Histidine–tryptophan–ketoglutarate solution for organ preservation in human liver transplantation—a prospective multi-centre observation study

Based on experimental work and clinical small studies, histidine–tryptophan–ketoglutarate (HTK) solution was found to be suitable not only for heart and kidney preservation but also for liver preservation. We decided, therefore, to use this preservation solution for clinical liver preservation in a prospective multi-centre trial. Enrolment to the study was from 1996 to 1999 in four European centres, and the results of 214 patients with HTK-preserved organs were analysed. Analysis showed a primary dysfunction (PDF) rate of 8.8%, with a primary non-function (PNF) rate of 2.3% and initial poor function (IPF) in 6.5%. Patient survival rate at 1 year was 83% and 1-year graft survival rate was 80%. In a univariate and a multivariate analysis PDF, early surgical complications and tendentiously severe infections (septicaemia, pneumonia, cholangitis) were identified as independent risk factors for graft and patient survival. Preservation with HTK can be regarded as an established alternative to preservation with University of Wisconsin (UW) solution when preservation times are short. Definitive assessment of the efficacy of preservation solutions requires further prospective randomised clinical trials that compare HTK and UW.     

Prospective evaluation of pancreatic tumors: accuracy of MR imaging with MR cholangiopancreatography and MR angiography

PURPOSE: To prospectively assess accuracy of magnetic resonance (MR) imaging, MR cholangiopancreatography (MRCP), and MR angiography in patients suspected of having pancreatic tumors. MATERIALS AND METHODS: Sixty-six patients suspected of having pancreatic tumors underwent MR imaging (unenhanced and contrast material-enhanced MR, MRCP, and contrast-enhanced MR angiography). Two blinded readers prospectively analyzed the images by consensus, and results were correlated with surgery, biopsy, or follow-up findings. Results were tabulated in two-by-two tables. RESULTS: MR assessment of pancreatic lesion status (differentiation of benign vs malignant) resulted in 60 correct diagnoses (accuracy, 91%), and six (10%) false diagnoses. Among histologically proved malignant tumors, MR imaging yielded correct diagnoses in 42 of 44 patients (sensitivity, 95%; 95% CI: 85%, 99%), whereas 18 of 22 patients with benign findings were classified correctly. At MR imaging, findings in four patients with chronic pancreatitis were wrongly categorized as malignant tumors (specificity, 82%; 95% CI: 60%, 95%), and in one patient, a distal common bile duct carcinoma was not detected. In no patient with pancreatic adenocarcinoma was this tumor misdiagnosed as benign. In patients with malignant tumors who underwent resection, local-regional tumor growth and vascular infiltration were accurately classified in 89% and 94%, respectively. MR imaging depicted histologically proved synchronous hepatic metastases in 82%. The positive and negative predictive values for cancer nonresectability were 90% and 83%, respectively, and the accuracy, sensitivity, and specificity were 85%, 69%, and 95%, respectively. CONCLUSION: Unenhanced and contrast-enhanced MR imaging with MRCP and MR angiography offers potential as a noninvasive tool for assessment of patients suspected of having pancreatic tumors.     

Revisiting the mammographic follow-up of BI-RADS category 3 lesions

OBJECTIVE: Using data collected for one series during 1987-1989 and data collected for another series during 1996, we sought to compare the frequency of and positive predictive value for carcinoma of the breast in nonpalpable, probably benign lesions that had been detected on and followed up with mammography. MATERIALS AND METHODS: During 1996, mammography was performed in 18,435 women of whom 544 (3.0%) had lesions assigned to Breast Imaging Reporting and Data System (BI-RADS) category 3 for nonpalpable, probably benign lesions. The lesions in the women were assessed as BI-RADS category 3 after the patients had undergone a diagnostic study that included additional imaging, sonography, and a focused physical examination. Patients with BI-RADS category 3 lesions were recommended for mammographic surveillance. A minimum of 2 years of follow-up data was available for 511 patients, our study population. We compared the findings for our study population with those of the previous study. RESULTS: Ninety-seven percent of the follow-up mammograms showed stability or regression of the BI-RADS category 3 lesions. Fourteen patients (3%) had nonpalpable interval progression revealed on mammography and underwent biopsy. The breast cancer detection rate in category 3 lesions among the study population was 0.4% (2/511), which was 14% of the patients who had undergone biopsies because of interval progression of the lesions. The pathologic stage of the cancers in these two patients was T1b N0. CONCLUSION: Compared with the findings from the 1987-1989 study, the frequency of BI-RADS category 3 lesions has remained stable; patient compliance for follow-up has increased; and the positive predictive value of category 3 lesions for cancer has decreased from 1.7% to 0.4% (p = 0.04).     

Five-year survival after resection of hepatic metastases from colorectal cancer in patients screened by positron emission tomography with F-18 fluorodeoxyglucose (FDG-PET)

OBJECTIVE: To report the first 5-year overall survival results in patients with colorectal carcinoma metastatic to the liver who have undergone hepatic resection after staging with [18F] fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET). SUMMARY BACKGROUND DATA: The 5-year overall survival after hepatic resection for colorectal cancer metastases without preoperative FDG-PET has been established in 19 studies (6070 patients). The median 5-year overall survival rate in these studies is 30% and has not improved over time. FDG-PET detects unsuspected tumor in 25% of patients considered to have resectable hepatic metastasis by conventional staging. METHODS: From March 1995 to June 2002, all patients having hepatic resection for colorectal cancer metastases had preoperative FDG-PET. A prospective database was maintained. RESULTS: One hundred patients (56 men, 44 women) were studied. Metastases were synchronous in 52, single in 63, unilateral in 78, and <5 cm in diameter in 60. Resections were major (>3 segments) in 75 and resection margins were > or = 1 cm in 52. Median follow up was 31 months, with 12 actual greater than 5-year survivors. There was 1 postoperative death. The actuarial 5-year overall survival was 58% (95% confidence interval, 46-72%). Primary tumor grade was the only prognostic variable significantly correlated with overall survival. CONCLUSIONS: Screening by FDG-PET is associated with excellent postresection 5-year overall survival for patients undergoing resection of hepatic metastases from colorectal cancer. FDG-PET appears to define a new cohort of patients in whom tumor grade is a very important prognostic variable.     

Salvage of a failed Keller resection arthroplasty

BACKGROUND: A number of typical complications have been associated with Keller resection arthroplasty. Recurrent valgus deformity, cock-up deformity, and a flail toe may be difficult problems for the treating surgeon because options for salvage are limited. In this study, we evaluated arthrodesis of the first metatarsophalangeal joint as a salvage technique following a failed Keller procedure. In addition, the outcomes of motion-preserving procedures were reviewed in a separate series. METHODS: Arthrodesis of the first metatarsophalangeal joint was performed in twenty-eight patients (twenty-nine feet, group A), and either a repeat Keller procedure or an isolated soft-tissue release was performed in eighteen patients (twenty-one feet, group B). The patients were evaluated at least twenty-four months postoperatively, with a personal interview and a clinical examination with use of a modification of the hallux metatarsal-interphalangeal scale. Radiographs were also made for the group treated with the arthrodesis. RESULTS: In group A, the average duration of follow-up was thirty-six months and fusion was achieved in twenty-six of the twenty-nine feet. Satisfaction was excellent or good in twenty-three cases, and the postoperative score according to the modified hallux metatarsal-interphalangeal scale averaged 76 points (maximum, 90 points). A repeat arthrodesis was necessary in five feet because of malposition or pseudarthrosis. In group B, the average duration of follow-up was seventy-four months. Satisfaction was excellent or good in only six cases, and the patient was dissatisfied in eleven cases. The score according to the modified hallux metatarsal-interphalangeal scale averaged 48 points. Valgus deviation and cock-up deformity had recurred in the majority of the feet at the time of follow-up. CONCLUSIONS: Although it is more technically demanding, we recommend arthrodesis for salvage following a failed Keller procedure since it may be associated with a higher rate of patient satisfaction and better clinical results.     

Factors influencing the acquisition of Stenotrophomonas maltophilia infection in cystic fibrosis patients

BackgroundStenotrophomonas maltophilia is one of the most common multi-drug resistant organisms causing pulmonary infections in CF patients. It is unknown whether S. maltophilia infection follows the same pattern and shares similar risk factors for acquisition as described for Pseudomonas aeruginosa.MethodsWe examined all clinical events from 1997 to 2008 in the Toronto CF Database to identify risk factors for the acquisition of S. maltophilia and to define distinct patterns of infection.ResultsWe followed 601 patients over 12 years, during which time one quarter of subjects had at least one positive culture for S. maltophilia; the incidence rate was slightly higher in children (11.6/100 person years) compared with adults (10.6/100 person years). Using multi-variable Cox proportional hazards models, steeper rate of FEV₁ decline was a significant risk factor for S. maltophilia acquisition, whereas new infections were less likely to occur with greater oral antibiotic use and a history of Burkholderia cepacia complex infection.ConclusionsThis study illustrates the evolution of S. maltophilia infection over time in a large cohort of adults and children with CF. Younger CF patients, and those with greater lung function decline were at increased risk of S. maltophilia infection. The use of oral antibiotics to maintain lung function may be a way of decreasing the risk of infection. However, the optimal management of CF patients with persistent S. maltophilia infection is not yet known and requires further studies.     

Glucose modulates food‐related salience coding of midbrain neurons in humans

Although early rat studies demonstrated that administration of glucose diminishes dopaminergic midbrain activity, evidence in humans has been lacking so far. In the present functional magnetic resonance imaging study, glucose was intravenously infused in healthy human male participants while seeing images depicting low‐caloric food (LC), high‐caloric food (HC), and non‐food (NF) during a food/NF discrimination task. Analysis of brain activation focused on the ventral tegmental area (VTA) as the origin of the mesolimbic system involved in salience coding. Under unmodulated fasting baseline conditions, VTA activation was greater during HC compared with LC food cues. Subsequent to infusion of glucose, this difference in VTA activation as a function of caloric load leveled off and even reversed. In a control group not receiving glucose, VTA activation during HC relative to LC cues remained stable throughout the course of the experiment. Similar treatment‐specific patterns of brain activation were observed for the hypothalamus. The present findings show for the first time in humans that glucose infusion modulates salience coding mediated by the VTA. Hum Brain Mapp 37:4376–4384, 2016. © 2016 Wiley Periodicals, Inc.     

Biomolecular Predictors of Urothelial Cancer Behavior and Treatment Outcomes

Urothelial carcinoma of the urinary bladder (UCB) is a highly heterogeneous malignancy that causes significant morbidity and mortality. Despite advances in surgical and medical treatment, there has been no change in mortality in UCB over the past decades. Standard pathological features (stage, grade, nodal status) provide only limited information regarding biological potential and clinical behavior. Molecular biomarkers may shed light on important mechanisms of pathogenesis, provide useful additional prognostic information, and serve as targets for therapy. This review summarizes recent advances and the most promising UCB tissue and blood biomarkers of the past few years. We discuss the predictive and prognostic value of biomarkers at different stages of UCB. There is no doubt that a panel of biomarkers will eventually improve our clinical decision-making with regard to treatment and follow-up.     

Subclassification of pT3 urothelial carcinoma of the renal pelvicalyceal system is associated with recurrence-free and cancer-specific survival: proposal for a revision of the current TNM classification

Background

The clinical course of pT3 upper tract urothelial carcinoma (UTUC) is highly variable.

Objectives

The aim of the current study was to validate the clinical and prognostic importance of pT3 subclassification in the renal pelvicalyceal system in a large international cohort of patients.

Design, setting, and participants

From a multi-institutional international database, 858 renal pelvicalyceal tumors treated with radical nephroureterectomy (RNU) were systematically reevaluated by genitourinary pathologists. Category pT3 pelvic tumors were categorized as pT3a (infiltration of the renal parenchyma on a microscopic level only) versus pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue).

Intervention

RNU.

Measurements

Associations of pT3 subclassifications with clinicopathologic features were assessed with the chi-square test. Prognostic impact was assessed with the log-rank test and multivariable Cox regression analyses.

Results and limitations

Of 858 patients with renal pelvicalyceal tumors, 266 (31%) had pT3 disease. Of these, 146 (54.9%) were classified as pT3a and 120 (45.1%) as pT3b. Compared with pT3a, pT3b cancers were associated with higher tumor grade, nodal disease, and tumor necrosis. Ten-year recurrence-free (pT3a 58% vs pT3b 38%; p < 0.001) and cancer-specific (pT3a 60% vs pT3b 39%; p = 0.002) survival rates were lower for patients with pT3b disease. In multivariable analyses, classification pT3b was an independent predictor of both disease recurrence (hazard ratio [HR]: 1.8, p = 0.003) and cancer-specific mortality (HR: 1.7; p = 0.02). The major limitation is the retrospective character of the study.

Conclusions

Subclassification of pT3 renal pelvicalyceal UTUC helps identify patients who are at increased risk of disease progression and cancer-related death. Further research may help assess the value of subclassification and its inclusion in future editions of the American Joint Committee on Cancer–International Union Against Cancer TNM classification system.