Temperature-driven heterochrony as a main evolutionary response to climate changes in conodonts.

Can we predict the evolutionary response of organisms to climate changes? The direction of greatest intraspecific phenotypic variance is thought to correspond to an 'evolutionary line of least resistance', i.e. a taxon's phenotype is expected to evolve along that general direction, if not constrained otherwise. In particular, heterochrony, whereby the timing or rate of developmental processes are modified, has often been invoked to describe evolutionary trajectories and it may be advantageous to organisms when rapid adaptation is critical. Yet, to date, little is known empirically as to which covariation patterns, whether static allometry, as measured in adult forms only, or ontogenetic allometry, the basis for heterochrony, may be prevalent in what circumstances. Here, we quantify the morphology of segminiplanate conodont elements during two distinct time intervals separated by more than 130 Myr: the Devonian-Carboniferous boundary and the Carnian-Norian boundary (Late Triassic). We evidence that the corresponding species share similar patterns of intraspecific static allometry. Yet, during both crises, conodont evolution was decoupled from this common evolutionary line of least resistance. Instead, it followed heterochrony-like trajectories that furthermore appear as driven by ocean temperature. This may have implications for our interpretation of conodonts' and past marine ecosystems' response to environmental perturbations.

Clinical and economic validation of grade B postoperative pancreatic fistula subclassification.

BACKGROUND: Grade B postoperative pancreatic fistula represents the largest fraction of postoperative pancreatic fistula. A subclassification of grade B postoperative pancreatic fistula has been recently proposed and seems to better stratify postoperative pancreatic fistula clinical and economic burden. Aim of this study was to validate, from a clinical and economic standpoint, grade B postoperative pancreatic fistula subclassification in patients submitted to pancreaticoduodenectomy. METHODS: All consecutive patients who underwent pancreaticoduodenectomy and developed biochemical leak or postoperative pancreatic fistula were included. Grade B postoperative pancreatic fistula was subclassified into 3 categories (B1: persistent drainage >21 days, B2: pharmacological treatments; B3: interventional procedures). Postoperative pancreatic fistula clinical and economic burden was assessed by evaluating postoperative complications, length of hospital stay, and overall hospital costs. RESULTS: Overall, 289 patients developed biochemical leak or postoperative pancreatic fistula. Of these, 34 had biochemical leak (12%), 25 had grade B1 postoperative pancreatic fistula (9%), 91 had grade B2 postoperative pancreatic fistula (31%), 94 had grade B3 postoperative pancreatic fistula (32%), and 45 experienced grade C postoperative pancreatic fistula (16%). The severity of postoperative complications significantly increased across biochemical leak and postoperative pancreatic fistula categories (P < .001), but it was comparable between biochemical leak and grade B1 postoperative pancreatic fistula. There was no significant difference in terms of length of hospital stay between patients with biochemical leak and those with grade B1 postoperative pancreatic fistula (P = 1.000). Overall hospital costs were similar for patients with biochemical leak and those with grade B1 postoperative pancreatic fistula (P = 1.000), whereas they significantly increased across all the other postoperative pancreatic fistula subgroups. CONCLUSION: A subclassification of grade B postoperative pancreatic fistula can better stratify the increasing clinical burden and economic impact of postoperative pancreatic fistula after pancreaticoduodenectomy. Grade B1 postoperative pancreatic fistula has minimal clinical and economic consequences and can be considered closer to a biochemical leak than to a grade B2 postoperative pancreatic fistula.

Impact of care pathway adherence on recovery following distal pancreatectomy within an enhanced recovery program.

BACKGROUND: In bowel surgery, adherence to enhanced recovery program (ERP) has been associated with improved recovery. The objective of this study was to evaluate the impact of adherence to ERP elements on outcomes, and identify factors associated with successful recovery following distal pancreatectomy (DP). METHODS: Data for 376 patients who underwent DP managed within an ERP including 16 perioperative elements were reviewed. Primary endpoint was successful recovery, a composite outcome defined as length of hospital stay≤7 days, no severe complications nor readmissions. RESULTS: Patients had a mean (SD) overall adherence of 76 (14)%. Overall, 166 (44%) patients had a successful recovery. There was a positive association between overall adherence and successful recovery (OR 1.19, 95%CI 1.08-1.31 for every additional element, p = 0.001), while an inverse relationship was found with comprehensive complication index (8% reduction, 95%CI -15 to -2%, p = 0.011). Adherence to postoperative phase interventions had the greatest impact on recovery (OR 1.29, 95%CI 1.13-1.47 for every additional postoperative element; p < 0.001). At multivariable regression, early termination of IV fluids was the only ERP element associated with successful recovery (OR 2.80, 95%CI 1.73-4.54; p < 0.001). CONCLUSION: Increased adherence to ERP elements was associated with successful early recovery and reduction of postoperative complication severity.

The role of acinar content at pancreatic resection margin in the development of postoperative pancreatic fistula and acute pancreatitis after pancreaticoduodenectomy.

BACKGROUND: A fatty infiltration of the pancreas has been traditionally regarded as the main histological risk factor for postoperative pancreatic fistula, whereas the role of the secreting acinar compartment has been poorly investigated. The aim of this study was to evaluate the role of acinar content at the pancreatic resection margin in the development of clinically relevant postoperative pancreatic fistula and clinically relevant postoperative acute pancreatitis after pancreaticoduodenectomy. METHODS: Data from 388 consecutive patients who underwent pancreaticoduodenectomy (2018-2019) were analyzed. Pancreatic section margins were histologically assessed for acinar, fibrosis, and fat content. Acinar content was categorized using median and third quartile as cut-offs. Univariate and multivariable analysis of possible predictors of clinically relevant postoperative pancreatic fistula and clinically relevant postoperative acute pancreatitis were performed. RESULTS: Acinar content was <60% in 166 patients (42.8%), ≥60% and ≤80% in 156 patients (40.2%), and >80% in 66 patients (17.0%). The rate of clinically relevant postoperative pancreatic fistula and clinically relevant postoperative acute pancreatitis was significantly higher in patients with acinar content >80% (39.4% and 33.3%, respectively) as well as in those with acinar content ≥60% and ≤80% (36.5% and 35.3%, respectively), compared with patients with acinar content <60% (10.2% and 5.4%, respectively) (P < .001). Acinar content was identified as an independent predictor of clinically relevant postoperative pancreatic fistula (≥60% and ≤80%, odds ratio 2.51, P = .008; >80%, odds ratio 2.93, P = .010) and clinically relevant postoperative acute pancreatitis (≥60% and ≤80%, odds ratio 9.42, P < .001; >80%, odds ratio 10.16, P < .001). CONCLUSION: An acinar content at the pancreatic resection margin ≥60% is associated to an increased risk of clinically relevant postoperative pancreatic fistula and clinically relevant postoperative acute pancreatitis. Fat content was associated neither with clinically relevant postoperative pancreatic fistula nor with clinically relevant postoperative acute pancreatitis.

The impact of minimally invasive surgery on hospital readmissions, emergency department visits and functional recovery after distal pancreatectomy.

BACKGROUND: A recent RCT showed similar postoperative outcomes and a reduced time to functional recovery in patients undergoing minimally invasive distal pancreatectomy (DP) compared to open approach. However, it reported very-high post-discharge readmission rates, calling for further investigation. The aim of our study was to evaluate the extent to which minimally invasive surgery impacts on postoperative readmissions following DP. METHODS: Clinical data for patients undergoing DP between 2011 and 2018 were reviewed. Primary outcome was hospital readmission at 90 days after surgery. Secondary outcomes included post-discharge emergency department (ED) visits and time to functional recovery. Regression analyses were performed to evaluate the impact of the laparoscopic approach and other perioperative factors. RESULTS: Overall, 376 consecutive patients underwent DP during the study period. Laparoscopy was successfully performed in 219 (58%) patients. Overall, 62 patients (16.5%) returned to the ED after discharge, 41 (18.7%) of laparoscopically operated patients, and 21 (13.4%) of those undergoing open surgery (p = 0.162). Forty-six (12.2%) of them required readmission, 31 (14.2%) after laparoscopic, and 15 (9.6%) after open procedures (p = 0.179). At multivariate regression, a low preoperative physical status (OR 2.3, 95% CI 1.2-4.7; p = 0.017), occurrence of pancreatic fistula (OR 6.8, 95% CI 2.9-15.9; p < 0.001), and post-pancreatectomy hemorrhage (OR 3.9, 95% CI 1.2-13.1; p = 0.025) were significantly associated with 90-day readmission, while laparoscopy had no impact. Median time to reach functional recovery was 5 (IQR 4-6) days. At multivariate analysis, laparoscopy reduced time to functional recovery by 13% (95% CI - 19 to - 6%; p < 0.001), time to adequate oral intake by 19% (95% CI - 27 to - 10%; p < 0.001), and time to adequate pain control by 12% (95% CI - 18 to - 5%; p < 0.001). CONCLUSION: Hospital readmissions and ED visits following DP were not influenced by the surgical approach. A low preoperative physical status, occurrence of postoperative pancreatic fistula and hemorrhage were significantly associated with post-discharge readmission within 90 days. Laparoscopy reduced time to functional recovery.

Hypothermic Machine Perfusion as an Alternative to Biopsy Assessment in Transplantation of Kidneys Donated After Cardiocirculatory Death: A Pilot Study.

BACKGROUND: Transplantation of kidneys from donation after cardiocirculatory death (DCD) donors is becoming an ever-increasing reality. So far, biopsy histologic assessment is the main parameter for evaluation of graft suitability, but it has several drawbacks and has poor reliability. The aim of this study is to verify if real-time renal resistance (RR) measurement during hypothermic machine perfusion (HMP) can be used as a reliable parameter to evaluate the quality of grafts from DCD and extracorporeal membrane oxygenation (ECMO) donors. METHODS: From January 2015 to September 2018, HMP has been systematically applied to all organs from DCD and ECMO donors. All grafts underwent preimplantation biopsy histologic assessment with Karpinski's score. Single kidney transplants (SKTs) or double kidney transplants (DKTs) were performed according to biopsy score results. Kidneys were considered suitable for transplant if RR reached ≤ 1.0 within 3 hours of perfusion. RR trend and postoperative outcome were analyzed considering biopsy score and donor type. RESULTS: A total of 30 kidneys (15 from DCD and 15 from ECMO donors) were used to perform 26 transplants (22 SKTs and 4 DKTs). Considering RR trend, all grafts were considered suitable for transplant within 1 hour of perfusion. Biopsy confirmed this result in all cases, and median score was 3 (range, 0-7). SKT score kidneys had lower starting RR than DKT ones (1.88 vs 2.88; P = .04) but identical final RR (0.58 vs 0.57; P = .76). DKT recipients had faster postoperative creatinine reduction than SKT recipients but similar postoperative day 30 value (1.42 vs 1.15 mg/dL; P = .20). No differences were found between DCD and ECMO grafts in terms of RR trend and postoperative outcome. CONCLUSIONS: HMP can be an alternative to histologic biopsy assessment for evaluation of transplant suitability of DCD and ECMO kidneys. If acceptability threshold is reached, SKT can be performed in all cases. ECMO donors should be considered like DCD donors.

Management of small asymptomatic nonfunctioning pancreatic neuroendocrine tumors: Limitations to apply guidelines into real life.

BACKGROUND: International guidelines suggest a watchful strategy for small nonfunctioning pancreatic neuroendocrine tumors. The aim of this study was to evaluate the management and indications for surgery in patients with asymptomatic nonfunctioning pancreatic neuroendocrine tumors ≤2 cm. METHODS: Patients with asymptomatic, incidental, sporadic nonfunctioning pancreatic neuroendocrine tumors ≤2 cm without nodal or distant metastases were included (2012-2016). A comparison between active surveillance and surgery groups was performed. RESULTS: Of the 101 included patients, 72% underwent active surveillanc and 28% were surgically treated. Patients submitted to surgery were significantly younger (53 vs 60 years, P = .013), had a higher incidence of positive 18F-fluorodeoxyglucose positron emission tomography (18% vs 50%, P = .003), and a higher incidence of cytologically determined G2 tumor (0% vs 14%, P = .008). Conservatively managed patients had a significantly smaller tumor size (12 vs 16 mm, P = .0001). The main reasons determining surgical choice were as follows: patient's preference (32%), positive 18F-fluorodeoxyglucose positron emission tomography (21.5%), main pancreatic duct dilation (17.5%), cytologically determined G2 tumor (14.5%), and young age (14.5%). At a median follow-up of 40 months, all of the 73 patients conservatively managed were alive, with no evidence of distant metastases and none underwent surgery. Only 5 patients had a tumor growth >20%. CONCLUSION: One-third of patients with asymptomatic small nonfunctioning pancreatic neuroendocrine tumors ≤2 cm underwent surgery. Patient's preference, initial tumor size, and young age were the main determinants of surgical indication. Preoperative diagnostic workup, including 18F-fluorodeoxyglucose positron emission tomography and cytologic grading, seems to be poorly accurate in determining malignant features in these small lesions.

Duodeno-jejunal or gastro-enteric leakage after pancreatic resection: a case-control study.

Duodeno-jejunal (DJ) and gastro-jejunal (GJ) anastomosis leakage represents a rare but life-threatening complication after pancreaticoduodenectomy or total pancreatectomy. The aim of this study was to assess its incidence, clinical presentation, and outcomes, and to identify perioperative risk factors for DJ/GJ leak. Prospectively collected perioperative data were reviewed, and a case-control study was performed. Patients who presented with a DJ/GJ leak (cases) were matched in a 1:5 ratio with patients who did not develop it. Match criteria included age, diagnosis, type of surgery, and anastomosis. Perioperative factors and outcomes were compared between groups. From January 2008 to present, 13 cases were observed and compared to 60 controls. Concerning pre-operative variables, cases showed lower pre-operative serum hemoglobin (p = 0.021) and increased pre-operative radiotherapy (p = 0.037). Cases experienced more severe post-operative complications than Controls, according to the CD classification (p < 0.001), with a higher mortality rate (23% vs. 2%; p < 0.016). They also experienced a more demanding intra-operative course including an increased estimated blood loss (median 600 vs. 400 mL; p = 0.002), a higher rate of blood transfusion (n4 31% vs. n5 8%; p = 0.047) with also a longer operative time (median 360 vs. 318 min; p = 0.038). Moreover, the occurrence of a DJ/GJ leak was significantly associated with other post-operative complications: clinically relevant pancreatic fistula (p = 0.006), bile leak (p = 0.021), and bleeding (p = 0.001). In addition, another post-operative finding significantly related to the DJ/GJ occurrence was sepsis (p < 0.001) The DJ/GJ fistula required a surgical treatment in the majority of cases (92.3%), while, in only one patient, a conservative management was accomplished. Length of hospital stay and mortality at 90 days were higher in the DJ/GJ leak group (p = 0.001). DJ/GJ leakage is a severe complication following pancreatic resection. A higher index of suspicion for DJ/GJ fistula should be maintained in case of concomitant relevant pancreatic fistula and post-operative hemorrhage.

Renal Resistance Trend During Hypothermic Machine Perfusion Is More Predictive of Postoperative Outcome Than Biopsy Score: Preliminary Experience in 35 Consecutive Kidney Transplantations.

Hypothermic machine perfusion (HPM) grants a better postoperative outcome in transplantation of organs procured from extended criteria donors (ECDs) and donors after cardiac death (DCD). So far, the only available parameter for outcome prediction concerning those organs is pretransplant biopsy score. The aim of this study is to evaluate whether renal resistance (RR) trend during HPM may be used as a predictive marker for post-transplantation outcome. From December 2015 to present, HMP has been systematically applied to all organs from ECDs and DCD. All grafts underwent pretransplantation biopsy evaluation using Karpinski's histological score. Only organs that reached RR value ≤1.0 within 3 hours of perfusion were transplanted. Single kidney transplantation (SKT) or double kidney transplantation (DKT) were performed according to biopsy score results. Sixty-five HMPs were performed (58 from ECDs and 7 from DCD/ECMO donors). Fifteen kidneys were insufficiently reconditioned (RR > 1) and were therefore discarded. Forty-nine kidneys were transplanted, divided between 21 SKT and 14 DKT. Overall primary nonfunction (PNF) and delayed graft function (DGF) rate were 2.9 and 17.1%, respectively. DGF were more common in kidneys from DCD (67 vs. 7%; P = 0.004). Biopsy score did not correlate with PNF/DGF rate (P = 0.870) and postoperative creatinine trend (P = 0.796). Recipients of kidneys that reached RR ≤ 1.0 within 1 hour of HMP had a lower PNF/DGF rate (11 vs. 44%; P = 0.033) and faster serum creatinine decrease (POD10 creatinine: 1.79 mg/dL vs. 4.33 mg/dL; P = 0.019). RR trend is more predictive of post-transplantation outcome than biopsy score. Hence, RR trend should be taken into account in the pretransplantation evaluation of the organs.

Treatment of Zenker's Diverticulum With Endoscopic Stapled Esophago-divertisculostomy (ESD): Analysis of Long-term Outcome.

BACKGROUND: Endoscopic Zenker diverticulum (ZD) treatment has become quite common because of the low complication rates, reduced procedure time, and shorter hospital stay. Many endoscopic treatments are available including the endoscopic stapled esophago-diverticulostomy (ESD). Many data regarding ESD are available on the short-term outcomes, but few on the long-term ones. MATERIALS AND METHODS: From March 1998 to July 2016, 126 patients with ZD were candidate for ESD. Since 2009, 2 stay sutures were routinely positioned at the lateral edges of the septum using Medtronic Endostitch 10 mm suturing device. Demographic and perioperative data, symptoms, and surgical outcomes were recorded. Long-term ESD results were analyzed. An extra-analysis on the surgical outcome was performed comparing patients treated with or without stay sutures. RESULTS: In total, 117 patients successfully underwent ESD. The mean age was 69.9 years with a male predominance. Intraoperative complications occurred in 6.8% of cases. Only 2.6% of the patients reported postoperative complications. For the long-term analysis, we were able to contact 92 patients for a mean period follow-up of 65.3 months. At 6-month outpatient visit 77.68% of patients were completely asymptomatic. In total, 22.3% of the patients needed an extratreatment due to incomplete section of the septum, reaching a success rate of 95.5%. The long-term resolution rate remained high (91.3%). The use of stay sutures did not statistically influence the operative time (22.8 vs. 26.7 min, P=0.070), nor intraoperative and postoperative complication rate, but a statistically significant higher complete resolution rate of symptoms with a single session of ESD was observed respect those treated without (87.3% vs. 65.3%, respectively). CONCLUSIONS: ESD is a safe and effective treatment of ZD and it can control symptoms even in a long-term follow-up. In our experience, the use of stay sutures placed with Endostitch increases short and long-term results reducing the need for further treatments.