In Neoadjuvant FOLFIRINOX Chemotherapy for Pancreatic Ductal Adenocarcinoma, Which Response is the More Reliable Indicator for Prognosis, Radiologic or Biochemical?

BACKGROUND: In this era of increasing neoadjuvant chemotherapy, methods for evaluating responses to neoadjuvant chemotherapy are still diverse among institutions. Additionally, the efficacy of adjuvant chemotherapy for patients undergoing neoadjuvant chemotherapy remains unclear. Therefore, this retrospective study was performed to evaluate the effectiveness of methods for assessing response to neoadjuvant chemotherapy and the need for adjuvant chemotherapy in treating patients with non-metastatic pancreatic ductal adenocarcinoma. METHODS: The study identified 150 patients who underwent neoadjuvant FOLFIRINOX chemotherapy followed by curative-intent pancreatectomy. The patients were stratified by biochemical response based on the normalization of carbohydrate antigen 19-9 and by radiologic response based on size change at imaging. RESULTS: The patients were classified into the following three groups based on their response to neoadjuvant chemotherapy and prognosis: biochemical responders (BR+), radiology-only responders (BR-/RR+), and non-responders (BR-/RR-). The 3-year overall survival rate was higher for BR+ (71.0%) than for BR-/RR+ (53.6%) or BR-/RR- (33.1%) (P < 0.001). Response to neoadjuvant chemotherapy also was identified as a significant risk factor for recurrence in a comparison between BR-/RR+ and BR+ (hazard ratio [HR], 2.15; 95% confidence interval [CI] 1.19-3.88; P = 0.011) and BR-/RR- (HR, 3.82; 95% CI 2.41-6.08; P < 0.001). Additionally, regardless of the response to neoadjuvant chemotherapy, patients who completed adjuvant chemotherapy had a significantly higher 3-year overall survival rate than those who did not. CONCLUSIONS: This response evaluation criterion for neoadjuvant chemotherapy is feasible and can significantly predict prognosis. Additionally, completion of adjuvant chemotherapy could be helpful to patients who undergo neoadjuvant chemotherapy regardless of their response to neoadjuvant chemotherapy.

Functional sequelae after pancreatic resection for cancer.

The morbidity and mortality of pancreatic cancer surgery has seen substantial improvement due to the standardization of surgical techniques, the optimization of perioperative multidisciplinary management and the organization of specialized care systems. The identification and treatment of postoperative functional and nutritional sequelae have thereby become major issues in patients who undergo pancreatic surgery. This review addresses the functional sequelae of pancreatic resection for cancerous and pre-cancerous lesions (excluding chronic pancreatitis). Its aim is to specify the prevalence and severity of sequelae according to the type of pancreatic resection and to document, where appropriate, the therapeutic management. Exocrine pancreatic insufficiency (ExPI) is observed in nearly one out of three patients at one year after surgery, and endocrine pancreatic insufficiency (EnPI) is present in one out of five patients after pancreatoduodenectomy (PD) and one out of three patients after distal pancreatectomy (DP). In addition, digestive functional disorders may appear, such as delayed gastric emptying (DGE), which affects 10 to 45% of patients after PD and nearly 8% after DP. Beyond these functional sequelae, pancreatic surgery can also induce nutritional and vitamin deficiencies secondary to a lack of uptake for certain vitamins or to the loss of absorption site in the duodenum. In addition to the treatment of ExPI with oral pancreatic enzymes, nutritional management is based on a high-calorie, high-protein diet with normal lipid intake in frequent small feedings, combined with vitamin supplementation adapted to monitored deficiencies. Better knowledge of the functional consequences of pancreatic cancer surgery can improve the overall management of patients.

Outpatient Pain Management in Children With Chronic Pancreatitis: A Scoping Systematic Review.

OBJECTIVES: Although pain management is central to pediatric chronic pancreatitis (CP) care, no evidence-based guidelines exist. In this scoping systematic review, we sought promising strategies for CP pain treatment in children. METHODS: We systematically reviewed literature on pain management in children and adults with CP, and 2 conditions with similar pain courses: juvenile idiopathic arthritis and sickle cell disease. RESULTS: Of 8997 studies identified, 287 met inclusion criteria. There are no published studies of analgesic medications, antioxidants, dietary modification, integrative medicine, or regional nerve blocks in children with CP. In adults with CP, studies of nonopioid analgesics, pancreatic enzymes, and dietary interventions have mixed results. Retrospective studies suggest that endoscopic retrograde cholangiopancreatography and surgical procedures, most durably total pancreatectomy with islet autotransplant, improve pain for children with CP. Follow-up was short relative to a child's life. Large studies in adults also suggest benefit from endoscopic therapy and surgery, but lack conclusive evidence about optimal procedure or timing. Studies on other painful pediatric chronic illnesses revealed little generalizable to children with CP. CONCLUSIONS: No therapy had sufficient high-quality studies to warrant untempered, evidence-based support for use in children with CP. Multicenter studies are needed to identify pain management "best practices."

Predicting pathologic venous invasion before pancreatectomy with venous resection: When does radiology tell the truth?

BACKGROUND: Patients factors in addition to radiological characteristics could predict the presence of pathologic venous invasion in patients undergoing pancreatectomy with venous resection. METHODS: We tested the predictive value of 6 radiological classification methods for predicting pathologic venous invasion-the Nakao, Ishikawa, MD Anderson, Lu, Raptopoulos, and National Comprehensive Cancer Network methods-on a cohort of 198 pancreatectomies (160 pancreaticoduodenectomies and 38 total pancreatectomies) with venous resection for pancreatic adenocarcinomas. Radiological and clinical factors determining pathologic venous invasion were identified by multivariable logistic analysis. RESULTS: Pathologic venous invasion was detected in 124 patients (63.2%). The multivariable logistic regression analysis identified Lu classification (odds ratio = 1.77, 95% confidence interval =1.34-2.35; P < .0001), elevated serum CA19-9 values (odds ratio = 1.97, 95% confidence interval = 1.00-3.90; P = .04), and preoperative neoadjuvant chemotherapy (odds ratio = 0.38, 95% confidence interval = 0.18-0.79; P = .009) as independent factors associated with pathologic venous invasion. Radiological tumor-vessel contact greater than 50% of the circumference or venous wall deformity was associated with a significantly higher rate of pathological venous invasion (80% vs 52%; P < .0001), deeper (media-intima) venous invasion (47% vs 25%; P < .0001), R1 resection (58% vs 41%; P = .03), higher transfusions (84% vs 66%; P = .005), and arterial resection rates (43% vs 27%; P < .0001). Tumor-vein circumference contact of >50% and/or venous wall deformity was still associated with significantly higher rates of pathologic venous invasion, regardless of whether neoadjuvant chemotherapy was used or not and CA19-9 normalized or not under preoperative treatment. CONCLUSION: Preoperative radiological detection of tumor-vein circumference contact >50% and/or venous wall deformity is associated with up to 80% of cases of pathological venous invasion. The combination of radiologic features with biological (CA19-9) and clinical (presence of preoperative chemotherapy) factors could better refine preoperatively the need for venous resection.

Preoperative Nutrition Support May Reduce the Prevalence of Postoperative Pancreatic Fistula after Open Pancreaticoduodenectomy in Patients with High Nutritional Risk Determined by NRS2002.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a severe complication which may be caused by a perioperative nutrition problem. We aimed to study whether patients with high nutritional risk (NRS2002 score ≥ 5) might benefit from preoperative nutrition support regarding the risk of CR-POPF after open pancreaticoduodenectomy. METHODS: Consecutive patients undergoing open pancreaticoduodenectomy with complete record of NRS2002 at two Chinese institutions between 2013 and 2018 were analysed. CR-POPF was diagnosed following the 2016 ISGPS criteria. Nutrition support included oral nutrition supplement and enteral and parenteral nutrition. Clinical and economic outcomes were analysed. RESULTS: 522 cases were included. 135 cases (25.9%) were at high nutritional risk (NRS2002 score ≥ 5), among which 41 cases (30.4%) received preoperative nutrition support. The CR-POPF rate was significantly lower in the preoperative nutrition support group compared with the no nutrition support group (12.2% versus 28.7%, P = 0.038). Multivariate analysis showed that preoperative nutrition support was a protective factor for CR-POPF in patients at high risk [OR 0.339, 95% CI (0.115-0.965), P = 0.039]. Higher albumin and a larger diameter of the main pancreatic duct were found to be other protectors for CR-POPF. CONCLUSIONS: Patients with high nutritional risk (NRS2002 score ≥ 5) may profit from preoperative nutritional support manifested in the reduction of CR-POPF.

Perioperative Nutritional Aspects in Total Pancreatectomy: A Comprehensive Review of the Literature.

Total pancreatectomy (TP) is a highly invasive procedure often performed in patients affected by anorexia, malabsorption, cachexia, and malnutrition, which are risk factors for bad surgical outcome and even may cause enhanced toxicity to chemo-radiotherapy. The role of nutritional therapies and the association between nutritional aspects and the outcome of patients who have undergone TP is described in some studies. The aim of this comprehensive review is to summarize the available recent evidence about the influence of nutritional factors in TP. Preoperative nutritional and metabolic assessment, but also intra-operative and post-operative nutritional therapies and their consequences, are analyzed in order to identify the aspects that can influence the outcome of patients undergoing TP. The results of this review show that preoperative nutritional status, sarcopenia, BMI and serum albumin are prognostic factors both in TP for pancreatic cancer to support chemotherapy, prevent recurrence and prolong survival, and in TP with islet auto-transplantation for chronic pancreatitis to improve postoperative glycemic control and obtain better outcomes. When it is possible, enteral nutrition is always preferable to parenteral nutrition, with the aim to prevent or reduce cachexia. Nowadays, the nutritional consequences of TP, including diabetes control, are improved and become more manageable.

Effect of preoperative nutritional supplementation on postoperative outcomes for patients undergoing pancreaticoduodenectomy for cancer: a systematic review protocol.

OBJECTIVE: This review aims to present the best available evidence related to the effect of preoperative nutritional supplementation on postoperative outcomes for patients undergoing pancreaticoduodenectomy for cancer. INTRODUCTION: Pancreaticoduodenectomy surgery is the only curative option for early head of pancreas and periampullary cancers. This complex, high-risk procedure is associated with significant morbidity, making opportunities to improve outcomes paramount. Nutritional supplementation in the preoperative period may enhance the body's ability to withstand the stress of major surgery and reduce postoperative complications. INCLUSION CRITERIA: This review will consider studies of patients undergoing pancreaticoduodenectomy for cancer who are provided preoperative nutritional supplementation in any form for a minimum of 48 hours. Randomized and quasi-randomized trials that compare any form of preoperative nutritional supplementation to standard care in these patients will be included. Outcome data will include hospital length of stay, mortality, infections, delayed gastric emptying, pancreatic fistula, anastomotic leak, hemorrhage, weight loss, body mass index, serum albumin, lymphocyte levels, and nutrition risk index score. METHODS: Electronic databases (PubMed, Scopus, CINAHL, and Cochrane Library) and trial registers will be searched for published and unpublished articles. All articles from database inception to present, published in any language will be included. One reviewer will perform the literature search, screen texts for inclusion, and extract data. Two authors will assess methodological quality of the literature using the JBI critical appraisal tool. Authors will be contacted where additional data or clarification is required. Statistical meta-analysis through synthesis and pooling of data for each intervention will be completed where meaningful. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020215307.

Hereditary vs Familial Pancreatic Cancer: Associated Genetic Syndromes and Clinical Perspective.

Pancreatic ductal adenocarcinoma (PDAC) is a disease marked by high rates of mortality; it is mostly incurable at the time of diagnosis. Only about 7% of patients survive 5 years after diagnosis. Diagnosis at a late stage and rapid progression with minimal response to available treatments are the main reasons for this poor outcome. It is crucial to identify individuals at high risk of developing PDAC so preventive and early detection measures can be employed. Approximately 10% to 15% of PDAC cases have a hereditary or familial basis. In the majority of PDAC cases, no main causative gene has been identified, but several known germline pathogenic mutations have been shown to be related to an increased risk of this cancer. The presence of 2 or more patients with pancreatic cancer within the circle of first-degree relatives, without the presence of a causative germline mutation, is defined as familial pancreatic cancer; this accounts for 4% to 10% of PDAC. Based on the growing evidence supporting the benefit of germline genetic testing in patients with PDAC, both the American Society of Clinical Oncology and the National Comprehensive Cancer Network recently updated their guidelines to include recommendations around genetic testing for patients with pancreatic cancer. However, there is no general consensus on the group of patients and individuals who should be studied and screened. We present a demonstrative case and review the available data on hereditary and familial PDAC.

Prognostic and predictive value of a five-molecule panel in resected pancreatic ductal adenocarcinoma: A multicentre study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a devastating prognosis. The performance of clinicopathologic parameters and molecules as prognostic factors remains limited and inconsistent. The present study aimed to construct a multi-molecule biomarker panel to more accurately predict post-resectional prognosis of PDAC patients. METHODS: Firstly, a novel computational strategy integrating prognostic evidence from omics and literature on the basis of bioinformatics prediction (CIPHER) to generate the network, was designed to systematically identify potential high-confidence PDAC-related prognostic candidates. After specimens from 605 resected PDAC patients were retrospectively collected, 23 candidates were detected immunohistochemically in tissue-microarrays for the development cohort to construct a multi-molecule panel. Lastly, the panel was validated in two independent cohorts. FINDINGS: According to the constructed five-molecule panel, disease-specific survival (DSS) was significantly poorer in high-risk patients than in low-risk ones in development cohort (HR 2.15, 95%CI 1.51-3.05, P<0.0001; AUC 0.67). In two validation cohorts, similar significant differences between the two groups were also observed (HR 3.18 and 3.31, 95%CI 1.89-5.37 and 1.78-6.16, All P<0.0001; AUC 0.72 and 0.73). In multivariate analyses, this panel was the sole prognosticator that was significant in each cohort. Furthermore, its predictive power for long-term survival, higher than its individual constituents, could be largely enhanced by combination with traditional clinicopathological variables. Finally, adjuvant chemotherapy (ACT) correlated with better DSS only in high-risk patients, uni- and multi-variately, in all the cohorts. INTERPRETATION: The novel prognostic panel developed by a systematically network-based strategy presents strong ability in prediction of post-resectional survival of PDAC patients. Furthermore, panel-defined high-risk patients might benefit more from ACT.

The Influence of Patients' Age on the Outcome of Treatment for Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: The aim of the study was to determine the impact of age on curative management and outcomes of patients with pancreatic ductal adenocarcinoma. METHODS: Patients who underwent resection for pancreatic ductal adenocarcinoma at 2 units were retrospectively reviewed (between 2005 and 2017) and stratified by age (older patients ≥70 years). Regression analysis was used to explore factors impacting administration of adjuvant chemotherapy and survival. The Kaplan-Meier method was used to estimate overall survival (time from surgery to death). Statistical significance was set at P < 0.05. RESULTS: From 2005 to 2014, 222 patients were identified (<70 years, n = 128; ≥70 years, n = 94). Elderly patients were less likely to receive adjuvant chemotherapy compared with younger patients (odds ratio, 0.57, P = 0.041). Tumor stage, margin, and year of surgery (post-2011 vs pre-2011) were not predictors for chemotherapy receipt (P > 0.05). Frailty was the commonest reason (36.8%) to decline chemotherapy in elderly patients. In patients receiving adjuvant chemotherapy, completion rates (P = 0.32) and overall survival (24 months vs 30 months, P = 0.50) were no different. CONCLUSIONS: Elderly patients demonstrate similar outcomes to younger yet are less likely to commence chemotherapy because of frailty. Holistic preoperative assessment may improve selection for curative treatment.

Neoadjuvant therapy versus upfront surgery for borderline-resectable pancreatic cancer.

BACKGROUND: Neoadjuvant therapy is recommended for patients with borderline-resectable pancreatic cancer (BRPC). In this study, we compare survival outcomes of neoadjuvant therapy with upfront surgery. METHODS: From January 2011 to June 2016, 1415 patients underwent treatments for pancreatic cancer in Samsung Medical Center. Among them, 112 (7.9%) patients were categorized as BRPC by the NCCN 2016 guideline. They were classified by type of initial treatments into neoadjuvant group (NA, N.=26) and upfront surgery group (US, N.=86). RESULTS: The median survival duration of all patients was 18.3 months. Patients in the NA group had more T4 disease than those in the US group (38.5% in NA versus 15.1% in the US group; P=0.010). Arterial involvement was more frequent in the NA group (42.3% versus 15.1%; P=0.003). In the NA group, ten (38.5%) patients underwent surgery, and seven of them had complete R0 resection. In the US group, 83 (96.5%) patients received radical surgery, and 42 (48.8%) had R0 resection. In survival analysis according to intent to treat, the overall two-year survival rate was 51.1% in the US group and 36.7% in the NA group (P=0.001). However, among patients who underwent surgery (N.=96), the two-year overall survival rate was not significantly different between the two groups (P=0.089). According to involved vessels, the survival rate was not different between patients with arterial or both arterial and venous involvement and in patients with only venous involvement (P=0.649). CONCLUSIONS: It is necessary to demonstrate the efficacy of neoadjuvant therapy and to standardize the regimens through large-scale, multicenter, randomized controlled studies.

Pathologic Response to Primary Systemic Therapy With FOLFIRINOX in Patients With Resectable Pancreatic Cancer.

BACKGROUND: Primary systemic therapy in resectable pancreatic cancer is currently under investigation. FOLFIRINOX has been shown to be effective in both the adjuvant and metastatic settings and is increasingly being used on and off study in the neoadjuvant setting. The objective pathologic response elicited by this regimen in truly resectable disease has not as yet been widely reported. METHODS: This analysis focuses on 14 patients with resectable pancreatic cancer who were treated in a pilot study of primary systemic therapy, using 4 cycles of neoadjuvant FOLFIRINOX before surgery. A dedicated pancreatic pathologist reviewed all of the subsequent surgical specimens to assess the degree of tumor regression elicited by this approach, according to the scoring system proposed by Evans. RESULTS: Four patients (28.6%) had Evans grade I, 4 (28.6%) Evans grade IIa, 2 (14.2%) Evans grade IIb, and 4 (28.6%) Evans grade III response to the primary systemic therapy. There were no Evans grade IV responses. CONCLUSIONS: The results are intriguing with 28% of the specimens showing destruction of <10% of tumor cells, and only 28% achieving >90% destruction of tumor cells. The significant variation in response once again confirms the known heterogeneity in the biology of this cancer and clearly FOLFIRINOX is not equally effective in all patients. Future studies evaluating primary systemic therapy in pancreatic cancer should examine the optimal duration of therapy before surgery and should include a standardized pathologic grading scheme to better enable comparison of results.

Synchronous pancreas and liver resection during CRS ± HIPEC. Results of 35 consecutive patients.

AIM: To evaluate the results of synchronous pancreas and liver resection in patients with metastatic carcinoma accompanied by peritoneal carcinomatosis (PC) who underwent cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC). MATERIAL AND METHODS: Overall, 35 patients with PC who underwent CRS/HIPEC at Umraniye Education and Research Hospital owing to different etiological causes were evaluated for operation procedure, age, sex, comorbid diseases, ASA score, systemic chemo/radiotherapy, duration of surgery, chemotherapy (CT) protocol applied in HIPEC, amount of bleeding, synchronous hepatobiliary resection interventions during operation and short/long-term mortality and morbidity. RESULTS: Fifteen patients were male and 20 were female. Mean age was 58.375 ± 13.02 (range, 27-85) years. CRS/HIPEC was performed in 12 patients (34.3%), whereas only CRS was performed in 23 (65.7%) patients. The lowest and highest perioperative bleeding amount was 50 cc and 2000 cc, respectively, and 6 (17.1%) patients had intraoperative bleeding of ≥1000 cc. Synchronous isolated pancreatic resection, hepatic + pancreatic resection and isolated liver resection was performed in 3 (8.6%), 5 (14.3%) and 27 (77.1%) patients treated with CRS/HIPEC. Two patients died within postoperative day 30, and the mortality rate was 5.7%. CONCLUSION: Hepatopancreatobiliary surgery is a difficult intervention and is associated with serious morbidities. Synchronisation of hepatopancreatobiliary surgery with CRS/HIPEC may be challenging for the surgeon and clinician. Here we emphasise that this combination can be performed safely by an experienced team with a multidisciplinary approach and good patient preparation. KEY WORDS: Cytoreductive surgery, HIPEC, Hepatopancreatobiliary surgery, Peritoneal carcinomatosis.

[Pure laparoscopic DP-CAR procedure with portal vein resection]. / Polnost'yu laparoskopicheskaya dp-car s rezektsiei vorotnoi veny (klinicheskoe nablyudenie).

OBJECTIVE: To improve short- and long-term outcomes of locally advanced pancreatic body-tail cancer followed by major vessels invasion. MATERIAL AND METHODS: A case report of pure laparoscopic DP-CAR procedure with portal vein resection for locally advanced pancreatic body-tail cancer followed by severe abdominal pain in a 49-year-old patient is presented. RESULTS: Liver or stomach ischemia was not observed. Portal wall resection wasn't associated with any complication and resulted R0-resection. Postoperative period was complicated by Grade B pancreatic fistula. Preoperative abdominal pain completely disappeared after surgery. Surgery time was 330 min, intraoperative blood loss - 300 ml. The patient is currently undergoing FOLFIRINOX adjuvant chemotherapy. CT in 90 days after surgery confirmed no progression of disease or liver/stomach blood supply congestion. CONCLUSION: Modern technologies provide the opportunity to perform pure laparoscopic advanced surgical procedures with major vessels resection. Pure laparoscopic DP-CAR procedure with portal vein resection is effective and safe procedure that can be performed with all principles of open surgery and is associated with acceptable short- and long-term results.

Protocol of a prospective, monocentric phase I/II feasibility study investigating the safety of multimodality treatment with a combination of intraoperative chemotherapy and surgical resection in locally confined or borderline resectable pancreatic cancer: the combiCaRe study.

INTRODUCTION: Pancreatic cancer is a devastating disease with an exceptionally poor prognosis. Complete resection of the primary tumour followed by adjuvant chemotherapy is the current standard treatment for patients with resectable disease and the only curative treatment option. However, long-term survival remains rare. Tumour cell dissemination due to manipulation during surgery may increase the rate of future metastases and local recurrence, and perioperative chemotherapy might diminish local, distant and circulating minimal residual disease. Yet, safety and feasibility of systemic chemotherapeutic treatments during pancreatic cancer resection have to be evaluated in a first instance. METHODS AND ANALYSIS: This is a prospective, single-centre phase I/II feasibility study to investigate the safety and tolerability of a combination of intraoperative chemotherapy and surgical resection in pancreatic cancer. Forty patients with locally confined or borderline resectable pancreatic cancer, meeting all proposed criteria will be included. Participants will receive 400 mg/m2 calcium folinate over 2 hours and 2000 mg/m2 5-fluorouracil over 48 hours, started on the day before pancreatic surgery and thus continuing during surgery. Participants will be followed until 60 days after surgery. The primary endpoint is the 30-day overall complication rate according to the Clavien-Dindo classification. Secondary endpoints comprise toxicity and treatment associated complications. Patients receiving perioperative chemotherapy will be compared with a propensity score matched contemporary control group of 70 patients with pancreatic cancer receiving the standard treatment. This trial also contains an ancillary translational study to analyse disseminated tumour cells and effects of pharmacological interventions in pancreatic cancer. ETHICS AND DISSEMINATION: CombiCaRe has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4042787) and the Medical Ethics Committee of Heidelberg University (reference number AFmo-269/2018). The results of this trial will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: German Clinical Trials Register (DRKS00015766).

Predicting Pancreatic Cancer Resectability and Outcomes Based on an Objective Quantitative Scoring System.

OBJECTIVE: To quantitatively assess the probability of tumor resection based on measurements of tumor contact with the major peripancreatic vessels. METHODS: This is a retrospective cohort study of pancreatic cancer patients treated between January 2001 and December 2015 in a single academic comprehensive cancer center. Radiographic measurements of the circumferential degree and length of solid tumor contact with major peripancreatic vessels were obtained from diagnostic pancreatic protocol computed tomography images and tested for correlation with tumor resection and margin status. RESULTS: Of 294 patients analyzed, 113 (38%) were resected, with 71 (63%) with negative margins. Based on the individual measurements of vascular involvement, a resectability scoring system (RSS) was created. The RSS correlated strongly with resection (P < 0.0001) and R0 resection (P < 0.0001) probabilities. Moreover, the RSS correlated with overall survival (P < 0.0001) and metastasis-free survival (P < 0.0001), being able to substratify resectable (P = 0.022) and unresectable patients (P = 0.014) into subgroups with different prognosis based on RSS scores. CONCLUSIONS: Based on a comprehensive and systematic quantitative approach, we developed a scoring system that demonstrated excellent accuracy to predict tumor resection, surgical margin status, and prognosis.

Conversion surgery for initially unresectable pancreatic cancer: current status and unresolved issues.

Pancreatic cancer is one of the most lethal of all malignancies. One of the reasons for the dismal prognosis is that most diagnoses are made when the disease is either locally advanced or metastatic. Recent advances in chemotherapy and chemoradiotherapy (CRT) enable "conversion surgery" to be performed for selected patients with initially unresectable pancreatic cancer following favorable responses to preoperative treatment. Using FOLFIRINOX as preoperative treatment, the resection rate was reported as 6-44% of patients with locally advanced cancer and the prognosis of these patients was favorable. Even for metastasized cancer, recent reports show the effectiveness of conversion surgery, which has achieved 27-56 months of median overall survival. However, there are many unanswered questions about conversion surgery. The optimal regimen and duration of preoperative treatment remain unclear and there is still debate regarding the safety and effectiveness of vascular resection, which is often required for curative resection of locally advanced cancer. Accumulation of more data on conversion surgery is required to establish the safety and effectiveness of this treatment. In this review, we summarize the current status and unresolved issues about conversion surgery for initially unresectable pancreatic cancer.

Added value of intra-operative ultrasound to determine the resectability of locally advanced pancreatic cancer following FOLFIRINOX chemotherapy (IMAGE): a prospective multicenter study.

BACKGROUND: Determining the resectability of locally advanced pancreatic cancer (LAPC) after FOLFIRINOX chemotherapy is challenging because CT-scans cannot reliably assess vascular involvement. This study evaluates the added value of intra-operative ultrasound (IOUS) in LAPC following FOLFIRINOX induction chemotherapy. METHODS: Prospective multicenter study in patients with LAPC who underwent explorative laparotomy with IOUS after FOLFIRINOX chemotherapy. Resectability was defined according to the National Comprehensive Cancer Network guidelines. IOUS findings were compared with preoperative CT-scans and pathology results. RESULTS: CT-staging in 38 patients with LAPC after FOLFIRINOX chemotherapy defined 22 patients LAPC, 15 borderline resectable and one resectable. IOUS defined 19 patients LAPC, 13 borderline resectable and six resectable. In 12/38 patients, IOUS changed the resectability status including five patients from borderline resectable to resectable and five patients from LAPC to borderline resectable. Two patients were upstaged from borderline resectable to LAPC. Tumor diameters were significantly smaller upon IOUS (31.7 ± 9.5 mm versus 37.1 ± 10.0 mm, p = 0.001) and resectability varied significantly (p = 0.043). Ultimately, 20 patients underwent resection of whom 14 were evaluated as (borderline) resectable on CT-scan, and 17 on IOUS. DISCUSSION: This prospective study demonstrates that IOUS may change the resectability status up to a third of patients with LAPC following FOLFIRINOX chemotherapy.

Duodenum-preserving pancreatic head resection: A retrospective analysis of the Hamburg Modification.

BACKGROUND: Chronic pancreatitis remains a challenging inflammatory disease, causing progressive, irreversible fibrosis of the pancreatic parenchyma. Several surgical options for treatment have been established, but duodenum-preserving pancreatic head resections seem to be the most favorable option other than pancreatoduodenectomy. The aim of this retrospective analysis is to evaluate the outcomes of the Hamburg modification of duodenum-preserving pancreatic head resections. METHODS: We retrospectively evaluated-for long-term outcomes concerning pain control, quality of life, and symptom control-500 consecutive patients suffering from painful chronic pancreatitis who had undergone the Hamburg modification of the duodenum-preserving pancreatic head resection. Additionally, the patients were compared with a database of 104 patients who underwent duodenum-preserving pancreatic head resections according to Beger or Frey. RESULTS: After a mean follow-up of 10 years, overall survival was 90% in those patients having undergone the Hamburg modification. Regarding analgetic medications, the median pain score for frequency of pain attacks, measured by a visual analog scale and inability to work, was 0 (0-100), and the global quality of life revealed a median of 92 (0-100). In addition, we found that a high rate of patients continued consuming alcohol after the operation (37.9%). The rate of redo surgery owing to the recurrence of chronic pancreatitis was 7.6% after this Hamburg modification. CONCLUSION: Duodenum-preserving pancreatic head resections provide adequate outcomes in terms of pain control, quality of life, and symptom control. In this retrospective analysis, the Hamburg modification was found to be a good alternative to other forms of duodenum-preserving pancreatic head resections. The choice of a certain modification of the duodenum-preserving pancreatic head resection may depend on the surgeon's expertise and the individual needs of the patient.