Performance in daily activities, cognitive impairment and perception in multiple sclerosis patients and their caregivers.

BACKGROUND: The relationship between cognitive assessment results in multiple sclerosis (MS) and performance in daily activities (DAs) remains unclear. Our study aimed to evaluate the relationship between cognitive functions (CF) measured by tests, performance in DAs, and the perception of CF in patients and their caregivers (CG) in MS. METHODS: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery was used to evaluate cognitive status. We created an ad hoc questionnaire (DaQ) to assess performance in DAs not requiring specific motor skills. We used the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) to measure each patient self-judgment and caregiver's perception of CF. RESULTS: Forty-nine patients and their caregivers were included in the study. Significant correlations were found between the BICAMS and the DaQ (Symbol Digit Modalities Test (SDMT): r = - 0.48, p < 0.001; California Verbal Learning Test (CVLT): r = - 0.33, p = 0.01; Brief Visual Memory Test (BVMT-R): r = - 0.42; p = 0.002); patients self-judgment (SDMT: r = - 0.38, p = 0.004; CVLT: r = - 0.26, p = 0.03); caregiver perception of patient's CF (SDMT: r = - 0.52, p < 0.001; CVLT: r = - 0.3, p = 0.01; BVMT-R: r = - 0.42, p = 0.002). The difference in perception between the patients and their caregivers was related to patient age (p = 0.001) and severity of cognitive impairment (p = 0.03). CONCLUSIONS: Cognitive assessment results show a significant correlation with performance in daily activities and with patients and, especially, caregiver perception of cognitive impairment. These data support the importance of a routine evaluation of cognitive function in MS that includes an anamnestic evaluation of patients, and, when possible, consideration of the caregiver's point of view.

Cognition in multiple sclerosis: Between cognitive reserve and brain volume.

BACKGROUND: Several correlations between cognitive impairment (CI), radiologic markers and cognitive reserve (CR) have been documented in MS. OBIECTIVE: To evaluate correlation between CI and brain volume (BV) considering CR as possibile mitigating factor. METHODS: 195 relapsing MS patients underwent a neuropsychological assessment using BICAMS. BV was estimated using SIENAX to obtain normalized volume of brain (NBV), white matter (NWV), gray matter (NGV) and cortical gray matter (CGV). CR was estimated using a previously validated tool. RESULTS: Pearson test showed a correlation between the symbol digit modality test (SDMT) score and NBV (r=0.38; p<0.000) NGV(r=0.31; p<0.000), CGV (r=0.35; p<0.000) and CRI score(r=0.42; p<0.000). Linear regression (dependent variable:SDMT) showed a relationship with CR scores (p=0.000) and NGV(p<0.000). A difference was detected between cognitive impaired and preserved patients regarding mean of NBV(p=0.002), NGV(p=0.007), CGV(p=0.002) and CR Scores (p=0.007). Anova showed a association between the presence of CI (dependent variable) and the interaction term CRIQ × CGV (p=0.004) whit adjustment for age and disability evaluated by EDSS. CONCLUSIONS: Our study shows a correlation between cognition and BV, in particular gray matter volume. Cognitive reserve is also confirmed as an important element playing a role in the complex interaction to determine the cognitive functions in MS.

Brain volume in early MS patients with and without IgG oligoclonal bands in CSF.

BACKGROUND: Oligoclonal bands of IgG (OB) are proposed as an early prognostic factor of the disease. Growing attention is directed towards brain volume evaluation as a possible marker of the severity of MS. Previous studies found that MS patients lacking OB have less brain atrophy. AIM: to evaluate a possible relationship between OB and cerebral volume in a cohort of early MS patients. METHODS: Inclusion criteria were: diagnosis of relapsing-remitting MS; CSF analysis and MRI acquired simultaneously and within 12 months from clinical onset. A total of 15 healthy controls underwent MRI. RESULTS: In 20 MS patients, CSF analysis did not show OB synthesis (OB negative group). A control group of 25 MS patients in whom OB was detected was also randomly recruited (OB positive group). T test showed a significant difference in NWV between the OB positive and OB negative groups (P value = 0.01), and between the OB positive group and the healthy controls (P value = 0.001). No differences were detected between OB negative group and healthy controls. Multivariable linear regression showed a relationship between NWV and OB synthesis (P value = 0.02) controlling for age, gender, and EDSS. CONCLUSIONS: Our preliminary results suggest that OB positive patients show more atrophy of white matter since early phases of the disease, supporting the role of CSF analysis as a prognostic factor in MS.

A risk score for predicting perioperative blood transfusion in liver surgery.

BACKGROUND: It would be desirable to predict which patients are most likely to benefit from preoperative autologous blood donation. This aim of this study was to develop a point scoring system for predicting the need for blood transfusion in liver surgery. METHODS: The medical records of 480 consecutive patients who underwent hepatic resection were analysed. The data set was split randomly into a derivation set of two-thirds and a validation set of one-third. Univariable analysis was carried out to determine the association between clinicopathological factors and blood transfusion. Significant variables were entered into a multiple logistic regression model, and a transfusion risk score (TRS) was developed. The accuracy of the system was validated by calculating the area under the receiver-operator characteristic (ROC) curve. RESULTS: Factors associated with blood transfusion in multivariable analysis included preoperative haemoglobin concentration below 12.5 g/dl, largest tumour more than 4 cm, need for exposure of the vena cava, need for an associated procedure, and cirrhosis. Each variable was assigned one point, and the total score was compared with the transfusion status of each patient in the validation set. The TRS accurately predicted the likelihood of blood transfusion. In the validation set the area under the ROC curve was 0.89. CONCLUSION: Use of the TRS could lead to substantial saving by improving the cost-effectiveness of the autologous blood donation programme.

A "steroid-free" tacrolimus and low-dose mycophenolate mofetil primary immunosuppression does not prevent early acute rejection after liver transplantation.

To assess the efficacy and safety of a primary immunosuppressive regimen with tacrolimus (Tac) and low-dose mycophenolate mofetil (MMF) without steroids and to determine the exposure to mycophenolic acid (MPA) in the early postoperative period, we performed a single-center, randomized 1:1, open-label, controlled study planned to be 60 liver transplantation patients randomized into 2 groups: group A, tacrolimus + MMF (750 mg orally twice a day); and group B, tacrolimus + MMF (750 mg orally twice a day) + steroids. After an interim analysis by the ethical committee patient enrollment was stopped. Data from 30 patients (12 in group A and 18 in group B with a mean follow-up period of 31 +/- 7 months) showed a patient survival rate of 91.7% in group A and 100% in group B and a graft survival rate of 91.7% and 88.9%, respectively. Nine patients (75%) in group A suffered an acute rejection episode, whereas in group B only 3 patients (16.7%) showed acute rejection (P = .002). All rejection episodes occurred in both groups at 1 week after transplantation. The difference in histological grading was statistically significant (P = .021). The toxicity profiles were similar in both groups. A primary immunosuppressive regimen based on Tac and low-dose MMF without steroids is safe but unable to prevent acute rejection at 1 week after transplantation even if early acute rejection does not affect the outcome in terms of morbidity and graft or patient survival.

Extrahepatic biliary stenoses after hepatic arterial infusion (HAI) of floxuridine (FUdR) for liver metastases from colorectal cancer.

Hepatic arterial infusion of floxuridine is an effective treatment for unresectable hepatic metastases from colorectal cancer. Despite its pharmacological advantage of higher tumor drug concentration with minimal systemic toxicity, hepatic arterial infusion of floxuridine is characterized by regional toxicity, including hepatobiliary damage resembling idiopathic sclerosing cholangitis (5-29% of treated cases). Unlike previous reports describing biliary damage of both intrahepatic and extrahepatic ducts, a case series of extrahepatic biliary stenosis after hepatic arterial infusion with floxuridine is herein described. Between September 1993 and February 1999, 54 patients received intraarterial hepatic chemotherapy based on continuous infusion of floxuridine (dose escalation 0.15-0.30 mg/kg/day for 14 days every 28 days) plus dexamethasone 28 mg. Twenty-seven patients underwent laparotomy to implant the catheter into the hepatic artery, the other 27 patients receiving a percutaneous catheter into the hepatic artery through a transaxillary access. Five patients (9.2%) developed biliary toxicity with jaundice and cholangitis (3 cases), alterations of liver function tests and radiological features of biliary tract abnormalities. They received from 9 to 19 cycles (mean 14.5 +/- 6.3 cycles) of floxuridine infusion with a total drug delivered dose ranging from 20.3 to 41.02 mg/kg (mean: 31.4 +/- 13.5 mg/kg). Extrahepatic biliary sclerosis was discovered by computed tomography scan and ultrasound, followed by endoscopic retrograde cholangiopancreatography and/or percutaneous cholangiography in 3 cases. Radiological findings included common hepatic duct complete obstruction in 1 case, common hepatic duct stenosis in 2 cases, common bile duct obstruction in 1 case, and intrahepatic bile ducts dilation without a well-recognized obstruction in 1 case. Two patients were treated by sequentially percutaneous biliary drainage and balloon dilation while 1 patient had an endoscopic transpapillary biliary prosthesis placed. Percutaneous or endoscopic procedures obtained the improvement of hepatic function and cholestatic indexes without subsequent jaundice or cholangitis. In two patients suppression of floxuridine infusion allowed the improvement of hepatic function. The present series suggests that in some patients receiving hepatic arterial infusion of floxuridine extrahepatic biliary stenosis may represent the primary event leading to a secondary intrahepatic biliary damage that does not correlate with specific floxuridine toxicity but results from bile stasis and infection, recurrent cholangitis and eventually biliary sclerosis. Aggressive research for extrahepatic biliary sclerosis is advised, since an early nonsurgical treatment of extrahepatic biliary stenosis may prevent an irreversible intrahepatic biliary sclerosis worsening the prognosis of metastatic liver disease.

Role of hepatic resection in the treatment of hepatolithiasis.

BACKGROUND: The aim of the present study was to evaluate the safety and the efficacy of hepatic resection in the treatment of hepatolithiasis with intrahepatic biliary strictures. EXPERIMENTAL DESIGN: retrospective study. SETTING: University hospital, Italy. PATIENTS: 6 consecutive patients with single lobe hepatolithiasis operated on during the 4-year period 1994-98 inclusive. INTERVENTIONS: major hepatic resections (3 left hepatectomies, 2 left lobectomies, 1 right hepatectomy). MAIN OUTCOME MEASURES: type and duration of the surgical procedure, intra/postoperative blood losses, intra/postoperative course and complications, pathology, and hepatolithiasis recurrence. RESULTS: Mean operative time was 3.34+/-0.02 hrs (range 3.0-4.3 hrs). Mean blood loss was 233+/-150 ml (range 100-500 ml). No patient required intra/postoperative blood transfusions. No intraoperative complication was recorded. Mean postoperative hospitalization was 17+/-7 days (range 6-28 days). Postoperative course was uneventful in 4 (66%) cases. No postoperative mortality was recorded. One pancreatitis and 1 biliary fistula occurred, for an overall postoperative morbidity of 33%. Pathology showed cholangiocarcinoma in 2 cases (33%). During the follow-up period (range 3-48 months, mean 19.1+/-16.4 months), 1 patient had recurrent cholangitis due to right lobe lithiasis and 1 patient died for cholangiocarcinoma. CONCLUSIONS: Hepatic resection is the treatment of choice in patients with single lobe hepatolithiasis and unreversible biliary strictures or possible presence of cholangiocarcinoma. An early indication for surgery may reduce the mortality/morbidity rates of hepatic resection for hepatolithiasis.

[Advanced age as risk factor in liver resection surgery]. / L'età avanzata come fattore di rischio nella chirurgia resettiva epatica.

To evaluate the influence of age on the outcome of liver resections, 105 consecutive patients undergoing hepatic resection were divided into two groups: age > or = 65 years [Old Group (O-Group)] and age < 65 years [Young Group (Y-Group)]. O-Group and Y-Group patients were analyzed comparatively in terms of primary diagnosis, concomitant diseases, previous surgery, type of operation (major or minor resection), associated procedures, presence and length of portal clamping, intraoperative blood losses and transfusions, and length of operation. The end points of the study were postoperative mortality, morbidity, transfusions, and length of post-operative hospitalization. The Y-Group included 61 resections in 60 patients, with a mean age of 52 +/- 10 years (mean +/- SD), range 23-64 years, and the O-Group 44 resections in 43 patients, with a mean age of 71 +/- 4 years, range 65-82 years. The O-Group included more cases of hepatoma (45.4% vs 18%, p = 0.002) and cirrhosis (40.9% vs 18.7%, p = 0.017). Median length of operation was slightly higher in the Y-Group (330 vs 270 minutes, p = 0.003). The O- and Y-Groups were comparable (p = n.s.) when evaluated for all other variables listed. As regards the end points of the study, length of post-operative hospitalization was identical in both groups (median 9 days, range 5-60 days) and neither PRBC transfusions (O-Group vs Y-Group: 16% vs 25%) nor FFP transfusions (O-Group vs Y-Group: 13.6% vs 6.5%) showed any statistically significant difference. Postoperative mortality consisted in 1 death among the younger patients while no deaths were recorded among the older patients. Postoperative morbidity was higher in the Y-Group than in the O-Group (31.1% vs 20.5%, p = 0.59). Advanced age does not negatively affect the outcome of liver resections.

Right hepatic artery indwelling catheter for adjuvant chemotherapy after right hepatectomy.

Intraarterial hepatic adjuvant chemotherapy after radical hepatic resection for liver metastases from colorectal carcinoma lowers the rate of liver disease relapse. The technique for catheter implantation in the right hepatic artery for subsequent intraarterial hepatic adjuvant chemotherapy after right hepatectomy is herein described and recommended as an effective alternative approach to the standard catheter implantation in the gastroduodenal artery in cases of hepatectomies for liver metastases from colorectal cancer.

Complications of blind placement technique in 980 subcutaneous infusion ports.

PURPOSE: Subcutaneous Infusion Ports (SIPs) for prolonged venous access are useful tools for drug administration in a wide range of chronic diseases. An extensive use of these devices has to be balanced against the potential complications worsening the length and the quality of life of frequently compromised patients. The aim of the present study is the prospective evaluation of early and late complications of the technique for the blind placement of totally implantable devices for prolonged venous access. METHODS: Between April l, 1991 and September 30, 1999, 980 SIPs were implanted in 967 patients. Thirteen patients received 2 SIPs. The surgical procedure, the catheter through peel-away technique after infraclavicular approach to the right or left subclavian vein, was performed without intraoperative fluoroscopy (blind placement technique) in the operating room under local anaesthesia. A postoperative chest radiography to rule out any procedure- related complications and to check the position of the catheter tip was obtained in all cases. For the purpose of the study, intraoperative complications as well as all SIP-related complications were recorded during the follow-up period and classified as major and minor complications. RESULTS: The study population consisted of 524 males/443 females, with a mean age of 56.3 +/- 11.4 years (range 19-85 years). Primary diagnosis was malignancy in 916 patients (94.7%), acquired immunodeficiency syndrome (AIDS) in 44 patients (4.5%), and short gut syndrome secondary to subtotal small bowel resection in 2 cases (0.2%), others in 5 cases (0.5%). Perioperative complications were recorded in 12.9% of the 980 insertion pro-cedures, including 77 cases of arterial puncture (7.8%) of the subclavian artery, 1 case of hemoptysis (without clinical and radiological evidence of pneumothorax) (0.1%), 23 cases of pneumothorax (2.3%), 20 of which (86.9%) required chest drainage, 10 cases of unsuccessful progression of the J-wire after the venepuncture (1%), 16 cases of catheter malposition (1.6%). As for the follow-up, 919 patients (95.0%) who had received 942 SIPs turned out to be suitable for long-term analysis, while 48 patients (5.0%) were excluded due to missing data. Seventy-seven SIPs (8.2%) were removed during the follow-up period, 13 of which received a second SIP. Long-term complications were recorded in 9.5% of the 942 SIPs, including mechanical complications (2.9%), infections (4.4%) and venous thrombosis (1.2%). Minor and major complication rates were 7.3% and 2.2% respectively. The overall incidence of SIP-related complications was 22.1%, including 44 major complications (4.5%) and 173 minor complications (17.6%). CONCLUSIONS: Given the low rate of major complications, SIPs should be considered safe and effective devices, representing the first choice approach for prolonged venous access. Blind placement technique performed by full-trained operators yields adequate success rate to be suggested as a routine procedure.

Arterial devices for regional hepatic chemotherapy: transaxillary versus laparotomic access.

Introduction. Intra-Arterial Hepatic Chemotherapy (IAHC) based on floxuridine (FUdR) infusion is an effective treatment for hepatic metastases from colorectal cancer. A percutaneously implanted intra-arterial device may overcome the surgical stress of the laparotomic placement allowing an increase in the number of patients treated by IAHC. The aim of the present study is the comparative analysis of surgical and percutaneous transaxillary approaches to implant the catheter into the hepatic artery (HA) for IAHC. Materials and Methods. Between September 1993 and February 1999, 56 patients received an implantable infu-sion system [SynchroMed(R) (Medtronic, USA) or Port-a-cath(R) (Deltec, USA) connected to an external infusion pump (CADD(R) , Deltec, USA)] for IAHC. Twenty-eight patients (LPT group) underwent laparotomy to implant the catheter into the HA, the other 28 patients (PCT group) received a percutaneous catheter into the HA through a transaxillary percutaneous access. Indications for the laparotomic placement were: 1) synchronous metastases not suitable [technically unresectable or large (>40% of liver parenchyma) or multiple (> 3) metas-tases] for hepatic resection during colorectal surgery; 2) metachronous metastases treated by radical hepatic resection and subsequent adjuvant IAHC. Indications for percutaneous placement were: 1) metachronous metastases not suitable [see above] for hepatic resection; 2) metachronous metastases suitable for hepatic resection after neoadjuvant IAHC for tumor downstaging. All patients received IAHC based on continuous infusion of FU-dR (dose escalation 0.15-0.30 mg/kg/day for 14 days every 28 days) plus dexamethasone 28 mg. For the purpose of the study, the LPT group and the PCT group were comparatively analyzed in terms of age, gender, primary diagnosis, vascular anatomy of HA, ligation/embolization of aberrant HA, previous intestinal or hepatic surgery, contextual systemic chemotherapy, concomitant diseases. Safety and efficacy of surgical and percutaneous transaxillary approaches were then comparatively analyzed in terms of number of IAHC cycles adminis-tered, device-related complications causing temporary or definitive suppression of IAHC, biological costs of the procedures (procedure-related complications, postoperative pain and hospitalization). LPT cases without concomitant surgical procedure other than catheter placement (Cath-LPT group - 10 cases) were also compared with the PCT group for the same end points of the study. Results. LPT group and PCT group were comparable (p=n.s.) when evaluated for all the above listed variables. As for the end points of the study, mean postoperative hospitalization was 8.2+/-2.2 days in the LPT group and 1.8+/-0.7 days in the PCT group (p<0.0001), while mean analgesic requirements were 9.7+/-3.2 doses in the LPT group and 2+/-0.9 doses in the PCT group (p<0.0001). Mean number of IAHC cycles administered was 6.5+/-4.2 in the LPT group and 4.3+/-3.4 in the PCT group (p=0.038). Device-related complications causing temporary or de-finitive suppression of IAHC included catheter displacement in 10 cases (35.7%), HA thrombosis in 1 case (3.5%) and catheter occlusion in 1 case (3.5%) in the PCT group, while in the LPT group 1 case (3.5%) of catheter occlusion and 1 case (3.5%) of HA thrombosis occurred. The overall incidence of device-related complications causing temporary or definitive suppression of IAHC was 42.7% in the PCT group and 7.1% in the LPT group (p=0.005). Comparison of Cath-LPT group and the PCT group showed mean postoperative hospitalization of 5.5+/-0.7 days in the Cath-LPT group and 1.8+/-0.7 days in the PCT group (p<0.0001), and mean anal-gesic requirements of 8+/-3.1 doses in the Cath-LPT group and 2+/-0.9 in the PCT group (p<0.0001). Conclusions. Surgically implanted indwelling catheters for IAHC present lower incidence of device-related complications than percutaneous transaxillary implanted catheters. In spite of its irreversibility and significant biological costs, surgical implant is still advised when laparotomy has to be performed for other contextual procedures, such as colorectal or hepatic resection, while percutaneous transaxillary catheter placement is indicated for palliative or neoadjuvant IAHC.