Centralization of Pancreaticoduodenectomy: A Systematic Review and Spline Regression Analysis to Recommend Minimum Volume for a Specialist Pancreas Service.

OBJECTIVE: Through a systematic review and spline curve analysis, to better define the minimum volume threshold for hospitals to perform (pancreaticoduodenectomy) and the high-volume center. BACKGROUND: The pancreaticoduodenectomy (PD) is a resource-intensive procedure, with high morbidity and long hospital stays resulting in centralization towards high-volume hospitals; the published definition of high volume remains variable. MATERIALS AND METHODS: Following a systematic review of studies comparing PD outcomes across volume groups, semiparametric regression modeling of morbidity (%), mortality (%), length of stay (days), lymph node harvest (number of nodes), and cost ($USD) as continuous variables were performed and fitted as a smoothed function of splines. If this showed a nonlinear association, then a "zero-crossing" technique was used, which produced "first and second derivatives" to identify volume thresholds. RESULTS: Our analysis of 33 cohort studies (198,377 patients) showed 55 PDs/year and 43 PDs/year were the threshold value required to achieve the lowest morbidity and highest lymph node harvest, with model estimated df 5.154 ( P <0.001) and 8.254 ( P <0.001), respectively. The threshold value for mortality was ~45 PDs/year (model 9.219 ( P <0.001)), with the lowest mortality value (the optimum value) at ~70 PDs/year (ie, a high-volume center). No significant association was observed for cost ( edf =2, P =0.989) and length of stay ( edf =2.04, P =0.099). CONCLUSIONS: There is a significant benefit from the centralization of PD, with 55 PDs/year and 43 PDs/year as the threshold value required to achieve the lowest morbidity and highest lymph node harvest, respectively. To achieve mortality benefit, the minimum procedure threshold is 45 PDs/year, with the lowest and optimum mortality value (ie, a high-volume center) at approximately 70 PDs/year.

The Anatomy of Nerve Transfers Used in Tetraplegic Hand Reconstruction.

PURPOSE: To evaluate the anatomy of nerve transfers used to reconstruct wrist extension, hand opening, and hand closing in tetraplegic patients. METHODS: Nerve transfers were completed on 18 paired cadaveric upper limbs. The overlap of donor and recipient nerves was measured, as well as the distance to the target muscle. Axons were counted in each nerve and branch, with the axon percentage calculated by dividing the donor nerve count by that of the recipient. RESULTS: Transfers with overlap of the donor and recipient nerve were from the radial nerve branch to extensor carpi radialis brevis to anterior interosseous nerve (AIN) and from the branch(es) to supinator to posterior interosseous nerve. The extensor carpi radialis brevis to AIN had the shortest distance to the target, with the branch to brachialis to AIN being the longest. The nerve transfers for wrist extension had the highest axon percentage. Of the transfers for hand closing, the brachialis to AIN had the highest axon percentage, and the branch to brachioradialis to AIN had the lowest. CONCLUSIONS: The anatomical features of nerve transfers used in tetraplegic hand reconstruction are variable. Differences may help explain clinical outcomes. CLINICAL RELEVANCE: This study demonstrates which nerve transfers may be anatomically favorable for restoring hand function in tetraplegic patients.

Reducing the incidence of hepatic artery thrombosis in pediatric liver transplantation: Effect of microvascular techniques and a customized anticoagulation protocol.

We aimed to assess the incidence of HAT over three eras following implementation of microvascular techniques and a customized anticoagulation protocol in a predominantly cadaveric split liver transplant program. We retrospectively reviewed pediatric liver transplants performed between April 1986 and 2016 and analyzed the incidence HAT over three eras. In E1, 1986-2008, each patient received a standard dose of 5 U/kg/h of heparin and coagulation profiles normalized passively. In E2, 2008-2012, microvascular techniques were introduced. In E3, 2012-2016, in addition, a customized anticoagulation protocol was introduced which included replacement of antithrombin 3, protein C and S, and early heparinization. A total of 317 liver transplants were completed during the study period, with a median age of 31.7 months. In E1, 22% of grafts were cadaveric in situ split grafts, while the second and third eras used split grafts in 59.0% and 64.9% of cases, respectively. HAT occurred in 9.5% in the first era, 11.5% (P=.661) in the second, and dropped to 1.8% in the third era (P=.043). A routine anticoagulation protocol has significantly reduced the incidence of HAT post-liver transplantation in children in a predominantly cadaveric in situ split liver transplant program.

Mitogen-activated protein kinase-activated protein kinase 2 in neuroinflammation, heat shock protein 27 phosphorylation, and cell cycle: role and targeting.

Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MAPKAPK-2 or MK2) is a downstream substrate of the p38 MAPK responsible for the signaling events influencing inflammation, cell division and differentiation, apoptosis, and cell motility in response to a wide range of extracellular stimuli. After the failure of p38 MAPK inhibitors in clinical trials, MK2 was unveiled as a potential target to regulate inflammatory cytokines' mRNA stability and translation. Recent work suggests that this mechanism may underlie the pathophysiology of brain disorders associated with inflammation. In addition, MK2 is a prominent kinase that phosphorylates heat shock protein 27 (Hsp27), an intensively investigated biomarker of cancer progression. This phosphorylation decreases the chaperone properties of Hsp27, making MK2 an endogenous inhibitor of Hsp27. MK2 is also one of the major players in the signal transduction pathways activated in response to DNA damage. Experimental evidence highlights the role of MK2 in G(2)/M and the mitotic spindle checkpoints, two mechanisms by which MK2 contributes to the maintenance of genomic stability. Thus, MK2 is considered a good molecular target to increase, in combination with chemotherapeutic agents, the sensitivity of treatment, especially in p53-mutated tumors. This review looks at the functions of MK2 in inflammation, Hsp27 regulation, and cell cycle checkpoint control with a focus on brain pathologies. Analysis of MK2 signaling in various disease models and a summary of the data on MK2 inhibitors suggest novel indications for MK2 inhibitors in addition to their mainstream use against peripheral inflammatory disorders.

Lipase-to-Amylase Ratio for the Prediction of Clinically Relevant Postoperative Pancreatic Fistula Following Pancreaticoduodenectomy.

OBJECTIVE: Postoperative pancreatic fistula (POPF) represents a leading cause of morbidity and mortality following major pancreatic resections. This study aimed to evaluate the use of postoperative drain fluid lipase-to-amylase ratio (LAR) for the prediction of clinically relevant fistulae (CR-POPF). METHODS: Consecutive patients undergoing pancreaticoduodenectomy between 2017 and 2021 at a tertiary centre were retrospectively reviewed. Univariable and multivariable analyses were performed to identify predictors for CR-POPF (ISGPS grade B/C). Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the performance of LAR and determine optimum prediction thresholds. RESULTS: Among 130 patients, 28 (21.5%) developed CR-POPF. Variables positively associated with CR-POPF included soft gland texture, acinar cell density, diagnosis other than PDAC or chronic pancreatitis, resection without neoadjuvant therapy, and postoperative drain fluid lipase, amylase, and LAR (all P <0.05). Multivariable regression analysis identified LAR as an independent predictor of CR-POPF ( P <0.05). ROC curve analysis showed that LAR had moderate ability to predict CR-POPF on POD1 (AUC,0.64; 95%CI,0.54-0.74) and excellent ability on POD3 (AUC,0.85; 95%CI,0.78-0.92) and POD 5 (AUC,0.86; 95%CI,0.79-0.92). Optimum thresholds were consistent over PODs 1 to 5 (ratio>2.6) and associated with 92% sensitivity and 46% to 71% specificity. CONCLUSIONS: Postoperative drain fluid LAR represents a reliable predictor for the development of CR-POPF. With early prognostication, the postoperative care of patients at risk of developing high-grade fistulas may be optimized.

A retrospective review of breast reconstruction outcomes comparing AlloDerm and DermaCELL.

Acellular dermal matrix (ADM) has become an accepted and advantageous adjunct to alloplastic breast reconstruction. The increase in demand has led to an upsurge of dermal-based products, both human and animal derived. There are few direct ADM comparative studies, but it is unclear whether there are any differences in complication rates. Our primary objective was to determine whether there is a difference in outcomes between AlloDerm and DermACELL in immediate alloplastic breast reconstruction. A retrospective chart review of those who underwent immediate alloplastic breast reconstruction from January to December 2016 was performed. This encompassed 64 consecutive patients (95 breasts) with tissue expander or direct-to-implant reconstruction and either AlloDerm or DermACELL ADM. Demographics, particulars of the surgery, additional treatments and complications were all recorded. Differences in seroma, haematoma and infection rates, as well as more serious complications including implant replacement, capsular contracture and failure, were all reviewed. The groups were comparable in terms of age, BMI and relevant comorbidities. Mastectomy weight and resulting implant volume were higher in the DermACELL group, with volume reaching statistical significance (p = 0.001). With an average follow-up of 18 months, there was no difference in capsular contraction or implant replacement. However, in those who developed capsular contracture in the DermACELL group, more breasts had no history of radiation, which was significant (p = 0.042). Overall, there were no significant differences in complication rates of seroma, haematoma, mastectomy flap necrosis and infection.

Comparison of cost of care for tethered versus non-tethered ureteric stents in the management of uncomplicated upper urinary tract stones.

BACKGROUND: Many surgeons use a stent after ureteroscopic lithotripsy (URSL). For short-term stenting purposes, a surgeon has the choice of either a tethered or a non-tethered stent. Stents may be associated with complications that entail an additional cost to their use. There is a paucity of data on the direct healthcare cost of using stent type after either primary or secondary URSL. METHODS: We retrospectively reviewed medical records for patients who underwent URSL for uncomplicated urolithiasis between January 2013 and December 2013 at two tertiary referral hospitals. Costs data was sourced from the costing department with complete data available for 134 patients. The overall medical care cost was estimated by computing the cost of surgery, stent-related emergency department presentations, re-admissions and stent removal. RESULTS: A total of 113 patients had tethered stents and 21 had non-tethered stents, with similar age and gender composition between the two groups and complications rates. The mean cost of URSL and stent placement was A$3071.7 ± A$906.8 versus A$3423.8 ± A$808.4 (P = 0.049), mean cost of managing complications was A$309.4 ± A$1744.8 versus A$31.3 ± A$98.9 (P = 0.096), mean cost of out-patient clinic stent removal was A$222.5 ± A$60 versus A$1013.6 ± A$75.4 (P < 0.001) for endoscopic stent removal, overall mean cost of care was A$3603.6 ± A$1896.7 versus A$4468.1 ± A$820.8 (P = 0.042) for tethered and non-tethered stents, respectively. CONCLUSION: It is cheaper to use a tethered ureteric stent compared with non-tethered stents for short-term stenting after uncomplicated URSL, with a mean cost saving of A$864.5.

Delayed primary closure and the incidence of surgical complications in pediatric liver transplant recipients.

PURPOSE: The purpose of this study was to analyze the general surgical complications in pediatric liver transplant recipients and the safety of delayed primary closure at a single tertiary center. METHODS: A retrospective review of all liver transplant recipients between April 1986 and May 2014 was performed. All general and gastrointestinal complications were recorded and analyzed. The incidence and risk of these complications were compared between children who had a primary versus those who had a delayed closure, with or without the use of Surgisis®, of their abdomen. RESULTS: 242 patients underwent 281 liver transplants. The median age of the children was 31months. Whole (77), reduced size (91), split (96), and living related grafts (17) were used. General surgical complications were observed in 33 cases (11.7%). 135 cases underwent delayed primary closure (DPC) of their abdomen, 35 with Surgisis®. Patients with biliary atresia had a higher rate (4.6%) of bowel perforation (p=0.013). The majority of complications occurred within 3months of transplantation. CONCLUSION: General surgical complications postpediatric liver transplantation were common but usually not life threatening. Delayed primary closure was safe, had no significant long-term issues, and was not associated with higher incidence of wound related complications.