograft Doppler ultrasonography in the immediate postoperative period allows for visualization of allograft perfusion. Elevated renal artery velocities in the immediate postoperative period do not necessarily represent stenosis requiring intervention. Failure of the PSV to normalize may require further intervention, and angiography continues to be the gold standard.

Forty-eight hour kidney transplant admissions.

Forty-eight hour kidney transplantation admissions are a feasible option in selected recipients of live-donor allografts through the use of standardized post-operative protocols, multidisciplinary team patient care, and intensive follow-up at outpatient centers. Age, gender, and pre-transplant dialysis status did not impact the ability to achieve 48-hour admissions. We did not identify any other pre-operative risk factors that contributed to increased length of stay. Although ABO and highly sensitized recipients had longer lengths of stay, the subgroup was too small to achieve statistical significance. We did not encounter any readmissions within the first seven post-operative days. Further improvements in clinical management will enhance the potential to shorten the length of hospital stay for all kidney transplant recipients.

Minimally Invasive Surgical Approaches for Peritoneal Surface Malignancy.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an evolving strategy in the locoregional management of peritoneal surface malignancies, and the role of laparoscopy is expanding. Staging laparoscopy is routinely used to obtain tissue for diagnosis and assess extent of tumor burden. Laparoscopic CRS and HIPEC with curative intent is safe and effective in patients with a low disease burden. In patients with refractory malignant ascites, complete resolution of ascites and improvement in quality of life have been demonstrated with palliative laparoscopic HIPEC. Laparoscopic CRS and HIPEC has an expanding role in the treatment of peritoneal surface disease.

Effect of Negative Pressure Wound Therapy on Wound Complications Post-Pancreatectomy.

Surgical site infection (SSI) and incisional hernia are common complications after major pancreatectomy. We investigated the effects of negative pressure wound therapy (NPWT) on short- and long-term wound outcomes in patients undergoing pancreatectomy. A randomized controlled trial comparing the effect of NPWT with standard surgical dressing (SSD) on wounds was performed in 265 patients undergoing open gastrointestinal resections from 2012 to 2016. We performed a subset analysis of 73 patients who underwent pancreatectomy. Wound complications in the first 30 days and incisional hernia rates were assessed. There were 33 (45%) female patients in the study and the average BMI was 27.6. The pancreaticoduodectomy rate was 68 per cent, whereas 27 per cent of patients underwent distal or subtotal pancreatectomy, and 4 per cent total pancreatectomy. Incisional hernia rates were 32 per cent and 14 per cent between the SSD and NPWT groups, respectively (P = 0.067). In the SSD (n = 37) and NPWT (n = 36) cohorts, the superficial SSI, deep SSI, seroma, and dehiscence rates were 16 per cent and 14 per cent (P > 0.99), 5 per cent and 8 per cent (P = 0.67), 16 per cent and 11 per cent (P = 0.74), and 5 per cent and 3 per cent (P ≥ 0.99), respectively. After adjusting for pancreatic fistula and delayed gastric emptying, no statistically significant differences in the primary outcomes were observed. These findings were true irrespective of the type of resection performed. Short- and long-term wound complications were not improved with NPWT. We observed a trend toward decreased incisional hernia rates in patients treated with NPWT. Owing to the multifactorial nature of wound complications, it is yet to be determined which cohorts of pancreatectomy patients will benefit from NPWT.

Inhibition of fatty acid synthase with C75 decreases organ injury after hemorrhagic shock.

BACKGROUND: Hemorrhagic shock is the primary cause of morbidity and mortality in the intensive care units in patients under the age of 35. Several organs, including the lungs, are seriously affected by hemorrhagic shock and inadequate resuscitation. Excess free fatty acids have shown to trigger inflammation in various disease conditions. C75 is a small compound that inhibits fatty acid synthase, a key enzyme in the control of fatty acid metabolism that also stimulates fatty acid oxidation. We hypothesized that C75 treatment would be protective against hemorrhagic shock. METHODS: Adult male Sprague-Dawley rats were cannulated with a femoral artery catheter and subjected to controlled bleeding. Blood was shed to maintain a mean arterial pressure of 30 mm Hg for 90 minutes, then resuscitated over 30 minutes with a crystalloid volume equal to twice the volume of shed blood. Fifteen minutes into the 30-minute resuscitation, the rats received either intravenous infusion of C75 (1 mg/kg body weight) or vehicle (20% dimethyl sulfoxide). Blood and tissue samples were collected 6 hours after resuscitation (ie, 7.5 hours after hemorrhage) for analysis. RESULTS: After hemorrhage and resuscitation, C75 treatment decreased the increase in serum free fatty acids by 48%, restored adenosine triphosphate levels, and stimulated carnitine palmitoyl transferase-1 activity. Administration of C75 decreased serum levels of markers of injury (aspartate aminotransferase, lactate, and lactate dehydrogenase) by 38%, 32%, and 78%, respectively. Serum creatinine and blood urea nitrogen were also decreased significantly by 38% and 40%, respectively. These changes correlated with decreases in neutrophil infiltration in the lung, evidenced by decreases in Gr-1-stained cells and myeloperoxidase activity and improved lung histology. Finally, administration of C75 decreased pulmonary mRNA levels of cyclooxygenase-2 and interleukin-6 by 87% and 65%, respectively. CONCLUSION: Administration of C75 after hemorrhage and resuscitation decreased the increase in serum free fatty acids, decreased markers of tissue injury, downregulated the expression of inflammatory mediators, and decreased neutrophil infiltration and lung injury. Thus, the dual action of inhibiting fatty acid synthesis and stimulating fatty acid oxidation by C75 could be developed as a promising adjuvant therapy strategy to protect against hemorrhagic shock.

WNT Agonist Decreases Tissue Damage and Improves Renal Function After Ischemia-Reperfusion.

Renal ischemia-reperfusion (IR) injury (IRI) after shock states or transplantation causes tissue damage and delayed graft function, respectively. The Wnt/ß-catenin signaling pathway plays a critical role in nephrogenesis. We therefore hypothesized that pharmacological activation of the Wnt/ß-catenin signaling by the Wnt agonist, a synthetic pyrimidine, could protect kidneys from IRI. Adult male rats were subjected to bilateral clamping of the renal pedicles with microvascular clips for 60 min, followed by reperfusion. The Wnt agonist (5 mg/kg body weight) or vehicle (20% dimethyl sulfoxide in saline) was administered intravenously 1 h before ischemia. Blood and renal tissues were collected 24 h after IR for evaluation. Renal IR caused a significant reduction of ß-catenin and its downstream target gene cyclin D1 by 65% and 39%, respectively, compared with the sham, whereas the Wnt agonist restored them to sham levels. The number and intensity of cells staining with the proliferation marker Ki67 in ischematized kidneys were enhanced by the Wnt agonist. The integrity of the renal histological architecture in the Wnt agonist group was better preserved than the vehicle group. The Wnt agonist significantly lowered serum levels of creatinine, aspartate aminotransferase, and lactate dehydrogenase and inhibited the production of interleukin 6 and interleukin 1ß and myeloperoxidase activities. Lastly, the Wnt agonist reduced inducible nitric oxide synthase, nitrotyrosine proteins, and 4-hydroxynonenal in the kidneys by 60%, 47%, and 21%, respectively, compared with the vehicle. These results indicate that the Wnt agonist improves renal regeneration and function while attenuating inflammation and oxidative stress in the kidneys after IR. Thus, pharmacologic stimulation of the Wnt/ß-catenin signaling provides a beneficial effect on the prevention of renal IRI.

Stimulation of Wnt/ß-catenin signaling pathway with Wnt agonist reduces organ injury after hemorrhagic shock.

BACKGROUND: Hemorrhagic shock is a leading cause of morbidity and mortality in surgery and trauma patients. Despite a large number of preclinical trials conducted to develop therapeutic strategies against hemorrhagic shock, there is still an unmet need for effective therapy for hemorrhage patients. Wnt/ß-catenin signaling controls developmental processes and cellular regeneration owing to its central role in cell survival and proliferation. We therefore hypothesized that the activation of Wnt signaling reduces systemic injury caused by hemorrhagic shock. METHODS: Adult male Sprague-Dawley rats underwent hemorrhagic shock by controlled bleeding of the femoral artery to maintain a mean arterial pressure of 30 mm Hg for 90 minutes, followed by resuscitation with crystalloid equal to two times the shed blood volume. After resuscitation, animals were infused with Wnt agonist (5 mg/kg) or vehicle (20% dimethyl sulfoxide in saline). Blood and tissue samples were collected 6 hours after resuscitation for analysis. RESULTS: Hemorrhagic shock increased serum levels of aspartate aminotransferase, lactate, and lactate dehydrogenase. Treatment with Wnt agonist significantly reduced these levels by 40%, 36%, and 77%, respectively. Wnt agonist also decreased blood urea nitrogen and creatinine by 34% and 56%, respectively. The treatment reduced lung myeloperoxidase activity and interleukin 6 messenger RNA by 55% and 68%, respectively, and significantly improved lung histology. Wnt agonist treatment increased Bcl-2 protein to sham values and decreased cleaved caspase 3 by 46%, indicating attenuation of hemorrhage-induced apoptosis in the lungs. Hemorrhage resulted in significant reductions of ß-catenin protein levels in the lungs as well as down-regulation of a Wnt target gene, cyclin D1, while Wnt agonist treatment preserved these levels. CONCLUSION: The administration of Wnt agonist attenuated hemorrhage-induced organ injury, inflammation, and apoptosis. This was correlated with the preservation of the Wnt signaling pathway. Thus, Wnt/ß-catenin activation could be protective in hemorrhagic shock.

Sirtuin 1 activation stimulates mitochondrial biogenesis and attenuates renal injury after ischemia-reperfusion.

BACKGROUND: Renal ischemia-reperfusion (I/R) is a major contributor to delayed graft function after renal transplantation. The pathophysiology of I/R can be summarized by a primary energy deficit during ischemia and a secondary phase of oxidative stress and inflammation. Sirtuin 1 is an energy-sensing enzyme involved in regulating multiple cellular functions. We hypothesized that stimulating Sirtuin 1 would increase mitochondrial biogenesis thereby enhancing energy metabolism and attenuating I/R-induced renal injury. METHODS: Adult male rats were subjected to 60 min of bilateral renal pedicle clamping. SRT1720 (5 mg/kg body weight) or vehicle (20% dimethyl sulfoxide in saline) was administered intravenously at reperfusion. Blood and renal tissues were collected 24 hr after reperfusion. RESULTS: Posttreatment with SRT1720 significantly improved renal histologic architecture, decreased apoptosis, and reduced serum aspartate aminotransferase and creatinine levels compared to the vehicle. Renal adenosine triphosphate (ATP) levels were reduced by 48% after I/R, whereas SRT1720 restored ATP to 77% of control. Further, SRT1720 reversed the loss of renal mitochondrial mass induced by I/R supported by an increased expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha and its downstream mediators. SRT1720 also increased ATP levels and mitochondrial mass in human renal HK-2 cells. Moreover, SRT1720 decreased the levels of malondialdehyde, nitrotyrosine, and inducible nitric oxide synthase expression compared to the vehicle. A marked decrease in macrophage infiltration by SRT1720 treatment was associated with a decrease in tumor necrosis factor-α expression and a decrease in IκB-α degradation and nuclear factor-κB phosphorylation after I/R. CONCLUSION: SRT1720 treatment enhanced energy metabolism by stimulating mitochondrial biogenesis as well as decreasing nitrosative stress and inflammation, thereby attenuating I/R-induced renal injury.

Wnt agonist attenuates liver injury and improves survival after hepatic ischemia/reperfusion.

The Wnt/ß-catenin signaling pathway is well characterized in stem cell biology and plays a critical role in liver development, regeneration, and homeostasis. We hypothesized that pharmacologic activation of Wnt signaling protects against hepatic ischemia/reperfusion (I/R) injury through its known proliferative and antiapoptotic properties. Sprague-Dawley rats underwent 70% hepatic ischemia by microvascular clamping of the hilum of the left and median lobes of the liver for 90 min, followed by reperfusion. Wnt agonist (2-amino-4-[3,4-(methylenedioxy)benzylamino]-6-(3-methoxyphenyl)pyrimidine, 5 mg/kg body weight) or vehicle (20% dimethyl sulfoxide in saline) in 0.5 mL was injected i.p. 1 h before ischemia or infused i.v. over 30 min right after ischemia. Blood and tissue samples from the pretreated groups were collected 24 h after reperfusion, and a survival study was performed. Hepatic expression of ß-catenin and its downstream target gene Axin2 were decreased after I/R, whereas Wnt agonist restored their expression to sham levels. Wnt agonist blunted I/R-induced elevations of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase and significantly improved the microarchitecture of the liver. The cell proliferation determined by Ki67 immunostaining significantly increased with Wnt agonist treatment, and inflammatory cascades were dampened in Wnt agonist-treated animals, as demonstrated by attenuations in interleukin 6, myeloperoxidase, inducible nitric oxide synthase, and nitrotyrosine. Wnt agonist also significantly decreased the amount of apoptosis, as evidenced by decreases in both TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining as well as caspase 3 activity levels. Finally, the 10-day survival rate was increased from 27% in the vehicle group to 73% in the pretreated Wnt agonist group and 55% in the Wnt agonist postischemia treatment group. Thus, we propose that direct Wnt/ß-catenin stimulation may represent a novel therapeutic approach in the treatment of hepatic I/R.

Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis.

A systemic inflammatory response is observed in patients undergoing hemorrhagic shock and sepsis. Here we report increased levels of cold-inducible RNA-binding protein (CIRP) in the blood of individuals admitted to the surgical intensive care unit with hemorrhagic shock. In animal models of hemorrhage and sepsis, CIRP is upregulated in the heart and liver and released into the circulation. In macrophages under hypoxic stress, CIRP translocates from the nucleus to the cytosol and is released. Recombinant CIRP stimulates the release of tumor necrosis factor-α (TNF-α) and HMGB1 from macrophages and induces inflammatory responses and causes tissue injury when injected in vivo. Hemorrhage-induced TNF-α and HMGB1 release and lethality were reduced in CIRP-deficient mice. Blockade of CIRP using antisera to CIRP attenuated inflammatory cytokine release and mortality after hemorrhage and sepsis. The activity of extracellular CIRP is mediated through the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex. Surface plasmon resonance analysis indicated that CIRP binds to the TLR4-MD2 complex, as well as to TLR4 and MD2 individually. In particular, human CIRP amino acid residues 106-125 bind to MD2 with high affinity. Thus, CIRP is a damage-associated molecular pattern molecule that promotes inflammatory responses in shock and sepsis.

Removal of foley catheters in live donor kidney transplant recipients on postoperative day 1 does not increase the incidence of urine leaks.

Catheterization of the urinary bladder during kidney transplantation is essential. The optimal time to remove the Foley catheter postoperatively is not universally defined. It is our practice to remove the Foley catheter on postoperative day 1 in live donor kidney transplant recipients who meet our standardized protocol criteria. We believe that early removal of Foley catheters increases patient comfort and mobility, decreases the risk of catheter associated urinary tract infections, and allows for decreased hospital length of stay. The hypothetical risk of early removal of Foley catheters would be the increased risk of urine leak. We reviewed 120 consecutive live donor kidney transplant recipients and found that there was not an increased incidence of urine leaks in patients whose Foley catheters were removed on postoperative day 1.

Shortened length of stay improves financial outcomes in living donor kidney transplantation.

Kidney transplantation is the preferred clinical and most cost-effective option for end-stage renal disease. Significant advances have taken place in the care of the transplant patients with improvements in clinical outcomes. The optimization of the costs of transplantation has been a constant goal as well. We present herein the impact in financial outcomes of a shortened length of stay after kidney transplant.