Pancreatoduodenectomy For Pancreatic Head Cancer Research Articles

Standard pancreatoduodenectomy versus extended pancreatoduodenectomy with modified retroperitoneal nerve resection in patients with pancreatic head cancer: a multicenter randomized controlled trial.

The extent of pancreatoduodenectomy for pancreatic head cancer remains controversial, and more high-level clinical evidence is needed. This study aimed to evaluate the outcome of extended pancreatoduodenectomy (EPD) with retroperitoneal nerve resection in pancreatic head cancer. This multicenter randomized trial was performed at 6 Chinese high-volume hospitals that enrolled patients between October 3, 2012, and September 21, 2017. Four hundred patients with stage I or II pancreatic head cancer and without specific pancreatic cancer treatments (preoperative chemotherapy or chemoradiation) within three months were randomly assigned to undergo standard pancreatoduodenectomy (SPD) or EPD, with the latter followed by dissection of additional lymph nodes (LNs), nerves and soft tissues 270° on the right side surrounding the superior mesenteric artery and celiac axis. The primary endpoint was overall survival (OS) by intention-to-treat (ITT). The secondary endpoints were disease-free survival (DFS), mortality, morbidity, and postoperative pain intensity. The R1 rate was slightly lower with EPD (8.46%) than with SPD (12.56%). The morbidity and mortality rates were similar between the two groups. The median OS was similar in the EPD and SPD groups by ITT in the whole study cohort (23.0 vs. 20.2 months, P = 0.100), while the median DFS was superior in the EPD group (16.1 vs. 13.2 months, P = 0.031). Patients with preoperative CA19-9 < 200.0 U/mL had significantly improved OS and DFS with EPD (EPD vs. SPD, 30.8 vs. 20.9 months, P = 0.009; 23.4 vs. 13.5 months, P < 0.001). The EPD group exhibited significantly lower locoregional (16.48% vs. 35.20%, P < 0.001) and mesenteric LN recurrence rates (3.98% vs. 10.06%, P = 0.022). The EPD group exhibited less back pain 6 months postoperation than the SPD group. EPD for pancreatic head cancer did not significantly improve OS, but patients with EPD treatment had significantly improved DFS. In the subgroup analysis, improvements in both OS and DFS in the EPD arm were observed in patients with preoperative CA19-9 < 200.0 U/mL. EPD could be used as an effective surgical procedure for patients with pancreatic head cancer, especially those with preoperative CA19-9 < 200.0 U/mL.

The impact of the presence of the aberrant right hepatic artery in pancreatoduodenectomy for pancreatic head cancer

An aberrant right hepatic artery usually originates from the superior mesenteric artery, it has an ascendant trajectory through the head of the pancreas or behind it and represents a technical challenge in pancreatic head tumors due to the fact that it needs to be carefully dissected and preserved in order to maintain an adequate blood supply for the right hemi-liver. Meanwhile, this dissection should be performed in an oncological manner in order to obtain the premises of a radical resection with negative margins. The aim of the current paper is to discuss about the influence of this anatomical arterial particularity and the possibility of obtaining a resection with curative intent in pancreatic head adenocarcinoma.

Standard Pancreatoduodenectomy Versus Radical Pancreatoduodenectomy With Retroperitoneal Nerve Resection in Patients With Pancreatic Head Cancer (RAPNER): A Multicentre Randomized Controlled Trial

Background: Pancreatic cancer is a highly fatal disease and is becoming an increasingly common cause of cancer mortality. The extent of pancreatoduodenectomy for pancreatic head cancer is still controversial, and more high-level clinical evidence is needed. We compared the outcomes of standard pancreatoduodenectomy (SPD) with those of radical pancreatoduodenectomy (RPD) with retroperitoneal nerve resection in pancreatic head cancer patients in this multicentre randomized controlled trial. Methods: RAPNER was open-label, multicentre randomised trial, patients aged 18–80 years with stage I or II pancreatic head cancer undergoing curative resection were enrolled at 6 centres from China. Patients were allocated (1:1) by use of a computer-based randomisation service to assigned to receive standard pancreatoduodenectomy (PD) or radical PD, with the latter followed by the combined dissection of additional lymph nodes (LNs), nerves and soft tissues 270° on the right side surrounding the superior mesenteric artery and celiac axis. This trial is registered with Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR-TRC-12002548. Findings: Between October 3, 2012, and February 15, 2017, 468 patients were enrolled; of these, 400 were randomly assigned to the RPD group (n=201) or the SPD group (n=199). The operation time was longer with RPD than with SPD, but the R1 resection rate was slightly higher in the SPD group (12·56%) than in the RPD group (8·46%). Both the total number of retrieved LNs and number of positive LNs were significantly higher in the RPD group (20 (7-63) and 1 (0-29)) than in the SPD group (15 (7-63) and 1 (0-11)). Both the morbidity and inpatient mortality rates were comparable between the two groups. The median overall survival (OS) of the RPD and SPD groups were 23·0 months and 20·2 months (p=0·100), and the disease-free survival (DFS) were 15·6 months and 13·5 months (p=0·060). In the subgroup with a preoperative CA19-9 level less than 200 U/ml, the median OS in the RPD group was 30·8 months, which was significantly longer than that in the SPD group (20·9 months; p=0·009), and the median DFS was significantly longer in the RPD group than in the SPD group (22·3 months vs. 15·0 months, p=0·002). Furthermore, clinical benefit could be found in the RPD group in the subgroup of well & moderate histological differentiation, preoperative CEA level less than 5·00 ng/ml, R0 resection and postoperative adjuvant chemotherapy based on DFS analysis. A multivariate Cox proportional hazards model showed that initial CA19-9≥200 U/ml, N1 stage and poor differentiation suggested poor OS. Radical resection achieved equivalent prognosis regardless of perineural invasion except for aortic nerve plexus invasion. The RPD group exhibited significantly lower locoregional and mesenteric LN recurrence rates but a higher peritoneal seeding frequency. The RPD group also exhibited significantly less back pain intensity 6 months after surgery than the SPD group. Interpretation: This study suggests that in pancreatic head cancer patients, RPD with retroperitoneal nerve resection does not provide a significant survival benefit compared with SPD. RPD can be performed safely, and be considered a treatment option with improving prognosis for patients with a low chance of systemic metastasis in pancreatic head cancer. Trial Registration: ChiCTR-TRC-12002548. Funding Statement: Sun Yat-sen University Clinical Research 5010 Program (Grant No. 2012007), China; National Natural Science Foundation of China (Grant No. 81871945). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: This study was approved and overseen by the clinical ethics committee of each participating hospital.

Impact of Preoperative Malnutrition on Postoperative Long-Term Outcomes of Patients With Pancreatic Head Cancer.

To evaluate the association between preoperative malnutrition and long-term outcomes in patients with pancreatic head cancer who underwent curative pancreatoduodenectomy (PD). From 2004 to 2018, 228 consecutive patients who underwent curative PD for pancreatic ductal adenocarcinoma were included. Preoperative malnutrition was defined by the Global Leadership Initiative in Malnutrition criteria. It is based on both phenotypic criteria (weight loss, low body mass index, and reduced muscle mass) and etiologic criteria (reduced intake or assimilation and inflammation). Seventy-five (32.9%) of 228 patients were classified as suffering from malnutrition. Preoperative malnutrition was associated with an increased risk of estimated blood loss (mL) (816.7 ± 875.2 vs 593.1 ± 489.9, P = 0.015) and longer hospital stay (days) (27.3 ± 15.7 vs 22.9 ± 17.7, P = 0.045). The median follow-up period was 24.5 months. The malnutrition group had poor overall survival compared with "without (WO)-malnutrition" group (P = 0.001) at 1 year (66.3% vs 81.3%), 3 years (18.0% vs 51.8%), and 5 years (12.0% vs 39.3%). The malnutrition group showed poor disease-free survival and cancer-specific survival compared with WO-malnutrition group (P = 0.001) at 1 year (38.9% vs 66.7%) and (69.0% vs 88.7%), 3 years (11.5% vs 45.1%) and (21.1% vs 61.6%), and 5 years (11.5% vs 37.3%) and (14.1% vs 51.2%). In multivariate analysis, the preoperative malnutrition was found to be the predictor of poor prognosis (harzard ratio = 2.29, 95% confidence interval = 1.60-3.29, P = 0.001). Preoperative malnutrition is associated with poor prognosis in patients who underwent curative PD for pancreatic head cancer.

The Impact of COVID-19 Infection on the Postoperative Outcomes in Pancreatic Cancer Patients

The aim of this study is to report a case series of three patients who developed postoperative severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) infection, although the initial tests were negative. Between April and September 2020, three patients submitted to pancreatoduodenectomy developed SARS-CoV-2 infection; their outcomes were compared to those of a similar group in which the postoperative outcomes were uneventful. There were no significant differences between the two groups in terms of pre- and intraoperative outcomes; however, all of the three cases who developed SARS-CoV-2 infection postoperatively required re-admission in the intensive care unit and a longer hospital in stay. The overall mortality rate was null. Patients submitted to pancreatoduodenectomy for pancreatic head cancer who develop SARS-COV-2 infection postoperatively need a more appropriate supportive care; however, the overall mortality does not appear to increase, justifying, in this way, the continuation of programmed oncological of surgeries.

Artery first versus traditional approach in pancreatoduodenectomy for pancreatic head cancer

Background: Artery first approach pancreatoduodenectomy (AFAPD) technique is one of the many modifications of the standard whipple procedure (sPD) thus enabling a complete dissection of the right side of this artery and of the portal vein, as well as a complete excision of the retroportal pancreatic lamina. Objective was to evaluate the clinical, perioperative and oncological outcomes of “artery first” approach compared with those of the traditional approach.Methods: Between 2010 and 2019, The present study includes two groups of patients. A first group of 28 patients with PD by “artery first” and a second group including 28 matched patients with PD by TAPD. Demographic characteristics (sex, age), intraoperative data (approach type, operative time, blood loss, intraoperative complications, need for vascular resections), histological diagnosis and pathology data (tumor location, TNM staging, tumor grading, tumor vascular invasion) and patient outcomes (postoperative length of stay, in-hospital postoperative mortality and morbidity, survival time) were collected.Results: There were no significant differences between the two groups regarding: total operative time (422 vs. 460.min, p=0.19), estimated blood loss (p=0.67), median length of stay (14 days in both groups) (p=0. 0.39), complication rates (32.1% and 35.7%) (p=0. 1.00), lymph node yield (22 and 21) and R0 resection rate (75% and 67.9%). Conclusions: We concluded that artery first” offers similar operative time, intraoperative blood loss, R0 resection rates, lymph node yield and long-term survival as TAPD.

En bloc proximal peri-mesenteric clearance for pancreatic head cancer surgery

The superior mesenteric artery (SMA) first approach and meso-pancreas excision (MPE) during pancreatoduodenectomy (PD) for pancreatic head cancer have been suggested for complete local tumor control, less operative blood loss, and early determination of resectability. However, SMA-first approach is merely a mode of approach and the concept of MPE has been challenged due to its anatomical obscurity. Dissection around proximal mesenteric vessels, superior mesenteric vein and SMA, is a critical procedure point for local tumor control as tumor infiltration is frequently observed both at the time of initial diagnosis and recurrence. The meso-pancreas, which encompasses the soft tissue between the uncinated process and SMA, does not include all the aforementioned points of proximal mesenteric areas. Therefore, the authors propose a new terminology named, “en bloc proximal peri-mesenteric clearance (PPMC)”, to describe the removal of all the lymph nodes including soft tissue around proximal mesenteric vessels, especially the SMA, to ensure complete local tumor control of pancreatic head cancer. The SMA-first approach applied either by the mesenteric approach or supra-colic approach can make this procedure more feasible. The extent of the circumferential dissection of the peri-SMA nerve plexus can be adjusted according to the primary disease. PPMC including the removal of all lymph nodes around the proximal SMA may be considered as a standard extent of PD for pancreatic head cancer.

An anatomical review of various superior mesenteric artery-first approaches during pancreatoduodenectomy for pancreatic cancer.

When pancreatic head cancer invades the superior mesenteric artery (SMA), attempts at curative resection are aborted. Preoperative imaging diagnostics to determine the surgical curability have yet to surpass the intraoperative information acquired via inspection, palpation, and trial dissection. Pancreatoduodenectomy (PD) is a standard measure for treating periampullary cancers. In conventional PD, SMA invasion is usually identified by dissecting the retroportal lamina, which connects the uncinate process and SMA nerve plexus after dividing the neck of the pancreas. During PD for pancreatic head cancer, this retroperitoneal margin frequently vitiates surgical curability. SMA-first approaches during PD are methods where the SMA is dissected first by severing the posterior pancreatic capsule to assess the SMA involvement of pancreatic cancer early in the operation. The first report of such an approach prompted subsequent reports of various maneuvers that are now known collectively as "artery-first" approaches. We herein review those approaches by classifying them according to (1) the side of the mesocolon from where the SMA approach occurs (supracolic or infracolic) and (2) the direction of access (right or left and anterior or posterior). The steps of the reported PD procedures are numbered according to a timeline and summarized using anatomical division of the SMA.

Multicenter randomized phase II trial of prophylactic right-half dissection of superior mesenteric artery nerve plexus in pancreatoduodenectomy for pancreatic head cancer.

AimRight‐half dissection of the superior mesenteric artery (SMA) nerve plexus in pancreatoduodenectomy for pancreatic cancer was initiated to accomplish R0 resection; however, subsequent refractory diarrhea was a major concern. This study aimed to evaluate the necessity of this technique.MethodsFrom April 2014 to June 2018, 74 patients with pancreatic head cancer were randomly allocated to either Group A, in which right‐half dissection of the SMA nerve plexus was performed (n = 37), or Group B, in which total preservation of the nerve plexus was performed (n = 37). Short‐term, long‐term, and survival outcomes were prospectively compared between the groups.ResultsThe patient demographics, including the R0 resection rate, were not significantly different between the groups. Postoperative diarrhea occurred in 26 (70.3%) patients in Group A and 18 (48.6%) patients in Group B. There was a tendency for the development of severe diarrhea in Group A within 1 year postoperatively, and the frequency of diarrhea gradually decreased within 2 years, although that did not affect tolerance to adjuvant chemotherapy. There was no difference in either locoregional recurrence (27.0% vs 32.4%) or systemic recurrence (46.0% vs 46.0%). The median overall survival time in Groups A and B was 37.9 and 34.6 months, respectively (P = 0.77).ConclusionWe did not demonstrate a clinical impact of right‐half dissection of the SMA nerve plexus on locoregional recurrence or survival. Therefore, the prophylactic dissection of the SMA nerve plexus is unnecessary given that refractory diarrhea could be induced by this technique (UMIN000012241).

Nakao mesenteric approach in pancreatoduodenectomy for pancreatic head cancer

Abstract The ideal surgery for pancreatic head cancer is isolated pancreatoduodenectomy (PD); that is, en bloc resection using a non-touch isolation technique. We have been developing isolated PD for pancreatic cancer since 1981, when we developed an anti-thrombogenic bypass catheter for the portal vein. In this operation, the first and most important step is the use of a mesenteric approach instead of Kocher's maneuver. The mesenteric approach allows dissection from the non-cancer infiltrating side and determination of cancer-free surgical margins and resectability, followed by systemic lymphadenectomy around the superior mesenteric artery. This approach enables early ligation of the inferior pancreatoduodenal artery and mesopancreas excision. The mesopancreas is the second portion of the pancreatic head nerve plexus. Isolated PD is the ideal surgery for pancreatic head cancer from both surgical and oncological viewpoints. In patients with resectable pancreatic head cancer, isolated PD using the mesenteric approach is suspected to have a higher survival rate than conventional PD using Kocher's maneuver. The precise surgical techniques of the mesenteric approach are herein described.

Prognostic role of the length of tumour-vein contact at the portal-superior mesenteric vein in patients having surgery for pancreatic cancer.

The length of tumour-vein contact between the portal-superior mesenteric vein (PV/SMV) and pancreatic head cancer, and its relationship to prognosis in patients undergoing pancreatic surgery, remains controversial. Patients diagnosed with pancreatic head cancer who were eligible for pancreatoduodenectomy between October 2002 and December 2016 were analysed. The PV/SMV contact was assessed retrospectively on CT. Using the minimum P value approach based on overall survival after surgery, the optimal cut-off value for tumour-vein contact length was identified. Among 491 patients included, 462 underwent pancreatoduodenectomy for pancreatic head cancer. PV/SMV contact with the tumour was detected on preoperative CT in 248 patients (53·7 per cent). Overall survival of patients with PV/SMV contact exceeding 20 mm was significantly worse than that of patients with a contact length of 20 mm or less (median survival time (MST) 23·3 versus 39·3 months; P =0·012). Multivariable analysis identified PV/SMV contact longer than 20 mm as an independent predictor of poor survival, whereas PV/SMV contact greater than 180° was not a predictive factor. Among patients with a PV/SMV contact length exceeding 20 mm on pretreatment CT, those receiving neoadjuvant therapy had significantly better overall survival than patients who had upfront surgery (MST not reached versus 21·6 months; P =0·002). The length of PV/SMV contact predicts survival, and may be used to suggest a role for neoadjuvant therapy to improve prognosis.

Central pancreatic body-preserving pancreatoduodenectomy for pancreatic head cancer following a combined total gastrectomy and distal pancreatectomy: a case report

BackgroundFollowing a total pancreatectomy and a total gastrectomy procedure, patients often present with nutritional and diabetes-related disorders, along with a corresponding decrease in their quality of life. Consequently, an appropriate surgical procedure should be selected, with which an R0 resection can be achieved while conserving optimum pancreatic function, in order to prevent adverse sequelae.Case presentationWe present a case of a 66-year-old female, with a history of primary gastric cancer, for which, she underwent total gastrectomy combined with a distal pancreatectomy, 21 years ago. She presented to us with a primary cancer of the head of the pancreas. We performed a central pancreatic body-preserving pancreatoduodenectomy, in order to conserve the pancreatic function. Since the splenic artery had already been resected in the earlier surgery, conserving the blood flow to the preserved pancreatic body was an important concern. By utilizing the techniques of preoperative angiography and intraoperative indocyanine green fluorescence imaging, the pancreatic body could be accurately resected while leaving its vascular supply intact and undamaged. Thus, the patient’s pancreatic endocrine function could be preserved.ConclusionsAn accurate evaluation of the pancreatic vascular supply enabled the operating surgeon to perform a safe, central pancreatic body-preserving pancreatoduodenectomy, even in patients who have undergone a combined total gastrectomy along with a distal pancreatectomy.

Radical modular pancreatoduodenectomy for pancreatic head cancer using a combination of multiple artery-first approaches technique.

The aim of this study was to describe and assess the efficacy of a combination of multiple artery-first approaches (CMAFA) in pancreatoduodenectomy (PD) depending on the tumor location from an embryonic point of view.Between January 2011 and December 2016, seventy-nine consecutive patients with pancreatic head cancer (PHC) underwent PD with curative intent. Patients were classified into two groups according to the surgical procedure: CMAFA-PD group (n = 38) and conventional PD (Co-PD) group (n = 41). Clinicopathlogical variables and clinical outcomes were compared among the two groups.The CMAFA technique demonstrated an improved rate of R0 resection (89.5% vs. 70.7%, P = .038) and a higher median lymph node yield (24 vs.20, P = .034). The CMAFA-PD group was associated with reduced blood loss (450 vs. 600 ml, P = .049), lower rate of blood transfusion (23.7% vs. 46.3%, P = .035), and shorter length of hospital stay (19 vs. 26 days, P < .001). The rates of 90-day mortality, major morbidity, and readmission were comparable among the two groups.This study demonstrates that CMAFA is a feasible and efficient technique with acceptable perioperative and oncological outcomes in treating patients with PHC.

A Case of Pancreatoduodenectomy for Pancreatic Head Cancer after Esophagectomy

A Case of Pancreatoduodenectomy for Pancreatic Head Cancer after Esophagectomy

Histopathological tumor invasion of the mesenterico-portal vein is characterized by aggressive biology and stromal fibroblast activation

BackgroundMesenterico-portal vein resection (PVR) during pancreatoduodenectomy for pancreatic head cancer was established in the 1990s and can be considered a routine procedure in specialized centers today. True histopathologic portal vein invasion is predictive of poor prognosis. The aim of this study was to examine the relationship between mesenterico-portal venous tumor infiltration (PVI) and features of aggressive tumor biology. MethodsPatients receiving PVR for pancreatic ductal adenocarcinoma of the pancreatic head were identified from a prospectively maintained database. Immunohistochemical staining of tumor tissue was performed for the markers of epithelial–mesenchymal transition (EMT) E-Cadherin, Vimentin and beta-Catenin. Morphology of cancer-associated fibroblasts (CAFs) was assessed as inactive or activated. Statistical calculations were performed with MedCalc software. ResultsIn total, 41 patients could be included. Median overall survival was 25 months. PVI was found in 17 patients (41%) and was significantly associated with loss of membranous E-Cadherin in tumor buds (p = 0.020), increased Vimentin expression (p = 0.03), activated CAF morphology (p = 0.046) and margin positive resection (p = 0.005). ConclusionOur findings suggest that PVI is associated with aggressive tumor biology and disseminated growth less amenable to margin-negative resection.

Safety and efficacy of cryopreserved homologous veins for venous reconstruction in pancreatoduodenectomy

There are several techniques for reconstructing the portal vein-superior mesenteric veinduring pancreatoduodenectomy. The aim of the present study was to present our results with portalvein-superior mesenteric vein reconstruction using cryopreserved homologous veins during pancreatoduodenectomy for patients with pancreatic head cancer. Patients who underwent pancreatoduodenectomy for pancreatic head cancer were reviewed retrospectively. In patients with portal vein-superior mesenteric vein resection, the detailed method of reconstruction and clinical outcomes were reviewed. Clinical characteristics, patient survival, and portal vein-superior mesenteric vein patency were compared between those with and without homologous vein grafts. Factors affecting the patency of reconstructed veins were assessed by univariate analysis. Among 144 patients undergoing pancreatoduodenectomy, portal vein-superior mesenteric vein resection was performed in 36 patients (25%); 18 (50%) underwent reconstruction with homologous veins, and the other 18 (50%) underwent reconstruction without homologous veins. The extent of portal vein-superior mesenteric vein involvement, operative time, duration of clamping of portal vein-superior mesenteric vein, intraoperative blood loss, and length of the venous resection were greater (P≤.013 each) in those with homologous vein grafts. There was no significant difference in postoperative morbidity/mortality, patient survival, or portal vein-superior mesenteric vein patency. The 1- and 2-year overall patency of portal vein-superior mesenteric vein was 76% and 71%, respectively, while the 2-year patencies were 67% and 67% in those with homologous veins and 87% and 73% in those without homologous veins without difference between the groups. Circumferential resection and pathologic portal vein-superior mesenteric vein involvement were associated with the patency of the reconstructed vein (P=.002 and P=.028, resp). Use of homologous venous grafts for portal vein-superior mesenteric vein reconstruction are feasible alternatives during pancreatoduodenectomy for advanced pancreatic head cancer.