Short-term Effects of Tolvaptan in Individuals With Autosomal Dominant Polycystic Kidney Disease at Various Levels of Kidney Function.

BACKGROUND: A recent study showed that tolvaptan, a vasopressin V2 receptor antagonist, decreased total kidney volume (TKV) growth and estimated glomerular filtration rate (GFR) loss in autosomal dominant polycystic kidney disease (ADPKD) with creatinine clearance≥60mL/min. The aim of our study was to determine whether the renal hemodynamic effects and pharmacodynamic efficacy of tolvaptan in ADPKD are dependent on GFR. STUDY DESIGN: Clinical trial with comparisons before and after treatment. SETTING & PARTICIPANTS: Patients with ADPKD with a wide range of measured GFRs (mGFRs; 18-148 mL/min) in a hospital setting. INTERVENTION: Participants were studied at baseline and after 3 weeks of treatment with tolvaptan given in increasing dosages, if tolerated (doses of 60, 90, and 120mg/d in weeks 1, 2, and 3, respectively). OUTCOMES: Change in markers for aquaresis (free-water clearance, urine and plasma osmolality, 24-hour urine volume, and plasma copeptin) and kidney injury (TKV and kidney injury biomarkers). MEASUREMENTS: GFR was measured by (125)I-iothalamate clearance; TKV, by magnetic resonance imaging; biomarker excretion, by enzyme-linked immunosorbent assay; and osmolality, by freezing point depression. RESULTS: In 27 participants (52% men; aged 46±10 years; mGFR, 69±39mL/min; TKV, 2.15 [IQR, 1.10-2.77] L), treatment with tolvaptan led to an increase in urine volume and free-water clearance and a decrease in urine osmolality, TKV, and kidney injury marker excretion. Changes in urine volume and osmolality with treatment were less in participants with lower baseline mGFRs (both P<0.01). However, change in fractional free-water clearance was greater at lower baseline mGFRs (P=0.001), suggesting that participants with decreased GFRs responded more to tolvaptan per functioning nephron. LIMITATIONS: Limited sample size, no control group. CONCLUSIONS: In patients with ADPKD with decreased kidney function, response to tolvaptan is lower for TKV, urinary volume, and osmolality, but larger for fractional free-water clearance. This latter finding suggests that patients with ADPKD with lower GFRs might benefit from long-term treatment with tolvaptan, as has been observed for patients with preserved GFRs.

EUS is superior for detection of pancreatic lesions compared with standard imaging in patients with multiple endocrine neoplasia type 1.

BACKGROUND: In multiple endocrine neoplasia type 1 (MEN1), pancreatic neuroendocrine tumors (pNETs) are the leading MEN1-related cause of death. OBJECTIVE: To evaluate EUS and (11)C-5-hydroxytryptophan positron emission tomography ((11)C-5-HTP PET), compared with the recommended screening techniques in MEN1 patients for early detection of pNETs. DESIGN: Cross-sectional study. SETTING: Tertiary-care university medical center. PATIENTS: This study involved 41 patients with a proven MEN1 mutation or with one MEN1 manifestation and a mutation carrier as a first-degree family member, with recent screening by abdominal CT or magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS). INTERVENTIONS: EUS by using a linear Pentax echoendoscope and Hitachi EUB-525 and (11)C-5-HTP PET. MAIN OUTCOME MEASUREMENTS: Patient-based and lesion-based positivity for pNET was calculated for all imaging techniques. The McNemar test was used to compare the yield of the 4 imaging techniques. RESULTS: In 35 of 41 patients, 107 pancreatic lesions were detected in total. EUS detected 101 pancreatic lesions in 34 patients, (11)C-5-HTP PET detected 35 lesions in 19 patients, and CT/MRI + SRS detected 32 lesions in 18 patients (P < .001). (11)C-5-HTP PET performed similarly to CT/MRI + SRS and better compared with SRS only (13 lesions in 12 patients), both at a patient-based and lesion-based level (P < .05). LIMITATIONS: Single-center study. CONCLUSION: EUS is superior to CT/MRI + SRS for pancreatic lesion detection in patients with MEN1. In this setting, (11)C-5-HTP PET is not useful. We recommend EUS as the first-choice pancreas imaging technique in patients with MEN1. ( CLINICAL TRIAL REGISTRATION NUMBER: NTR1668.).

Duct-to-duct reconstruction in liver transplantation for primary sclerosing cholangitis is associated with fewer biliary complications in comparison with hepaticojejunostomy.

There is no consensus on the preferred type of biliary reconstruction for patients undergoing orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC). The aim of this study was to compare long-term outcomes after OLT for PSC using either duct-to-duct anastomosis or Roux-en-Y hepaticojejunostomy for biliary reconstruction. In a consecutive series of 98 adult patients undergoing OLT for PSC, 45 underwent duct-to-duct reconstruction, and 53 underwent Roux-en-Y biliary reconstruction. The median follow-up was 8.2 years (interquartile range = 3.9-14.5 years). The outcomes of the 2 groups were compared. There were no significant differences in patient demographics or general surgical variables between the groups. The overall patient and graft survival rates were similar for the 2 groups. The incidence of biliary strictures and biliary leakage within the first year after transplantation did not differ between the 2 groups. However, significantly more patients in the Roux-en-Y group suffered at least 1 episode of cholangitis within the first year (9% in the duct-to-duct group versus 25% in the Roux-en-Y group, P = 0.04). In addition, Roux-en-Y reconstruction was associated with a significantly higher rate of late-onset (>1 year after transplantation) nonanastomotic biliary strictures (NAS) in comparison with duct-to-duct reconstruction (24% versus 7% at 5 years and 30% versus 7% at 10 years, P = 0.01). In conclusion, duct-to-duct biliary reconstruction in patients with PSC is associated with lower rates of posttransplant cholangitis and late-onset NAS in comparison with Roux-en-Y hepaticojejunostomy. If technically and anatomically feasible, duct-to-duct anastomosis can be performed safely in patients undergoing OLT for PSC.

Influence of preoperative chemotherapy on CT volumetric liver regeneration following right hemihepatectomy.

BACKGROUND: An increasing number of patients undergo major liver resection following preoperative chemotherapy. Liver regeneration may be impaired in these patients, predisposing them to postoperative liver dysfunction. The aim of the present study was to evaluate the effects of preoperative chemotherapy on liver regeneration after partial liver resection. METHODS: Patients planned to receive right hepatectomy either with (group B) or without (group A) prior chemotherapy were identified retrospectively from a prospective multi-institutional database created in the conduct of a national randomized controlled trial (RCT). Prior chemotherapy was neither an inclusion nor an exclusion criterion of the trial. Future remnant liver volume (FRLV) was calculated by measuring total functional liver volume and resection specimen on preoperative computed tomography (CT) scans. Remnant liver volume after 7 days (V RLV7days) was measured on scheduled postoperative CT scans. The early regeneration index 7 days after surgery (RI early) was calculated as [(V RLV7days - FRLV) / FRLV] × 100 %. Data are expressed as median (interquartile range). RESULTS: A total of 72 patients were enrolled: 45 in group A and 27 in group B. For the whole group, the liver remnant showed a 58 % (39 %) increase in volume at day 7 (1) day. The RI early was not significantly different between groups A and B, 60 % (36 %) and 50 % (43 %), respectively (p = 0.47). The RI early was significantly lower in patients who had undergone more than six cycles of chemotherapy. CONCLUSIONS: Preoperative chemotherapy does not seem to have a negative impact on early liver regeneration after partial liver resection.

The impact of hepatic steatosis on liver regeneration after partial hepatectomy.

BACKGROUND & AIM: Experimental studies in animals have suggested that liver regeneration is impaired in steatotic livers. However, few studies have focused on the impact of steatosis in patients undergoing partial hepatectomy (PH). This study aims to determine the role of steatosis on liver regeneration in humans following PH. METHODS: Eighty-eight patients undergoing PH were included in this study. All patients underwent CT-scanning of the liver preoperatively and 7 days after surgery. Additional CT-scans were performed 6 months post-operatively. Preoperative and post-operative volumes of the total liver (TLV), future liver remnant (FLR) and liver remnant (LR) were measured on CT-scans. Regeneration indices (RI) were calculated at 7 days and 6 months using the formula: (Volume LR-Volume FLR)/Volume FLR × 100%. Based on histological examination of the resected part of the liver, patients were classified into three groups: (1) no steatosis, (2) mild steatosis (1-29%) and (3) moderate-to-severe steatosis (≥30%). RESULTS: The early RI (at day 7) was 40%, 24% and 20% for patients in group 1, 2 and 3 respectively. Late RI (at 6 months) was 81% for group 1, 44% for group 2 and 22% for group 3 (P = 0.019). At 7 days, the LR represented 79%, 80% and 79% of the TLV for groups 1-3. At 6 months, this was 93%, 92% and 79% respectively. CONCLUSION: Although early RI after PH did not differ in patients with or without steatosis, the late RI in patients with moderate-to-severe steatosis was lower, suggesting that late liver regeneration is impaired in these patients.

Fibrin sealant for prevention of resection surface-related complications after liver resection: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of fibrin sealant in reducing resection surface-related complications in liver surgery. BACKGROUND: Bile leakage, bleeding, and abscess formation are major resection surface-related complications after liver resection. It is unclear whether application of fibrin sealant to the resection surface is effective in reducing these complications. METHODS: In a multicenter, randomized trial in 310 noncirrhotic patients undergoing liver resection, we compared prophylactic application of fibrin sealant to the resection surface (156 patients) with no application of fibrin sealant (154 patients). In addition to clinical assessments, patients underwent protocolized computerized tomography (CT) scan 1 week postoperatively. Primary endpoint was a composite of postoperative resection surface-related complications (bile leakage, bleeding, or abscess), as adjudicated by a clinical-events committee that was unaware of the study-group assignments. RESULTS: Overall rate of resection surface-related complications was not different between the 2 groups: 24% (38/156 patients) in the fibrin sealant group and 24% (37/154 patients) in the control group. Bile leakage was detected in 14% of patients in the fibrin sealant group and in 14% of controls. CT scans showed a fluid collection at the resection surface 100 mL or more in 28% of patients in the fibrin sealant group and in 26% of controls (P = 0.800). The rate of reinterventions for resection surface-related complications (12% vs 10%; P = 0.492) and severity of complications did also not differ between the 2 groups. CONCLUSIONS: This randomized multicenter trial shows that prophylactic application of fibrin sealant at the resection surface after liver resections does not lead to a reduction in the incidence or severity of postoperative bile leakage or other resection surface-related complications (Controlled trial number, ISRCTN85205641).

Cost-effectiveness of adding FDG-PET or CT to the diagnostic work-up of patients with stage III melanoma.

OBJECTIVE: The aim of this prospective study was to assess predictive value of fludeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) and to analyze their cost-effectiveness in several diagnosis-treatment combinations. BACKGROUND: The incidence of melanoma continues to rise. A proportion will present or recur with lymph node metastases (American Joint Committee on Cancer/Union for International Cancer Control stage III). To detect distant metastases, CT and/or FDG-PET are available. However, few studies have assessed their value and costs in stage III. METHODS: All consecutive patients with melanoma with palpable, proven lymph node metastases (2003-2008) referred for examination with FDG-PET and CT were prospectively included. Sensitivity, specificity, and accuracy, and positive predictive value (PPV) and negative predictive value (NPV) were calculated. In economic evaluation, the costs of diagnostic work-up with and without FDG-PET and CT were compared. RESULTS: Overall, 253 patients with melanoma were included. FDG-PET showed a higher sensitivity than CT: 86.1% compared with 78.2%. Specificity was higher for CT (93.7%) compared with FDG-PET (93.1%). Overall, FDG-PET showed a higher PPV and NPV. Cost-consequence analysis showed that adding CT (True-Positive upstaging in 61 patients) to diagnostic work-up decreased cost by 5.5%, adding FDG-PET (True-Positive upstaging in 68 patients) increased cost by 7.2%, and adding both (True-Positive upstaging in 78 patients) increased cost by 15.1%. CONCLUSIONS: In this study, FDG-PET had higher sensitivity and predictive value, whereas CT had a higher specificity. Adding one of these diagnostic tools improved the staging of stage III patients with less than 10% cost increase. A proposal for stage-specific use of imaging modalities for clinicians caring for patients with melanoma is presented.

Increase in volume of ablation zones during follow-up is highly suggestive of ablation site recurrence in colorectal liver metastases treated with radiofrequency ablation.

PURPOSE: To test the hypothesis that volume changes of ablation zones (AZs) on successive computed tomography (CT) scans could predict ablation site recurrences (ASRs) in patients with colorectal liver metastases treated by radiofrequency (RF) ablation. MATERIALS AND METHODS: RF ablation was performed in 58 patients with 117 metastases. Metastasis volumes and AZ volumes were measured before RF ablation, 1 week after RF ablation (t1), and every 3 months in the first year after RF ablation (t2-t5). Volumetry was performed semiautomatically on CT scans by drawing freehand regions of interest in the portal venous phase on 2-mm-thickness slices. ASR was defined as contrast enhancement on follow-up imaging or by a hot spot on fludeoxyglucose F 18 positron emission tomography combined with computed tomography (FDG-PET/CT) scanning. Proportional volume change of an AZ was defined as the difference in volume percentages between two successive time points of measurement. Negative values represented a volume decrease, and positive values represented a volume increase. Intraobserver variability and interobserver variability were evaluated by using intraclass correlation coefficients (ICCs). RESULTS: ASRs occurred in 15 patients with 27 AZs. An increase in volume occurred in 26 AZs (96%) with ASRs. AZs without ASR showed no volume increase. Although proportional volume changes at t1-t2 were not predictive for ASR, subsequent volume changes were predictive for ASR. Contrast-enhanced CT-based evaluation detected ASRs in 17 (63%) of 27 AZs, 7 (26%) of 27 AZs were negative, and there was doubt in 3 (11%) of 27 AZs. Intraobserver variability and interobserver variability were good (0.998 [95% confidence interval [CI] 0.996-0.999; P < .001] and 0.993 [95% CI 0.987-0.996; P < .001]). CONCLUSIONS: Volumetry of AZs is useful because a volume increase of an AZ during follow-up is highly suggestive of ASR. Negative volume changes of the AZ from t1-t2 were not correlated with the development of ASRs, but subsequent volume changes were predictive for ASRs.

The combination of primary sclerosing cholangitis and CCR5-Δ32 in recipients is strongly associated with the development of nonanastomotic biliary strictures after liver transplantation.

BACKGROUND: The role of the immune system in the pathogenesis of nonanastomotic biliary strictures (NAS) after orthotopic liver transplantation (OLT) is unclear. A loss-of-function mutation in the CC chemokine receptor 5 (CCR5-Δ32) leads to changes in the immune system, including impaired chemotaxis of regulatory T cells. AIM: To investigate the impact of the CCR5-Δ32 mutation on the development of NAS. METHODS: In 384 OLTs, we assessed the CCR5 genotype in donors and recipients and correlated this with the occurrence of NAS. RESULTS: The CCR5-Δ32 allele was found in 65 (16.9%) recipients. The cumulative incidence of NAS at 5 years was 6.5% in wild-type (Wt) recipients vs 17.2% for carriers of the CCR5-Δ32 allele (P<0.01). In recipients with CCR5-Δ32, 50% of all NAS occurred >2 years after OLT, compared with 10% in the Wt group. In multivariate regression analysis, the adjusted risk of developing NAS was four-fold higher in recipients with CCR5-Δ32 (P<0.01). The highest risk of NAS was seen in patients transplanted for primary sclerosing cholangitis (PSC), who also carried CCR5-Δ32 (relative risk 5.4, 95% confidence interval 2.2-12.9; P<0.01). Donor CCR5 genotype had no impact on the occurrence of NAS. CONCLUSIONS: Patients with the CCR5-Δ32 mutation have a four-fold higher risk of developing NAS, compared with Wt recipients. This risk is even higher in patients with CCR5-Δ32 transplanted for PSC. Late development of NAS is significantly more present in patients with CCR5-Δ32. These data suggest that the immune system plays a critical role in the development of NAS after OLT.

Association of urinary biomarkers with disease severity in patients with autosomal dominant polycystic kidney disease: a cross-sectional analysis.

BACKGROUND: Disease monitoring of autosomal dominant polycystic kidney disease (ADPKD) will become more important with potential upcoming therapeutic interventions. Because serum creatinine level is considered of limited use and measurement of effective renal blood flow (ERBF) and total renal volume are time consuming and expensive, there is a need for other biomarkers. We aimed to investigate which urinary markers have increased levels in patients with ADPKD; whether these urinary markers are associated with measured glomerular filtration rate (mGFR), ERBF, and total renal volume; and whether these associations are independent of albuminuria (urine albumin excretion [UAE]). STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: 102 patients with ADPKD (Ravine criteria) and 102 age- and sex-matched healthy controls. INDEX TEST: 24-hour urinary excretion of glomerular (immunoglobulin G), proximal tubular (kidney injury molecule 1 [KIM-1], N-acetyl-ß-d-glucosaminidase, neutrophil gelatinase-associated lipocalin [NGAL], and ß(2)-microglobulin), and distal tubular (heart-type fatty acid binding protein [H-FABP]) damage markers and inflammatory markers (monocyte chemotactic protein 1 [MCP-1] and macrophage migration inhibitory factor). REFERENCE TEST: Disease severity assessed using measures of kidney function (mGFR and ERBF, measured using clearance of iothalamate labeled with iodine 125 and hippuran labeled with iodine 131 during continuous infusion, respectively) and structure (total renal volume, measured using magnetic resonance imaging). OTHER MEASUREMENTS: 24-hour UAE. RESULTS: In 102 patients with ADPKD (aged 40 ± 11 years; 58% men), levels of all measured urinary biomarkers were increased compared with healthy controls. Excretion of immunoglobulin G and albumin relatively were most increased. ERBF and mGFR values were associated with urinary excretion of ß(2)-microglobulin, NGAL, and H-FABP independent of UAE, whereas total renal volume was associated with KIM-1, NGAL, and MCP-1 independent of UAE. LIMITATIONS: Cross-sectional, single center. CONCLUSIONS: Levels of markers for multiple parts of the nephron are increased in patients with ADPKD. In addition to measurement of UAE, measurement of urinary ß(2)-microglobulin, KIM-1, H-FABP, MCP-1, and especially NGAL could be of value for determination of disease severity in patients with ADPKD.

Hepatocellular carcinomas in cirrhotic and noncirrhotic human livers share angiogenic characteristics.

BACKGROUND: The antiangiogenic drug sorafenib has been shown to be an effective treatment for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. It might also be effective in noncirrhotic HCC provided that the angiogenic properties of both tumor types are comparable. The aim of this study is to compare endothelial cell dynamics, microvessel density (MVD), and vessel maturation as indirect markers of angiogenesis in human HCC in cirrhotic and noncirrhotic livers. MATERIALS AND METHODS: In a tertiary care setting, 70 consecutive HCC tumors were analyzed for endothelial cell dynamics. CD34 was applied to identify tumor microvessels, double immunolabeling Ki67/CD34 and activated caspase-3/CD34 to assess endothelial cell proliferation and apoptosis, and alpha-smooth muscle actin/CD34 for pericyte coverage. These characteristics were compared in cirrhotic (n = 33) and noncirrhotic HCCs (n = 37). Microvessel density was correlated with radiological signs of hypervascularity as obtained with dynamic four-phase CT scans during the arterial and portal phase of contrast enhancement. RESULTS: Microvessels in cirrhotic and noncirrhotic HCC were mainly mature. In both groups endothelial cell turnover was low and MVD was not different. There was no correlation between MVD and venous invasion, tumor size, and turnover of tumor cells or endothelial cells. MVD was negatively correlated with contrast washout in the portal venous phase of CT scanning. In transplanted patients, MVD was not correlated with survival, whereas in patients after liver resection a high MVD was associated with a better prognosis. CONCLUSION: Angiogenic characteristics of HCC in cirrhotic and noncirrhotic livers have a remarkable similarity.

Is Roux-en-Y choledochojejunostomy an independent risk factor for nonanastomotic biliary strictures after liver transplantation?

Biliary reconstruction using Roux-en-Y choledochojejunostomy has been suggested as a risk factor for the development of nonanastomotic biliary strictures (NAS) after liver transplantation. Roux-en-Y reconstruction, however, is preferentially used in patients transplanted for primary sclerosing cholangitis (PSC), and the disease itself is also associated with a higher incidence of NAS. The aim of this study was to determine whether Roux-en-Y reconstruction is really an independent risk factor for NAS. A series of 486 consecutive adult liver transplants were studied. Biliary reconstruction in patients transplanted for PSC was either by Roux-en-Y choledochojejunostomy or by duct-to-duct anastomosis, depending on the quality of the recipient's extrahepatic bile duct. Univariate and multivariate statistical analyses were used to identify risk factors for the development of NAS. The overall incidence of NAS was 16.5% (80/486). In univariate analyses, the following variables were significantly associated with NAS: PSC as the indication for transplantation, type of biliary reconstruction (Roux-en-Y versus duct-to-duct), and postoperative cytomegalovirus infection. After multivariate logistic regression analysis, PSC as the indication for transplantation (odds ratio, 2.813; 95% confidence interval, 1.624-4.875; P < 0.001) and postoperative cytomegalovirus infection (odds ratio, 2.098; 95% confidence interval, 1.266-3.477; P = 0.004) remained as independent risk factors for NAS. Biliary reconstruction using Roux-en-Y choledochojejunostomy was not identified as an independent risk factor for NAS. In conclusion, the association between Roux-en-Y choledochojejunostomy and NAS observed in previous studies can be explained by the more frequent use of Roux-en-Y reconstruction in patients with PSC. Roux-en-Y reconstruction itself is not an independent risk factor for NAS. Liver Transpl 15:924-930, 2009. (c) 2009 AASLD.

Routine or on demand radiological contrast examination in the diagnosis of anastomotic leakage after esophagectomy.

BACKGROUND: To detect anastomotic leakage after esophagectomy in esophageal carcinoma patients, many surgeons perform a radiological contrast examination routinely. The aim of this retrospective study is to determine the clinical relevance of a routine contrast examination after esophagectomy and to evaluate criteria for contrast examination on demand. METHODS: Data were obtained from 211 patients with cancer of the esophagus or gastro-esophageal junction who underwent an esophagectomy during the period 1991-2004. Retrospectively, we analyzed patients regarding anastomosis-related characteristics and clinical signs including sepsis, fever > or = 39.0 degrees C, leukocytosis > or = 20 x 10(9)/ml and pleural effusion. RESULTS: Anastomotic leakage had appeared in 35 of the 211 patients. The clinical signs sepsis (odds ratio (OR) 6.72: 95% confidence interval (CI) (2.57-17.56); P < 0.0001), leukocytosis (OR 2.62 (1.10-6.22); P < 0.030), and fever (OR 2.34 (1.01-5.42); P < 0.047) were significantly related to anastomotic leakage. Pleural effusion was not significantly related to anastomotic leakage (OR 2.83 (0.98-8.13); P = 0.054). CONCLUSION: Our study suggests that the clinical value for a routinely performed contrast examination is debatable. We recommend performing a contrast examination based on clinical suspicion and clinical signs of anastomotic leakage including sepsis, fever > or = 39.0 degrees C and leukocytosis > or = 20 x 10(9)/ml.

Correlation between serum ferritin levels and liver iron concentration determined by MR imaging: impact of hematologic disease and inflammation.

Liver iron concentration was determined in 28 patients by magnetic resonance imaging using the method of Gandon et al. (Non-invasive assessment of hepatic iron stores by MRI. Lancet 2004;363:357-362). The result showed a significant correlation with blood plasma ferritin content (Spearman's r=.66; P<.001) and a slightly improving correlation coefficient when limited to those patients not known to have inflammation (r=.82; n=17; P<.001). Zooming in on patients with hematologic disease also had a beneficial effect on the correlation between liver iron content and plasma ferritin level (r=.79; n=13; P=.001). It is concluded that in patients without inflammation and in patients with hematologic disease, the content of ferritin in blood is a better predictor of liver iron content than in other patient categories.

Mycophenolate mofetil and bronchiectasis in kidney transplant patients: a possible relationship.

Bronchiectasis is a rare acquired condition, generally resulting from long-term chronic pulmonary inflammation. Mycophenolate mofetil (in short, mofetil) is a commonly used immunosuppressant in kidney transplantation. In the literature, there is no report of a relationship between mofetil use and development of bronchiectasis. Five kidney transplant patients developed complaints of cough, dyspnea, and abundant sputum production without apparent cause. Pulmonary complaints started at a range of 0-20 months after the start of mofetil treatment. Lesions were classified as bronchiectasis(-like), based on clinical presentation, chest x-ray, and computed tomography scan. Withdrawal of mofetil greatly relieved pulmonary complaints. Since the first kidney transplantation in our center in 1968, we have had no diagnosis of bronchiectasis in over 1,500 patients without mofetil treatment. These cases suggest an association between mofetil and development of bronchiectasis. Converting mofetil to another immunosuppressive drug should be considered when unexplained pulmonary complaints develop in patients receiving mofetil.

Potential value of EUS in pancreatic surveillance of VHL patients.

BACKGROUND: Patients with von Hippel-Lindau (VHL) disease are prone to develop pancreatic neuroendocrine tumors (pNETs). However, the best imaging technique for early detection of pNETs in VHL is currently unknown. In a head-to-head comparison, we evaluated endoscopic ultrasound (EUS) and (11)C-5-hydroxytryptophan positron emission tomography ((11)C-5-HTP PET) compared with conventional screening techniques for early detection of pancreatic solid lesions in VHL patients. METHODS: We conducted a cross-sectional, prospective study in 22 patients at a tertiary care university medical center. Patients with VHL mutation or with one VHL manifestation and a mutation carrier as first-degree family member, with recent screening by abdominal computed tomography (CT) or magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS), were eligible. Patients underwent EUS by linear Pentax echoendoscope and Hitachi EUB-525, and (11)C-5-HTP PET. Patient-based and lesion-based positivity for pancreatic solid lesions were calculated for all imaging techniques with a composite reference standard. RESULTS: In 10 of the 22 patients, 20 pancreatic solid lesions were detected: 17 with EUS (P < 0.05 vs CT/MRI+ SRS), 3 with (11)C-5-HTP PET, 3 with SRS, 9 with CT/MRI, and 9 with CT/MRI + SRS. EUS evaluations showed solid lesions with a median size of 9.7 mm (range 2.9-55 mm) and most of them were homogeneous, hypoechoic, isoelastic, and hypervascular. Moreover, EUS detected multiple pancreatic cysts in 18 patients with a median of 4 cysts (range 1-30). CONCLUSIONS: EUS is superior to CT/MRI + SRS for detecting pancreatic solid lesions in VHL disease.(11)C-5-HTP PET has no value as a screening method in this setting. EUS performs well in early detection of pNETs, but its role in VHL surveillance is unclear.

Positron emission tomography with F-18-fluorodeoxyglucose in a combined staging strategy of esophageal cancer prevents unnecessary surgical explorations.

Distant metastases or local invasion are frequently found during the explorative phase of surgery for esophageal cancer. This study was performed to determine the rate of patients with incurable disease encountered during exploration and to examine the impact of preoperative staging, including positron emission tomography (PET), on the number of unnecessary explorations. The records of 203 patients with esophageal cancer who were eligible for curative resection were retrospectively reviewed. The surgical reports were analyzed to obtain the reasons for abandoning resection. Furthermore, the different staging modalities according to the related time interval were reviewed for each patient to analyze the influence of them on the number of explorations. After exploratory surgery, resection was abandoned in 78 of the 203 patients (38%) because of distant metastases (n=59; 29%), metastatic spread and local irresectability (n=5; 2%), and local irresectability (n=14; 7%). In a logistic regression model with all preoperative staging modalities and the year of examination as independent variables, F-18-fluorodeoxyglucose (FDG)-PET) was the only modality that predicts intended curative resection in these patients (P<0.001). In patients with esophageal cancer who are suitable for potentially curative surgery, resection was abandoned mainly because of distant metastases encountered during exploration. The addition of FDG-PET may have reduced the rate of unnecessary surgery in this group of patients.

Hepatocellular carcinoma in tyrosinemia type 1 without clear increase of AFP.

Patients with hereditary tyrosinemia type 1 have an elevated risk of developing hepatocellular carcinoma, especially if initiation of treatment with 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione is delayed. Hepatocellular carcinoma can usually be suspected when there are increased α1-fetoprotein levels and characteristic imaging features. The present case shows that a lack of a clear increase in α1-fetoprotein should still lead to consideration of liver transplantation when imaging features change.

Evaluation of progression prior to surgery after neoadjuvant chemoradiotherapy with computed tomography in esophageal cancer patients.

BACKGROUND: The risk of tumor progression during neoadjuvant chemoradiotherapy (CRT) in esophageal cancer (EC) is around 8% to 17%. We assessed the efficacy of computed tomography (CT) to identify these patients before esophagectomy. METHODS: Ninety-seven patients with locally advanced EC treated with Carboplatin/Paclitaxel and 41.4 Gy neoadjuvantly were restaged with CT. Two radiologists reviewed pre- and post-CRT CT images. The primary outcome was detection of clinically relevant progressive disease. Missed metastases were defined as metastatic disease found during surgery or within 3 months after post-CRT CT. RESULTS: Progressive disease was detected in 9 patients (9%). Both radiologists detected 5 patients with distant metastases (liver, n = 4; lung metastasis, n = 1), but missed progressive disease in 4 cases. One radiologist falsely assessed 2 metastatic lesions, but after agreement progressive disease was detected with sensitivity and specificity of 56% and 100%, respectively. CONCLUSION: CT is effective in detecting clinically relevant progressive disease in EC patients, after neoadjuvant treatment.