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Biomedical subjects

P E Majno

Publications and source records attributed to P E Majno.

14 recordsLinked to original sources

Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery.

BACKGROUND: The purpose of the study was to characterize histological response to chemotherapy of hepatic colorectal metastases (HCRM), evaluate efficacy of different chemotherapies on histological response, and determine whether tumor regression grading (TRG) of HCRM predicts clinical outcome. PATIENTS AND METHODS: TRG was evaluated on 525 HCRM surgically resected from 181 patients, 112 pretreated with chemotherapy. Disease-free survival (DFS) and overall survival (OS) were correlated to TRG. RESULTS: Tumor regression was characterized by fibrosis overgrowing on tumor cells, decreased necrosis, and tumor glands (if present) at the periphery of HCRM. With irinotecan/5-fluorouracil (5-FU), major (MjHR), partial (PHR), and no (NHR) histological tumor regression were observed in 17%, 13%, and 70% of patients, respectively. With oxaliplatin/5-FU, MjHR, PHR, and NHR were observed in 37%, 45%, and 18% of patients, respectively. Five patients, treated with oxaliplatin, had complete response in all their metastases. MjHR was associated with an improved 3-year DFS compared with PHR or NHR. MjHR and PHR were associated with an improved 5-year OS compared with NHR. CONCLUSION: Histological tumor regression of HCRM to chemotherapy corresponds to fibrosis overgrowth and not to increase of necrosis. TRG should be considered when evaluating efficacy of chemotherapy for HCRM. Histological tumor regression was most common among oxaliplatin-treated patients and associated with better clinical outcome.

Adult↗

Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary.

BACKGROUND: In many patients with advanced synchronous liver metastases from colorectal tumours, the metastases progress during treatment of the primary, precluding curative treatment. The authors have investigated a management strategy that involves high-impact chemotherapy first, resection of liver metastases second and finally removal of the primary tumour in patients with adverse prognostic factors. METHODS: Twenty consecutive patients with non-obstructive colonic (nine patients) or rectal (11 patients) cancer and advanced synchronous liver metastases were treated according to this strategy. Median age was 56 years. Patients received between two and six cycles of 5-fluorouracil, oxaliplatin and irinotecan-based chemotherapy. Data were collected prospectively. RESULTS: Overall survival rates at 1, 2, 3 and 4 years after the start of treatment were 85, 79, 71 and 56 per cent respectively, with a median survival of 46 months. Sixteen of the 20 patients had complete removal of liver metastases and colorectal tumours (resectability rate 80 per cent). CONCLUSION: This new strategy produced resectability and survival rates better than those expected from the published data on patients with disease of similar severity. It allows initial control and downstaging of liver metastases, and delivery of preoperative radiotherapy for rectal cancer without the fear that liver metastases will meanwhile progress beyond the possibility of cure.

Adult↗

Impact of a sirolimus/tacrolimus-based immunosuppressive regimen on kidney function after islet transplantation.

AIM: Islet transplantation is gaining recognition as a therapeutic option for selected diabetic patients. The immunosuppressive regimen based on sirolimus/low-dose tacrolimus is considered a major breakthrough that allowed considerable improvement in graft survival. A high incidence of side effects associated with such a regimen has been reported in the literature, but this immunosuppressive protocol is generally considered safe or even protective to the kidney. Herein, we analyze the impact of the sirolimus/low-dose tacrolimus-based protocol on kidney function. PATIENTS AND METHODS: Five islet-after-kidney and 5 islet-transplant-alone patients were enrolled and followed up. Renal function was assessed by the periodic measurement of serum creatinine and by the presence of albuminuria. Metabolic control markers and graft function were followed, as well as immunosuppressive whole blood trough levels. RESULTS: Kidney function significantly decreased in 6 of 10 patients. Neither metabolic markers nor immunosuppressive drugs levels were significantly associated with the decreased kidney function. CONCLUSION: Although a specific etiology was not identified, subsets of patients presented a higher risk for decrease of kidney function. The presence of low creatinine clearance, albuminuria, and long-established kidney graft were associated with poorer outcomes.

Creatinine↗

Biliary strictures: classification based on the principles of surgical treatment.

The classification of biliary strictures used at Hopital Paul Brousse is based on the lowest level at which healthy biliary mucosa is available for anastomosis. The classification is intended to help the surgeon choose the appropriate technique for the repair. Type I strictures, with a common duct stump longer than 2 cm, can be repaired without opening the left duct and without lowering the hilar plate. Type II strictures, with a stump shorter than 2 cm, require opening the left duct for a satisfactory anastomosis. Lowering the hilar plate is not always necessary but may improve the exposure. Type III lesions, in which only the ceiling of the biliary confluence is intact, require lowering the hilar plate and anastomosis on the left ductal system. There is no need to open the right duct if the communication between the ducts is wide. With type IV lesions the biliary confluence is interrupted and requires either reconstruction or two or more anastomoses. Type V lesions are strictures of the hepatic duct associated with a stricture on a separate right branch, and the branch must be included in the repair. Although this classification is intended for established strictures, it is commonly used to describe acute bile duct injuries. The surgeon must be aware, however, that the established stricture is generally one level higher than the level of the injury at the original operation.

Bile Ducts↗

Living donor liver transplantation for early hepatocellular carcinoma: A life-expectancy and cost-effectiveness perspective.

Cadaveric liver transplantation (CLT) is an excellent treatment for early hepatocellular carcinoma (HCC). Its use, however, is limited by the shortage of grafts, with up to 30% of patients developing contraindications to the procedure while waiting for a donor. Living donor liver transplantation (LDLT) has emerged as an alternative to overcome this limitation. We compared the consequences of LDLT versus CLT using a Markov model balancing the gains and losses in life expectancy among donors and recipients. For a 60-year-old recipient with a 70% 5-year survival after transplantation, a 4% monthly drop-out rate, and a donor with 1% mortality, LDLT became more effective than CLT after 3.5 months on the waiting list. These results varied with the probability of developing contraindications to transplantation, the survival after transplantation, and the donor's mortality. For a 12-month delay saved on the waiting list, the gain in survival provided by LDLT compared with CLT ranged between 0 and 2.8 life years depending on survival after transplantation, time spent on the waiting list, and drop-out rate. LDLT was cost-effective (less than $50,000 per quality-adjusted life year saved) in all scenarios of waiting lists exceeding 7 months, and this figure ranged from 2 to 16 months when varying the drop-out rate. LDLT for early HCC offered substantial gains in life expectancy with acceptable cost-effectiveness ratios when the waiting list exceeds 7 months. The gain in life expectancy and the cost-effectiveness of LDLT were more dependent on the drop-out rate and the outcome after transplantation than on donor's mortality.

Carcinoma, Hepatocellular↗

Hepatobiliary surgery.

The transformation of liver and biliary tract surgery into a full speciality began with the application of functional anatomy to segmental surgery in the 1950's, reinforced by ultrasound and new imaging techniques. The spectrum of gall-stone disease encountered by the hepatobiliary surgeon has changed with the laparoscopic approach to cholecystectomy. There is increased need for conservation techniques to repair the bile duct injuries that arise more often in the laparoscopic approach to cholecystectomy. These and other surgical interventions on the bile ducts should be selected as a function of risk versus benefit in relation to the patient's requirements and the institutional expertise. Bile duct cancers, including hilar cholangiocarcinoma, and gallbladder cancers have a dismal reputation, but evidence is accumulating for better survivals from aggressive approaches performed by specialist hepatobiliary surgeons. Hepatic surgery has increased in safety and effectiveness, largely due to the segmental approach, but also to experience with techniques for vascular control and exclusion used in liver transplantation. Techniques such as portal vein embolisation, which induces hypertrophy of the future remnant liver, percutaneous local tumour destruction using cryotherapy or radiofrequency tumour coagulation and more effective chemotherapy are beginning to increase the number of patients who can undergo curative resection. In liver transplantation, segmental surgery has been applied to graft reduction and to split liver grafts, and is opening new perspectives for living donor transplantation. Today the limitation to survival in primary and metastatic liver cancer lies not in the surgical technique but in the difficulty of dealing with microscopic and extrahepatic disease. Progress in these fields will enable the hepatobiliary surgeon to further extend the possibilities for proposing curative resections.

Bile Duct Neoplasms↗

Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: an outcome-oriented decision analysis.

Two treatments are accepted for patients with solitary hepatocellular carcinoma </=5 cm in size and with preserved hepatic function: (1) liver resection, which can be performed without delay but has a high recurrence rate, and (2) liver transplantation, which has a better long-term survival, but is not easily available because grafts are scarce. A third possibility is to offer liver resection first and liver transplantation for tumor recurrence or deteriorating liver function ("salvage" transplantation). We investigated the implications of such a strategy with a Markov-based decision analytic model. In a scenario assuming intermediate values for 4 main variables (12-month waiting list; tumor progression outside transplantation criteria: 4% per month; recurrence after resection: 20% per year; recurrences eligible for transplantation: 60%), the life expectancy was 8.8 years for primary transplantation versus 7.8 years for primary resection and salvage transplantation, with a calculated use of grafts at 5 years of 52% for primary transplantation versus 23% for salvage transplantation. This study estimates of the survival and graft-saving of a strategy of primary resection and salvage transplantation according to variables that are to some extent predictable. This strategy may be a rational way to cope with lengthening waiting lists, especially for patients with tumors close to the limit for transplantation criteria, if the results of liver resection are good, if patients with the lowest risks of recurrence can be selected, and if a strict follow-up can detect recurrences when the patients are still transplantable.

Carcinoma, Hepatocellular↗

Biliary migration of hepatocellular carcinoma fragment after transcatheter arterial chemoembolization therapy.

Occasional side-effects of transcatheter arterial chemoembolization therapy in hepatocellular carcinoma are essentially related to tissue necrosis. We report the case of a patient with hepatocellular carcinoma who experienced an acute common bile duct obstruction a few weeks after such a procedure, in the absence of obvious biliary tract invasion. An endoscopic sphincterotomy relieved the obstruction. At histology, the intra-biliary material was identified as a fragment of hepatocellular carcinoma. We discuss the causes of obstructive jaundice in the setting of hepatocellular carcinoma as well as in the specific situation of transcatheter arterial chemoembolization therapy.

Aged↗

Liver transplantation for hepatocellular carcinoma.

Liver transplantation for hepatocellular carcinoma (HCC) in patients with cirrhosis is a radical treatment of the tumor and associated precancerous state. It is potentially curative in a proportion of patients. The outcomes of early studies of liver transplantation in this indication were initially unfavorable. Selection of transplant candidates at an early stage, in the absence of extrahepatic spread, gives better survival than surgical resection and alternative nonsurgical treatments. Transarterial chemoembolization can be used for preoperative control of the disease. Adjuvant chemotherapy may be indicated in the postoperative period for the prevention of recurrence in patients with histologic features of invasiveness in the surgical specimen. Liver transplantation as the treatment of choice for early HCC in screening programs in cirrhotic patients may become limited by graft availability as the numbers of hepatitis C-related cases increase. Resection may be indicated if the waiting time is likely to be long.

Adolescent↗

Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis.

OBJECTIVE: To investigate the impact of preoperative transarterial lipiodol chemoembolization (TACE) in the management of patients undergoing liver resection or liver transplantation for hepatocellular carcinoma. PATIENTS AND METHODS: TACE was performed before surgery in 49 of 76 patients undergoing resection and in 54 of 111 patients undergoing liver transplantation. Results were retrospectively analyzed with regard to the response to treatment, the type of procedure performed, the incidence of complications, the incidence and pattern of recurrence, and survival. RESULTS: In liver resection, downstaging of the tumor by TACE (21 of 49 patients [42%]) and total necrosis (24 of 49 patients [50%]) were associated with a better disease-free survival than either no response to TACE or no TACE (downstaging, 29% vs. 10% and 11 % at 5 years, p = 0.08 and 0.10; necrosis, 22% vs. 13% and 11% at 5 years, p = 0.1 and 0.3). Five patients (10%) with previously unresectable tumors could be resected after downstaging. In liver transplantation, downstaging of tumors >3 cm (19 of 35 patients [54%]) and total necrosis (15 of 54 patients [28%]) were associated with better disease-free survival than either incomplete response to TACE or no TACE (downstaging, 71 % vs. 29% and 49% at 5 years, p = 0.01 and 0.09; necrosis, 87% vs. 47% and 60% at 5 years, p = 0.03 and 0.14). Multivariate analysis of the factors associated with response to TACE showed that downstaging occurred more frequently for tumors >5 cm. CONCLUSIONS: Downstaging or total necrosis of the tumor induced by TACE occurred in 62% of the cases and was associated with improved disease-free survival both after liver resection and transplantation. In liver resection, TACE was also useful to improve the resectability of primarily unresectable tumors. In liver transplantation, downstaging in patients with tumors >3 cm was associated with survival similar to that in patients with less extensive disease.

Aged↗

Operative injury to the hepatic artery. Consequences of a biliary-enteric anastomosis and principles for rational management.

Although the interruption of the hepatic arterial flow usually is well tolerated, this is not always the case, and it is important to predict in which circumstances complications are likely to occur. The main determinants that should guide the surgeon confronted with this problem are (1) whether the portal circulation is normal, (2) whether structures carrying collateral blood supply have been interrupted, and (3) whether some form of biliary reconstruction is needed. We present our experience with three patients in whom the hepatic artery was damaged at operation as examples of how this injury can be dealt with in practice and discuss the measures to prevent or treat the complications that developed.

Adult↗

Mini-review: tumor necrosis factor (TNF) and TNF soluble receptors (TNF-sR) in liver disease and liver transplantation.

Tumor necrosis factor (TNF) is a powerful cytokine with an important role in the inflammatory acute phase response and in the activation of the immune system. It exerts its action through the adherence to cellular receptors, known as the TNF-R55 und TNF-R75. High levels of these receptors are present in the blood in a soluble form and binding circulating TNF can neutralise its systemic effects. Although the knowledge on the biology of TNF and TNF-sR is progressing rapidly, little is known on the action of this cytokine and of its soluble receptors in liver disease and liver transplantation. The literature on the subject is reviewed, and trends for future research are discussed.

Humans↗

Sitting a transverse colostomy.

Traditional teaching suggests that a transverse colostomy should be sited in the right upper quadrant. This study of 67 colostomies (26 right upper quadrant and 41 right iliac fossa) indicates that they should be placed in the optimum position for each patient, which is usually the right iliac fossa.

Colostomy↗