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.

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.

[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.

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.

Adjuvant Intraarterial Lipiodol or ¹³¹I-Lipiodol After Curative Treatment of Hepatocellular Carcinoma: A Prospective Randomized Trial.

UNLABELLED: The prevention of tumor recurrence after curative treatment of hepatocellular carcinoma (HCC) is unresolved. Postoperative intraarterial injection of (131)I-labeled lipiodol has been proposed as adjuvant treatment. The aim of this prospective randomized trial was to evaluate if a single dose of postoperative adjuvant intraarterial (131)I-lipiodol (vs. unlabeled lipiodol) could reduce the rate of intrahepatic recurrence at 2 y. METHODS: Patients who underwent curative treatment for HCC and recovered within 6 wk were randomly assigned to receive a single 2,200-MBq (131)I-lipiodol dose or a single unlabeled lipiodol dose on a 1:1 basis. Recurrence-free and overall survival rates were analyzed. RESULTS: Between June 2005 and February 2009, we included 58 patients (median age of 63 y [range, 23-85 y]): 29 received intraarterial (131)I-lipiodol and 29 received lipiodol adjuvant treatment. At 2 y after treatment, the rate of patients with intrahepatic recurrence was 28% in the (131)I-lipiodol group and 56% in the lipiodol group (P = 0.0449). The Kaplan-Meier analysis confirmed this result, with a 2-y recurrence-free survival in the (131)I-lipiodol and lipiodol groups of 73% and 45%, respectively (P = 0.0259). The 5-y recurrence-free survival rates in the (131)I-lipiodol and lipiodol groups were 40% and 0%, respectively (P = 0.0184). The overall and specific survivals were not significantly different between groups (P = 0.9378 and P = 0.1339, respectively). (131)I-lipiodol had no severe toxic effects. CONCLUSION: After curative treatment of patients with HCC, one 2,200-MBq dose of intraarterial (131)I-lipiodol significantly decreased the rate of intrahepatic recurrence but failed to improve overall or specific survival.

Toward a better understanding of pancreatic ductal adenocarcinoma: glimmers of hope?

Pancreatic ductal adenocarcinoma (PDAC) imposes a heavy burden of disease, especially in the most developed countries, and the mortality rate has not declined over the past decades. Therefore, there is an urgent need for a better understanding of the molecular mechanisms of PDAC, which may help to improve early detection, prognosis, and treatment efficiency.This review focuses on PDAC epidemiology and on recent advances in our understanding of the molecular mechanisms of PDAC carcinogenesis. We discuss the cancer stem cell hypothesis, which provides a rationale for the pervasive resistance of PDAC to chemoradiotherapy and explains the disease recurrence after the currently used genotoxic treatment.Identification of an inherited predisposition to PDAC due to genetic factors should allow high-risk groups to benefit from early detection programs. The presence in biofluids of stable tumor-specific microRNAs (miRs) makes them the most promising biomarkers potentially capable of detecting tumors long before their clinical manifestation. The cancer stem cell hypothesis made it realistic to anticipate a clinical impact of miR-based therapy (miR mimics and antagomirs) to overcome the otherwise insurmountable barrier of frequent resistance of PDAC to chemoradiotherapy.The investigation of miRs in PDAC may provide exciting novel strategies for both diagnosis and treatment.

Primary neuroendocrine tumors of the main pancreatic duct: a rare entity.

Very few cases of primary neuroendocrine tumors of the main pancreatic duct have been reported. This paucity has hampered an accurate description of the distinctive clinical and pathological features of these tumors and the correct evaluation of the diagnostic and therapeutic problems which they may raise. We report here five additional cases in order to underline the clinical, histological, and immunohistochemical features of this tumor entity. There were three male and two female, aged 43-72 years; in all patients, but one, who presented with epigastric pain, the diagnosis was made after the incidental discovery of a dilatation of the main pancreatic duct. The preoperative diagnosis was ductal adenocarcinoma in one case, IPMN in one case and neoplastic stenosis of unknown etiology in four cases. Surgical resection was performed in all cases. The diagnosis of neuroendocrine tumor was made at histological examination. All lesions were small, ranging from 5 to 15 mm. They had a predominantly intramural growth. The growth pattern was nodular in three cases, circumferential in two; there was no intra-luminal component. All cases were well-differentiated neuroendocrine neoplasms of low histological grade (G1); four cases expressed serotonin. One case was associated with regional lymph node metastases. All cases were cured by surgery alone; no recurrence was observed at the end of the follow-up period. In conclusion, despite their rarity, primary neuroendocrine tumors of the main pancreatic duct deserve recognition and must be considered in the etiological diagnosis of ductal stenosis.

Neuroendocrine tumors of Meckel's diverticulum: lessons from a single institution study of eight cases.

INTRODUCTION: Endocrine tumors of Meckel's diverticulum are rare. Their clinical and pathological characteristics are not well known, making it difficult to assess the best strategy for therapeutic management. MATERIALS AND METHODS: Eight cases of endocrine tumors of Meckel's diverticulum, submitted to surgical resection in our institution between 1977 and 2009, were studied. Clinical charts were reviewed; classification, grading, and staging were performed according to recent international recommendations. Five cases, including two associated with the carcinoid syndrome, were revealed by mesenteric mass or liver metastases; three cases were diagnosed incidentally at laparotomy or laparoscopy. RESULTS: All cases presented as typical well-differentiated midgut endocrine tumors. Five cases were associated with mesenteric lymph node metastases; three presented with liver metastases. Seven cases were classified as well-differentiated endocrine carcinomas, one as well-differentiated endocrine tumor of benign behavior. DISCUSSION: All tumors >1 cm, but one, had regional or distant disease. All patients had complete surgical resection of the primary. One patient deceased after 25 months; the others were alive after 12-101 months. CONCLUSION: In conclusion, endocrine tumors of Meckel's diverticulum are rarely symptomatic and often diagnosed at an advanced stage. All tumors measuring more than 1 cm in diameter must be resected according to oncological principles.

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.

Long-term survival after pancreaticoduodenectomy for endocrine tumors of the ampulla of Vater and minor papilla.

OBJECTIVE: Endocrine tumors of the ampullary region are rare, and accurate indications for their management are lacking. We aimed to evaluate the outcome of surgical treatment in this indication. METHOD: We reviewed all patients who submitted to a pancreaticoduodenectomy for ampullary endocrine tumors between 1982 and 2003 in our center. RESULTS: Eight patients, 3 men and 5 women, with a mean age of 47.8 years (range, 37-57 years) were included. Two patients presented with Zollinger-Ellison syndrome, and 1 had neurofibromatosis. Operative mortality was nil. The mean size of the tumors was 17.4 mm (range, 5-40 mm). There were 7 well-differentiated and 1 poorly differentiated endocrine carcinomas. Seven patients had satellite lymph node metastases, and 1 had diffuse liver metastases. Median follow-up was 131 months (range, 17-315 months). At the end of the follow-up period, 5 patients were alive and disease-free; 1 patient was alive with stable liver metastases. Two patients died 17 months and 13 years after surgery, respectively, from metastasis and an unrelated cause. CONCLUSION: This study demonstrates the high frequency of lymph node invasion in these uncommon tumors, even at an early clinical stage. Pancreaticoduodenectomy may result in prolonged survival of patients with well-differentiated tumors.

Histopathological response to preoperative chemoradiation for resectable pancreatic adenocarcinoma: the French Phase II FFCD 9704-SFRO Trial.

PURPOSE: This study suggests that pancreatic adenocarcinoma is a chemoradiosensitive tumor and that preoperative chemoradiation provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate. Evaluation of histopathological response to neoadjuvant therapy may serve as a surrogate marker for treatment efficacy and remains an active area of investigation. OBJECTIVES: The chemoradiosensitive of pancreatic adenocarcinoma has not yet fully been assessed. The purpose of this study is to determine the efficacy of preoperative chemoradiation, measured by the impact on the R0 resection rate and the histopathological response rate in patients presenting with resectable pancreatic adenocarcinoma. METHODS: Patients with localized, potentially resectable pancreatic adenocarcinoma were treated with 50 Gy irradiation combined with 5-fluorouracil by continuous infusion (300 mg . m(-2) . d(-1); day 1-5; week 1-5) and cisplatin (20 mg . m(-2) . d(-1); day 1-5 and day 29-33). Patients presenting with resectable disease at restaging, without metastatic dissemination, underwent surgical resection. RESULTS: Forty-one patients were enrolled. Twenty-seven patients (67.5%) completed chemoradiation receiving at least 75% prescribed chemotherapy dose without grade 4 nonhematological toxicity. Twenty-six patients (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0 resection. Thirteen of 26 specimens (50%) presented a major pathologic response with more than 80% of severely degenerative cancer cells. Complete pathologic response was observed in one specimen. Median survival time and 2-year survival rate were 9.4 months and 20% for the entire cohort. The local recurrence and 2-year survival rates were 4% and 32%, respectively, for the 26 operated patients. CONCLUSIONS: This study suggests that some pancreatic adenocarcinomas are chemoradiosensitive and that preoperative chemoradiation provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate. Further research is needed to determine the biologic difference between responders and nonresponders, to evaluate the predictive value of treatment response parameters, and to optimize the chemoradiation regimen.

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.

Death during laparoscopy: can 1 gas push out another? Danger of argon electrocoagulation.

We report the death of a young man during a laparoscopic partial splenectomy performed with an argon plasma coagulator to remove a benign cyst. The report analyzes the very particular mechanism of a gas embolism, which caused death here. This analysis leads us to recommend a close attention on the use of argon coagulators during laparoscopy. The aim of this article is to draw surgeons' attention to the conclusions of a court-ordered expert assessment intended to elucidate the mechanisms responsible for the death of a 20-year-old man during a laparoscopic partial splenectomy performed with an argon plasma coagulator to remove a benign cyst.

Long-term survival (5-20 years) after pancreatectomy for pancreatic ductal adenocarcinoma: a series of 30 patients collected from 3 institutions.

OBJECTIVES: Long-term survival after pancreatectomy for pancreatic duct adenocarcinoma has been rarely reported. Factors influencing survival are still debated. The aim of the study is to report a French multicentric series of long-term survivors after pancreatectomy for pancreatic duct adenocarcinoma. METHODS: Data of patients who survived >5 years (February 1983-January 2000) were analyzed. All operative specimens were reviewed. Patients with intraductal-papillary-mucinous-neoplasia, cystadenocarcinoma, acinous-adenocarcinoma, neuroendocrine, or mixed tumors were excluded. RESULTS: Long-term survivors were 20 men and 10 women, with median age of 61 years. Twenty-five patients had pancreaticoduodenectomies (6 pylorus preserving pancreatoduodenectomy [PPPD]), 3 had total pancreaticoduodenectomies, and 2 had splenopancreatectomies. Three patients had portal vein resection, 1 had hepatic artery resection-reconstruction, and 1 had segmentectomy for liver metastasis. All resections were complete macroscopic and microscopic resection (R0). Median tumor size was 30 mm. Tumors were pT2 (n = 1), pT3 (n = 24), pT4 (n = 5), 12 N+, 1 M+. Twenty patients had adjuvant radiotherapy, and 18 had concomitant chemotherapy. Median survival was 7.3 years (range, 5.2-21 years). Nineteen patients are alive, 1 with recurrence and 18 with no evidence of disease (2 had more than 20 years of follow-up). Eleven patients died, 6 from recurrence. CONCLUSIONS: Pancreatic duct adenocarcinoma can be cured, and long-term survival after R0 curative surgery has become a reality. Long-term survivors did not fulfil the ideal prognostic criteria and even presented with advanced stage.

Mixed hepato/cholangiocarcinoma with paraneoplastic hypercalcemia.

Malignant hypercalcemia without bone metastasis may result from the abnormal secretion of parathyroid hormone (PTH) or PTH-related protein (PTH-rP). We present a case of possible PTH-rP-secreting mixed hepato/cholangiocarcinoma. In July 2000, a 52-year-old woman presented with right hypochondrial pain and weight loss. Imaging procedures revealed a 10-cm lesion involving the right hepatic lobe and the hilum. Retrohepatic inferior vena caval invasion was detected by abdominal angiography. Serum calcium was elevated, while intact PTH was undetectable. The rising level of hypercalcemia rapidly became life-threatening. Medical treatment with diphosphonate and octreotide was ineffective. Chemoembolization of the right branch of the hepatic artery, preceded by right portal vein embolization, helped regain normocalcemia and improve the patient's general condition. Extended right hepatectomy with prosthetic replacement of the vena cava and resection of the left portal vein was performed. Histopathology revealed mixed hepato/cholangiocarcinoma. Hypocalcemia appeared postoperatively but was successfully corrected. Recurrence of diffuse hepatic nodules resulted in recurrent hypercalcemia and death 3 and a half years after the surgery. This is the third case to be reported in the English-language literature. Paraneoplastic PTH-rP-induced hypercalcemia, which may be a fatal complication, can respond to arterial chemoembolization. Extensive hepatic resection may offer a good chance for survival.

Central pancreatectomy: single-center experience of 50 cases.

Central pancreatectomy is a nonstandard operation for unusual lesions. This study reports a single-center experience of central pancreatectomy. Thirty-eight women and 12 men with a mean age of 49.4 years (range, 13.4-79.2 years) underwent central pancreatectomy from January 1987 to October 2005. Indications included 18 neuroendocrine tumors (11 nonfunctioning), 10 serous and 10 mucinous cystadenomas, 5 intraductal papillary mucinous neoplasms, 3 main pancreatic duct strictures, 2 solid cystic papillary tumors, 1 hydatid cyst, and 1 acinar cell carcinoma. The proximal pancreatic remnant was suture ligated. The distal pancreatic end was anastomosed to a Roux-en-Y jejunal loop (n = 6) or to the stomach (n = 44). Three patients had associated procedures, 1 each for metastatic liver cytoreduction (VIPoma), hydatid liver disease, and pancreatic resection for multifocal mucinous cystadenoma. The median operative time was 3 hours 21 minutes (range, 1 hour 50 minutes to 6 hours). The mean length of the resected pancreas was 45 mm (range, 20-80 mm) and the mean tumor size was 23 mm (5-60 mm). The perioperative mortality was nil. Complications included the following: 4 patients (8%) had pancreatic anastomotic leak, 5 patients (10%) had acute pancreatitis, 7 patients (14%) had intra-abdominal collection, and 3 patients (6%) had bleeding. Six patients (12%) required a reoperation during the postoperative period. Eight patients (16%) required endoscopic (1 with biliary endoscopic stent) or radiological (7 with percutaneous drainage) intervention. No patients developed de novo diabetes. On long-term follow-up, 2 patients with invasive intraductal papillary mucinous neoplasia had recurrence; one was treated successfully by completion pancreatectomy and the other died at 20 months. One patient with serous cystadenoma died at 16.8 years without recurrence. One patient with metastatic VIPoma had a liver transplant 9 years postoperatively and is alive. The median follow-up was 55 months (range, 2 months to 16.8 years). The actuarial 5-year patient and pancreatic remnant survival rates were 98% and 95%, respectively. In our series, central pancreatectomy led to effective preservation of both cephalic and distal pancreatic remnants without a significant increase in postoperative morbidity compared with conventional pancreatectomy.

Congenital intrahepatic bile duct dilatation is a potentially curable disease: long-term results of a multi-institutional study.

OBJECTIVE: To report clinical presentation, perioperative outcome, and long-term results of surgical management of congenital intrahepatic bile duct (IHBD) dilatations (including Caroli disease) in a multi-institutional setting. SUMMARY BACKGROUND DATA: Congenital IHBD dilatations are a rare congenital disorder predisposing to intrahepatic stones, cholangitis, and cholangiocarcinoma. The management remains difficult and controversial for bilobar forms of the disease or when concurrent congenital hepatic fibrosis is associated. METHODS: From 1976 to 2004, 33 patients (range 11 to 79 years) were retrospectively enrolled. Disease extent into the liver was unilobar in 26 patients and bilobar in 7 patients (21%). Cholangiocarcinoma, congenital hepatic fibrosis, and intrahepatic stones were present in 2, 10, and 20 patients, respectively. Transplantations or liver resections were performed in 5 and 27 patients, respectively, whereas 1 asymptomatic patient was managed conservatively. RESULTS: Postoperative mortality was nil. Postoperative complications occurred in 16 of 32 operated patients (50%) and additional procedures for residual stones were required in 5 patients. During a median follow-up of 80 months (1 patient being lost for follow-up) no patient developed metachronous carcinoma. Six patients (30%) developed recurrent intrahepatic stones but satisfactory late outcome was achieved in 27 patients (87%). CONCLUSIONS: Partial or total liver resection achieves satisfactory late outcome in congenital IHBD dilatations, when the affection is treated at an early stage and when the extent of liver resection is tailored to intrahepatic disease extent and takes into consideration the presence and severity of underlying chronic liver and renal diseases.