Background The role of orthotopic liver transplantation in the treatment of patients with cirrhosis and hepatocellular carcinoma is controversial, and determining which patients are likely to have a good outcome after liver transplantation is difficult. Methods We studied 48 patients with cirrhosis who had small, unresectable hepatocellular carcinomas and who underwent liver transplantation. In 94 percent of the patients, the cirrhosis was related to infection with hepatitis B virus, hepatitis C virus, or both. The presence of tumor was confirmed by biopsy or serum alpha-fetoprotein assay. The criteria for eligibility for transplantation were the presence of a tumor 5 cm or less in diameter in patients with single hepatocellular carcinomas and no more than three tumor nodules, each 3 cm or less in diameter, in patients with multiple tumors. Twenty-eight patients with sufficient hepatic function underwent treatment for the tumor, mainly chemoembolization, before transplantation. After liver transplantation...

Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis

For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phag...

/pdf/the-nox-family-of-ros-generating-nadph-oxidases-physiology-zjc88zvh59.pdf

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

Postoperative pancreatic fistula: an international study group (ISGPF) definition.

Background. Postoperative pancreatic fistula (POPF) is still regarded as a major complication. The incidence of POPF varies greatly in different reports, depending on the definition applied at each surgical center. Our aim was to agree upon an objective and internationally accepted definition to allow comparison of different surgical experiences. Methods. An international panel of pancreatic surgeons, working in well-known, high-volume centers, reviewed the literature on the topic and worked together to develop a simple, objective, reliable, and easyto-apply definition of POPF, graded primarily on clinical impact. Results. A POPF represents a failure of healing/sealing of a pancreatic-enteric anastomosis or a parenchymal leak not directly related to an anastomosis. An all-inclusive definition is a drain output of any measurable volume of fluid on or after postoperative day 3 with an amylase content greater than 3 times the serum amylase activity. Three different grades of POPF (grades A, B, C) are defined according to the clinical impact on the patient’s hospital course. Conclusions. The present definition and clinical grading of POPF should allow realistic comparisons of surgical experiences in the future when new techniques, new operations, or new pharmacologic agents that may impact surgical treatment of pancreatic disorders are addressed. (Surgery 2005;138:8-13.)

Special article Postoperative pancreatic fistula: An international study group (ISGPF) definition

EASL–EORTC Clinical Practice Guidelines (CPG) on the management of hepatocellular carcinoma (HCC) define the use of surveillance, diagnosis, and therapeutic strategies recommended for patients with this type of cancer. This is the first European joint effort by the European Association for the Study of the Liver (EASL) and the European Organization for Research and Treatment of Cancer (EORTC) to provide common guidelines for the management of hepatocellular carcinoma. These guidelines update the recommendations reported by the EASL panel of experts in HCC published in 2001 [1]. Several clinical and scientific advances have occurred during the past decade and, thus, a modern version of the document is urgently needed. The purpose of this document is to assist physicians, patients, health-care providers, and health-policy makers from Europe and worldwide in the decision-making process according to evidencebased data. Users of these guidelines should be aware that the recommendations are intended to guide clinical practice in circumstances where all possible resources and therapies are available. Thus, they should adapt the recommendations to their local regulations and/or team capacities, infrastructure, and cost– benefit strategies. Finally, this document sets out some recommendations that should be instrumental in advancing the research and knowledge of this disease and ultimately contribute to improve patient care. The EASL–EORTC CPG on the management of hepatocellular carcinoma provide recommendations based on the level of evidence and the strength of the data (the classification of evidence is adapted from National Cancer Institute [2]) (Table 1A) and the strength of recommendations following previously reported systems (GRADE systems) (Table 1B).

http://www.bclc.cat/download/easl-guidelines.pdf

EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma European Association for the Study of the Liver ⇑ , European Organisation for Research and Treatment of Cancer

Background:  Because of specific methodological difficulties in conducting randomized trials, surgical research remains dependent predominantly on observational or non-randomized studies. Few validated instruments are available to determine the methodological quality of such studies either from the reader's perspective or for the purpose of meta-analysis. The aim of the present study was to develop and validate such an instrument.

Methods:  After an initial conceptualization phase of a methodological index for non-randomized studies (MINORS), a list of 12 potential items was sent to 100 experts from different surgical specialities for evaluation and was also assessed by 10 clinical methodologists. Subsequent testing involved the assessment of inter-reviewer agreement, test-retest reliability at 2 months, internal consistency reliability and external validity.

Results:  The final version of MINORS contained 12 items, the first eight being specifically for non-comparative studies. Reliability was established on the basis of good inter-reviewer agreement, high test-retest reliability by the κ-coefficient and good internal consistency by a high Cronbach's α-coefficient. External validity was established in terms of the ability of MINORS to identify excellent trials.

Conclusions:  MINORS is a valid instrument designed to assess the methodological quality of non-randomized surgical studies, whether comparative or non-comparative. The next step will be to determine its external validity when used in a large number of studies and to compare it with other existing instruments.

Methodological index for non-randomized studies (minors): development and validation of a new instrument.

To determine whether a careful evaluation of tumor extension by preoperative computed tomography scan after intra-arterial injection of ultrafluid lipiodol and by intraoperative ultrasound examination reduced the recurrence rate of hepatocellular carcinoma after resection, a series of 47 cirrhotic patients with a single tumor operated on from 1984 was studied. Alphafetoprotein level was less than 100 ng/mL in 26 patients (55%), size of the tumor was less than 5 cm in 28 patients (59%), and capsule was present in 30 patients (63%). The resection was performed with free margin measuring 1 cm or more. The overall cumulative survival rates at 3 and 5 years were 35% and 17%, respectively. Intrahepatic recurrence was observed in 28 patients (60%), located less than 2 cm from the resection margin in only four patients. The cumulative intrahepatic recurrence rate at 3 years was 81% and was significantly higher in patients with tumor greater than or equal to 5 cm and in patients with preoperative alphafetoprotein level of greater than or equal to 100 ng/mL. In this series the cumulative intrahepatic recurrence rate at 5 years was 100%. This high recurrence rate after resection, even with careful evaluation of tumor extension, indicates that liver transplantation might be envisaged for the treatment of cirrhotic patients with resectable hepatocellular carcinoma.

Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis.

Paradoxically, reactive oxygen species (ROS) can promote normal cellular proliferation and carcinogenesis, and can also induce apoptosis of tumor cells. In this report, we study the contribution of ROS to various cellular signals depending on the nature and the level of ROS produced. In nontransformed NIH 3T3 cells, ROS are at low levels and originate from NADPH oxidase. Hydrogen peroxide (H(2)O(2)), controlled by the glutathione system, is pivotal for the modulation of normal cell proliferation. In CT26 (colon) and Hepa 1-6 (liver) tumor cells, high levels of ROS, close to the threshold of cytotoxicity, are produced by mitochondria and H(2)O(2) is controlled by catalase. N-acetylcysteine, which decreases H(2)O(2) levels, inhibits mitogen-activated protein kinase and normal cell proliferation but increases tumor cell proliferation as H(2)O(2) concentration drops from the toxicity threshold. In contrast, antioxidant molecules, such as mimics of superoxide dismutase (SOD), increase H(2)O(2) levels through superoxide anion dismutation, as well as in vitro proliferation of normal cells, but kill tumor cells. CT26 tumors were implanted in mice and treated by oxaliplatin in association with one of the three SOD mimics manganese(III)tetrakis(4-benzoic acid) porphyrin, copper(II)(3,5-diisopropylsalicylate)2, or manganese dipyridoxyl diphosphate. After 1 month, the volumes of tumors were respectively 35%, 31%, and 63% smaller than with oxaliplatin alone (P < 0.001). Similar data were gained with Hepa 1-6 tumors. In conclusion, antioxidant molecules may have opposite effects on tumor growth. SOD mimics can act in synergy with cytotoxic drugs to treat colon and liver cancers.

https://cancerres.aacrjournals.org/content/canres/65/3/948.full.pdf

Controlling Tumor Growth by Modulating Endogenous Production of Reactive Oxygen Species

Hypothesis Better knowledge of independent risk factors might decrease mortality and morbidity rates following colorectal surgery. Design Prospective multicenter study. Interventions From June to September 2002, consecutive patients undergoing open or laparoscopic surgery (electively or on an emergent basis) for colorectal cancers or diverticular disease were prospectively included. Exclusion criteria were colectomy for other causes (eg, inflammatory bowel diseases, benign polyps). The structured sheet of data collection included more than 200 items on all perioperative data concerning the patient, the disease, and the operating surgeons. Postoperative mortality and morbidity were defined as in-hospital death and complications. Results Among 1421 patients, the in-hospital death rate was 3.4% and the overall morbidity rate was 35%. Four independent preoperative risk factors of mortality were found: emergency surgery, loss of more than 10% of weight, neurological comorbidity, and age older than 70 years. Six independent risk factors of morbidity were found: age older than 70 years, neurologic comorbidity, hypoalbuminemia, cardiorespiratory comorbidity, long duration of operation, and peritoneal contamination. Conclusion Colorectal resection in France is associated with a 3.4% mortality rate and a 35% morbidity rate. Knowledge of the risk factors could help surgeons manage cases.

https://jamanetwork.com/journals/jamasurgery/articlepdf/508425/soa4112_278_283.pdf

Postoperative mortality and morbidity in French patients undergoing colorectal surgery: results of a prospective multicenter study.

The aim of this study was to determine by
univariate and multivariate analyses the factors associated with
clinically significant anastomotic leakage (AL) after large bowel
resection. From 1990 to 1997 a series of 707 patients underwent
colonic or rectal resection (without a stoma). Patients were divided
into two groups: those with clinical anastomotic leakage (group 1) and
those without it (group 2). AL occurred in 43 of 707 patients (6%).
The overall mortality was 2.2% and was significantly higher in
patients with AL than in those without: 5 of 43 (12%) versus 11 of 664
(1.6%), p <0.001. Univariate analysis showed 15
variables associated with the risk of AL: previous abdominal or pelvic
irradiation (p = 0.02), American Society of
Anesthesiologists (ASA) score > 2 (p = 0.04),
leukocytosis (p = 0.02), renal failure
(p = 0.03), steroid treatment (p =
0.01), duration of operation (p = 0.001),
intraoperative septic conditions (p = 0.006), total
colectomy (p = 0.009), transverse colectomy
(p = 0.02), difficulties encountered during
anastomosis (p = 0.001), ileorectal anastomosis
(p = 0.02), colocolic anastomosis (p
= 0.01), abdominal drainage (p = 0.05), and blood
transfusion intraoperatively (p = 0.006) and
postoperatively (p = 0.001). Multivariate analysis
showed that only preoperative leukocytosis (p = 0.04),
intraoperative septic conditions (p = 0.001),
difficulties encountered during anastomosis (p =
0.007), colocolic anastomosis (p = 0.004), and
postoperative blood transfusion (p = 0.0007) were
independent factors associated with AL. The risk of AL increased from a
range of 12% to 30% if one risk factor was present, to 38% with two
factors, to 50% with three factors. After colorectal resection and
intraperitoneal anastomosis, a temporary protective stoma is proposed
in selected patients with high risk factors for AL, as observed in our
study.

Yves Panis

Papers

Methodological index for non-randomized studies (minors): development and validation of a new instrument.

Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis.

Controlling Tumor Growth by Modulating Endogenous Production of Reactive Oxygen Species

Postoperative mortality and morbidity in French patients undergoing colorectal surgery: results of a prospective multicenter study.

Factors associated with clinically significant anastomotic leakage after large bowel resection: multivariate analysis of 707 patients.