Peak Risk of Recurrence Occurs during the First Two Years after a Pancreatectomy in Patients Receiving Neoadjuvant FOLFIRINOX.

No codified/systematic surveillance program exists for borderline/locally advanced pancreatic ductal carcinoma treated with neoadjuvant FOLFIRINOX and a secondary resection. This study aimed to determine the trend of recurrence in patients who were managed using such a treatment strategy. From 2010, 101 patients received FOLFIRINOX and underwent a pancreatectomy, in a minimum follow-up of 5 years. Seventy-one patients (70%, R group) were diagnosed with recurrence after a median follow-up of 11 months postsurgery. In the multivariable analysis, patients in the R-group had a higher rate of weight loss (p = 0.018), higher carbohydrate antigen (CA 19-9) serum levels at diagnosis (p = 0.012), T3/T4 stage (p = 0.017), and positive lymph nodes (p < 0.01) compared to patients who did not experience recurrence. The risk of recurrence in patients with T1/T2 N0 R0 was the lowest (19%), and all recurrences occurred during the first two postoperative years. The peak risk of recurrence for the entire population was observed during the first two postoperative years. The probability of survival decreased until the second year and rebounded to 100% permanently, after the ninth postoperative year. Close monitoring is needed at reduced intervals during the first 2 years following a pancreatectomy and should be extended to later than 5 years for those with unfavorable pathological results.

Preoperative liver arterial conditioning in patients scheduled for a Mayo Clinic class Ia distal pancreatectomy: embolization or ligation?

BACKGROUND: Liver ischemia may occur during intraoperative common hepatic artery ligation in Mayo Clinic class I distal pancreatectomy with en bloc celiac axis resection (DP-CAR). Preoperative liver arterial conditioning could be used to avoid this outcome. This retrospective study compared arterial embolization (AE) or laparoscopic ligation (LL) of the common hepatic artery before class Ia DP-CAR. METHODS: From 2014 to 2022, 18 patients were scheduled for class Ia DP-CAR after neoadjuvant FOLFIRINOX treatment. Two were excluded due to hepatic artery variation, six underwent AE, ten underwent LL. RESULTS: Two procedural complications occurred in the AE group: an incomplete dissection of the proper hepatic artery and a distal migration of coils in the right branch of the hepatic artery. Neither complication prevented surgery. The median delay between conditioning and DP-CAR was 19 days; decreased to five days in the last six patients. None required arterial reconstruction. Morbidity and 90-day mortality rates were 26.7% and 12.5%, respectively. No patient developed postoperative liver insufficiency after LL. CONCLUSION: Preoperative AE and LL seem comparable in averting arterial reconstruction and postoperative liver insufficiency in patients scheduled for class Ia DP-CAR. However, serious complications that may arise during AE led us to prefer the LL technique.

Establishment and external validation of neutrophil-to-lymphocyte ratio in excluding postoperative pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Factors excluding postoperative pancreatic fistula (POPF), facilitating early drain removal and hospital discharge represent a novel approach in patients undergoing enhanced recovery after pancreatic surgery. This study aimed to establish the relevance of neutrophil-to-lymphocyte ratio (NLR) in excluding POPF after pancreatoduodenectomy (PD). METHODS: A prospectively maintained database of patients who underwent PD at two high-volume centres was used. Patients were divided into three cohorts (training, internal, and external validation). The primary endpoints of this study were accuracy, optimal timing, and cutoff values of NLR for excluding POPF after PD. RESULTS: From 2012 to 2020, in a 2:1 ratio, 451 consecutive patients were randomly sampled as training (n = 301) and validation (n = 150) cohorts. Additionally, the external validation cohort included 197 patients between 2018 and 2020. POPF was diagnosed in 135 (20.8 per cent) patients. The 90-day mortality rate was 4.1 per cent. NLR less than 8.5 on postoperative day 3 (OR, 95 per cent c.i.) was significantly associated with the absence of POPF in the training (2.41, 1.19 to 4.88; P = 0.015), internal validation (5.59, 2.02 to 15.43; P = 0.001), and external validation (5.13, 1.67 to 15.76; P = 0.004) cohorts when adjusted for relevant clinical factors. Postoperative outcomes significantly differed using this threshold. CONCLUSION: NLR less than 8.5 on postoperative day 3 may be a simple, independent, cost-effective, and easy-to-use criterion for excluding POPF.

Readmission after pancreaticoduodenectomy: Birmingham score validation.

BACKGROUND: The Birmingham score predicts the risk of hospital readmission after pancreaticoduodenectomy (PD). This study aimed to validate the risk score in a different healthcare cohort. METHODS: From 2017 to 2021, 301 patients underwent PD. The Birmingham score was applied to 276 patients. Postoperative deceased patients (n = 7) or those requiring a completion of pancreatectomy (n = 18) were excluded. RESULTS: Forty-seven (17%) patients were readmitted after a median delay of 9 (range 1-49) days and stayed for 5 (range 1-27) days; 4 (8.5%) died during the hospital stay. The leading cause of readmission was a septic condition (53%), mostly resolved by medical treatment (77%). A multivariate analysis identified the occurrence of a clinically relevant postoperative pancreatic fistula, the score criteria, and the score itself as independent factors favouring readmission. Readmission rates in patients with low [n = 97 (35%)], intermediate [n = 98 (36%)], and high [n = 81 (29%)] scores were 5%, 17%, and 31%, respectively (P < 0.01). CONCLUSION: This study confirmed the relevance and robustness of the Birmingham risk score. Patients with a high risk of readmission after PD, identified based on the score, were discharged to a partnership medical centre close to the pancreatic centre to plan readmission and avoid futile unplanned hospitalisation.

Intraoperative frozen section analysis of para-aortic lymph nodes after neoadjuvant FOLFIRINOX: will it soon become useless?

PURPOSE: Positive para-aortic lymph nodes (PALN) (station 16) are commonly detected in the final pathologic examination (ranging from 15 to 26%) among patients who undergo upfront pancreatoduodenectomy for resectable pancreatic ductal adenocarcinoma. However, after neoadjuvant treatment (NAT) the role of positive PALN as a watershed for surgical resection remains unclear. We aimed to determine the incidence of intraoperative detection of PALN after NAT with FOLFIRINOX for pancreatic head adenocarcinoma and its impact on survival, as our policy was to not resect the tumor in such situations. METHODS: From January 2014 to December 2020, 136 patients with non-metastatic cancer who received neoadjuvant FOLFIRINOX and underwent explorative laparotomy were included. RESULTS: Intraoperative positive PALN were observed in 7 patients (5%). Patients had resectable (n = 5) or locally advanced (n = 2) disease at the time of surgery, but none of them underwent surgical resection. Positive PALN were significantly associated with a lower median number of FOLFIRINOX cycles (4 vs. 6, P = 0.05). There was no significant difference in overall survival between patients with positive loco-regional lymph nodes after resection and patients with non-resection owing to positive PALN (22 versus 16 months, P = 0.16), Overall survival with positive PALN, carcinomatosis, and liver metastasis was 16, 14, and 10 months, respectively (P > 0.05). CONCLUSIONS: Our results suggest that NAT may lower PALN involvement. We have modified our policy, positive PALN after NAT are no longer a contraindication to resection, rather a holistic picture of the disease guides management.

Double purse-string telescoped pancreaticogastrostomy is not superior in preventing pancreatic fistula development in high-risk anastomosis: a 6-year single-center case-control study.

PURPOSE: The double purse-string telescoped pancreaticogastrostomy (PG) technique has been suggested as an alternative approach to reduce the risk of postoperative pancreatic fistula (POPF). Its efficacity in high-risk situations has not yet been explored. This study compared the incidence of clinically relevant POPF (CR-POPF) between patients with high-risk anastomosis undergoing PG and those undergoing pancreaticojejunostomy (PJ). METHODS: From 2013 to 2019, 198 consecutive patients with high-risk anastomosis, an updated alternative fistula risk score > 20%, and who underwent pancreatoduodenectomy with the PJ (165) or PG (33) technique were included. Optimal mitigation strategy (external stenting/octreotide omission) was applied for all patients. The primary endpoint was the incidence of CR-POPF. RESULTS: The mean ua-FRS was 33%. CR-POPF (grade B/C) was found in 42 patients (21%) and postoperative hemorrhage in 30 (15%); the mortality rate was 4%. CR-POPF rates were comparable between the PJ (19%) and PG (33%) groups (P = 0.062). The PG group had a higher rate of POPF grade C (24% vs. 10%; P = 0.036), longer operative time (P = 0.019), and a higher transfusion rate (P < 0.001), even after a matching process on ua-FRS. In the multivariate analysis, the type of anastomosis (P = 0.88), body mass index (P = 0.47), or main pancreatic duct diameter (P = 0.7) did not influence CR-POPF occurrence. CONCLUSIONS: For patients with high-risk anastomosis, the double purse-string telescoped PG technique was not superior to the PJ technique for preventing CR-POPF.

Protective peritoneal patch for arteries during pancreatoduodenectomy: good value for money.

PURPOSE: This study proposes and details a simple and inexpensive protective technique of wrapping the hepatic and gastroduodenal artery stumps with a peritoneal patch during pancreatoduodenectomy (PD) in order to decrease post-pancreatectomy hemorrhage (PPH). METHODS: Among the 85 patients who underwent PD between July 2020 and March 2021, 16 patients with high-risk pancreatic anastomosis received a peritoneal patch. The Updated Alternative Fistula Risk Score (ua-FRS) was calculated. Post-operative pancreatic fistula (POPF) and PPH were diagnosed and graded according to the International Study Group of Pancreatic Surgery. The mortality rate was calculated up to 90 days after PD. RESULTS: The mean ua-FRS of the 16 patients was 43% (range: 21-63%). Among them, 6 (38%) experienced clinically relevant-POPF, and a PPH was observed in two patients (13%). In these two patients who required re-intervention, the peritoneal patch was remarkably intact, and neither the gastroduodenal stump nor hepatic artery was involved. None of the patients experienced 90-day mortality. CONCLUSION: Although the outcomes are encouraging, the evaluation of a larger series to assess the effectiveness of the peritoneal protective patch for arteries in a high-risk pancreatic anastomosis is ongoing.

Will Patients With Liver Metastasis From Aggressives Cancers Benefit From Surgical Resection?

Background: We aimed to evaluate the outcomes of resections for liver metastases (LMs) originating from pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and esophagus/gastric cancers (EGCs), which we label as major killers (MKs; overall survival (OS) under 10%). We hypothesized that LM resection must provide the patient with almost a year of OS postoperatively that is considered beneficial. Methods: From January 2005 to December 2020, 23 patients underwent resection for isolated LM from MKs. These patients underwent surgery after a multidisciplinary discussion about their performance status, disease evolution during prolonged medical treatment, and the existence or absence of extrahepatic metastases. Results: LM originated from an PDAC, EGC, or NSCLC in 10 patients (43%), nine patients (39%), and four patients (18%), respectively. The median delay between primary cancer and LM diagnoses was 12 months, and the median delay between LM diagnosis and liver resection was 10 months. Most patients, who had objectively responded to medical treatment (57%), had a solitary (61%) and unilobar (70%) LM. Severe morbidity and 90-day mortality rates were 13% and 4.3%, respectively. Margin-free resection was achieved in 16 patients (70%). After liver resection, the median OS was 24 months without a statistical difference when considering the primary tumor site; 1, 3-, and 5-year OS were 70%, 23%, and 23%, respectively. Conclusion: Selection based on criteria such as good clinical condition, response to treatment, and long observation period helped identify patients with LM of MKs who seemed to benefit from resection.

Root-cause Analysis of Mortality After Pancreatic Resection (CARE Study): A Multicenter Cohort Study.

OBJECTIVES: Analyze a multicenter cohort of deceased patients after pancreatectomy in high-volume centers in France by performing a root-cause analysis (RCA) to define the avoidable mortality rate. BACKGROUND: Despite undeniable progress in pancreatic surgery for over a century, postoperative outcome remains particularly worse and could be further improved. METHODS: All patients undergoing pancreatectomy between January 2015 and December 2018 and died postoperatively within 90 days after were included. RCA was performed in 2 stages: the first being the exhaustive collection of data concerning each patient from preoperative to death and the second being blind analysis of files by an independent expert committee. A typical root cause of death was defined with the identification of avoidable death. RESULTS: Among the 3195 patients operated on in 9 participating centers, 140 (4.4%) died within 90 days after surgery. After the exclusion of 39 patients, 101 patients were analyzed. The cause of death was identified in 90% of cases. After RCA, mortality was preventable in 30% of cases, mostly consequently to a preoperative assessment (disease evaluation) or a deficient postoperative management (notably pancreatic fistula and hemorrhage). An inappropriate intraoperative decision was incriminated in 10% of cases. The comparative analysis showed that young age and arterial resection, especially unplanned, were often associated with avoidable mortality. CONCLUSIONS: One-third of postoperative mortality after pancreatectomy seems to be avoidable, even if the surgery is performed in high volume centers. These data suggest that improving postoperative pancreatectomy outcome requires a multidisciplinary, rigorous, and personalized management.

The iPhone, the reflex, and the vinyl record: is the smartphone taking the best intraoperative photographs?

Surgical field photography is a tough exercise: surgeons dedicate the required time for photography even during complex surgeries; the intense lighting of the operating field works against photography, and the surgeon has to utilise whatever equipment is available. We selected five complex interventions and two surgeons (one with an iPhone® and one with a Digital Single Lens Reflex [DSLR] camera) who each took a photograph of the operating field. The source of photographs was blinded, and the image quality was scored using a 5-point Likert scale by three groups of team members with differing experiences: six senior surgeons, two junior surgeons, and four surgical residents. We evaluated the resolution (adequate for clinical interpretation), colour (appear true and natural), contrast (adequate to distinguish different structures), and overall quality. The mean ± SEM overall image quality was similar for both the smartphone and DSLR (3.7 ± 0.1 vs. 3.8 ± 0.11; p = 0.87), as were most of the scores for each image characteristic. Surgeons seek objectivity and efficiency. The smartphone is a more convenient photographic equipment and produces identical results than the DSLR. Human beings can be sensitive to image quality. The DSLR image was found to be sharper, however, this was found to be imperceptible.

Prospective Evaluation of Resection Margins Using Standardized Specimen Protocol Analysis among Patients with Distal Cholangiocarcinoma and Pancreatic Ductal Adenocarcinoma.

PURPOSE: Using a standardized specimen protocol analysis, this study aimed to evaluate the resection margin status of patients who underwent resection for either distal cholangiocarcinoma (DC) or pancreatic ductal adenocarcinoma (PDAC). This allowed a precise millimetric analysis of each inked margin. METHODS: From 2010 to 2018, 355 consecutively inked specimens from patients with PDAC (n = 288) or DC (n = 67) were prospectively assessed. We assessed relationships between the tumor and the following margins: transection of the pancreatic neck, bile duct, posterior surface, margin toward superior mesenteric artery, and the surface of superior mesenteric vein/portal vein groove. Resection margins were evaluated using a predefined cut-off value of 1 mm; however, clearances of 0 and 1.5 mm were also evaluated. RESULTS: Patients with DC were mostly men (64% vs. 49%, p = 0.028), of older age (68 yo vs. 65, p = 0.033), required biliary stenting more frequently (93% vs. 77%, p < 0.01), and received less neoadjuvant treatment (p < 0.001) than patients with PDAC. The venous resection rate was higher among patients with PDAC (p = 0.028). Postoperative and 90-day mortality rates were comparable. Patients with PDAC had greater tumor size (28.6 vs. 24 mm, p = 0.01) than those with DC. The R1 resection rate was comparable between the two groups, regardless of the clearance margin. Among the three types of resection margins, a venous groove was the most frequent in both entities. In multivariate analysis, the R1 resection margin did not influence patient survival in either PDAC or DC. CONCLUSION: Our standardized specimen protocol analysis showed that the R1 resection rate was comparable in PDAC and DC.

Acute Pancreatitis as the Initial Presentation of Pancreatic Adenocarcinoma does not Impact Short- and Long-term Outcomes of Curative Intent Surgery: A Study of the French Surgical Association.

BACKGROUND: Acute pancreatitis (AP) can be one of the earliest clinical presentation of pancreatic ductal adenocarcinoma (PDAC). Information about the impact of AP on postoperative outcomes as well as its influences on PDAC survival is scarce. This study aimed to determine whether AP as initial clinical presentation of PDAC impact the short- and long-term outcomes of curative intent pancreatic resection. PATIENTS AND METHODS: From 2004 to 2009, 1449 patients with PDAC underwent pancreatic resection in 37 institutions (France, Belgium and Switzerland). We used univariate and multivariate analysis to identify factors associated with severe complications and pancreatic fistula as well as overall and disease-free survivals. RESULTS: There were 764 males (52,7%), and the median age was 64 years. A total of 781 patients (53.9%) developed at least one complication, among whom 317 (21.8%) were classified as Clavien-Dindo ≥ 3. A total of 114 (8.5%) patients had AP as the initial clinical manifestation of PDAC. This situation was not associated with any increase in the rates of postoperative fistula (21.2% vs 16.4%, P = 0.19), postoperative complications (57% vs 54.2%, P = 0.56), and 30 day mortality (2.6% vs 3.4%, P = 1). In multivariate analysis, AP did not correlate with postoperative complications or pancreatic fistula. The median length of follow-up was 22.4 months. The median overall survival after surgery was 29.9 months in the AP group and 30.5 months in the control group. Overall recurrence rate and local recurrence rate did not differ between groups. CONCLUSION: AP before PDAC resection did not impact postoperative morbidity and mortality, as well as recurrence rate and survival.

Is percutaneous destruction of a solitary liver colorectal metastasis as effective as a resection?

BACKGROUNDS/AIMS: Surgical resection remains the gold standard in the treatment of colorectal liver metastasis. However, when a patient presents with a deep solitary colorectal liver metastasis (S-CLM), the balance between the hepatic volume sacrificed and the S-CLM volume is sometimes clearly unappropriated. Thus, alternatives to surgery, such as operative and percutaneous radiofrequency ablation (RFA) and microwave ablation (MWA), have been developed. This study aimed to identify the prognostic factors affecting survival of patients with S-CLM who undergo curative-intent liver resection or local destruction (RFA or MWA). METHODS: We retrospectively identified 211 patients with synchronous or metachronous S-CLM who underwent either surgical resection (n=182) or local destruction (RFA or MWA; n=29) according to the S-CLM size, location, and surrounding Glissonian structures. RESULTS: Patients who underwent RFA or MWA had S-CLM of a smaller size than those who underwent resection (mean 19.7 vs. 37.3 mm, p<.01). The 1-, 3-, and 5-year overall survival (OS) rates were 97.4%, 84.9%, and 74.9%, respectively. The 1-, 3-, and 5-year disease-free survival (DFS) rates were 77.9%, 47%, and 38.9%, respectively. S-CLM located in the left liver (p=.04), S-CLM KRAS mutation (p<.01), and extra-hepatic recurrence (p<.01) were identified as independent poor risk factors for overall survival (OS); the OS and DFS were comparable in patients with surgical procedure or percutaneous MWA. CONCLUSIONS: In eligible S-CLM cases, percutaneous MWA seems to be as oncologically efficient as surgical resection and should be include in the decision-tree for treatment strategies.

Does pre-operative embolization of a replaced right hepatic artery before pancreaticoduodenectomy for pancreatic adenocarcinoma affect postoperative morbidity and R0 resection? A bi-centric French cohort study.

BACKGROUND: Sacrificing a replaced right hepatic artery (rRHA) from the superior mesenteric artery is occasionally necessary to obtain an R0 resection after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA). Preoperative embolization (PEA) of the rRHA has been proposed to avoid the onset of postoperative biliary and ischemic liver complications. METHODS: Eighteen patients with cephalic PA with an rRHA underwent PEA of the rRHA from 2013 to 2019. The monitoring after embolization and PD was systematic and included a clinical-biological evaluation and a computed tomography scan. This study aimed to determine the feasibility of PEA of the rRHA, postoperative morbidity at 90 days, and quality of oncologic resection after PD. RESULTS: Feasibility of PEA was 100% without complications. A PD was performed in 16/18 patients. Mortality was 2/16 with one death after septic shock with hepatic ischemia without an arterial obstruction. Overall morbidity was 44% including one hepatic abscess after hepatic ischemia (6%). Two resections were R1 (<1 mm) in contact with the origin of the rRHA (2/4 R1). CONCLUSION: PEA of the rRHA before PD was safe and reproducible. PEA of the rRHA followed by en bloc PD resection seems to limit the risk of bilio-hepatic ischemia and could facilitate oncologic resection.

Parenchymal Sparing Resection: Options in Duodenal and Pancreatic Surgery.

Parenchymal sparing duodenal and pancreatic resection are safe procedures in selected patients with the aim to reduce endocrine and exocrine long-term dysfunction. When the tumor is benign or borderline malignant, this appears to be a good option for the surgeon, associated with low rates of severe surgery-related early postoperative complications and low in-hospital mortality. This mini review offers comments, tips and tricks, and a review of literature concerning those different options with specific illustrations in order to clarify their indication.

Standardized salvage completion pancreatectomy for grade C postoperative pancreatic fistula after pancreatoduodenectomy (with video).

BACKGROUND: Emergency completion pancreatectomy (CP) after pancreatoduodenectomy (PD) is a technically demanding procedure. We report our experiences with a four-step standardized technique used at our center since 2012. METHODS: In the first step, the gastrojejunostomy is divided with a stapler to quickly access the pancreatic anastomosis and permit adequate exposure, especially in cases of active bleeding. Second, the bowel loops connected to the pancreatic anastomosis is divided in cases of pancreaticojejunostomy. Third, the pancreatectomy is completed with or without the splenic vessels and spleen conservation according to the local conditions. Finally, the fourth step reconstructs in a Roux-en-Y fashion and ensures drainage. RESULTS: From January 2012 to December 2019, 450 patients underwent PD at our center. Reintervention for grade C postoperative pancreatic fistula was decided for 30 patients, and CP was performed in 21 patients. The mean intraoperative blood loss and operative duration were relatively low (600 ml and 240 min, respectively). During the perioperative period, three patients died from multiple organ failure, and two patients died intraoperatively from a cataclysmic hemorrhage originating from the superior mesenteric artery. DISCUSSION: Our standardized procedure appears to be relatively safe, reproducible, and could be particularly useful for young surgeons.