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Pascal Hammel

Publications and source records attributed to Pascal Hammel.

At least 19 recordsLinked to original sources

Impact of Tumor Genomic Profile on Adjuvant Chemotherapy Efficacy in Resected Pancreatic Adenocarcinoma: Results From the PRODIGE-24/CCTG PA6 Study.

PURPOSE: Modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX/mFFX) is the standard adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC), offering survival benefits over gemcitabine (GEM). However, the contribution of molecular biomarkers to treatment selection remains unclear. Here, we characterize the molecular landscape of tumors from the PRODIGE-24/CCTG PA6 trial and assess the clinical impact of genomic alterations and molecular subtypes. PATIENTS AND METHODS: Tumor DNA sequencing was successfully performed in 317/350 tumors (168 mFFX; 149 GEM), complemented by transcriptomic subtyping using the PurIST classifier. Mutational status of four key PDAC driver genes and 24 homologous recombination repair (HRR)-associated genes was analyzed, alongside single-base substitution (SBS) mutational signatures. Primary and secondary end points were disease-free survival (DFS) and cancer-specific survival (CSS), respectively. RESULTS: In the mFFX group, the PurIST subtype was prognostic, with classical tumors showing superior DFS compared with basal-like tumors (stratified hazard ratio [sHR], 0.48 [95% CI, 0.31 to 0.77]). Among KRAS-mutated patients, mFFX significantly improved DFS compared with GEM (sHR, 0.60 [95% CI, 0.45 to 0.79]; P < .001), while no benefit was observed in KRAS wild-type tumors (interaction test, Pint. = 0.010). HRR and BRCA status were not predictive (Pint. = .568 and Pint. = .785, respectively). The benefit of mFFX was consistent across SBS-positive and SBS-negative subgroups. CONCLUSION: Overall, these results do not support a change in current adjuvant treatment strategies. mFFX remains the standard adjuvant regimen in PDAC, and the observed lack of benefit in KRAS wild-type tumors should be considered hypothesis-generating and warrants further investigation.

Humans↗

Natural history of intraductal papillary mucinous tumors of the pancreas: actuarial risk of malignancy.

BACKGROUND & AIMS: Natural history of intraductal papillary mucinous tumors of the pancreas (IPMTs) is unknown. Cross-sectional studies suggest that exclusive branch duct (BD) involvement is associated with a lower risk of carcinoma than main pancreatic duct (MPD) involvement. The aim of our study was to calculate longitudinal risk of malignant transformation of IPMT since the first sign. METHODS: All the patients with a diagnosis of highly probable or histologically proven IPMT were included. Actuarial risks of occurrence of at least low-grade dysplasia (>or=LGD), high-grade dysplasia (>or=HGD), or invasive carcinoma (IC) were calculated by Kaplan-Meier method from the first sign attributable to IPMT. The risks according to sex, acute pancreatitis, tumor size, and involvement of MPD were compared by log-rank test. RESULTS: One hundred six patients were included with a proven (n = 76) or probable (n = 30) IPMT. The tumor was confined to BD in 53 cases. Median duration since the onset of the first sign to the end of follow-up was 21 months (range, 0-241). Ten-year actuarial risk that IPMT grade was >or=LGD, >or=HGD, or IC was 67%, 49%, and 29%, respectively. The only morphologic risk factor of malignant transformation was involvement of MPD, with a 5-year actuarial risk of >or=HGD of 63% in the MPD group compared with 15% in the BD group (P < .001). CONCLUSIONS: Longitudinal risk of at least HGD or IC is time-dependent. Patients with BD IPMT present a much lower risk, justifying a nonoperative surveillance.

Actuarial Analysis↗

Long-term outcome of biliary and duodenal stents in palliative treatment of patients with unresectable adenocarcinoma of the head of pancreas.

BACKGROUND: Life expectancy in patients with unresectable pancreatic cancer has improved by using new chemotherapeutic regimens. Biliary and digestive stenoses can be endoscopically treated in most cases. However, long-term efficacy of these stenting procedures remains unknown. AIM: To evaluate the incidence of biliary and duodenal stenoses as well as technical success and short- and long-term patency of endoscopically deployed stents in patients with unresectable pancreatic cancer. PATIENTS AND METHODS: All consecutive patients with unresectable cancer of the pancreatic head seen between January 1999 and September 2003 in our center were retrospectively studied. Patients with biliary and/or duodenal stenoses underwent endoscopic stent insertion as first intention therapy. Outcomes included technical and clinical success, stent patency, and survival. RESULTS: One hundred patients, median age 65 yr (32-85), with locally advanced (62%) or metastatic (38%) pancreatic cancer were studied. Eighty-three percent received at least one line of chemotherapy. The actuarial median survival was 11 months (0.7-29.3). Biliary and duodenal stenoses occurred in 81 and 25 patients, respectively. A biliary stent was successfully placed in 74 patients (91%). When a self-expandable metallic stent was first introduced (N = 59), a single stent was sufficient in 41 patients (69%) (median duration of stent patency 7 months (0.4-21.1)). Duodenal stenting was successful in 24 patients (96%); among them, 96% required a single stent (median duration of stent patency 6 months [0.5-15.7]). In the 23 patients who developed both biliary and duodenal stenoses, combined stenting was successful in 91% of cases. No major complication or death occurred related to endoscopic treatment. CONCLUSION: Endoscopic palliative treatment of both biliary and duodenal stenoses is safe and effective in the long term, including in patients with combined obstructions. Use of such palliative management is justified as repeat procedures are rarely required even in patients who have a long survival.

Adenocarcinoma↗

[Pancreatic cancer: what is new in 2005?].

During the year 2005, many publications were presented about pancreatic tumours concerning the palliative treatment of advanced adenocarcinoma, perioperative strategies (i.e., adjuvant and neoadjuvant), and genetic or environmental factors that predispose to this cancer. Several valuable first lines of chemotherapy for unresectable cancers will be soon available, in view of promising results of biotherapies (i.e., erlotinib) or capecitabine combined with gemcitabine. Perioperative treatments may provide additional chances to cure the disease or to delay the tumor relapse. In addition, it should allow to better select the patients for a surgical resection (neoadjuvant strategy). About basic research, new developments of proteomic and pharmacogenomic are promising. Early detection of pancreatic adenocarcinoma in high-risk patients (about 10% of pancreatic adenocarcinomas), although delicate to perform, may become soon a reality in our practice. The deleterious role of tobacco consumption and way of feeding has been confirmed by several communications this year.

Adenocarcinoma↗

[Acute pancreatitis revealing Behçet disease].

We report here a case of acute pancreatitis revealing Behcet's disease in an 18-year-old woman. Pancreatitis was due to ischemia secondary to severe abnormalities of the celiac trunk arteries with pseudo-aneurysms. The outcome was favourable after the administration of corticosteroids and cyclophosphamide. The patient did not experience relapse of pancreatitis 2 years after diagnosis.

Acute Disease↗

[Pseudo Zollinger-Ellison syndrome in a patient with duodenal stenosis caused by tuberculosis].

We report the case of a 32-year-old Indian man with symptoms suggesting Zollinger-Ellison syndrome including abdominal pain, esaphagitis, duodenal stenosis that did not improve with antisecretory medication, elevated fasting gastrin serum levels that increased after intravenous secretin injections, elevated chromogranin A serum levels and tumoral aspect of pancreatic uncus on CT scan examination. A pancreaticoduodenectomy was performed. Histological examination of the resected specimen showed that there was no endocrine tumour of the pancreas or the duodenum, but identified marked lesions of follicular and caseous tuberculosis. The final diagnosis retained pseudo Zollinger-Ellison syndrome due to gastric outlet obstruction caused by duodenal stenosis of a tuberculosis origin.

Adult↗

Is idiopathic chronic pancreatitis an autoimmune disease?

BACKGROUND & AIMS: The proportion of patients with idiopathic chronic pancreatitis (ICP) that have an autoimmune origin is unknown. Three forms of ICP have been described: pseudotumoral, duct-destructive, and usual chronic pancreatitis. The aim of this study was to identify autoimmune stigmata in the 3 forms. METHODS: All patients who underwent exploration for ICP were included. The following data were recorded: examination by an internal medicine specialist, autoantibodies and immunoglobulin screening, and pancreatic duct imaging. RESULTS: Sixty patients were included (pseudotumoral, n = 11; duct-destructive, n = 27; usual, n = 22). There were no significant differences among the 3 types with regard to sex ratio, age, frequency of acute pancreatitis, or obstructive jaundice. Pancreatic calcifications were seen only in the usual form (81%; P = .0001). Autoimmune disease was present in 10 patients: ulcerative colitis in 5 patients, primary sclerosing cholangitis in 2 patients, and Sjögren's syndrome, Hashimoto's thyroiditis, and Graves' disease in 1 patient each. Autoimmune diseases were not more frequent in patients with pseudotumoral (36%) or duct-destructive (19%) forms than in those with the usual form (5%, P = .06). Immunoglobulin G4 levels were increased in 2 of 6 in the pseudotumoral, 1 of 9 in the duct-destructive, and 0 of 12 patients in the usual group. Combining clinical and biochemical autoimmune parameters, 24 patients (40%) had at least 1 autoimmune marker or disease. CONCLUSIONS: Clinical or biochemical autoimmune stigmata are present in 40% of patients with ICP. Autoimmune mechanisms may be frequent in idiopathic pancreatitis.

Adolescent↗

Endocrine tumor and intraductal papillary mucinous neoplasm of the pancreas: a fortuitous association?

OBJECTIVES: Pancreatic endocrine tumors (PETs) and intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are rare diseases of the pancreas. Cases of association of endocrine and exocrine neoplasms of the pancreas have been reported, corresponding to mixed or amphicrine tumors. The aim of this report is to describe a series of 6 patients with an original association of IPMN and PET of the pancreas. METHODS: Among 108 and 103 patients operated on in our center between January 1997 and December 2003 for PETs and IPMNs, respectively, we identified 6 patients with both PET and IPMN, diagnosed on pathologic examination with an immunohistochemical study. RESULTS: Preoperative diagnosis was unspecified pancreatic tumor (n = 1), IPMN (n = 2), and association of PET and IPMN (n = 3). IPMN involved the main pancreatic duct in 4 patients and was classified as benign (n = 4), borderline (n = 1), or malignant noninvasive (n = 1). PETs measured 1.1 to 3 cm and were malignant in 1 patient (lymph node invasion). When analyzed by immunohistochemistry, 2 cases expressed glucagon, 1 expressed somatostatin, and 1 expressed insulin. CONCLUSION: This study describes a new aspect of endocrine-exocrine pancreatic neoplasm association. The frequency of the association of PET and IPMN is too large to be fortuitous. Further studies are needed to understand its mechanism.

Adenocarcinoma, Mucinous↗

Frozen sectioning of the pancreatic cut surface during resection of intraductal papillary mucinous neoplasms of the pancreas is useful and reliable: a prospective evaluation.

OBJECTIVE: To prospectively evaluate the accuracy of frozen sectioning (FS) of the pancreatic transection margin and its influence on surgery during resection of intraductal papillary and mucinous neoplasms (IPMNs). SUMMARY BACKGROUND DATA: Preoperative assessment of IPMN extension is difficult and transection margin is frequently tumoral on the surgical specimen. PATIENTS AND METHODS: FS was performed in 127 patients who underwent partial pancreatectomy for IPMN from 1996 to 2004, corresponding to 90 pancreaticoduodenectomies (1-4 successive FS; total = 132), 25 distal pancreatectomies (1-2 FS; total = 27), and 12 medial pancreatectomies (2-4 FS; total = 29). Dysplasia was graded in both main (MD) and branch ducts (BD), and pancreatectomy was extended if FS revealed at least IPMN adenoma on the MD or borderline IPMN on BD (defined as "significant" lesions). RESULTS: The 188 FS revealed that MD and BD epithelium comprised significant noninvasive lesions in 49 and 13 cases, respectively, and infiltrating carcinoma in 4 other ones. Definitive examination corroborated FS in 176 of 188 cases (94%). Altogether, 54 of 188 (29%) FS comprised significant lesions that resulted in 46 additional resections in 38 patients (30%). Eight patients did not have additional resection because of either high operative risk or preoperative diagnosis of noncurable infiltrating carcinoma. The 134 FS without significant lesions were associated with 7 additional resections mainly because of macroscopic suspicion of another tumor location. Conflicting results between FS and definitive examination resulted in inadequate extent of pancreatectomy in 4 patients (3%). CONCLUSIONS: Results of FS of the transection margin are confirmed by definitive examination in 94% of cases. According to our protocol, FS changes the extent of resection in 30% of patients and allows adequate resection in 97% of patients.

Adenocarcinoma, Mucinous↗

Severe cholangitis following pancreaticoduodenectomy for pseudotumoral form of lymphoplasmacytic sclerosing pancreatitis.

Cholangitis associated with lymphoplasmacytic sclerosing pancreatitis may occur simultaneously or following diagnosis of pancreatitis. The natural history following inappropriate pancreatic surgery and treatment of cholangitis in this setting are ill-defined. Three patients underwent pancreaticoduodenectomy for pseudotumoral lymphoplasmacytic sclerosing pancreatitis. Jaundice or ascending cholangitis revealed severe biliary strictures at 1, 6, and 11 months, respectively, following surgery. Treatment combining corticosteroids with or without biliary stenting was efficacious in all patients. One patient with subsequent clinical and morphological relapse responded well to reintroduction of steroids. Biliary changes appeared to be immune-related based on pathological examination and response to corticosteroids.

Adrenal Cortex Hormones↗

Staging of pancreatic head adenocarcinoma with spiral CT and endoscopic ultrasonography: an indirect evaluation of the usefulness of laparoscopy.

BACKGROUND: The interest of laparoscopy in the preoperative staging of pancreatic head adenocarcinoma before curative pancreaticoduodenectomy is a matter of controversy and depends on the accuracy of preoperative imaging techniques. AIM: To assess the potential value of laparoscopy when a standardised and optimal preoperative staging is performed, including spiral computed tomography (CT) and endoscopic ultrasonography (EUS). METHODS: All consecutive patients operated on with a view to curative pancreaticoduodenectomy for pancreatic head or ampullary adenocarcinoma in our centre from January 1998 to August 2000 were retrospectively studied. All of them had preoperative spiral CT and EUS. Tumour resectability was considered as highly probable (HP) or uncertain (U) according to well-defined criteria. Operative records of patients were reviewed to indirectly assess the effective resectability rate and the criteria responsible for unresectability and which of them would have been identified by laparoscopy if initially performed. RESULTS: 69 consecutive patients were studied. Resectability was HP (n = 56) or U (n = 13) after preoperative staging. Curative pancreatoduodenectomy was performed in 53 patients (77%) (48 HP, 5 U). Positive predictive value of preoperative imaging for highly probable resectability was 86% (48/56). Among the 16 unresectable tumours (8 HP, 8 U), the cause of non-resection would have been found at laparoscopy in 9 patients (56%) (6 HP, 3 U). Finally, if initially performed, laparoscopy would have avoided laparotomy in 9/69 patients (13%) (6/56 HP (11%); 3/13 U (23%)). CONCLUSIONS: With accurate preoperative staging using spiral CT and EUS, laparoscopy would detect tumours which were unresectable in 13% of patients with pancreatic head cancer. Laparoscopy remains useful in selected patients, such as those with preoperative uncertain resectability, in whom it can prevent unnecessary laparotomy in one fourth of patients.

Adenocarcinoma↗

Macrocystic pancreatic cystadenoma: The role of EUS and cyst fluid analysis in distinguishing mucinous and serous lesions.

BACKGROUND: Benign pancreatic serous cystadenoma usually is morphologically distinguishable from mucinous cystadenomas, which require resection because of their malignant potential. A macrocystic variant of serous cystadenoma recently has been described, rendering this important distinction more difficult. The aim of this study was to determine the EUS and tumor marker characteristics of mucinous cystadenoma compared with macrocystic serous cystadenomas. METHODS: Medical records for consecutive patients seen between 1995 and 2002, with a histopathologic diagnosis of mucinous cystadenoma or macrocystic serous cystadenoma after surgery, who had undergone a detailed EUS examination, including EUS-guided FNA, were retrospectively reviewed. RESULTS: A resection specimen was available for 32 mucinous cystadenomas and 9 macrocystic serous cystadenomas. No significant differences were observed with regard to clinical data (age, gender, presence of symptoms), lesion size, and location within the pancreas. All mucinous cystadenomas had a discernible cyst wall (thickened, 66%; focal parietal nodules, 25%) compared with 56% of macrocystic serous cystadenomas (p<0.0001). A thick echo content also was more frequent in mucinous cystadenoma (56% vs. 11%; p=0.04; statistical significance removed by the Bonferroni correction). Microcysts were only observed in macrocystic serous cystadenomas (44%; p=0.0008). The combination of a cyst wall that is thickened and the absence of microcysts had a sensitivity of 100% and specificity of 78% for the diagnosis of mucinous cystadenoma compared with macrocystic serous cystadenoma. Although intracystic carbohydrate-associated antigen 72-4 and mucins M1 were non-discriminatory, low carcinoembryonic antigen (<5 ng/mL) and carbohydrate-associated antigen 19-9 (<50,000 U/mL) values were found in macrocystic serous lesions (respectively, 100% and 100%; p=0.0002 and p=0.0002). CONCLUSIONS: Although there is considerable overlap, helpful EUS characteristics that differentiate mucinous cystadenoma from macrocystic serous cystadenoma include a thick cyst wall and microcysts. These features, coupled with analysis of aspirated fluid for tumor markers (especially carcinoembryonic antigen), should help to confirm the diagnosis.

Adolescent↗

Pancreatic metastases: a multicentric study of 22 patients.

AIMS OF THE STUDY: To evaluate the diagnosis, treatment and outcome of patients with pancreatic metastases. PATIENTS AND METHODS: We retrospectively reviewed the records of patients with pancreatic metastasis managed in the Paris area between 1990 and 2000. RESULTS: The series analyzed included 22 patients, 10 men and 12 women, mean age 61 years (range: 35-76). The primary tumors were renal-cell carcinoma (N=10), colorectal cancer (N=4), lung cancer (N=4), breast cancer (N=2), cutaneous melanoma (N=1) and ileal carcinoid (N=1). The mean interval between primary treatment and presentation was 73.5 months (range: 2-151). Diagnosis was established because of clinical symptoms (N=15) or during surveillance (N=7). Computed tomography (N=19) and endoscopic ultrasound (EUS) (N=18) mainly showed solitary and hypodense/or hypoechoic masses. Histological diagnosis was obtained before surgery by EUS-guided fine needle aspiration (N=6), ultrasound-guided biopsy (N=3) or duodenoscopy (N=3). Among 10 patients with primary renal-cell carcinoma, 7 were treated by surgery. Median global survival was 33 months. Median survival was 61 months in the event of surgical treatment and 20 months in the other patients (ns). Mean survival depended on the type of primary tumor, 61 months for renal-cell carcinoma and 33 for colorectal cancer (P=0.06). CONCLUSIONS: Most pancreatic metastases develop from renal-cell carcinoma and can occur several years after nephrectomy. Histological diagnosis is often obtained before surgery. Surgical resection must be discussed as it can allow long-term survival.

Adult↗

Intraductal papillary mucinous tumors of the pancreas: the preoperative value of cytologic and histopathologic diagnosis.

BACKGROUND: The preoperative diagnosis of intraductal papillary mucinous tumors of the pancreas must be as certain as possible because removal of a large portion of the pancreas or even total pancreatectomy may be necessary. The value of cytologic and histopathologic analysis of specimens obtained by preoperative endoscopic investigations is unknown. The aim of this study was to assess the value of such analyses of specimens obtained by EUS-guided FNA and/or biopsy, or transpapillary biopsy specimens obtained during endoscopic retrograde pancreatography for the diagnosis of intraductal papillary mucinous tumors of the pancreas and for the detection of malignancy. METHODS: Between 1992 and 2001, 42 patients (22 men, 20 women; median age 64 years) underwent surgical resection for intraductal papillary mucinous tumors of the pancreas and had preoperative pancreatic tissue sampling. In the case of isolated dilatation of pancreatic ducts, pancreatic juice was obtained by EUS-guided FNA for cytologic analysis. In the presence of a solid lesion or main pancreatic duct stenosis, biopsy specimens were obtained by EUS-guided FNA biopsy or endoscopic retrograde pancreatography, which permitted histopathologic assessment. The accuracy of cytology and histopathology was evaluated for the following: (1) positive diagnosis of intraductal papillary mucinous tumors of the pancreas and (2) assessment of malignancy, by comparison with histopathologic examination of surgical resection specimens. RESULTS: Cytologic analysis was performed in 19 patients; it was positive in 4 (21%) and noninformative in 15 (79%). Histopathologic analysis was performed in 23 patients; it was positive in 21 (91%) and negative in 2 (9%). Histopathologic analysis yielded a positive result in 83% of patients who did not have extrusion of mucus from a patulous papilla. The sensitivity, specificity, and positive and negative predictive values of histopathologic analysis for the diagnosis of malignancy were, respectively, 44%, 100%, 100%, and 33%. When histopathologic analysis was positive, the tumor grade was similar to that determined by final histopathologic examination in 38% of patients, whereas the grade was underestimated in 62%. No complication occurred as a result of tissue sampling. CONCLUSIONS: The sensitivity of histopathologic analysis of EUS-guided FNA biopsy specimens or transpapillary biopsy specimens is 91% for the positive diagnosis of intraductal papillary mucinous tumors of the pancreas with a solid component, which is of particular interest as extrusion mucus from the papilla was absent in most patients. Histopathologic analysis of biopsy specimens of malignant intraductal papillary mucinous tumors of the pancreas often underestimates tumor grade. The result for cytologic analysis of juice obtained from dilated pancreatic ducts is disappointing.

Aged↗

Discrimination of unilocular macrocystic serous cystadenoma from pancreatic pseudocyst and mucinous cystadenoma with CT: initial observations.

PURPOSE: To compare the computed tomographic (CT) appearance of pancreatic unilocular macrocystic serous cystadenoma, mucinous cystadenoma, and pseudocyst to determine if there are findings that assist in the differential diagnosis. MATERIALS AND METHODS: CT findings in 33 patients (24 women, nine men; age range, 18-84 years; mean age, 41 years) with unilocular pancreatic lesions (macrocystic serous cystadenoma, n = 12; mucinous cystadenoma, n = 11; pseudocyst, n = 10) were retrospectively and jointly reviewed by two blinded observers. Twenty-three patients underwent helical CT, which included pancreatic and portal venous phase imaging with delays of 40 seconds and 65 seconds, respectively, after contrast material injection. Ten patients underwent conventional (nonhelical) CT. The number, size, location, and contour of lesions were reviewed, along with wall thickness and enhancement and other signs of pancreatic and peripancreatic involvement. Diagnosis was based on lesion resection (n = 22) or on a combination of cytologic findings, biochemical markers, and tumor markers (n = 11). The Fisher exact test was used to analyze the results. RESULTS: Three of four CT findings were independently specific for macrocystic serous cystadenoma: location in the pancreatic head, lobulated contour, and absence of wall enhancement. When two of these four criteria were used in combination, 83% (10 of 12) of patients with unilocular macrocystic serous cystadenoma were identified. When three or four of these criteria were used, a specificity of 100% was achieved. Location in the pancreatic head (P <.05), lobulated contour (P <.005), and lack of wall enhancement (P <.005) were specific for macrocystic serous cystadenoma in comparison with mucinous cystic tumor. Lobulated contours (P <.005) were specific for macrocystic serous cystadenoma in comparison with pseudocyst. Other CT findings were not helpful in distinguishing between the three types of lesions. CONCLUSION: A combination of CT findings is helpful in making the diagnosis of pancreatic unilocular macrocystic serous cystadenoma.

Adolescent↗