Patient outcome according to the 2017 international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVE: We evaluated the usefulness of the 2017 definition of borderline pancreatic ductal adenocarcinoma (BR-PDAC) in fit patients (performance status 0-1) based on anatomical (A) and biological dimensions (B). METHODS: From 2011 to 2018, 139 resected patients with BR-PDAC according to the 2017 definition were included: 18 patients underwent upfront pancreatectomy (CA 19-9 > 500 U/mL and/or regional lymph node metastasis; BR-B group), and 121 received FOLFIRINOX (FX) induction chemotherapy and were divided into BR-A (CA 19-9 < 500 U/mL, no regional lymph node metastasis; n = 68) and BR-AB (CA 19-9 > 500 U/mL and/or regional lymph node metastasis; n = 53) groups. RESULTS: The 3 groups were comparable according to patient characteristics (except for back pain (P < .01) and CA 19-9 (P < .01)), intraoperative data, and postoperative courses. BR-AB patients required more venous resections (P < .01). The 3 groups were comparable on pathologic findings, except that BR-B patients had more lymph node invasions (P = .02). Median overall survival (OS) of the 121 patients was 45 months. In multivariate analysis, venous resection (P = .039) and R1 resection (P = .012) were poorly linked with OS, whereas BR-A classification (P < .01) independently favored OS. Median survival times of BR-A, BR-AB, and BR-B groups were undetermined, 27 months, and 20 months (P < .001), respectively. CONCLUSIONS: The 2017 definition was relevant for sub-classifying patients with BR-PDAC. The anatomical dimension (BR-A) was a favorable prognostic factor, whereas the biological dimension (BR-AB and BR-B) poorly impacted survival.

Has the non-resection rate decreased during the last two decades among patients undergoing surgical exploration for pancreatic adenocarcinoma?

PURPOSE: To determine if improvement in imaging reduces the non-resection rate (NRR) among patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: From 2000 to 2019, 751 consecutive patients with PDAC were considered eligible for a intention-to-treat pancreatectomy and entered the operating room. In April 2011, our institution acquired a dual energy spectral computed tomography (CT) scanner and liver diffusion weighted magnetic resonance imaging (DW-MRI) was included in the imaging workup. We consequently considered 2 periods of inclusion: period #1 (February 2000-March 2011) and period #2 (April 2011-August 2019). RESULTS: All patients underwent a preoperative CT scan with a median delay to surgery of 18 days. Liver DW-MRI was performed among 407 patients (54%). Median delay between CT and surgery decreased (21 days to 16 days, P < .01), and liver DW-MRI was significantly most prescribed during period #2 (14% vs 75%, P < .01). According to the intraoperative findings, the overall NRR was 24.5%, and remained stable over the two periods (25% vs 24%, respectively). While vascular invasion, liver metastasis, and carcinomatosis rates remained stable, para-aortic lymph nodes invasion rate (0.4% vs 4.6%; P < 0.001) significantly increased over the 2 periods. The mean size of the bigger extra pancreatic tumor significantly decrease (7.9 mm vs 6.4 mm (P < .01), respectively) when the resection was not done. In multivariate analysis, CA 19-9 < 500 U/mL (P < .01), and liver DW-MRI prescription (P < .01) favoured the resection. CONCLUSIONS: Due to changes in our therapeutic strategies, the NRR did not decrease during two decades despite imaging improvement.

'Peripheric' pancreatic cysts: performance of CT scan, MRI and endoscopy according to final pathological examination.

OBJECTIVE: To assess the accuracy of pre-operative staging in patients with peripheral pancreatic cystic neoplasms (pPCNs). METHODS: From 2005 to 2011, 148 patients underwent a pancreatectomy for pPCNs. The pre-operative examination methods of computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS) were compared for their ability to predict the suggested diagnosis accurately, and the definitive diagnosis was affirmed by pathological examination. RESULTS: A mural nodule was detected in 34 patients (23%): only 1 patient (3%) had an invasive pPCN at the final histological examination. A biopsy was performed in 79 patients (53%) during EUS: in 55 patients (70%), the biopsy could not conclude a diagnosis; the biopsy provided the correct and wrong diagnosis in 19 patients (24%) and 5 patients (6%), respectively. A correct diagnosis was affirmed by CT, EUS and pancreatic MRI in 60 (41%), 103 (74%) and 80 (86%) patients (when comparing EUS and MRI; P = 0.03), respectively. The positive predictive values (PPVs) of CT, EUS and MRI were 70%, 75% and 87%, respectively. CONCLUSIONS: Pancreatic MRI appears to be the most appropriate examination to diagnose pPCNs accurately. EUS alone had a poor PPV. Mural nodules in a PCN should not be considered an indisputable sign of pPCN invasiveness.

BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer.

BACKGROUND: Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways. A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and had activity in advanced pancreatic cancer (APC) patients. The BAYPAN study was a multicentric, placebo-controlled, double-blind, randomized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC. PATIENTS AND METHODS: The patient eligibility criteria were locally advanced or metastatic pancreatic adenocarcinoma, no prior therapy for advanced disease and a performance status of zero to two. The primary end point was progression-free survival (PFS). The patients received gemcitabine 1000 mg/m(2) i.v., weekly seven times followed by 1 rest week, then weekly three times every 4 weeks plus sorafenib 200 mg or placebo, two tablets p.o., twice daily continuously. RESULTS: Between December 2006 and September 2009, 104 patients were enrolled on the study (52 pts in each arm) and 102 patients were treated. The median and the 6-month PFS were 5.7 months and 48% for gemcitabine/placebo and 3.8 months and 33% for gemcitabine/sorafenib (P = 0.902, stratified log-rank test), respectively. The median overall survivals were 9.2 and 8 months, respectively (P = 0.231, log-rank test). The overall response rates were similar (19 and 23%, respectively). CONCLUSION: The addition of sorafenib to gemcitabine does not improve PFS in APC patients.

Reduced interleukin-12 release from stimulated monocytes in patients with sepsis after major cancer surgery.

BACKGROUND: Major cancer surgery is a high-risk situation for sepsis in the post-operative period. The aim of this study was to assess the relation between the monocyte production of IL-12 and the development of post-operative sepsis in patients undergoing major cancer surgery. METHODS: In 19 patients undergoing major cancer surgery, the production of cytokines by basal and lipolysaccharide (LPS)-stimulated monocytes was measured before and after (from day 1 to day 3 and day 7) surgery. Seven of them developed a post-operative sepsis. Ten healthy volunteers were used as controls for the assessment of pre-operative values. RESULTS: Before surgery, the production of interleukin (IL)-12 p40 by LPS-stimulated monocytes was similar in the patients and the healthy volunteers. The production of IL-12 p40 by unstimulated monocytes was higher in the patients than in the healthy volunteers. IL-12 production did not differ between the septic and the non-septic patients. After surgery, the production of IL-12 p40 was dramatically reduced in the LPS-stimulated monocytes of the septic patients from day 1 to day 3, as compared with that of the non-septic patients. Before surgery, the production of IL-6, IL-10, and IL-1 receptor antagonist (IL-1ra) in the patients was significantly higher than that of the healthy volunteers for both stimulated and unstimulated monocytes. After surgery, the production of these cytokines by both stimulated and unstimulated monocytes of the septic patients was similar to that of the non-septic patients. Intragroup analysis showed significant changes for IL-6, IL-10, and IL-1ra under all conditions, with the exception of changes in unstimulated monocytes of septic patients that were not significant for IL-10 release. CONCLUSION: After surgery, the septic patients showed drastic failure to up-regulate monocyte LPS-stimulated production of IL-12 p40.

Genetic alterations in precancerous pancreatic lesions and their clinical implications.

Pancreatic adenocarcinoma, with an incidence/death ratio of 0.99, has the worst prognosis of all cancers. Risk factors associated with the sporadic form of pancreatic adenocarcinoma are unknown and less than 10% of patients receive curative treatment (surgery associated with radiation therapy or chemotherapy) with a low 5-year survival rate (10 to 20%). In more than 90% of patients, the tumor discovered at diagnosis is not resectable or has already metastasized. Thus, a better understanding of the etiology of pancreatic cancer is essential to identify new prognostic markers and new therapeutic targets. There is a wealth of data on the identification of genetic alterations associated with pancreatic cancer and their role in its development. This review will focus on the current knowledge of genetic alterations associated with two pancreatic lesions that can potentially evolve into pancreatic adenocarcinoma, Pancreatic Intraepithelial Neoplasia (PanIN) and Intraductal Papillary Mucinous Neoplasm (IPMN). These two lesions share a large panel of typical genetic alterations which are close to those found in pancreatic adenocarcinoma. A better understanding of these alterations may lead to therapeutic targets that could help prevent the progression of PanIN and IPMN to cancer.

Outcomes of pancreatic adenocarcinoma that was not resected because of isolated para-aortic lymph node involvement.

PURPOSE: Survival appears to be poor in cases of pancreatic ductal adenocarcinoma (PDAC) with para-aortic lymph node involvement (PALN+). However, resection is still performed in these cases because the prognostic impact of PALN+remains controversial. METHODS: PALN+was intraoperatively found in 14 patients (4.8%) with resectable PDAC who consequently did not undergo pancreatectomy. RESULTS: The median overall survival time after laparotomy was 21 months. The 1- and 3-year overall survival rates were 58.3% and 25%, respectively. CONCLUSIONS: We support the advisability of reconsidering pancreatectomy in patients with intraoperatively detected PALN+because the reported survival of such patients who undergo pancreatectomy is poorer than the survival observed for patients in our series.

Risk factors of exocrine and endocrine pancreatic insufficiency after pancreatic resection: A multi-center prospective study.

Management of functional consequences after pancreatic resection has become a new therapeutic challenge. The goal of our study is to evaluate the risk factors for exocrine (ExoPI) and endocrine (EndoPI) pancreatic insufficiency after pancreatic surgery and to establish a predictive model for their onset. PATIENTS AND METHODS: Between January 1, 2014 and June 19, 2015, 91 consecutive patients undergoing pancreatoduodenectomy (PD) or left pancreatectomy (LP) (72% and 28%, respectively) were followed prospectively. ExoPI was defined as fecal elastase content<200µg per gram of feces while EndoPI was defined as fasting glucose>126mg/dL or aggravation of preexisting diabetes. The volume of residual pancreas was measured according to the same principles as liver volumetry. RESULTS: The ExoPI and EndoPI rates at 6 months were 75.9% and 30.8%, respectively. The rate of ExoPI after PD was statistically significantly higher than after LP (98% vs. 21%; P<0.001), while the rate of EndoPI was lower after PD vs. LP, but this difference did not reach statistical significance (28% vs. 38.5%; P=0.412). There was no statistically significant difference in ExoPI found between pancreatico-gastrostomy (PG) and pancreatico-jejunostomy (PJ) (100% vs. 98%; P=1.000). Remnant pancreatic volume less than 39.5% was predictive of ExoPI. CONCLUSION: ExoPI occurs quasi-systematically after PD irrespective of the reconstruction scheme. The rate of EndoPI did not differ between PD and LP.

Strategies for the treatment of synchronous liver metastasis.

AIM: Observe the outcomes after complete simultaneous or delayed resection of synchronous liver metastasis (SLM) from colorectal cancer (CRC). METHODS: From 1994 to 2005, 119 patients were diagnosed with CRC and SLM; 57 patients had simultaneous resection (group I) and 62 patients had staged resection (group II). Perioperative chemotherapy was considered completed if all expected cycle were administrated. RESULTS: Overall survival rates of group I-group II at 1, 3 and 5 years were respectively 91%-93% (p=0,3), 59%-57% (p=0,09) and 32%-25% (p=0,06). The median survival time of group I-group II were respectively 46 months-40 months (p=0,07). There was no statistical difference on survival regarding location of metastasis (p=0,09) or primary tumor location (p=0,2). Patients with simultaneous or staged resection receiving optimal treatment (R0 liver surgery and complete chemotherapy) were respectively 89% and 67% (p=0,04). Twenty three patients developed isolated liver recurrence with higher frequency in staged patients (26% vs 9% p=0,03) without impairment of survival. CONCLUSIONS: Because of postoperative morbidity and prolonged tiring treatment, many patients having staged resection were under treated. However we did not observe statistical difference on survival but we supported that simultaneous resection has to be prefer to achieve an optimal treatment. Lung and bone metastasis are the new challenge for oncologists.

Resectable pancreatic head adenocarcinoma: Is R0 resection an illusion? Genetic evaluation of venous resection margin affirmed unrecognized disease.

PURPOSE: To assess the K-ras gene mutation in the histologically negative venous margin of a pancreaticoduodenectomy (PD) specimen and its impact on survival. METHOD: From 2007 to 2010, 22 patients underwent R0 PD for resecable pancreatic adenocarcinoma. All specimens were stained and the portal vein (PV) bed was identified by blue ink; a 2mm3 sample (including the blue ink) was cut from a microscopic free-tumor block. DNA was extracted and assessed by quantitative real time polymerase chain reaction to detect the K-ras gene mutation. Twelve specimens (55%) (kras+ group) were identified with a K-ras mutation in the venous margin resection, and 10 specimens (kras- group) did not have K-ras mutation detected in the venous margin resection. RESULTS: The two groups were comparable. Overall 3years survival of patients of kras+ group versus patients of kras- group was 0 and 17% (P=0.03), respectively. Median survival time of patients of kras+ group versus patients of kras- group was 16months vs 25months (P=0.04; 95% confidence interval [1,11-1,88]), respectively. CONCLUSION: Genetic evaluation of venous resection margin affirmed unrecognized disease with strong impact on survival in more than 50% of patients with histologically R0 resection.

Resectable invasive IPMN versus sporadic pancreatic adenocarcinoma of the head of the pancreas: Should these two different diseases receive the same treatment? A matched comparison study of the French Surgical Association (AFC).

PURPOSE: To compare survival and impact of adjuvant chemotherapy in patients who underwent pancreaticoduodenectomy (PD) for invasive intraductal papillary mucinous neoplasm (IIPMN) and sporadic pancreatic ductal adenocarcinoma (PDAC). METHODS: From 2005 to 2012, 240 patients underwent pancreatectomy for IIPMN and 1327 for PDAC. Exclusion criteria included neoadjuvant treatment, pancreatic resection other than PD, vascular resection, carcinoma in situ, or <11 examined lymph nodes. Thus, 82 IIPMN and 506 PDAC were eligible for the present study. Finally, The IIPMN group was matched 1:2 to compose the PDAC group according to TNM disease stage, perineural invasion, lymph node ratio, and margin status. RESULTS: There was no difference in patient's characteristics, intraoperative parameters, postoperative outcomes, and histologic parameters. Overall survival and disease-free survival times were comparable between the 2 groups. In each group, overall survival time was significantly poorer in patients who did not achieve adjuvant chemotherapy (p = 0.03 for the IIPMN group; p = 0.03 for the PDAC group). In lymph-node negative patients of the IIPMN group, adjuvant chemotherapy did not have any significant impact on overall survival time (OR = 0.57; 95% CI [0.24-1.33]). Considering the whole population (i.e. patients with IIPMN and PDAC; n = 246), patients who did not achieve adjuvant chemotherapy had poorer survival (p < 0.01). CONCLUSIONS: The courses of IIPMN and PDAC were similar after an optimized stage-to-stage comparison. Adjuvant chemotherapy was efficient in both groups. However, in lymph node negative patients, adjuvant chemotherapy seemed not to have a significant impact.

Long term morbidity of neoadjuvant chemoradiation for pancreatic head adenocarcinoma.

PURPOSE: To report the long term risks of neoadjuvant chemoradiation (NCRT) after duodenopancreatectomy (DP) for adenocarcinoma of the head of pancreas. METHODS: Between January 1996 and December 2002, 26 patients with biopsy-proven adenocarcinoma of the head of pancreas were treated by this combination of therapies. RESULTS: Two patients had delayed NCRT-related small bowel infarction: one died from superior mesenteric artery stenosis 36 months after DP without recurrence at laparotomy; there was one limited infarction 16 months after DP. CONCLUSIONS: Long term vascular morbidity after NCRT is significant.

[Locally advanced pancreatic adenocarcinoma. Chemoradiotherapy, reevaluation and secondary resection]. / Adénocarcinomes pancréatiques localement évolués. Chimioradiothérapie, réévaluation et résection secondaire ?

UNLABELLED: Induction chemoradiotherapy (CRT) may downstage locally advanced pancreatic tumors but secondary resections are unfrequent. However some responders' patients may benefit of a R0 resection. PATIENTS AND METHODS: We report 18 resections among 29 locally advanced pancreatic cancers; 15 patients were treated with neoadjuvant 5-FU-cisplatin based (13) or taxotere based (2 patients) chemoradiotherapy (45 Gy), and 3 patients without histologically proven adenocarcinoma were resected without any preoperative treatment. RESULTS: The morbidity rate was 28% and the mortality rate was 7%; one patient died after resection (5.5%) and one died after exploration (9%). The R0 resection rate was 50%. The median survival for the resected patients was not reached and the actuarial survival at 3 years was 59%. Two specimens showed no residual tumor and the two patients were alive at 15 and 46 months without recurrence; one specimen showed less than 10% viable tumoral cells and the patient was alive at 36 months without recurrence. A mesenteric infarction was the cause of a late death at 3 years in a disease free patient (radiation induced injury of the superior mesenteric artery). The median survival of the 11 non-resected patients was 21 months and the actuarial survival at 2 years was 0%. When the number of the resected patients (18) was reported to the entire cohort of the patients with locally advanced pancreatic cancer treated during the same period in our institution, the secondary resectability rate was 9%. CONCLUSION: Preoperative chemoradiotherapy identifies poor surgical candidates through observation and may enhance the margin status of patients undergoing secondary resection for locally advanced tumors. However it remains difficult to evaluate the results in the literature because of the variations in the definitions of resectability. The best therapeutic strategy remains to be defined, because the majority of patients ultimately succumb with distant metastatic disease.

[Major hepatectomy for metastasis of colorectal cancer improves survival in the elderly]. / Hépatectomie majeure pour métastases de cancers colorectaux chez le sujet âgé.

OBJECTIVE: Assessing impact of major liver resection (LR) for hepatic metastasis of colorectal cancer (HMCC) on post operative courses and long term survival in the elderly. PATIENTS AND METHOD: Thirty-three consecutive patients aged over 70 years-old were treated in our institution for up to 3 resectable metachronous HMCC. Fifteen patients had major LR (9 right hepatectomy, 3 extended right hepatectomy, 3 left hepatectomy) without pre or postoperative chemotherapy (group 1) and 18 patients were exclusively treated by chemotherapy (group 2) because of high ASA score (ASA 3) or patients refusal. RESULTS: No patients died of another cause that colorectal cancer disease during observation time. All patients of group 2 died during observation time. Post operative mortality and morbidity of group 1 were respectively 0% and 33%. Survival at 1 and 2 years of group 1-2 were respectively 73-50% (P=0,04) and 47-15% (P=0,05). Median survival of group 1 and 2 were respectively 22 and 12 months (P=0,03). CONCLUSIONS: Major LR for HMCC could be proposed regardless the age. High ASA score, multiple (more than 4) metastasis location, evolutive disease could justify an exclusive medical approach.

Gastric duplication in an adult mimicking mucinous cystadenoma of the pancreas.

Gastric duplication cyst (GDC) in an adult can have several clinical presentations. A review of the literature showed previously reported cases of GDC presenting as pancreatic pseudocyst or with greatly raised concentrations of carbohydrate antigen 19-9 (CA 19-9). It is often difficult to discriminate GDC from pancreatic cystic tumour, in particular pancreatic mucinous cystadenoma, in which concentrations of carcinoembryonic antigen and CA 19-9 are classically raised. This report describes an adult case of GDC mimicking a mucinous cystadenoma of the pancreas. This is the first report of a simultaneous increase in carcinoembryonic antigen and CA 19-9 in GDC in the absence of malignancy. Although few cases of carcinoma arising from a GDC having been reported, the production of oncofetal antigens raises the problem of a precancerous condition in long standing intestinal duplications. In this situation surgical resection must be performed.

A reappraisal of preoperative chemoradiation for localized pancreatic head ductal adenocarcinoma in a 5-year single-institution experience.

Resection of localized pancreatic head ductal adenocarcinoma (LPHDA) has a limited impact on survival. Mechanisms of improvement provided by preoperative chemoradiation therapy (CRT) remain under debate. This study analyzes the outcome of patients treated for LPHDA to delineate the benefits of CRT. Among 87 patients with LPHDA, 17 had a pancreaticoduodenectomy alone (group I). Thirty-nine with initially resectable cancers received CRT with 5-fluorouracil-based chemotherapy (group II). Thirty-one with initially unresectable cancers were similarly treated by CRT (group III). Patients in groups II and III were restaged after completion of CRT. In patients with resectable disease, resection was planned. Patients in groups I and II were statistically comparable in terms of age, sex, and pretherapeutic stage. Median survival and 2-year overall survival in group I were 13.7 months and 31%, respectively. In group II, 23 patients (59%) had a pancreaticoduodenectomy (group IIa) and 16 patients (41%) did not have resection (group IIb). Median survival and 2-year overall survival were as follows: group IIa, 26.6 months and 51%; and group IIb, 6.1 months and 0%, respectively. In group IIa, pathologic examination revealed eight major responses (35%) including two sterilized specimens, and none of the patients had locoregional recurrence. In group III, none of the patients had resection, and median survival was 8 months with one 2-year survivor. Patient selection appears to play a major role with regard to results achieved with preoperative CRT followed by pancreaticoduodenectomy. However, a high histologic response rate and excellent local control can also be achieved.

High incidence of colic anastomotic leakage complicating upper abdominal en bloc evisceration for cancer: a 47-patient series.

BACKGROUND/AIMS: The purpose of this study was to analyze the early outcome of en bloc extended resection for upper abdominal locally advanced cancer. METHODOLOGY: A retrospective medical chart review was performed in 47 consecutive patients who underwent an upper abdominal en bloc resection for cancer involving multiple organs or structures at Paoli-Calmettes Institute and Conception Hospital from October 1988 through April 1997. A third of patients underwent a resection of 4 sus mesocolic organs or more. RESULTS: The postoperative morbidity and mortality rate were respectively, 57% and 19%. Despite a high number of theoretically risky procedures including pancreatic resection and pancreatojejunostomy, total gastrectomy and esophagojejunostomy, total hepatectomy and liver transplantation, the higher percentage of complication was found with colic anastomosis. Five of the 30 patients (17%) who underwent a colic anastomosis developed a colic anastomotic leakage, 4 patients were reoperated and 2 patients died. CONCLUSIONS: Because of this unacceptably high rate of complications, we propose to systematically perform a protective stoma when an upper abdominal evisceration includes a colic anastomosis.

Pancreatic neuroendocrine tumor: A multivariate analysis of factors influencing survival.

BACKGROUND: The outcomes of pancreatic neuroendocrine tumors are extremely diverse, and determining the best strategy, optimal timing of therapy and the therapeutic results depend on understanding prognostic factors. We determined the clinical, radiological and histological factors associated with survival and tumor recurrence for patients with pancreatic neuroendocrine tumor. METHODS: From January 1, 1991 to December 31, 2011, 127 patients with pancreatic neuroendocrine tumor underwent pancreatectomy. The variables including clinical characteristics, surgical data and pathological findings were examined by univariate and multivariate analyses. RESULTS: There were 103 patients with non-functional tumors (81%). Sixty-four patients (50%) underwent left pancreatectomy, 51 (42%) patients underwent pancreatico-duodenectomy, 12 (9%) patients underwent enucleation and 2 patients (1%) underwent central pancreatectomy. Forty-eight patients (38%) had synchronous liver metastases. Six patients (5%) required portal vein resection, and 19 (15%) patients required enlarged "en-bloc" resection of adjacent organs. The overall morbidity and mortality rates were 48% and 2.3%, respectively. The 1-, 3- and 5-year overall survival rates were 94%, 84%, and 74%, respectively. In multivariate analyses, synchronous liver metastases (p = 0.02) and portal vein resection (p < 0.01) were independent prognostic factors of survival. CONCLUSIONS: Synchronous liver metastases and portal vein resection were found to be independent factors influencing survival.