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.

Implementing protocol-based relaparoscopy for severe complications in laparoscopic colorectal surgery.

BACKGROUND: Although laparoscopy has demonstrated growing applications for either primary colorectal resections or reoperations, no standardized criteria for implementing laparoscopy in revisional surgery have been reported. This study analyzes a single-center series of major complications after laparoscopic colorectal surgery, undergoing laparoscopic (LR), or open reoperations in compliance with a hemodynamics-based institutional management. METHODS: This study retrospectively analyzes a series of consecutive patients who primarily underwent either laparoscopic left colectomy or low anterior resection in a tertiary referral center between 2016 and 2021. Major complications requiring reoperation (MCR) were managed through an interdisciplinary protocol and submitted to reoperation according to patient hemodynamics and intra-abdominal contamination. A cohort analysis primarily assessed treatment failure rates (i.e., 90-day mortality and need for further surgery), while postoperative morbidity was secondarily examined. RESULTS: Out of 1137 laparoscopic colorectal resections, 497 patients met eligibility criteria, while 45 (9.1%) developed MCRs were managed according to the standardized interdisciplinary protocol. Revisional surgery was performed through either LR (66.7%) or (33.3%). Treatment failure was 13.3% overall, including additional surgery (11.1%) and 90-day mortality (6.6%) after reoperation. In both overall and anastomotic leak-specific MCRs, relaparoscopy resulted in minimized length of hospital stay, postoperative morbidity, and intensity of care. CONCLUSIONS: Relaparoscopy for MCR preserves clinical benefits related to minimally invasive colorectal surgery. Further studies should investigate applicative determinants and impediments related to the center volume.

Spontaneous idiopathic liver hemorrhage: a systematic review of a rare entity.

BACKGROUND: Spontaneous idiopathic liver hemorrhage (SILH) is a rare life-threatening condition occurring without a clear and specific etiology. A systematic review was performed to provide guidelines for the perioperative management of patients affected by SILH. A case report was also included. METHODS: A systematic search of the last 24-year literature was conducted and the manuscript was structured following point-by-point the PRISMA guidelines. RESULTS: After an initial selection of 6995 titles, 15 articles were considered for the final qualitative analysis (n = 22 patients, including the present report). Conservative treatment was chosen in 12 cases (54.5%) with stable clinical conditions, while 9 patients (40.9%) required a primary operative approach for emergency presentation at diagnosis. Direct liver resection was the preferred surgical treatment (n = 6), mostly major hepatectomies (n = 4). Hepatic arterial embolization was performed as the primary operative approach in three patients, followed by emergency laparotomy during the same hospitalization because of rebleeding in one case. Contrast-enhanced CT scan was the gold standard for diagnosis (n = 19). CONCLUSIONS: Conservative treatment of SILH is mainly based on stable clinical conditions and may be considered even in case of a limited arterial blush found on imaging. The absence of underlying hepatic or systemic disorders seems to correlate with favorable outcomes and no mortality.

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.

In Vitro Antibody Quantification with Hyperspectral Imaging in a Large Field of View for Clinical Applications.

Hyperspectral imaging (HSI) is a non-invasive, contrast-free optical-based tool that has recently been applied in medical and basic research fields. The opportunity to use HSI to identify exogenous tumor markers in a large field of view (LFOV) could increase precision in oncological diagnosis and surgical treatment. In this study, the anti-high mobility group B1 (HMGB1) labeled with Alexa fluorophore (647 nm) was used as the target molecule. This is the proof-of-concept of HSI's ability to quantify antibodies via an in vitro setting. A first test was performed to understand whether the relative absorbance provided by the HSI camera was dependent on volume at a 1:1 concentration. A serial dilution of 1:1, 10, 100, 1000, and 10,000 with phosphatase-buffered saline (PBS) was then used to test the sensitivity of the camera at the minimum and maximum volumes. For the analysis, images at 640 nm were extracted from the hypercubes according to peak signals matching the specificities of the antibody manufacturer. The results showed a positive correlation between relative absorbance and volume (r = 0.9709, p = 0.0013). The correlation between concentration and relative absorbance at min (1 µL) and max (20 µL) volume showed r = 0.9925, p < 0.0001, and r = 0.9992, p < 0.0001, respectively. These results demonstrate the HSI potential in quantifying HMGB1, hence deserving further studies in ex vivo and in vivo settings.

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.

Surgical Models of Liver Regeneration in Pigs: A Practical Review of the Literature for Researchers.

The remarkable capacity of regeneration of the liver is well known, although the involved mechanisms are far from being understood. Furthermore, limits concerning the residual functional mass of the liver remain critical in both fields of hepatic resection and transplantation. The aim of the present study was to review the surgical experiments regarding liver regeneration in pigs to promote experimental methodological standardization. The Pubmed, Medline, Scopus, and Cochrane Library databases were searched. Studies evaluating liver regeneration through surgical experiments performed on pigs were included. A total of 139 titles were screened, and 41 articles were included in the study, with 689 pigs in total. A total of 29 studies (71% of all) had a survival design, with an average study duration of 13 days. Overall, 36 studies (88%) considered partial hepatectomy, of which four were an associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). Remnant liver volume ranged from 10% to 60%. Only 2 studies considered a hepatotoxic pre-treatment, while 25 studies evaluated additional liver procedures, such as stem cell application, ischemia/reperfusion injury, portal vein modulation, liver scaffold application, bio-artificial, and pharmacological liver treatment. Only nine authors analysed how cytokines and growth factors changed in response to liver resection. The most used imaging system to evaluate liver volume was CT-scan volumetry, even if performed only by nine authors. The pig represents one of the best animal models for the study of liver regeneration. However, it remains a mostly unexplored field due to the lack of experiments reproducing the chronic pathological aspects of the liver and the heterogeneity of existing studies.

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.

Hyperspectral Imaging in Major Hepatectomies: Preliminary Results from the Ex-Machyna Trial.

Ischemia-reperfusion injury during major hepatic resections is associated with high rates of post-operative complications and liver failure. Real-time intra-operative detection of liver dysfunction could provide great insight into clinical outcomes. In the present study, we demonstrate the intra-operative application of a novel optical technology, hyperspectral imaging (HSI), to predict short-term post-operative outcomes after major hepatectomy. We considered fifteen consecutive patients undergoing major hepatic resection for malignant liver lesions from January 2020 to June 2021. HSI measures included tissue water index (TWI), organ hemoglobin index (OHI), tissue oxygenation (StO2%), and near infrared (NIR). Pre-operative, intra-operative, and post-operative serum and clinical outcomes were collected. NIR values were higher in unhealthy liver tissue (p = 0.003). StO2% negatively correlated with post-operative serum ALT values (r = -0.602), while ΔStO2% positively correlated with ALP (r = 0.594). TWI significantly correlated with post-operative reintervention and OHI with post-operative sepsis and liver failure. In conclusion, the HSI imaging system is accurate and precise in translating from pre-clinical to human studies in this first clinical trial. HSI indices are related to serum and outcome metrics. Further experimental and clinical studies are necessary to determine clinical value of this technology.

Effect of preoperative biliary stent on postoperative complications after pancreaticoduodenectomy for cancer: Neoadjuvant versus upfront treatment.

BACKGROUND: Limited data are available regarding the effect of preoperative biliary stent, during long-course neoadjuvant chemotherapy, on postoperative complications. The aim of the study is to analyze whether the association of neoadjuvant chemotherapy and biliary stent increases overall and infectious complications after pancreaticoduodenectomy. METHODS: Data for 538 consecutive pancreatic ductal adenocarcinoma patients who underwent pancreaticoduodenectomy between 2015 and 2020 were retrospectively analyzed. Four groups of patients were identified: neoadjuvant chemotherapy + biliary stent (171 patients), neoadjuvant chemotherapy-no biliary stent (65 patients), upfront surgery + biliary stent (184 patients), and upfront surgery-no biliary stent (118 patients). Median neoadjuvant chemotherapy duration was 6 months. The main outcome of the study was the occurrence of postoperative infections. RESULTS: No differences among the 4 groups were observed for pancreaticoduodenectomy-specific complications (ie, POPF, DGE, PPH). Infectious complications, in particular surgical site infections, were more frequent in neoadjuvant chemotherapy + biliary stent group (P = 0.001). At multivariate analysis, biliary stent was significantly associated with postoperative infectious complications in the overall cohort (odds ratio 1.996, confidence interval 95% 1.29-3.09, P = .002) and in neoadjuvant chemotherapy patients (odds ratio 5.974, 95% confidence interval 2.52-14.13, P < .001). Biliary stent significantly increased the comprehensive complication index by 9.5% (95% confidence interval 0.04-0.64, P = 0.024) in the overall cohort and 18.9% (95% confidence interval 0.22-1.23, P = .005) in the neoadjuvant chemotherapy group. The presence of multidrug-resistant microorganisms in intraoperative bile culture was not influenced by long-course neoadjuvant chemotherapy. CONCLUSION: In neoadjuvant chemotherapy patients, biliary stent increased the occurrence of postoperative infectious complications and surgical site infections, while the incidence of multidrug-resistant bacteria in intraoperative bile culture was similar between groups.

Computer-Assisted Differentiation between Colon-Mesocolon and Retroperitoneum Using Hyperspectral Imaging (HSI) Technology.

Complete mesocolic excision (CME), which involves the adequate resection of the tumor-bearing colonic segment with "en bloc" removal of its mesocolon along embryological fascial planes is associated with superior oncological outcomes. However, CME presents a higher complication rate compared to non-CME resections due to a higher risk of vascular injury. Hyperspectral imaging (HSI) is a contrast-free optical imaging technology, which facilitates the quantitative imaging of physiological tissue parameters and the visualization of anatomical structures. This study evaluates the accuracy of HSI combined with deep learning (DL) to differentiate the colon and its mesenteric tissue from retroperitoneal tissue. In an animal study including 20 pig models, intraoperative hyperspectral images of the sigmoid colon, sigmoid mesentery, and retroperitoneum were recorded. A convolutional neural network (CNN) was trained to distinguish the two tissue classes using HSI data, validated with a leave-one-out cross-validation process. The overall recognition sensitivity of the tissues to be preserved (retroperitoneum) and the tissues to be resected (colon and mesentery) was 79.0 ± 21.0% and 86.0 ± 16.0%, respectively. Automatic classification based on HSI and CNNs is a promising tool to automatically, non-invasively, and objectively differentiate the colon and its mesentery from retroperitoneal tissue.

In Vivo Imaging Evaluation of Fluorescence Intensity at Tail Emission of Near-Infrared-I (NIR-I) Fluorophores in a Porcine Model.

Over the last decade fluorescence-guided surgery has been primarily focused on the NIR-I window. However, the NIR-I window has constraints, such as limited penetration and scattering. Consequently, exploring the performance of NIR-I dyes at longer wavelengths (i.e., the NIR-II window) is crucial to expanding its application. Two fluorophores were used in three pigs to identify the mean fluorescence intensity (MFI) using two commercially available NIR-I and NIR-II cameras. The near-infrared coating of equipment (NICE) was used to identify endoluminal surgical catheters and indocyanine green (ICG) for common bile duct (CBD) characterization. The NIR-II window evaluation showed an MFI of 0.4 arbitrary units (a.u.) ± 0.106 a.u. in small bowel NICE-coated catheters and an MFI of 0.09 a.u. ± 0.039 a.u. in gastric ones. In CBD characterization, the ICG MFI was 0.12 a.u. ± 0.027 a.u., 0.18 a.u. ± 0.100 a.u., and 0.22 a.u. ± 0.041 a.u. at 5, 35, and 65 min, respectively. This in vivo imaging evaluation of NIR-I dyes confirms its application in the NIR-II domain. To the best of our knowledge, this is the first study assessing the MIF of NICE in the NIR-II window using a commercially available system. Further comparative trials are necessary to determine the superiority of NIR-II imaging systems.

Treatment strategies for neuroendocrine liver metastases: a systematic review.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors are often diagnosed when metastatic. The liver is the main site of metastases. Unfortunately, optimal management of neuroendocrine liver metastases remains a topic of debate. The aim of this study was to make a systematic review of the current literature about the results of the different treatments of neuroendocrine liver metastases. METHODS: A systematic review was conducted for English language publications from 1995 to 2021. Outcomes were analyzed according to survival, disease-free survival, and in the case of systemic therapies, progression-free survival. RESULTS: 5509 patients were analyzed in the review. 67% of patients underwent surgery achieving 5 years overall survival despite only 30% percent without a recurrence. 60% of patients that had received a transplant reached 5 years survival with a low disease-free survival rate (20%). Five-year survival rate was 36.2% for patients undergoing loco-regional therapies. CONCLUSION: Surgical resection is the best treatment when metastases are resectable, with the highest rate of survival, although liver transplantation shows good results for patients not eligible for surgery. Loco-regional therapies may be useful when surgical resection is contraindicated, or selectively used as a bridge to surgery or transplantation. Systemic therapies are indicated in patients for whom curative treatment cannot be obtained.

Applicative Limitations of Indocyanine Green Fluorescence Assistance to Laparoscopic Lymph Node Dissection in Total Gastrectomy for Cancer.

BACKGROUND: Indocyanine green (ICG) fluorescence has been recently introduced as a novel imaging technique improving the accuracy of lymph node (LN) dissection in gastric cancer (GC) surgery, although procedure standardization and achievements have not been clearly defined. This study analyzed the feasibility and effectiveness of ICG-guidance for laparoscopic D2-lymphadenectomy during total gastrectomy for cancer. METHODS: This study retrospectively analyzed a single-center series of patients who underwent laparoscopic total gastrectomy for cancer between April 2015 and August 2021. All patients underwent surgery with standard D2 LN dissection. Intraoperative ICG-fluorescence was institutionally implemented in April 2018 and was performed routinely afterward. Primary outcomes were LN harvest and ratio. Secondary endpoints included operative time and subgroup analysis to assess variables potentially affecting LN retrieval. RESULTS: The study population included 102 patients, and ICG-fluorescence was applied in 38 (37.3%). ICG and no-ICG groups presented similar median age, gender proportions, ASA score and comorbidities (age-adjusted Charlson Comorbidity Index), body mass index, and advanced pathological stage. The median of LNs retrieved was significantly higher after the intraoperative ICG-guidance (44 vs. 32; p = 0.004), although this association was not significant after neoadjuvant therapy or among patients with positive LNs. Lymph node ratio and operative time were not significantly impacted by ICG fluorescence. Multivariate analysis identified the ICG-assistance as the only independent determinant for LN harvest (p = 0.029). CONCLUSIONS: ICG-guidance contributes to a significantly wider LN retrieval after laparoscopic D2-lymphadenectomy during total gastrectomy for cancer. However, neoadjuvant therapy and positive LN stage appeared to limit the procedural effectiveness to ICG-assisted LN identification.

Evaluation of factors predicting loss of benefit provided by laparoscopic distal pancreatectomy compared to open approach.

Several studies showed safety and feasibility of laparoscopic distal pancreatectomy (LDP) as compared to open distal pancreatectomy (ODP). Patients who underwent LDP or ODP (2015-2019) were included. A 1:1 propensity score matching (PSM) was used to reduce the effect of treatment selection bias. Aim of this study was to identify those factors influencing the loss of benefit (defined as a significantly better outcome compared to ODP) after LDP. Overall, 387 patients underwent DP (n = 250 LDP, n = 137 ODP). After PSM, 274 patients (n = 137 LDP, n = 137 ODP) were selected. LDP was associated with reduced intraoperative blood loss (median: 200 mL vs. 250 mL, p < 0.001), decreased wound infection rate (1% vs. 9%, p = 0.044) and shorter time to functional recovery (TFR) (median: 4 days vs. 5 days, p = 0.002). Consequently, TFR > 5 days and blood loss > 250 mL were defined as loss of benefit after LDP. In the LDP group, age > 70 years [Odds Ratio (OR) 2.744, p = 0.022] and duration of surgery > 208 min (OR 2.957, p = 0.019) were predictors of TFR > 5 days and intraoperative blood loss > 250 mL, respectively. No differences in terms of TFR were found between ODP and LDP groups in patients > 70 years (p = 0.102). Intraoperative blood loss was significantly higher in the ODP group, also when the analysis was limited to surgical procedures with operative time > 208 min (p = 0.003). In conclusion, LDP seems comparable to ODP in terms of TFR in patients aged > 70 years. This finding could be helpful in the choice of the best surgical approach in elderly patients undergoing potentially challenging DPs.

Single Snapshot Imaging of Optical Properties (SSOP) for Perfusion Assessment during Gastric Conduit Creation for Esophagectomy: An Experimental Study on Pigs.

Anastomotic leakage (AL) is a serious complication occurring after esophagectomy. The current knowledge suggests that inadequate intraoperative perfusion in the anastomotic site contributes to an increase in the AL rate. Presently, clinical estimation undertaken by surgeons is not accurate and new technology is necessary to improve the intraoperative assessment of tissue oxygenation. In the present study, we demonstrate the application of a novel optical technology, namely Single Snapshot imaging of Optical Properties (SSOP), used to quantify StO2% in an open surgery experimental gastric conduit (GC) model. After the creation of a gastric conduit, local StO2% was measured with a preclinical SSOP system for 60 min in the antrum (ROI-A), corpus (ROI-C), and fundus (ROI-F). The removed region (ROI-R) acted as ischemic control. ROI-R had statistically significant lower StO2% when compared to all other ROIs at T15, T30, T45, and T60 (p < 0.0001). Local capillary lactates (LCLs) and StO2% correlation was statistically significant (R = -0.8439, 95% CI -0.9367 to -0.6407, p < 0.0001). Finally, SSOP could discriminate resected from perfused regions and ROI-A from ROI-F (the future anastomotic site). In conclusion, SSOP could well be a suitable technology to assess intraoperative perfusion of GC, providing consistent StO2% quantification and ROIs discrimination.

Preoperative risk stratification of postoperative pancreatic fistula: A risk-tree predictive model for pancreatoduodenectomy.

BACKGROUND: Existing postoperative pancreatic fistula risk scores rely on intraoperative parameters, which limits their value in the preoperative setting. A preoperative predictive model to stratify the risk of developing postoperative pancreatic fistula before pancreatoduodenectomy was built and externally validated. METHODS: A regression risk-tree model for preoperative postoperative pancreatic fistula risk stratification was developed in the Verona University Hospital training cohort using preoperative variables and then tested prospectively in a validation cohort of patients who underwent pancreatoduodenectomy at San Raffaele Hospital of Milan. RESULTS: In the study period 566 (training cohort) and 456 (validation cohort) patients underwent pancreatoduodenectomy. In the multivariable analysis body mass index, radiographic main pancreatic duct diameter and American Society of Anesthesiologists score ≥3 were independently associated with postoperative pancreatic fistula. The regression tree analysis allocated patients into 3 preoperative risk groups with an 8%, 21%, and 32% risk of postoperative pancreatic fistula (all P < .01) based on main pancreatic duct diameter (≥ or <5 mm) and body mass index (≥ or <25). The 3 groups were labeled low, intermediate, and high risk and consisted of 206 (37%), 188 (33%), and 172 (30%) patients, respectively. The risk-tree was applied to validation cohort, successfully reproducing 3 risk groups with significantly different postoperative pancreatic fistula risks (all P < .01). CONCLUSION: In candidates for pancreatoduodenectomy, the risk of postoperative pancreatic fistula can be quickly and accurately determined in the preoperative setting based on the body mass index and main pancreatic duct diameter at radiology. Preoperative risk stratification could potentially guide clinical decision-making, improve patient counseling and allow the establishment of personalized preoperative protocols.