Elective subtotal colectomy with ileosigmoid anastomosis for colon cancer preserves bowel function and quality of life.

AIM: We report on our experience of elective subtotal colectomy and ileosigmoid anastomosis for colon cancer with focus on postoperative results, function and quality of life. METHOD: Between 1998 and 2011, 106 consecutive patients with colonic malignancy underwent this procedure electively. Function and quality of life (EORTC QLQ-C30) were evaluated retrospectively with questionnaires sent to all patients free of recurrence. RESULTS: There were 62 men and 44 women (mean age 63 years). Postoperative mortality and morbidity rates were 1.9 and 26.4%, respectively. Persistent ileus was the main early complication (16%). After a mean follow-up of 67 ± 36 months, 50 (78.1) out of 64 patients have been evaluated for function and quality of life. The mean number of bowel movements per 24 h was 3 ± 2 and significantly lower when the length of the remaining sigmoid colon was more than 15 cm (P = 0.049). Compared with a European reference population for EORTC QLQ-C30 results, our patients had significantly more diarrhoea (26 vs 3, P = 0.0002) but less pain (10 vs 25, P < 0.0001) and better global quality of life (77 vs 62, P < 0.0001). CONCLUSION: Elective subtotal colectomy for colon cancer is safe and associated with good function and quality of life. Ileosigmoid anastomosis should be discussed when extended colectomy is required, providing the rectosigmoid junction and its vascular supply can be oncologically preserved. For tumours located in the transverse colon or at the splenic flexure, this procedure may be the best surgical option.

Liver preservation with SCOT 15 solution decreases posttransplantation cholestasis compared with University of Wisconsin solution: a retrospective study.

BACKGROUND: SCOT 15 is a new solution to preserve abdominal organs for transplantation. Its principal characteristic is the use of polyethylene glycol. Herein We report our experience using SCOT 15 compared with the reference University of Wisconsin (UW) solution for hepatic transplantation. METHODS: We compared 2 groups: SCOT 15 (n = 33; 2009-2010) versus UW (n = 34; 2008-2010), which were paired for cold and warm ischemic times, donor ages, and graft weights. Endpoints were biologic tests in the first 2 months after the operation. A linear mixed model was used to evaluate longitudinal changes and influences of each solution. RESULTS: No primary failure was observed. At postoperative day 0, transaminase values were higher in the SCOT 15 than in the UW group: aspartate transaminase: 2,435 ± 399 vs 589 ± 83 IU/L (P < .01); alanine transaminase: ALT: 1,207 ± 191 vs 484 ± 64 IU/L (P < .05), then returned to low levels in both groups. From day 0 to 8, coagulation factors reached normal values; there was no difference between the 2 groups. Total bilirubin decreased similarly in the 2 groups. However, from the second postoperative week (W1) to W8, the SCOT 15 group showed a slow decrease in the mean values of gamma-glutamyltranspeptidase (gGT) from 233 ± 125 to 130 ± 161 IU/L, which were significantly lower than those in the UW group, where the gGT remained around 300 IU/L (P < .01). The End-Stage Liver Disease, Child-Pugh, or United Network for Organ Sharing scores, primary liver diseases, hepatitic C virus status, arterial or biliary complications, and male/female ratio, which was different in the 2 groups, did not statistically influence these results. CONCLUSIONS: The main effect of cold storage of human liver using SCOT 15 compared with UW solution was to decrease cholestasis following transplantation.

Perioperative management of combined heart-liver transplantation in patients with cirrhosis, renal insufficiency, or pulmonary hypertension.

UNLABELLED: STATING THE MAIN PROBLEM: Only few reports have detailed perioperative management and outcome of combined heart and liver transplantation (CHLT), and none describe the long-term renal function. METHODS: Three patients presented clinical signs of cardiomyopathy with reduced ejection fraction and proven cirrhosis with evidence of portal hypertension. Two of them presented renal failure, and the other pulmonary hypertension. After cardiac transplantation and closure of the sternum, liver transplantation was performed using systematically venovenous double-limb (portal and caval) bypass. RESULTS: Mean cold ischemic time for heart and liver was 2 h 46 min and 12 h 47 min, respectively. Intraoperative hemodynamics remained grossly stable during surgery. Mean transfusions were 12 red blood cell packs. All three patients received anti-R-Il2 antibodies at post-operative day 1 and 4. Mean plasma creatinine concentration was 90 ± 8 µmol/L one yr post-CHLT, vs 160 ± 62 µmol/L pre-CHLT. All three patients are alive with functional grafts after a mean follow-up of 26 months (12-38). CONCLUSION: CHLT could be performed safely through two consecutive and independent usual procedures. Perioperative hemodynamic stability, minimal blood loss, and routine splanchnic decompression are probably major determinants of a favorable outcome and good long-term renal function.

[Hepatotoxicity of metastatic colorectal cancer chemotherapy: systematic review]. / Toxicité hépatique de la chimiothérapie du cancer colorectal métastatique: revue de la littérature.

AIM: Hepatic toxicity of chemotherapy for colorectal cancer and its complications after hepatic metastasis surgery are unclear. Studies reporting hepatic lesions after chemotherapy for colorectal cancer and published before July 2009 have been identified by searching the Medline database. Data concerning these hepatic lesions and outcome after surgery are resumed in this review. RESULTS: Studies concerning the link between hepatic steatosis and chemotherapy have contradictory results but steatosis is clearly associated to an increase of postoperative morbidity. Steatohepatitis, especially due to irinotecan, is associated with increased postoperative mortality. Sinusoidal obstruction syndrome, a severe form of vascular hepatic lesion, associated to oxaliplatin, seems to be linked with an increase of postoperative morbidity, but not mortality. Bevacizumab would not increase, when used in combination with oxaliplatin, the rate of postoperative complications. Some studies suggest a decrease of vascular hepatic lesions when bevacizumab is administered with chemotherapy. The literature concerning hepatic toxicity of anti-EGF-R antibody is freak. CONCLUSION: The fact that irinotecan may be linked to an increased risk of hepatic failure and postoperative death, which is not the case of oxaliplatine, must be taken in consideration in the choice of the preoperative chemotherapy before resection of hepatic metastasis of colorectal cancer.

[Lymphoepithelial cyst of the pancreas: a new case report]. / Le kyste lymphoépithélial du pancréas : à propos d'un nouveau cas.

We report the case of a lymphoepithelial cyst of the pancreas discovered by chance on imaging in a 54-year old man. CT-scan showed a 10 cm hypodense multilocular cystic tumor of the pancreatic isthmus. Fine-needle aspiration did not provide further information. Due to the lack of preoperative diagnosis and mostly because it was not known if the cyst was malignant or benign, the patient underwent a cephalic duodenopancreatectomy. Lymphoepithelial cyst of the pancreas is a rare benign lesion which is difficult to diagnose before surgery. Histologically, the cyst wall is lined by mature keratinizing squamous epithelium and a distinct surrounding lymphoid tissue layer. The cysts are filled with keratin plugs that are not always visualized on imaging. Cytological and histological analysis of fine-needle aspiration material if the sample material is sufficient may help avoid extensive surgery.

Phenotypic expression of ferroportin disease in a family with the N144H mutation.

Ferroportin is a putative transmembrane channel involved in the exit of iron out of the enterocytes, the macrophages and the hepatocytes. Mutations in the human gene coding ferroportin have been linked to an unusual form of iron overload, now referred to as "hemochromatosis type IV" or "ferroportin disease" characterized by a prevalent iron overload of macrophages and liver Küpffer cells. We report four patients from a same family with ferroportin disease associated with the N144H mutation. We show that in this family the mutation which is fully penetrant, may act through an increased iron export from macrophages as suggested by the unexpected absence of iron overload in the spleen and bone marrow detected by magnetic resonance imaging, that it co-segregates with a phenotype close to the classical form of HFE-associated hemochromatosis and was associated, in the oldest patient, with the development of hepatocellular carcinoma in a non cirrhotic liver. Our findings illustrate the existence of a genotype-phenotype relationship in "ferroportin disease", suggest that MRI may be useful in determining this phenotype and show that hepatocellular carcinoma may occur in these patients even without cirrhosis. This observation justifies careful follow-up of this subgroup of patients.

Sonographic preoperative assessment of liver volume before major liver resection.

OBJECTIVE: The use of ultrasonography is widespread for both the diagnosis and treatment of liver tumors. However, the measurement of liver volume by ultrasonography is not commonly done. We report an original method of liver volumetry using ultrasonography and an investigation into the usefulness of ultrasonography in this context. METHODS: The data for 50 patients undergoing various types of major hepatectomy were collected. We preoperatively measured liver volume using ultrasonography, dividing the liver into three main compartments according to precise anatomical landmarks, and then made comparisons with the volume of the actual specimen after hepatectomy, for all of the study participants. RESULTS: Total volume correlation between the two groups was good (r = 0.916, P < 0.001). However, the correlation was weaker in cases of right hepatectomy compared with other types of hepatectomy. CONCLUSION: This study demonstrates the possibility of doing liver volumetry using an ultrasound device. Further investigation to establish the reliability of this easily available and noninvasive approach is needed.

[Late complications of a skin oesophagoplasty realized 45 years before: an historical case]. / Complications tardives d'une oesophagoplastie cutanée, réalisée 45 ans plus tôt.

We report the case of a patient operated for the late complications of a skin-lined tube reconstruction of the esophagus performed 45 years ago. We recall the historical interest of this method for total esophageal reconstruction and emphasize the fact that it can still be a solution of last resort when intestinal tubes are no longer available.

[Epidermoid carcinomas of anal canal treated with radiation therapy and concomitant chemotherapy (5-fluorouracil and cisplatin)]. / Carcinomes épidermoïdes du canal anal traités par association concomitante de radiothérapie et de chimiothérapie. Evaluation des résultats fonctionnels.

PURPOSE: To evaluate our results after radiation therapy and concomitant chemotherapy in terms of local control, survival and toxicity in patients with anal cancer. METHODS AND PATIENTS: Between November 1990 and January 2002, 60 patients (pts) were treated with radiation therapy and concomitant chemotherapy. The T-stage according to the 2001 UICC classification were: 2 T1, 26 T2, 25 T3, and 7 T4. There were 20 pts with nodal involvement at presentation. The treatment started with external beam RT (median dose: 45 Gy) and concomitant chemotherapy using 5-fluorouracil and cisplatin during the first week and the fifth week of external beam RT (EBRT). After a rest period of 4 to 6 weeks, a boost of 20 Gy was delivered by EBRT in 58 pts and by interstitial (192)Ir brachytherapy in 2 pts. Mean follow-up were 78.5 months. RESULTS: At the end of RT with concomitant chemotherapy local tumor clinical complete response rate was 83%. Out of 10 non responders or local progression, 5 (50%) were salvaged with abdominoperineal resection (APR). Out of 5 local tumor relapses, 3 were salvaged with APR. The overall local tumor control (LC) rate with or without salvage local treatment were 88%. LC rate with a good anal function scoring (score 0 and 1) was 70%. Among 43 pts who preserved their anus, 98% had a good anal function scoring. The 5-year disease-free survival was 75%. After multivariate analysis, 2 independent predicting factors significantly influenced the disease-free survival: HIV-positive pts (negative vs positive, P=0.032) and clinical tumor response after the first course of radiotherapy (<50% vs >or=50%, P=0.00032). Acute grade 2 or 3 toxicities were low: haematological toxicity in 4 pts and intestinal complication corresponding to diarrhea in 10 pts. Late severe complication was observed in 3 pts: 2 pts with painful necrosis of the anus requiring colostomy and 1 pt with grade 3 rectal bleeding. CONCLUSION: We confirm the good results with RT and concomitant chemotherapy. The clinical tumor response after the first course of RT and concomitant chemotherapy is probably the most important predictive factor on the disease-free survival. For patients with T3 or T4 lesion and tumor regression

Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tract adenocarcinoma: a GERCOR study.

BACKGROUND: Since gemcitabine-oxaliplatin (GEMOX) has been used in pancreatic adenocarcinoma, we studied its activity and tolerability in advanced biliary tract adenocarcinoma (ABTA). PATIENTS AND METHODS: Consecutive adult patients with confirmed ABTA were recruited from four centers. Those in group A had performance status (PS) 0-2, bilirubin <2.5x normal and received GEMOX as first-line chemotherapy. Those in group B had PS >2 and/or bilirubin >2.5x normal and/or prior chemotherapy. All received gemcitabine 1000 mg/m2 as a 10 mg/m2/min infusion on day 1, followed by oxaliplatin 100 mg/m2 as a 2-h infusion on day 2, every 2 weeks. RESULTS: Tumor sites were gallbladder (19), extrahepatic bile ducts (5), ampulla of vater (3) and intrahepatic bile ducts (29). Results for group A (n = 3) were: objective response 36% [95% confidence interval (CI) 18.7% to 52.3%], stable disease 26%, progressive disease 39%, median progression-free survival (PFS) 5.7 months and overall survival (OS) 15.4 months. Results for group B (n = 23) were: objective response 22% (95% CI 6.5% to 37.4%), stable disease 30%, progressive disease 48%, PFS 3.9 months and OS 7.6 months. National Cancer Institute Common Toxicity Criteria grade 3-4 toxicities were neutropenia 14% of patients, thrombocytopenia 9%, nausea/vomiting 5% and peripheral neuropathy 7%. CONCLUSION: The GEMOX combination is active and well tolerated in ABTA.

Effects of irradiation on Plasmodium falciparum sporozoite hepatic development: implications for the design of pre-erythrocytic malaria vaccines.

Immunization with irradiation-attenuated Plasmodium sporozoites confer protection against live sporozoite challenge. Protection relies primarily on cytotoxic lymphocyte activity against infected hepatocytes, and is suppressed when sporozoites are over-irradiated. Here, we demonstrate that over-irradiated (25-30 krad) Plasmodium falciparum sporozoites invade human hepatocytes and transform into uninucleate liver-trophozoites with the same efficiency as non-irradiated and irradiation-attenuated (12-15 krad) sporozoites. Since hepatocytes infected with over-irradiated non-protective sporozoites are likely to express sporozoite-derived peptide/major histocompatibility complex class I molecules on their surface, our results strongly suggest that sporozoite proteins are not the main immunogens involved in protection, and thus may not per se constitute proper malaria vaccine candidates.

High prevalence of cfxA beta-lactamase in aminopenicillin-resistant Prevotella strains isolated from periodontal pockets.

This prospective study was designed to investigate amoxicillin-resistant oral anaerobes, and to identify their beta-lactamase-encoding genes. Three subgingival bacterial samples were collected from 12 patients suffering from periodontitis. One to seven beta-lactamase-producing strains were obtained from each patient, mostly belonging to the Prevotella genus (Bacteroides eggerthii, 2/35 strains; Prevotella sp., 33/35 strains). PCR assays were used to detect cfxA and cepA/cblA, the genes encoding class A/group2e beta-lactamases previously described in the Bacteroides fragilis group. The present investigation confirmed the role of Prevotella species as beta-lactamase producers in periodontal pockets. Additionally, this PCR screening showed (1): the high prevalence of CfxA beta-lactamase production by aminopenicillin-resistant Prevotella (32/33: 97.0% positive strains) vs. cepA/cblA (1/33: 3.0% positive strains), and (2) the presence of cfxA in the periodontal reservoir in the absence of antimicrobial therapy during the previous 6 months.

Functional metabolic characteristics of intact pig livers during prolonged extracorporeal perfusion: potential for a unique biological liver-assist device.

BACKGROUND: The clinical development of liver-support devices based on perfusion of either pig hepatocytes cartridges or whole pig livers has been hampered by the ability to use sufficient liver cell mass to provide adequate metabolic support, limited perfusion times, and the potential for patient exposure to pig zoonotic diseases. METHODS: We designed an original system in which an isolated intact pig liver was perfused extracorporeally under physiological conditions in a closed loop circuit with allogeneic pig blood and constant monitoring of major physiological and functional parameters. The perfusion circuit further included an interface membrane to provide for separation of patient and liver perfusion circulation. RESULTS: Prolonged (6-21 hr) liver perfusion did not produce significant liver damage as reflected by modest rises in the levels of the serum transaminases, stability of main biochemical parameters (including potassium), and the maintenance of normal cellular morphology. Optimal liver function was documented as measured by lactate consumption, control of glycemia, and the results of clotting studies and functional assays. The perfused liver cleared 82% and 79% of peak bilirubin and ammonia concentrations with clearing kinetics identical throughout perfusion. Indocyanine green clearance was identical to that observed in the living donor before explant surgery. CONCLUSIONS: In conclusion, the extracorporeal pig liver perfusion apparatus described here allows optimal pig liver function for prolonged periods of time. The microporous membrane to provide separation of donor organ and recipient and the high level of functional activity suggest that this form of liver metabolic support may have important clinical applications.

Prevention of proteolysis in cold-stored rat liver by addition of amino acids to the preservation solution.

BACKGROUND: One process identified as detrimental in liver preservation is proteolysis. METHODS: We tested the effects of adding antiproteolytic amino acids (L-alanine, L-glutamine, L-histidine, L-leucine, L-methionine, L-phenylalanine, L-proline, L-tryptophan) to the preservation medium, in a model of reperfusion of 24 h cold-stored rat livers. RESULTS: During the preservation period, antiproteolytic amino acids inhibited the proteolysis observed in stored livers as shown by branched-chain amino acid fluxes, which switched from release to uptake. During reperfusion, cold storage of lives without the addition of antiproteolytic amino acids resulted in a decrease in the total amino acid and branched-chain amino acid uptake and a lower perfusion flow rate. The addition of antiproteolytic amino acids during liver storage resulted in the maintenance of total amino acid and branched-chain amino acid uptake and a significant improvement in the perfusion flow rate during reperfusion. CONCLUSIONS: The presence of antiproteolytic amino acids in the preservation medium might be of interest in improving hepatic graft viability in transplantation.

Cold preservation injury in rat liver: effect of liposomally-entrapped adenosine triphosphate.

BACKGROUND/AIMS: Energy charge and capacity for adenosine triphosphate (ATP) synthesis have been demonstrated to play a major role in the maintenance of organ function after liver preservation for transplantation. The aim of this study was to evaluate whether a supply of liposomally-entrapped ATP during preservation could improve the energy state and metabolism of cold-stored rat liver. METHODS: In the first set of experiments, the uptake of ATP-containing liposomes and their effects on hepatic viability were determined in isolated perfused unstored rat liver. In the second set of experiments, rat livers were preserved for 18 h at 4 degrees C in UW solution in the presence of these liposomes, and effects on energy state, cell volume and metabolism were evaluated. In each part, data were compared with adequate control, unloaded liposome-treated, and free ATP-treated groups (n=6 in each group). RESULTS: In non-stored livers, ATP-containing liposomes were taken up by the liver; they did not alter hepatic viability and induced a decrease in energy substrate consumption (glucose and amino acids), and an improvement in intrahepatic ATP content (+23% vs. Control). Addition of liposomally-entrapped ATP during cold storage produced a significant attenuation of the decrease in hepatic ATP content (Lip ATP 2: 524+/-45 vs. Control 2: 364+/-106 nmol/g; p<0.05), and induced, during reperfusion, a decrease in proteolysis associated with an increase in cell volume compared with the other groups (Lip ATP 2: 633+/-63 vs. Control 2: 532+/-38, Unloaded Lip 2: 483+/-55 and Free ATP 2: 500+/-29 microl/g; p<0.01). CONCLUSIONS: These data indicate that liposomally-entrapped ATP represents an effective means to improve liver graft energy state and function. The decrease in protein degradation may be related to the modification of cell volume.

Combined radiotherapy and chemotherapy (cisplatin and 5-fluorouracil) as palliative treatment for localized unresectable or adjuvant treatment for resected pancreatic adenocarcinoma: results of a feasibility study.

PURPOSE: To evaluate a cisplatin-containing chemoradiotherapy (CRT) regimen followed by chemotherapy for unresectable (locally advanced group, n = 32) and resected (adjuvant group, n = 10) pancreatic adenocarcinoma. The quality of palliation and percentage of secondary resections were also studied for unresectable disease. METHODS AND MATERIALS: The protocol comprised CRT (45 Gy over 5 weeks), combined with 5-fluorouracil and cisplatin during the first and fifth weeks, followed, 3 weeks later, by 4 cycles of the same chemotherapy plus leucovorin. RESULTS: All patients completed CRT but only 50% of each group finished the entire protocol. Gastrointestinal toxicity and weight loss were the major side effects during CRT. Enhanced hematological toxicity limited the post-CRT chemotherapy. For the locally advanced group, median survival was 9 months; 1- and 2-year survival rates were 31 and 12. 5%, respectively. The overall response rate was 16% and 50% had stable disease. A lasting palliative effect defined as improved performance status and decreased analgesic consumption, was recorded for 43% of the patients. Only three secondary resections have been performed. For the adjuvant group, median survival was 17 months. CONCLUSIONS: Although toxic in advanced disease, this regimen significantly lowered pain and analgesic consumption, but had poor impact on secondary resectability. In an adjuvant setting, although equally toxic, this series was too small to allow conclusions to be drawn.

Surgical treatment of hepatocellular carcinoma in cirrhosis.

Hepatocellular carcinoma is one of the most frequent forms of cancer worldwide and its diagnosis and treatment have changed substantially during the last few years. Recent advances in ultrasonography, spiral computed tomography scan and nuclear magnetic resonance have further simplified the diagnostic approach to hepatocellular carcinoma. Ultrasonography is the reference examination, giving a wide variety of information on tumour size, location, relationship with portal and hepatic veins and splanchnic haemodynamics. Surgical resection and liver transplantation can both be defined as curative treatment while other techniques such as percutaneous ethanol injection and chemoembolization must be considered as palliative. Therapeutic strategies for hepatocellular carcinoma are based upon data concerning the characteristics of the tumour the functional status of non-tumoural liver parenchyma and patients' general conditions. Surgery of hepatocellular carcinoma in cirrhotic liver is mainly restricted by lack of functional hepatic reserve and by the limited capacity of hepatic regeneration. The best surgical results are obtained in early tumoural stages which generally need limited resection. Nevertheless, major liver resections have a specific role in selected cases. Recurrence rate after surgical resection is high and is related to a large number of factors. For this reason, liver transplantation, removing at the same time, the tumour and the underlying disease, is considered, theoretically, the best treatment for hepatocellular carcinoma, but its role is still debated and limited by difficult organ sharing. Integration of present therapeutic schemes are under evaluation with promising preliminary results.