[Epidemiology of pancreatic adenocarcinomas]. / Épidémiologie des adénocarcinomes pancréatiques.

Pancreatic cancer, mostly represented by pancreatic ductal adenocarcinoma, is a major public health burden in developed countries. More than half a million people are expected to die from pancreatic cancer, worldwide, in 2030. Age and tobacco are the main identified risk factors in sporadic cases, when many genetic syndromes increase the risk significantly. History of pancreatic cancer is a significant risk factor for pancreatic cancer for any first-degree related individual, known as familial pancreatic cancer. The genetic signature of this syndrome is probably due to a still not identified autosomal dominantly inherited gene with reduced penetrance. The risk increases with the number of first-degree relatives involved. Precursor lesions are known to give rise to invasive pancreatic cancer. These particular lesions are either macroscopic (intraductal papillary mucinous neoplasia and mucinous cystic neoplasms), or microscopic (pancreatic intraepithelial neoplasia). It is possible to identify a orouo of hig h-risk individuals who could be candidate for screening.

Prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis.

BACKGROUND AND AIMS: Recurrent liver/biliary sepsis are rare and can occur in different situations. Curative treatment of acute septic episodes is based on antibiotics. Nevertheless, recurrent sepsis can be life-threatening, and the treatment of the underlying disease could be complex, and eventually not possible. The aim of the present study was to report our experience on prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis in a large cohort of patients with long follow-up. METHODS: All patients who received a prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis in our institution from 2005 to 2020 were included. Prophylactic sequential antibiotic therapy was based on per os antibiotics with expected antibacterial activity on digestive bacteria, mainly Gram-negative bacilli. The primary end-point was the reduction of the number of septic episodes to 1 or less episode per year, and not severe (not requiring hospitalization). RESULTS: Were included 33 adult patients and the main initial disease/condition leading to prophylaxis was history of hepaticojejunostomy (78.8%). The majority of septic episodes required hospitalization (57.6%). First line prophylactic sequential antibiotic therapy was weekly ciprofloxacin in all cases. First line therapy was successful in the long-term in 19 patients (57.6%), with a median follow-up of 92 months (range: 25-206). Global efficacy (first-second-third lines) was 28/33 (84.8%). CONCLUSIONS: The results of the present study with very long follow-up suggest that prophylactic sequential antibiotic therapy can successfully prevent recurrent liver/biliary sepsis with good tolerance.

Pancreatic surgery in France.

In 2006, French cancer registries showed that pancreatic cancer was ranked 14th for estimated incidence (8.7/100,000) and mortality 11.4/100,000) for men, and 12th for women (5.1/100,000 and 7.4/100,000) (age-standardized rate). Long-term survival after pancreatectomy has become a reality, albeit in only a small number of patients. A series of 30 patients who survived more than 5 years postoperatively was collected from three French institutions and was published in 2008. The results of a trial using preoperative chemoradiation in potentially resectable pancreatic adenocarcinoma (French phase II FFCD 9704-SFRO trial) suggested that some tumors are chemoradiosensitive. It further suggested that preoperative chemoradiation provides an antitumor effect, which is associated with a major histopathological response in 50% of patients. Since the quality of assessment is of major concern for surgeons and for national health authorities, there is a current prospective evaluation of the role of resection margins and lymph node invasion (with precise identification of the status of superior mesenteric artery lymph nodes and nerve plexus), and the adequacy of the surgical procedure and prognosis that is ongoing in France. The objectives of this trial are to define and standardize quality criteria for surgical resection and histopathological examination of surgical specimens.

Right-sided posttraumatic diaphragmatic rupture and delayed hepatic hernia.

The early diagnosis of posttraumatic diaphragmatic lesions is often difficult which explains the 30 to 50% of non diagnosed cases. This is due to the lack of sensitivity and specificity of the radiographic exams. Missed diaphragmatic lesions results in herniation of abdominal contents into the chest and may be revealed many years from the time of the original trauma. Symptoms such as dyspnea and chronic abdominal complaints are often observed and life-threatening complications, such as visceral strangulation or perforation, contribute to the late morbidity and mortality of the missed injury. Liver herniation is rare and few cases are described in the literature. We report two cases of delayed discovery of the diaphragmatic injury resulting in liver herniation. In one case, there was also an involvement of the duodeno-pancreas. The diagnosis was made 3 and 12 years after the original trauma, respectively, and respiratory embarrassment was the major presenting symptom. The surgical approach was different in the two patients; the first patient was managed by thoracotomy whereas the second patient was treated by laparotomy. The diaphragmatic defect was repaired and reinforced by a prosthetic mesh in the first case. It was closed only by suturing in the second patient. From these two cases, we reviewed the relevant literature and analysed the different approaches for diaphragmatic repair.

Hepatic epithelioid hemangioendothelioma: long-term results of surgical management.

BACKGROUND AND OBJECTIVES: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular neoplasm of the liver. Its therapeutic management remains difficult to define in curative intent. The aim of this study was to report long-term results of surgically managed patients. METHODS: From 1990 to 2006, nine patients (25-64 years) were retrospectively enrolled in this study. Intrahepatic disease extent was monolobar and bilobar in two and seven patients, respectively. As primary treatment, liver resection (LR) and liver transplantation (LT) were performed in three (two monolobar and one bilobar extent) and six patients, respectively. RESULTS: Postoperative mortality was nil. During a median follow-up of 117 months, four patients developed intrahepatic and/or extrahepatic recurrence. One resected patient (with bilobar extent) presented with intrahepatic recurrence was secondary treated by LT. At the time of the follow-up, seven out of the nine patients treated (two after LR, and five after LT) were alive and disease-free. CONCLUSIONS: Surgical treatment offers good long-term results in patients suffering from HEHE when LR is tailored to the intrahepatic disease extent: LT has to be considered in patients with bilobar intrahepatic disease whereas LR should be strictly limited to patients presenting with localized and monolobar intrahepatic disease.

Cystic involvement of the roof of the main biliary convergence in adult patients with congenital bile duct cysts: a difficult surgical challenge.

BACKGROUND: Complete cyst excision of the extrahepatic disease component with biliary reconstruction on proximal healthy bile ducts is considered to be the treatment of choice in patients with congenital bile duct cysts (BDC). Proximal cystic disease that extends to the roof of the main biliary convergence (MBC) might challenge this standard of surgical care. METHODS: A retrospective multicenter study was conducted in 4 European surgical centers concerning their experience with adult patients suffering from type I and IV BDC according to the Todani classification. Clinical presentation, operative management, and postoperative outcome were compared between patients with or without proximal extrahepatic cystic disease that involved at least the roof of the MBC (defined as being BDC with MBC involvement subgroup). RESULTS: From an overall series of 49 adult patients suffering from type I or IV BDC according to the Todani classification, 7 patients had BDC with MBC involvement (14%). Patient age, clinical presentation, duration of symptoms, associated major coexistent hepatobiliary and pancreatic diseases, and synchronous cancer were not significantly different in these patients compared with a control group of 42 adult patients with BDC without MBC involvement. Incomplete proximal cyst excision rate was 86% in the cases of BDC with MBC involvement. Early and late postoperative results were similar in BDC with MBC involvement and in the control group of adult patients, but the incidence of subsequent cancer was significantly higher in the BDC with MBC involvement group (29% vs 0%; P < .02). CONCLUSION: BDC that involves the roof of the MBC is a real surgical challenge to obtain complete proximal cystic disease excision. As suggested in this small study, primary incomplete excision of this particular form of BDC might expose the patient to the risk of subsequent cancer, a feature that must be confirmed in larger series.

Survival and prognostic factors after adjuvant 131iodine-labeled lipiodol for hepatocellular carcinoma: a retrospective analysis of 106 patients over 20 years.

OBJECTIVE: Hepatocellular carcinoma (HCC) has high recurrence rate after curative treatment. The aim of the present study was to report our experience with adjuvant use of 131I-lipiodol after curative treatment of HCC in terms of recurrence and survival in a large cohort of patients with a long follow-up. METHODS: All patients treated with 131I-lipiodol after curative treatment of HCC in two French centers from 1991 to 2009 were included in a retrospective cohort study. RESULTS: One hundred and six patients were included. The median (range) follow-up was 6 years (0.3-22). Forty-three patients (41%) had cirrhosis. Recurrence-free survival rates at 1, 2, 5, 10, and 20 years were 73, 57, 40, 30, and 14%, respectively. Cirrhosis was an independent predictive factor of recurrence [RR = 1.18, 95% CI (1.11-3.02), p = 0.019]. Overall, survival rates at 1, 2, 5, 10, and 20 years were 90, 83, 59, 37, and 23%, respectively. Prognostic factors were recurrence [RR = 2.73, 95% CI (1.35-5.54); p = 0.005], age over 60 years (RR = 1.91, 95% CI [1.02-3.61]; p = 0.044), and tumor number over 3 [RR = 3.31, 95% CI (1.25-8.77); p = 0.016]. CONCLUSION: Our results suggest that the effect of 131I-lipiodol after curative treatment of HCC could be related to a beneficial impact on risk factors of early tumor recurrence. This could be evaluated in further studies using modern radioembolization methods.

Feasibility of preoperative combined radiation therapy and chemotherapy with 5-fluorouracil and cisplatin in potentially resectable pancreatic adenocarcinoma: The French SFRO-FFCD 97-04 Phase II trial.

PURPOSE: More than 80% of patients who undergo a potentially curative resection for pancreatic cancer develop local or distant recurrence. Neoadjuvant chemoradiotherapy might offer potential benefits regarding local and systemic control and survival. This multi-institutional Phase II trial explored the feasibility of preoperative chemoradiation in this situation. METHODS AND MATERIALS: Treatment consisted of concurrent radiotherapy (50 Gy within 5 weeks), and chemotherapy with 5-fluorouracil (300 mg/m(2)/day, 5 days/week, 5 consecutive weeks) and cisplatin (20 mg/m(2)/day, Days 1-5 and 29-33), followed by surgical resection of the pancreatic tumor in patients without progression. RESULTS: A total of 41 patients were enrolled. Of these, 38 (93%) received > or =47 Gy; 30 patients (73%) received > or =75% of the prescribed doses of chemotherapy. Surgical resection was performed in 26 patients (63%). Because of local or metastatic progression, 5 patients (12%) did not undergo surgery and 10 underwent surgery without resection of the pancreatic tumor. Operative mortality was 2.8%. Among 40 evaluable patients, 27 were successfully treated (67.5%; 95% CI, 50.9-81.4%). CONCLUSIONS: Pancreatic cancer is chemo-radiosensitive. The proposed pre-operative scheme is feasible, does not prevent successful surgery, and must be tested on a Phase III setting. Yet, the large proportion of tumor progression during and after chemoradiation justifies the use of more efficient drugs such as Gemcitabine, and optimized radiotherapy including new techniques such as intensity-modulated radiation therapy.

[The role of neoadjuvant chemoradiation in pancreatic cancer]. / Intérêt de la chimio-radiothérapie néo-adjuvante dans le cancer pancréatique.

Although complete surgical resection, when possible, leads to prolonged survival in pancreatic cancer, if used alone, its results remain sub-optimal. Neoadjuvant strategies are recent in pancreatic cancer: in primary resectable tumors, they ensure that all patients obtain additional treatment to complete surgery; in locally advanced tumors, they allow a better selection of candidates for curative resection. By delaying surgery, neoadjuvant strategies modify the initial diagnostic process and the symptomatic treatment of pancreatic cancer. Several recent phase I-II studies have confirmed the feasibility and efficacy of the association of chemotherapy and radiotherapy, which is well-tolerated and is associated with better local control and survival. Due to the aggressiveness of pancreatic cancers, most recent cytotoxic agents should be associated with modern radiation techniques. Neoadjuvant chemoradiation is under evaluation in pancreatic cancers, and no randomized phase III trials comparing neoadjuvant and adjuvant therapeutic sequences has been reported. Moreover, radiological and pathological evaluations, not only at diagnosis, but also after preoperative chemoradiation, must be standardized to improve the selection of patients who will benefit from this multi-modal treatment.

[Autoimmune pancreatitis: beneficial effects of corticosteroid therapy on biliary and metabolic complications]. / Pancréatite auto-immune: intérêt de la corticothérapie pour le traitement des complications biliaires et métaboliques.

Auto-immune pancreatitis is rare and its evolution includes both the usual complications of chronic pancreatites, such as diabetes and specific consequences and complications including extension of inflammatory lesions of the extra or intrahepatic biliary tract. One particular characteristic of these complications is that they are sensitive to cortisone therapy, as illustrated by the case we report here.

Improved sphincter preservation in low rectal cancer with high-dose preoperative radiotherapy: the lyon R96-02 randomized trial.

PURPOSE: The potential advantage of high-dose preoperative radiotherapy to increase tumor response and improve the chance of sphincter preservation for low rectal cancer remains controversial. The aim of this trial was to evaluate the role of escalating the dose of preoperative radiation to increase sphincter-saving procedures. PATIENTS AND METHODS: Patients with rectal carcinoma located in the lower rectum, staged T2 or T3, Nx, or M0 with endorectal sonography, and not involving more than two-thirds circumference, were randomly assigned to one of two groups: preoperative external-beam radiotherapy (EBRT; 39 Gy in 13 fractions over 17 days) versus the same EBRT with boost (85 Gy in three fractions) using endocavitary contact x-ray. RESULTS: Between 1996 and 2001, 88 patients were enrolled onto the study. A significant improvement was seen in favor of the contact x-ray boost for complete clinical response (24% v 2%) and for a complete or near-complete sterilization of the operative specimen (57% v 34%). A significant increase in sphincter preservation was observed in the boost group (76% v 44%; P =.004). At a median follow-up of 35 months, there was no difference in morbidity, local relapse, and 2-year overall survival. CONCLUSION: A dose escalation with endocavitary irradiation provides increased tumor response and sphincter preservation with no detrimental effect on treatment toxicity and early clinical outcome.

Radiochemotherapy in the management of pancreatic cancer--part I: neoadjuvant treatment.

In pancreatic cancer, complete resection offers the only hope of cure, but results of surgery alone are suboptimal. Many studies have been conducted in which the treatment regimen consists of surgery in combination with radiation and chemotherapy to improve local control and outcome. Neoadjuvant chemoradiotherapy is a fairly recent approach that appears to be feasible in resectable and locally advanced pancreatic cancer. In resectable tumors, chemoradiation therapy has been shown to be at least as effective in a neoadjuvant setting as in an adjuvant setting. Neoadjuvant therapy offers a few theoretical advantages: (1) beginning the multimodality treatment with chemoradiation therapy increases the chance that more patients will receive all of its components; (2) preoperative chemoradiation therapy provides an observation period to exclude from surgical resection those patients with rapidly progressive disease; and (3) in locally advanced tumors, it provides the opportunity for downstaging and infrequently allows patients to undergo resection. To evaluate the scope and applicability of neoadjuvant treatment, a number of areas need to be addressed. First, the definition of locally advanced disease needs to be more adequately standardized because the resectability definition sometimes varies among surgeons. In addition, because imaging examinations may underestimate the effectiveness of preoperative chemoradiation therapy, some researchers have tried to evaluate treatment response via a pathological examination of the tumor specimen; however, complete pathological response appears to be rare. Finally, more efficient novel neoadjuvant approaches are required to address the high metastatic potential of pancreatic cancer. These areas are discussed in depth.

Medial pancreatectomy: a multi-institutional retrospective study of 53 patients by the French Pancreas Club.

BACKGROUND: The results of medial pancreatectomy have been previously reported anecdotally. The purpose of the study was to provide short- and long-term results of MP in a large multicenter collective series. METHODS: From 1990 to 1998, 53 patients (mean age +/- SD = 49 +/- 15 years) underwent medial pancreatectomy for primary cystic neoplasms of pancreas (n = 19), endocrine neoplasms (n = 17), intraductal papillary mucinous neoplasms (IPMN) (n = 6), fibrotic stenosis of the Wirsung's duct (n = 4), or other benign (n = 4) or malignant (n = 3) diseases. The proximal (right) pancreatic remnant was sutured (n = 53), and the distal (left) remnant was either anastomosed to a jejunal loop (n = 26), to the stomach (n = 25), or oversewn (n = 2). Medial pancreatectomy was indicated in 3 patients (6%) because of failed enucleation, in 3 (6%) to prevent worsening of preexisting diabetes, or to prevent de novo diabetes in a patient with chronic pancreatitis, and deliberately in the 47 others. RESULTS: The length of the resected pancreas was 5.0+/- 2.2 cm (range, 2-15). One patient (2%) died from a pancreatic fistula and portal thrombosis. Three patients were reoperated on because of complications related to the left pancreas, which was partially or totally resected. Pancreatic fistula developed in 16 patients (30%). Mean delay for the return of oral feeding was related to the presence of a pancreatic fistula. At follow-up (median = 26 months, range, 12-131), 1 pancreatic recurrence and 1 de novo diabetes occurred in patients without IPMN. In patients with IPMN, the rates of pancreatic recurrence and diabetes were 40% (2/5), respectively. CONCLUSIONS: Medial pancreatectomy effectively preserves long-term endocrine function and is associated with a low risk of local recurrence, except in patients with IPMN. However, there is a high risk (30%) of PF after medial pancreatectomy.

Intraductal papillary-mucinous tumors of the pancreas: predictive criteria of malignancy according to pathological examination of 53 cases.

BACKGROUND: One of the main problems in the management and treatment of intraductal papillary-mucinous tumors is the lack of a reliable predictive factor for malignancy. HYPOTHESIS: Surgical treatment could be adapted to macroscopic criteria (presence of mural nodules and diameter of the pancreatic duct and of the lesion) or to tumor location (main duct, branch duct, or combined lesions) associated with benign or malignant forms. DESIGN: Retrospective study. SETTING: Two university and tertiary referral centers. PATIENTS: Fifty-three consecutive patients who underwent pancreatic resection for intraductal papillary-mucinous tumors between January 1, 1985, and December 31, 2000. RESULTS: Macroscopic analyses of tumors showed 6 main duct lesions, 12 branch duct lesions, and 35 combined lesions. A carcinoma was present in 33 cases (62%): 22 (41%) were invasive and 11 (21%) were noninvasive; 9 (17%) were borderline tumors and 11 (21%) were benign. Carcinoma and invasive carcinoma forms were less frequent in branch duct lesions (P<.001 and P =.009, respectively). Mural nodules were more frequent in carcinomas (P =.006) and invasive carcinomas (P<.001), with a positive predictive value of malignancy of 81%. The diameter of lesions (branch duct lesion > or =30 mm) or main duct (main pancreatic duct > or =15 mm in combined or main pancreatic duct lesions) did not correlate with malignancy. CONCLUSIONS: No carcinoma occurred in branch duct types smaller than 30 mm without mural nodules. Limited resection may be appropriate only in this type of tumor.

Endocrine tumors of the extrahepatic bile ducts. Pathological and clinical aspects, surgical management and outcome.

Endocrine tumors of the extrahepatic bile ducts are an extremely rare clinical entity with only very few cases being reported to date. Two additional cases of extrahepatic endocrine tumors are presented and a review of the literature is analyzed to provide a comprehensive data collection. Thirty-four cases of extrahepatic endocrine tumor, including our 2 cases, have been reported; 16 (47%) being carcinoma. The mean age of presentation was 48.2 years with a male/female ratio of 0.36. Jaundice, the most common symptom, was found in 63% of the patients. The common bile duct and the hilar region were the two most frequent anatomic locations. The mean size of resectable tumors was 2.37cm (0.2- 5.5cm). Metastases were present in 11 patients (32.35%) and local invasion was found only in 6 patients (17.6%). Curative surgery was realized in the majority of the patients. Long-term disease-free survival as long as 20 years was reported when surgery was curative. Endocrine tumors of the extrahepatic duct are exceptional and represent 0.2% of all cancers of these anatomic sites. Curative resection is the most important prognostic factor. Therefore, aggressive surgical therapy with curative intention offers the only chance for cure and has to be considered whenever possible.

Primary and secondary liver endocrine tumors: clinical presentation, surgical approach and outcome.

BACKGROUND/AIMS: The aim of this study was to evaluate the role of surgical treatment in the management of primary and secondary liver endocrine tumors. METHODOLOGY: We reviewed our experience of surgical treatment for primary and secondary liver endocrine tumors in 34 patients from 1980 to 1999. There were 31 cases of liver metastases from distant primary endocrine tumors treated by curative resection in 11 patients, cytoreductive surgery in 15 and orthotopic liver transplantation in 5. The remaining 3 consisted of primary liver endocrine tumor in 2 patients, liver invasion from primary bile duct endocrine tumor in 1, and all of them were treated by curative liver resection. RESULTS: In patients with distant primary endocrine tumors, the actuarial 5-year survival after curative liver resection, cytoreductive surgery, and orthotopic liver transplantation was of 91%, 50% (being 90% for non-functioning tumors), and 60%, respectively. In patients with primary liver endocrine tumors, long-term survival and disease-free survival (52-240 months) was achieved after curative resection. CONCLUSIONS: When indicated, liver surgery can offer cure and/or improve survival in patients with primary or secondary liver endocrine tumors. The choice of the surgical modality should be evaluated carefully.

[Pancreatic acinar cell carcinoma in a patient with familial adenomatous polyposis]. / Carcinome pancréatique à cellules acineuses et polypose adénomateuse familiale.

The relative risk of pancreatic cancer has been shown to be about 4 times that of the general population in familial adenomatous polyposis patients, but its frequency remains low, and the histological nature of these pancreatic tumors has been rarely reported. We describe the case of a 65-year-old patient, with a history of familial adenomatous polyposis coli, who developed advanced duodenal polyposis and a synchronous 25 mm tumor of the pancreatic isthmus. After total pancreatectomy and antrectomy, histological examination revealed an acinar cell carcinoma and duodenal adenomas with low and high-grade dysplasia, but no cancer. To our knowledge, this is the first description of the association of familial adenomatous polyposis with acinar cell carcinoma of the pancreas.

[Endocrine carcinoma of the pancreas revealed by a pseudocyst]. / Un vrai faux-kyste du pancréas révélant une vraie tumeur.

Pancreatic pseudocysts are the most frequent cystic lesions of the pancreas. They always are associated with acute or chronic pancreatitis. We here report the case of a pseudocyst of the pancreas associated with obstructive chronic pancreatitis and diagnosed in a 47-year-old man without previous history of acute pancreatitis and without risk factor. The examination of the surgical specimen resulted in the incidental discovery of an obstructive nodule of endocrine carcinoma, measuring 9 mm in diameter and located immediately at the contact of the pseudocyst. The tumor was ill limited and associated with metastatic spread in 2 peripancreatic lymph nodes. Immunohistochemical studies showed that 60% of tumor cells expressed serotonin. This case report underlines that the diagnosis of pseudocyst must be done much cautiously in patients without a clinical history of pancreatitis and without risk factor. In most cases, the lesion corresponds to a misdiagnosed cystic tumor. Even if the lesion actually corresponds to a pseudocyst, as in the present case, an unusual cause, and particularly, an obstructive tumor, must be searched for.

[Endoscopic and surgical treatment of chronic pancreatitis]. / Traitements endoscopiques et chirurgicaux des pancréatites chroniques.

Therapeutic management of patients with chronic pancreatitis is a multidisciplinary approach. Although interventional endoscopy and external lithotripsy have an important role to play, surgery keeps a prominent position in the therapeutic armentarium. The progress in radiology and endoscopy, the possibility of a preliminary therapeutic approach by a nonsurgical therapy have led to precise guidelines in the management. Surgery is indicated not only for rescue when endoscopic treatment is unsuccessful, but also as a one step procedure when failure of nonsurgical therapy can be anticipated right away. A key point is that nonsurgical and surgical therapeutic modalities are now complementary instead of being competitive.

Esophageal stem cells and genetics/epigenetics in esophageal cancer.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the relationship between stem cells, cancer, and the esophagus; the behavior of esophageal stem cells; and the role of genetics and epigenetics in approaches to translational research.