Postoperative Hyperamylasemia (POH) is an Early Predictor of Pancreatic Fistula Occurrence and Severity after Distal Pancreatectomy: Results from a European Multicentric Study.

OBJECTIVES: The aim of this international multicentric study is to characterize postoperative hyperamylasemia (POH) after distal pancreatectomy (DP), with particular focus on its relationship with postoperative pancreatic fistula (POPF) occurrence and severity. BACKGROUND: The clinical relevance of POH after DP and its relationship with the occurrence and severity of POPF have not been explored yet. METHODS: All patients undergoing DP for any indication between 2015 and 2021 at three European referral Centers for pancreatic surgery were retrospectively analyzed. Drain fluid amylase (DFA), C-reactive protein (C-RP), and serum amylase were examined from postoperative-day (POD) 1 to 3. Biochemical leak (BL), POPF, POH, and post-pancreatectomy hemorrhage (PPH) were defined and graded according to ISGPS definitions. RESULTS: In total 1192 patients were included. Overall rates of POH and POPF were 18% (n= 210) and 29% (n= 344), respectively. The presence of DFA ≥2000 U/L on POD 1 (OR=2.11, 95% CI 1.68-2.86), C-RP ≥200 mg/L on POD 3 (OR=2.19, 95% CI 1.68-2.86), and POH (OR=1.58, 95% CI 1.14-2.19) were all independent early predictors of POPF (all P< 0.01). The presence of POH almost doubled the rate of POPF (43% vs. 26%, P<0.001), and higher POPF severity presented also higher POH rates (no POPF= 12%; BL= 19%; B POPF= 24%; C POPF= 52%). Among patients developing POPF, patients with POH had higher rates of PPH (22% vs 9%, P= 0.001), sepsis (24% vs 13%; P=0.011), re-operation (21% vs 8%; P< 0.01), and mortality (3% vs 0.3%; P= 0.025). CONCLUSIONS: The occurrence of POH is an early predictor of POPF and its severity after DP. The diagnosis of POH might define patients at higher risk for a complicated course, targeting them for prevention / mitigation strategies against pancreas specific complications.

REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.

The Five Periampullary Cancers, not Just Different Siblings but Different Families: An International Multicenter Cohort Study.

BACKGROUND: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. METHODS: This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC. RESULTS: Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P = 0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size. CONCLUSIONS: Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.

Surgical optomics: hyperspectral imaging and deep learning towards precision intraoperative automatic tissue recognition-results from the EX-MACHYNA trial.

BACKGROUND: Hyperspectral imaging (HSI), combined with machine learning, can help to identify characteristic tissue signatures enabling automatic tissue recognition during surgery. This study aims to develop the first HSI-based automatic abdominal tissue recognition with human data in a prospective bi-center setting. METHODS: Data were collected from patients undergoing elective open abdominal surgery at two international tertiary referral hospitals from September 2020 to June 2021. HS images were captured at various time points throughout the surgical procedure. Resulting RGB images were annotated with 13 distinct organ labels. Convolutional Neural Networks (CNNs) were employed for the analysis, with both external and internal validation settings utilized. RESULTS: A total of 169 patients were included, 73 (43.2%) from Strasbourg and 96 (56.8%) from Verona. The internal validation within centers combined patients from both centers into a single cohort, randomly allocated to the training (127 patients, 75.1%, 585 images) and test sets (42 patients, 24.9%, 181 images). This validation setting showed the best performance. The highest true positive rate was achieved for the skin (100%) and the liver (97%). Misclassifications included tissues with a similar embryological origin (omentum and mesentery: 32%) or with overlaying boundaries (liver and hepatic ligament: 22%). The median DICE score for ten tissue classes exceeded 80%. CONCLUSION: To improve automatic surgical scene segmentation and to drive clinical translation, multicenter accurate HSI datasets are essential, but further work is needed to quantify the clinical value of HSI. HSI might be included in a new omics science, namely surgical optomics, which uses light to extract quantifiable tissue features during surgery.

International survey on opinions and use of robot-assisted and laparoscopic minimally invasive pancreatic surgery: 5-year follow up.

BACKGROUND: Evidence on the value of minimally invasive pancreatic surgery (MIPS) has been increasing but it is unclear how this has influenced the view of pancreatic surgeons on MIPS. METHODS: An anonymous survey was sent to members of eight international Hepato-Pancreato-Biliary Associations. Outcomes were compared with the 2016 international survey. RESULTS: Overall, 315 surgeons from 47 countries participated. The median volume of pancreatic resections per center was 70 (IQR 40-120). Most surgeons considered minimally invasive distal pancreatectomy (MIDP) superior to open (ODP) (94.6%) and open pancreatoduodenectomy (OPD) superior to minimally invasive (MIPD) (67.9%). Since 2016, there has been an increase in the number of surgeons performing both MIDP (79%-85.7%, p = 0.024) and MIPD (29%-45.7%, p < 0.001), and an increase in the use of the robot-assisted approach for both MIDP (16%-45.6%, p < 0.001) and MIPD (23%-47.9%, p < 0.001). The use of laparoscopy remained stable for MIDP (91% vs. 88.1%, p = 0.245) and decreased for MIPD (51%-36.8%, p = 0.024). CONCLUSION: This survey showed considerable changes of MIPS since 2016 with most surgeons considering MIDP superior to ODP and an increased use of robot-assisted MIPS. Surgeons prefer OPD and therefore the value of MIPD remains to be determined in randomized trials.

Early and Sustained Elevation in Serum Pancreatic Amylase Activity: A Novel Predictor of Morbidity After Pancreatic Surgery.

OBJECTIVE: To characterize early postoperative serum pancreatic amylase (spAMY) trends after pancreatic resections. SUMMARY BACKGROUND DATA: A postoperative spAMY elevation is a common finding but uncertainties remain about its meaning and prognostic implications. METHODS: Analysis of patients who consecutively underwent pancreatectomy from 2016 to 2019. spAMY activity was assessed from postoperative day (POD) 0 to 3. Different patterns of spAMY have been identified based on the spAMY standard range (10-52 U/l). RESULTS: Three patterns were identified: (#1) spAMY values always < the lower limit of normal/within the reference range /a single increase in spAMY > upper limit of normal at any POD; (#2) Sustained increase in spAMY activity on POD 0 + 1; (#3) Sustained increase in spAMY activity including POD 1 + 2. Shifting through spAMY patterns was associated with increase morbidity (21% in #1 to 68% in #3 at POD 7; log rank < 0.001). Almost all severe complications (at least Clavien-Dindo ≥3) occurred in patients with pattern #3 (15% vs 3% vs 5% in #1 and #2 at POD 7, P = 0.006), without difference considering >3-times or >the spAMY normal limit ( P = 0.85). POPF (9% in #1 vs 48% in #3, P < 0.001) progressively increased across patterns. Pre-operative diabetes (OR 0.19), neoadjuvant therapy (OR 0.22), pancreatic texture (OR 8.8), duct size (OR 0.78), and final histology (OR 2.2) were independent predictors of pattern #3. CONCLUSIONS: A sustained increase in spAMY activity including POD 1 + 2 (#3) represents an early postoperative predictor of overall and severe early morbidity. An early and dynamic evaluation of spAMY could crucially impact the subsequent clinical course with relevant prognostic implications.

Postoperative Serum Hyperamylasemia Adds Sequential Value to the Fistula Risk Score in Predicting Pancreatic Fistula after Pancreatoduodenectomy.

OBJECTIVE: To evaluate whether postoperative serum hyperamylasemia (POH), with drain fluid amylase (DFA) and C-reactive protein (CRP), improves the Fistula Risk Score (FRS) accuracy in assessing the risk of a postoperative pancreatic fistula (POPF). SUMMARY BACKGROUND DATA: The FRS predicts POPF occurrence using intraoperative predictors with good accuracy but intrinsic limits. METHODS: Outcomes of patients who underwent pancreaticoduodenectomies between 2016 and 2021 were evaluated across FRS-risk zones and POH occurrence. POH consists of serum amylase activity greater than the upper limit of normal (52 U/l), persisting within the first 48 hours postoperatively (postoperative day -POD- 1 and 2). RESULTS: Out of 905 pancreaticoduodenectomies, some FRS elements, namely soft pancreatic texture (odds ratio (OR) 11.6), pancreatic duct diameter (OR 0.80), high-risk pathologic diagnosis (OR 1.54), but not higher blood loss (OR 0.99), were associated with POH. POH was an independent predictor of POPF, which occurred in 46.8% of POH cases ( P <0.001). Once POH occurs, POPF incidence rises from 3.8% to 42.9%, 22.9% to 41.7%, and 48.9% to 59.2% in patients intraoperatively classified at low, moderate and high FRS risk, respectively. The predictive ability of multivariable models adding POD 1 drain fluid amylase, POD 1-2 POH and POD 3 C-reactive protein to the FRS showed progressively and significantly higher accuracy (AUC FRS=0.82, AUC FRS-DFA=0.85, AUC FRS-DFA-POH=0.87, AUC FRS-DFA-POH-CRP=0.90, DeLong always P <0.05). CONCLUSIONS: POPF risk assessment should follow a dynamic process. The stepwise retrieval of early, postoperative biological markers improves clinical risk stratification by increasing the granularity of POPF risk estimates and affords a possible therapeutic window before the actual morbidity of POPF occurs.

Either High or Low Risk: The Acinar Score at the Resection Margin Dichotomizes the Risk Spectrum of Pancreas-specific Complications After Pancreatoduodenectomy.

BACKGROUND: Pancreatic acinar content (Ac) has been associated with pancreas-specific complications after pancreatoduodenectomy. The aim of this study was to improve the prediction ability of intraoperative risk stratification by integrating the pancreatic acinar score. METHODS: A training and validation cohort underwent pancreatoduodenectomy with a subsequent histologic assessment of pancreatic section margins for Ac, fibrosis (Fc), and fat. Intraoperative risk stratification (pancreatic texture, duct diameter) and pancreas-specific complications (postoperative hyperamylasemia [POH], postpancreatectomy acute pancreatitis [PPAP], pancreatic fistula [POPF]) were classified according to ISGPS definitions. RESULTS: In the validation cohort (n= 373), the association of pancreas-specific complications with higher Ac and lower Fc was replicated (all P <0.001). In the entire cohort (n= 761), the ISGPS classification allocated 275 (36%) patients into intermediate-risk classes B (POH 32%/PPAP 3%/POPF 17%) and C (POH 36%/PPAP 9%/POPF 33%). Using the acinar score (Ac ≥60% and/or Fc ≤10%), intermediate-risk patients could be dichotomized into a low-risk (POH 5%/PPAP 1%/POPF 6%) and a high-risk (POH 51%/PPAP 9%/POPF 38%) group (all P <0.001). The acinar score AUC for POPF prediction was 0.70 in the ISGPS intermediate-risk classes. Overall, 239 (31%) patients were relocated into the high-risk group from lower ISGPS risk classes using the acinar score. CONCLUSIONS: The risk of pancreas-specific complications appears to be dichotomous-either high or low-according to the acinar score, a tool to better target the application of mitigation strategies in cases of intermediate macroscopic features.

Long-term Outcomes After Laparoscopic, Robotic, and Open Pancreatoduodenectomy for Distal Cholangiocarcinoma: An International Propensity Score-matched Cohort Study.

OBJECTIVE: This study aimed to compare surgical and oncological outcomes after minimally invasive pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) for distal cholangiocarcinoma (dCCA). BACKGROUND: A dCCA might be a good indication for MIPD, as it is often diagnosed as primary resectable disease. However, multicenter series on MIPD for dCCA are lacking. METHODS: This is an international multicenter propensity score-matched cohort study including patients after MIPD or OPD for dCCA in 8 centers from 5 countries (2010-2021). Primary outcomes included overall survival (OS) and disease-free interval (DFI). Secondary outcomes included perioperative and postoperative complications and predictors for OS or DFI. Subgroup analyses included robotic pancreatoduodenectomy (RPD) and laparoscopic pancreatoduodenectomy (LPD). RESULTS: Overall, 478 patients after pancreatoduodenectomy for dCCA were included of which 97 after MIPD (37 RPD, 60 LPD) and 381 after OPD. MIPD was associated with less blood loss (300 vs 420 mL, P =0.025), longer operation time (453 vs 340 min; P <0.001), and less surgical site infections (7.8% vs 19.3%; P =0.042) compared with OPD. The median OS (30 vs 25 mo) and DFI (29 vs 18) for MIPD did not differ significantly between MIPD and OPD. Tumor stage (Hazard ratio: 2.939, P <0.001) and administration of adjuvant chemotherapy (Hazard ratio: 0.640, P =0.033) were individual predictors for OS. RPD was associated with a higher lymph node yield (18.0 vs 13.5; P =0.008) and less major morbidity (Clavien-Dindo 3b-5; 8.1% vs 32.1%; P =0.005) compared with LPD. DISCUSSION: Both surgical and oncological outcomes of MIPD for dCCA are acceptable as compared with OPD. Surgical outcomes seem to favor RPD as compared with LPD but more data are needed. Randomized controlled trials should be performed to confirm these findings.

Pathological staging in postneoadjuvant pancreatectomy for pancreatic cancer: implications for adjuvant therapy.

BACKGROUND: It is unclear whether pathological staging is significant prognostically and can inform the delivery of adjuvant therapy after pancreatectomy preceded by neoadjuvant therapy. METHODS: This multicentre retrospective study included patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma after neoadjuvant treatment at two Italian centres between 2013 and 2017. T and N status were assigned in accordance with the seventh and eighth editions of the AJCC staging system, as well as according to a modified system with T status definition combining extrapancreatic invasion and tumour size. Patients were then stratified by receipt of adjuvant therapy. Survival analysis and multivariable interaction analysis of adjuvant therapy with pathological parameters were performed. The results were validated in an external cohort from the USA. RESULTS: The developmental set consisted of 389 patients, with a median survival of 34.6 months. The modified staging system displayed the best prognostic stratification and the highest discrimination (C-index 0.763; 1-, 2- and 3-year time-dependent area under the curve (AUC) 0.746, 0.722, and 0.705; Uno's AUC 0.710). Overall, 67.0 per cent of patients received adjuvant therapy. There was no survival difference by receipt of adjuvant therapy (35.0 versus 36.0 months; P = 0.772). After multivariable adjustment, interaction analysis suggested a benefit of adjuvant therapy for patients with nodal metastases or with tumours larger than 2 cm with extrapancreatic extension, regardless of nodal status. These results were confirmed in the external cohort of 216 patients. CONCLUSION: Modified staging with a T status definition combining extrapancreatic invasion and tumour size is associated with better prognostic segregation after postneoadjuvant pancreatectomy. This system allows identification of patients who might benefit from adjuvant therapy.

No role for protease inhibitors as a mitigation strategy for postpancreatectomy acute pancreatitis (PPAP): Propensity score matching analysis.

BACKGROUND: While the use of protease inhibitor gabexate mesylate (GM) is still controversial in acute pancreatitis, it has never been tested for postpancreatectomy acute pancreatitis (PPAP). This study aims to assess the impact of GM on postoperative serum hyperamylasaemia (POH) or PPAP after pancreatoduodenectomy (PD). METHODS: Consecutive patients developing POH after PD between 2016 and 2021 were included. According to GM administration, patients were divided into GM-treated and control (CTR) groups. GM was administered from postoperative day 1-3 in POH patients who underwent surgery before 2017. A 2:1 propensity matching was used to minimize the risk of bias. RESULTS: Overall, 264 patients with POH were stratified in the GM (59 patients) and CTR (104 patients) cohorts, which showed balanced baseline characteristics after matching. No difference in postoperative complications was observed between the groups (all p > 0.05), except for PPAP occurrence, which was significantly higher in the GM group (37% vs. 22%, p = 0.037). A total of 45 patients (28%) evolved to PPAP. Comparing PPAP patients in the GM and CTR groups, no significant differences in POPF, relaparotomy, and mortality (all p > 0.09) were found. No difference in intravenous crystalloid administration was found in patients with PPAP, whether or not they developed major complications or pancreatic fistula (p > 0.05) CONCLUSION: Protease inhibitor seems ineffective in preventing a PPAP after PD once a POH has occurred. Further studies are needed to achieve benchmarks for treating PPAP and identify mitigation strategies to prevent the evolution of POH into additional morbidity.

Quantification of bowel ischaemia using real-time multispectral Single Snapshot Imaging of Optical Properties (SSOP).

BACKGROUND: Single snapshot imaging of optical properties (SSOP) is a relatively new non-invasive, real-time, contrast-free optical imaging technology, which allows for the real-time quantitative assessment of physiological properties, including tissue oxygenation (StO2). This study evaluates the accuracy of multispectral SSOP in quantifying bowel ischaemia in a preclinical experimental model. METHODS: In six pigs, an ischaemic bowel segment was created by dividing the arcade branches. Five regions of interest (ROIs) were identified on the bowel loop, as follows: ROI 1: central ischaemic; ROI 2: left marginal; ROI 3: left vascularised; ROI 4: right marginal; and ROI 5: right vascularised. The Trident imaging system, specifically developed for real-time tissue oxygenation imaging using SSOP, was used to image before (T0) and after ischaemia induction. Capillary and systemic lactates were measured at each time point (T0, T15, T30, T45, T60), as well as StO2 values acquired by means of SSOP (SSOP-StO2). RESULTS: The mean value of SSOP-StO2 in ROI 1 was 30.08 ± 6.963 and was significantly lower when compared to marginal ROIs (ROI 2 + ROI 4: 45.67 ± 10.02 p = < 0.0001), and to vascularised ROIs (ROI 3 + ROI 5: 48.08 ± 7.083 p = < 0.0001). SSOP-StO2 was significantly correlated with normalised lactates r = - 0.5892 p < 0.0001 and with histology r =- 0.6251 p = 0.0002. CONCLUSION: Multispectral SSOP allows for a contrast-free accurate assessment of small bowel perfusion identifying physiological tissue oxygenation as confirmed with perfusion biomarkers.

Fluorescence-based sentinel lymph node mapping and lymphography evaluation: results from the IHU-IRCAD-EAES EURO-FIGS registry.

BACKGROUND: The identification of metastatic lymph nodes is one of the most important prognostic factors in gastrointestinal (GI) cancers. Near-infrared fluorescence (NIRF) imaging has been successfully used in GI tumors to detect the lymphatic pathway and the sentinel lymph node (SLN), facilitating fluorescence image-guided surgery (FIGS) with the purpose to achieve a correct nodal staging. The aim of this study was to analyze the current results of NIRF SLN navigation and lymphography through data collected in the EURO-FIGS registry. METHODS: Prospectively collected data regarding patients and ICG-guided lymphadenectomies were analyzed. Additional analyses were performed to identify predictors of metastatic SLN and determinants of fluorescence positivity and nodal metastases outside the boundaries of standard lymphadenectomies. RESULTS: Overall, 188 patients were included by 18 surgeons from 10 different centers. Colorectal cancer was the most reported pathology (77.7%), followed by gastric (19.1%) and esophageal tumors (3.2%). ICG was injected with higher doses (p < 0.001) via extraparietal side (63.3%), and with higher volumes (p < 0.001) via endoluminal side (36.7%). Overall, NIRF SLN navigation was positive in 75.5% of all cases and 95.5% of positive SLNs were retrieved, with a metastatic rate of 14.7%. NIRF identification of lymph nodes outside standard lymphatic stations occurred in 52.1% of all cases, 43.8% of which were positive for metastatic involvement. Positive NIRF SLN identification was an independent predictor of metastasis outside standard lymphatic stations (OR = 4.392, p = 0.029), while BMI independently predicted metastasis in retrieved SLNs (OR = 1.187, p = 0.013). Lower doses of ICG were protective against NIRF identification outside standard of care lymphadenectomy (OR = 0.596, p = 0.006), while higher volumes of ICG were predictive of metastatic involvement outside standard of care lymphadenectomy (OR = 1.597, p = 0.001). CONCLUSIONS: SLN mapping helps identifying potentially metastatic lymph nodes outside the boundaries of standard lymphadenectomies. The EURO-FIGS registry is a valuable tool to share and analyze European surgeons' practices.

Pancreatic Anastomosis in Robotic-Assisted Pancreaticoduodenectomy: Different Surgical Techniques.

Robot-assisted pancreatoduodenectomy (R-PD) may provide challenges but potential benefits for pancreatic-enteric anastomosis fashioning. Despite numerous trials comparing different pancreatic-enteric anastomosis techniques, an ideal method is still missing. This study aims to describe different management strategies and surgical techniques of standardized pancreatic-enteric anastomoses during an R-PD. This study reported the robotic technical steps of the modified end-to-side Blumgart pancreaticojejunostomy, the Cattel-Warren duct-to-mucosa pancreatojejunostomy, with internal or external pancreatic duct stent, and the modified end-to-side, double-layer pancreogastrostomy. A dual-console da Vinci Xi Surgical System® (Intuitive Surgical Xi, Sunnyvale, CA) was used to perform all the R-PD. Different robotic pancreatic-enteric anastomosis techniques can be used during the reconstruction phase, possibly reproducing the open technique. The type of anastomosis and applied mitigation strategies should balance surgical strategy adaptability and operative technique standardization. R-PD should be performed in high-volume centers by surgeons with extensive experience in pancreatic and advanced MI surgery, enabling different but standardized anastomotic techniques based on patients' risk factors and intraoperative findings. Future studies on robotic pancreatic anastomosis should focus on personalized approaches after adequate risk stratification.

BF2-Azadipyrromethene Fluorophores for Intraoperative Vital Structure Identification.

A series of mono- and bis-polyethylene glycol (PEG)-substituted BF2-azadipyrromethene fluorophores have been synthesized with emissions in the near-infrared region (700-800 nm) for the purpose of fluorescence guided intraoperative imaging; chiefly ureter imaging. The Bis-PEGylation of fluorophores resulted in higher aqueous fluorescence quantum yields, with PEG chain lengths of 2.9 to 4.6 kDa being optimal. Fluorescence ureter identification was possible in a rodent model with the preference for renal excretion notable through comparative fluorescence intensities from the ureters, kidneys and liver. Ureteral identification was also successfully performed in a larger animal porcine model under abdominal surgical conditions. Three tested doses of 0.5, 0.25 and 0.1 mg/kg all successfully identified fluorescent ureters within 20 min of administration which was sustained up to 120 min. 3-D emission heat map imaging allowed the spatial and temporal changes in intensity due to the distinctive peristaltic waves of urine being transferred from the kidneys to the bladder to be identified. As the emission of these fluorophores could be spectrally distinguished from the clinically-used perfusion dye indocyanine green, it is envisaged that their combined use could be a step towards intraoperative colour coding of different tissues.

Postpancreatectomy Acute Pancreatitis (PPAP): Definition and Grading From the International Study Group for Pancreatic Surgery (ISGPS).

OBJECTIVE: The ISGPS aimed to develop a universally accepted definition for PPAP for standardized reporting and outcome comparison. BACKGROUND: PPAP is an increasingly recognized complication after partial pancreatic resections, but its incidence and clinical impact, and even its existence are variable because an internationally accepted consensus definition and grading system are lacking. METHODS: The ISGPS developed a consensus definition and grading of PPAP with its members after an evidence review and after a series of discussions and multiple revisions from April 2020 to May 2021. RESULTS: We defined PPAP as an acute inflammatory condition of the pancreatic remnant beginning within the first 3 postoperative days after a partial pancreatic resection. The diagnosis requires (1) a sustained postoperative serum hyperamylasemia (POH) greater than the institutional upper limit of normal for at least the first 48 hours postoperatively, (2) associated with clinically relevant features, and (3) radiologic alterations consistent with PPAP. Three different PPAP grades were defined based on the clinical impact: (1) grade postoperative hyperamylasemia, biochemical changes only; (2) grade B, mild or moderate complications; and (3) grade C, severe life-threatening complications. DISCUSSIONS: The present definition and grading scale of PPAP, based on biochemical, radiologic, and clinical criteria, are instrumental for a better understanding of PPAP and the spectrum of postoperative complications related to this emerging entity. The current terminology will serve as a reference point for standard assessment and lend itself to developing specific treatments and prevention strategies.

Modified Frailty Index to Assess Risk in Elderly Patients Undergoing Distal Pancreatectomy: A Retrospective Single-Center Study.

BACKGROUND: To compare the postoperative course of elderly patients (≥70 years) submitted to minimally invasive (MIDP) versus open distal pancreatectomy (ODP) and to evaluate if the modified Frailty Index (mFI) predicts the surgical course of elderly patients submitted to DP. METHODS: Data of patients aged ≥70 who underwent DP at a single institution between March 2011 and December 2019 were retrospectively retrieved. A 2:1 propensity score matching (PSM) was used to correct for differences in baseline characteristics. Then, postoperative complications were compared between the two groups (MIDP vs. ODP). Additionally, the entire cohort of DP elderly patients was stratified according to the mFI into three groups: non-frail (mFI = 0), mildly frail (mFI = 1/2), or severely frail (mFI = 3) and then compared. RESULTS: A total of 204 patients were analyzed. After PSM, 40 MIDP and 80 ODP patients were identified. The complications considered stratified homogenously between the two groups, with no statistically significant differences. The severity of the postoperative course increased as mFI did among the three groups regarding any complication (p = 0.022), abdominal collection (p = 0.014), pulmonary complication (p = 0.001), postoperative confusion (p = 0.047), Clavien-Dindo severity ≥3 events (p = 0.036), and length of stay (p = 0.018). CONCLUSIONS: Elderly patients can be safely submitted to MIDP. The mFI identifies frail elderly patients more prone to develop surgical and non-surgical complications after DP.

Postoperative Acute Pancreatitis Following Pancreaticoduodenectomy: A Determinant of Fistula Potentially Driven by the Intraoperative Fluid Management.

OBJECTIVE: The aim of the study is to characterize postoperative acute pancreatitis (POAP). SUMMARY BACKGROUND DATA: A standardized definition of POAP after pancreaticoduodenectomy (PD) has been recently proposed, but specific studies are lacking. METHODS: The patients were extracted from the prospective database of The Pancreas Institute of Verona. POAP was defined as an elevation of the serum pancreatic amylase levels above the upper limit of normal (52 U/L) on postoperative day (POD) 0 or 1. The endpoints included defining the incidence and predictors of POAP and investigating the association of POAP with postoperative pancreatic fistula (POPF). RESULTS: The study population consisted of 292 patients who underwent PD. The POAP and POPF rates were 55.8% and 22.3%, respectively. POAP was an independent predictor of POPF (OR 3.8), with a 92% sensitivity and 53.7% specificity (AUC 0.79). Preoperative exocrine insufficiency (OR 0.39), neoadjuvant therapy (OR 0.29) additional resection of the pancreatic stump margin (OR 0.25), soft pancreatic texture (OR 4.38), and Main Pancreatic Duct (MPD) diameter ≤3 mm (OR 2.86) were independent predictors of POAP. In high-risk patients, an intraoperative fluid administration of ≤3 ml/kg/h was associated with an increased incidence of POAP (24.6 vs. 0%, P = 0.04) and POPF (27.6 vs. 11.4%, P = 0.05). CONCLUSION: This study represents the first clinical application of the only available definition of POAP as a specific complication of pancreatic surgery. POAP is associated with an increased occurrence of POPF and overall morbidity and could potentially be avoided through a specific intraoperative fluid regimen in high-risk pancreas.

Colonic stenting as a bridge to surgery versus emergency surgery for malignant colonic obstruction: results of a multicentre randomised controlled trial (ESCO trial).

BACKGROUND: The aim of colonic stenting with self-expandable metallic stents in neoplastic colon obstruction is to avoid emergency surgery and thus potentially reduce morbidity, mortality, and need for a stoma. Concern has been raised, however, about the effect of colonic stenting on short-term complications and long-term survival. We compared morbidity rates after colonic stenting as a bridge to surgery (SBTS) versus emergency surgery (ES) in the management of left-sided malignant large-bowel obstruction. METHODS: This multicentre randomised controlled trial was designed with the endorsement of the European Association for Endoscopic Surgery. The study population was consecutive patients with acute, symptomatic malignant left-sided large-bowel obstruction localised between the splenic flexure and 15 cm from the anal margin. The primary outcome was overall morbidity within 60 days after surgery. RESULTS: Between March 2008 and November 2015, 144 patients were randomly assigned to undergo either SBTS or ES; 29/144 (13.9%) were excluded post-randomisation mainly because of wrong diagnosis at computed tomography examination. The remaining 115 patients (SBTS n = 56, ES n = 59) were deemed eligible for analysis. The complications rate within 60 days was 51.8% in the SBTS group and 57.6% in the ES group (p = 0.529). Although long-term follow-up is still ongoing, no statistically significant difference in 3-year overall survival (p = 0.998) and progression-free survival rates between the groups has been observed (p = 0.893). Eleven patients in the SBTS group and 23 in the ES group received a stoma (p = 0.031), with a reversal rate of 30% so far. CONCLUSIONS: Our findings indicate that the two treatment strategies are equivalent. No difference in oncologic outcome was found at a median follow-up of 36 months. The significantly lower stoma rate noted in the SBTS group argues in favour of the SBTS procedure when performed in expert hands.