Adult patients with sporadic polycystic kidney disease: the importance of screening for mutations in the PKD1 and PKD2 genes

Background

ADPKD is one of the most common inherited disorders, with high risk for end-stage renal disease. Numerous patients, however, have no relatives in whom this disorder is known and are unsure whether they may transmit the disease to their offsprings. The aim of this study was to evaluate whether germline mutation analysis adds substantial information to clinical symptoms for diagnosis of ADPKD in these patients.

Methods

Clinical data included renal function and presence of liver or pancreas cysts, heart valve insufficiency, intracranial aneurysms, colonic diverticles, and abdominal hernias. Family history was evaluated regarding ADPKD. Germline mutation screening of the PKD1 and PKD2 genes was performed for intragenic mutations and for large deletions.

Results

A total of 324 adult patients with ADPKD including 30 patients without a family history of ADPKD (sporadic cases) were included. PKD1 mutations were found in 24/30 and PKD2 mutations in 6 patients. Liver cysts were present in 14 patients and intracranial aneurysms in 2 patients. Fourteen patients (45%) had no extrarenal involvement. Compared to the 294 patients with familial ADPKD, the clinical characteristics and the age at the start of dialysis were similar in those with sporadic ADPKD.

Conclusion

The clinical characteristics of patients with sporadic and familial ADPKD are similar, but sporadic ADPKD is often overlooked because of the absence of a family history. Molecular genetic screening for germline mutations in both PKD1 and PKD2 genes is essential for the definitive diagnosis of ADPKD.     

[18F]Fluciclatide in the in vivo evaluation of human melanoma and renal tumors expressing αvβ3 and αvβ5 integrins

Purpose

[¹⁸F]Fluciclatide is an integrin-targeted PET radiopharmaceutical. α_vβ₃ and α_vβ₅ are upregulated in tumor angiogenesis as well as on some tumor cell surfaces. Our aim was to use [¹⁸F]fluciclatide (formerly known as [¹⁸F]AH111585) for PET imaging of angiogenesis in melanoma and renal tumors and compare with tumor integrin expression.

Methods

Eighteen evaluable patients with solid tumors ≥2.0 cm underwent [¹⁸F]fluciclatide PET/CT. All patients underwent surgery and tumor tissue samples were obtained. Immunohistochemical (IHC) staining with mouse monoclonal antibodies and diaminobenzidine (DAB) was applied to snap-frozen tumor specimens, and additional IHC was done on formalin-fixed paraffin-embedded samples. DAB optical density (OD) data from digitized whole-tissue sections were compared with PET SUV_{80% max}, and Patlak influx rate constant (K _i) data, tumor by tumor.

Results

Tumors from all 18 patients demonstrated measurable [¹⁸F]fluciclatide uptake. At the final dynamic time-point (55 min after injection), renal malignancies (in 11 patients) demonstrated an average SUV_{80% max} of 6.4?±?2.0 (range 3.8 – 10.0), while the average SUV_{80% max} for metastatic melanoma lesions (in 6 patients) was 3.0?±?2.0 (range 0.7 – 6.5). There was a statistically significant difference in [¹⁸F]fluciclatide uptake between chromophobe and nonchromophobe renal cell carcinoma (RCCs, with SUV_{80% max} of 8.2?±?1.8 and 5.4?±?1.4 (P?=?0.020) and tumor-to-normal kidney (T/N) ratios of 1.5?±?0.4 and 0.9?±?0.2, respectively (P?=?0.029). The highest Pearson's correlation coefficients were obtained when comparing Patlak K _i and α_vβ₅ OD when segregating the patient population between melanoma and RCC (r?=?0.83 for K _i vs. melanoma and r?=?0.91 for K _i vs. RCC). SUV_{80% max} showed a moderate correlation with α_vβ₅ and α_vβ₃ OD.

Conclusion

[¹⁸F]Fluciclatide PET imaging was well tolerated and demonstrated favorable characteristics for imaging α_vβ₃ and α_vβ₅ expression in melanoma and RCC. Higher uptake was observed in chromophobe than in nonchromophobe RCC. [¹⁸F]Fluciclatide may be a useful radiotracer to improve knowledge of integrin expression.     

Intraoperative low-dose S-ketamine has no preventive effects on postoperative pain and morphine consumption after major urological surgery in children

BACKGROUND: Clinical studies suggest low-dose ketamine may have preemptive effects on postoperative pain in adults. The objective of this study was to determine whether intraoperative low-dose S-ketamine reduces postoperative pain and morphine consumption in children undergoing major urological surgery. MATERIALS: Thirty children scheduled for major urological surgery were included in this prospective study. Anesthesia was performed as total intravenous anesthesia (TIVA) with alfentanil and propofol. Fifteen patients additionally received an intravenous bolus of S-ketamine (0.2 mg.kg-1) followed by a continuous infusion of 5 microg.kg-1.min-1, which was stopped immediately after skin closure (Ketamine Group). Another 15 patients received an infusion of saline (Control group). After transfer to the PACU, pain intensity was evaluated using a numeric rating scale (NRS). First patient controlled analgesia (PCA) request, cumulative morphine consumption and pain intensities within the first 72 h were compared. RESULTS: Morphine consumption was not significantly different during the first 72 h (Control: 0.4 mg.kg-1, 0.24-0.51 mg.kg-1, Ketamine: 0.32 mg.kg-1, 0.19-0.61 mg.kg-1; median, 25-75% percentile; n.s.). However, differences were found in pain intensity during the first postoperative hour (Control: 4.0, 3.2-4.6, Ketamine: 2.5, 1.3-3.5; median, 25-75% percentile; P<0.05) and in the time to first PCA use (Control: 37, 28-46 min, Ketamine: 62, 38-68 min; median, 25-75% percentile; P<0.05). CONCLUSIONS: Intraoperative low-dose S-ketamine had no effect on morphine consumption during the first 72 h after surgery. The differences in pain intensity and time to first PCA use probably reflect additional sedation and antinociceptive effects of S-ketamine rather than a true 'prevention' of pain.     

[<Superscript>11</Superscript>C]choline PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy

Objective  

To evaluate [¹¹C]choline positron emission tomography/computed tomography ([¹¹C]choline PET/CT) for the detection of a biochemical recurrence of prostate cancer after radical prostatectomy.     

Estimation of the time since death—reconsidering the re-establishment of rigor mortis

In forensic medicine, there is an undefined data background for the phenomenon of re-establishment of rigor mortis after mechanical loosening, a method used in establishing time since death in forensic casework that is thought to occur up to 8 h post-mortem. Nevertheless, the method is widely described in textbooks on forensic medicine. We examined 314 joints (elbow and knee) of 79 deceased at defined time points up to 21 h post-mortem (hpm). Data were analysed using a random intercept model. Here, we show that re-establishment occurred in 38.5% of joints at 7.5 to 19 hpm. Therefore, the maximum time span for the re-establishment of rigor mortis appears to be 2.5-fold longer than thought so far. These findings have major impact on the estimation of time since death in forensic casework.     

Influence of observer experience and training on proficiency in coronary CT angiography interpretation

Purpose

To assess the influence of experience and training on the proficiency in coronary CT angiography (CCTA) interpretation of practitioners with different levels of experience.

Methods and materials

Nine radiologist and cardiologist observers with varying prior CCTA experience ranging from novice to expert independently analyzed two case series of 50 catheter-correlated CCTA studies for coronary artery stenosis (0%, ≤49%, 50–74%, 75–99%, or 100%). Results of the first case series were unblinded and presented along with catheter angiography results to each reader before proceeding to the second series. Diagnostic accuracy on a per-segment basis was compared for all readers and both case series, respectively.

Results

Correlation coefficients between CCTA and catheter angiography initially ranged between good (r = 0.87) and poor (r = 0.26), depending on reader experience, and significantly (p < 0.05) improved in the second case series (range: r = 0.42 to r = 0.91). Diagnostic accuracy was significantly (p < 0.05) higher for more experienced readers (range: 96.5–97.8%) as compared to less experienced observers (range: 90.7–93.6%). After completion of the second case series for less experienced readers sensitivity and PPV significantly (p < 0.05) improved (range: 62.7–67.8%/51.4–84.1%), but still remained significantly (p < 0.05) lower as compared to more experienced observers (range: 89.8–93.3%/80.6–93.3%).

Conclusion

The level of experience appears to be a strong determinant of proficiency in CCTA interpretation. Limited one-time training improves proficiency in novice readers, but not to clinically satisfactory levels.     

Boerhaave’s syndrome: Primary repair vs. esophageal resection—Case reports and meta-analysis of the literature

Boerhaave’s syndrome is a life-threatening disease with a high mortality. With regard to the heterogeneity of treatment strategies, no comparative studies exist and recommendations remain controversial. Seventeen cases of Boerhaave’s syndrome operated on between 1989 and 2000 at our hospital were reviewed retrospectively to compare the time period between perforation and diagnosis, and the morbidity and mortality among the different treatment options. In addition, we conducted a meta-analysis of the literature including all series containing five or more patients and compared the findings with our own data. Our patients with a perforation history of less than 12 hours showed significantly fewer signs of sepsis compared to patients with a history of more than 12 hours. In a comparison of patients with primary repair vs. patients treated with esophageal resection or an exclusion operation, no differences were found. In the literature, patients with a long period of perforation (more than 24 hours) were treated more often with an esophageal resection than patients with primary repair. In cases of Boerhaave’s syndrome, primary suturing of the esophageal perforation should be reserved only for those patients presenting within 12 hours after perforation. In all other cases, depending on the extent of the tissue damage, a two-stage esophageal resection with cervical esophagostomy and gastrostomy is recommended as the safest treatment.     

First demonstration of leukemia imaging with the proliferation marker 18F-fluorodeoxythymidine

Acute myeloid leukemia (AML) is a neoplasm of hematopoietic stem cells with partial or complete loss of the ability to differentiate but with preserved proliferation capacity. The aim of our study was to evaluate if the in vivo proliferation marker 3'-deoxy-3'-18F-fluorothymidine (FLT) is suitable for visualizing leukemia manifestation sites and if 18F-FLT is a surrogate marker for disease activity. METHODS: In this pilot study, 10 patients with AML underwent pretherapeutic imaging with 18F-FLT PET or 18F-FLT PET/CT. The biodistribution of 18F-FLT was assessed 60 min after intravenous injection of the radiotracer. Standardized uptake values were calculated for reference segments of bone marrow, spleen, and normal organs. 18F-FLT PET in 10 patients with benign pulmonary nodules and the absence of malignant or inflammatory disease served as controls. RESULTS: Retention of 18F-FLT was observed predominantly in bone marrow and spleen and was significantly higher in AML patients than in controls (mean 18F-FLT SUV in bone marrow, 11.5 and 6.6, P < 0.05; mean 18F-FLT SUV in spleen, 6.1 and 1.8, P < 0.05). Outside bone marrow, focal 18F-FLT uptake showed extramedullary manifestation sites of leukemia in 4 patients (meningeal disease, pericardial, abdominal, testicular, and lymph node), proven by other diagnostic procedures. CONCLUSION: This pilot study indicated that PET using 18F-FLT is able to visualize extramedullary manifestation sites of AML and reflects disease activity. Because 18F-FLT uptake in bone marrow is caused by a combination of both neoplastic and normal hematopoietic cells, the correlation of 18F-FLT uptake in bone marrow and leukemic blast infiltration did not reach statistical significance.     

Computer-aided detection of pulmonary embolism: Influence on radiologists’ detection performance with respect to vessel segments

The purpose was to assess the sensitivity of a CAD software prototype for the detection of pulmonary embolism in MDCT chest examinations with regard to vessel level and to assess the influence on radiologists' detection performance. Forty-three patients with suspected PE were included in this retrospective study. MDCT chest examinations with a standard PE protocol were acquired at a 16-slice MDCT. All patient data were read by three radiologists (R1, R2, R3), and all thrombi were marked. A CAD prototype software was applied to all datasets, and each finding of the software was analyzed with regard to vessel level. The standard of reference was assessed in a consensus read. Sensitivity for the radiologists and CAD software was assessed. Thirty-three patients were positive for PE, with a total of 215 thrombi. The mean overall sensitivity for the CAD software alone was 83% (specificity, 80%). Radiologist sensitivity was 77% = R3, 82% = R2, and R1 = 87%. With the aid of the CAD software, sensitivities increased to 98% (R1), 93% (R2), and 92% (R3) (p<0.0001). CAD performance at the lobar level was 87%, at the segmental 90% and at the subsegmental 77%. With the use of CAD for PE, the detection performance of radiologists can be improved.