Re‐examination of the Lymphocytotoxic Crossmatch in Liver Transplantation: Can C4d Stains Help in Monitoring?

C4d-assisted recognition of antibody-mediated rejection (AMR) in formalin-fixed paraffin-embedded tissues (FFPE) from donor-specific antibody-positive (DSA+) renal allograft recipients prompted study of DSA+ liver allograft recipients as measured by lymphocytotoxic crossmatch (XM) and/or Luminex. XM results did not influence patient or allograft survival, or cellular rejection rates, but XM+ recipients received significantly more prophylactic steroids. Endothelial C4d staining strongly correlates with XM+ (<3 weeks posttransplantation) and DSA+ status and cellular rejection, but not with worse Banff grading or treatment response. Diffuse C4d staining, XM+, DSA+ and ABO- incompatibility status, histopathology and clinical-serologic profile helped establish an isolated AMR diagnosis in 5 of 100 (5%) XM+ and one ABO-incompatible, recipients. C4d staining later after transplantation was associated with rejection and nonrejection-related causes of allograft dysfunction in DSA- and DSA+ recipients, some of whom had good outcomes without additional therapy. Liver allograft FFPE C4d staining: (a) can help classify liver allograft dysfunction; (b) substantiates antibody contribution to rejection; (c) probably represents nonalloantibody insults and/or complete absorption in DSA- recipients and (d) alone, is an imperfect AMR marker needing correlation with routine histopathology, clinical and serologic profiles. Further study in late biopsies and other tissue markers of liver AMR with simultaneous DSA measurements are needed.     

Screening for CLCN5 mutation in renal calcium stone formers patients

Thirty-five patients (23 males and 12 females), age 35 +/- 13 years old, presenting either idiopathic calcium nephrolithiasis, nephrocalcinosis or mild renal failure with idiopathic calcium nephrolithiasis were selected for the analysis of low molecular weight proteinuria and the possible mutations occurrence in the chloride channel gene CLCN5. The urinary ratio of beta2-microglobulin and creatinine (beta2M/Cr) was very high in a transplanted woman with nephrocalcinosis (> 3.23 mg/mmol) and slightly high in five patients (> 0.052 or < 1.0 mg/mmol) with multiple urological manipulations. Other studied patients showed beta2M/Cr ratio at normal range (0.003-0.052 mg/mmol) without gender difference (p > 0.05). Mutation analysis of CLCN5 gene was performed in 26 patients of 35 selected (11 with idiopathic hypercalciuria; 6 men with normal calciuria; 3 with mild renal insufficiency and 6 with nephrocalcinosis) and was normal in all subjects even in those with abnormal molecular weight proteinuria. Conclusion: CLCN5 gene mutation is not a common cause of kidney stone disease or nephrocalcinosis in a group of Brazilian patients studied.     

Comparison of 1.5- and 3-T MR imaging for evaluating the articular cartilage of the knee

Purpose

The aim of this prospective study was to compare routine MRI scans of the knee at 1.5 and 3 T obtained in the same individuals in terms of their performance in the diagnosis of cartilage lesions.

Methods

One hundred patients underwent MRI of the knee at 1.5 and 3 T and subsequent knee arthroscopy. All MR examinations consisted of multiplanar 2D turbo spin-echo sequences. Three radiologists independently graded all articular surfaces of the knee joint seen at MRI. With arthroscopy as the reference standard, the sensitivity, specificity, and accuracy of 1.5- and 3-T MRI for detecting cartilage lesions and the proportion of correctly graded cartilage lesions within the knee joint were determined and compared using resampling statistics.

Results

For all readers and surfaces combined, the respective sensitivity, specificity, and accuracy for detecting all grades of cartilage lesions in the knee joint using MRI were 60, 96, and 87 % at 1.5 T and 69, 96, and 90 % at 3 T. There was a statistically significant improvement in sensitivity (p < 0.05), but not specificity or accuracy (n.s.) for the detection of cartilage lesions at 3 T. There was also a statistically significant (p < 0.05) improvement in the proportion of correctly graded cartilage lesions at 3 T as compared to 1.5 T.

Conclusion

A 3-T MR protocol significantly improves diagnostic performance for the purpose of detecting cartilage lesions within the knee joint, when compared with a similar protocol performed at 1.5 T.

Level of evidence

III.     

PET/CT assessment in follicular lymphoma using standardized criteria: central review in the PRIMA study

Purpose

We aimed to compare the standardized central review of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scans performed after induction therapy for follicular lymphoma (FL) in the PRIMA study (Salles et al., Lancet 377:42–51, 2011; Trotman et al., J Clin Oncol 29:3194–3200, 2011) to scan review at local centres.

Methods

PET/CT scans were independently evaluated by two nuclear medicine physicians using the 2007 International Harmonization Project (IHP) criteria (Cheson et al., J Clin Oncol 25:579–586, 2007; Juweid et al., J Clin Oncol 25:571–578, 2007; Shankar et al., J Nucl Med 47:1059–1066, 2006) and Deauville 5-point scale (5PS) criteria (Meignan et al., Leuk Lymphoma 50:1257–1260, 2009; Meignan et al., Leuk Lymphoma 51:2171–2180, 2010; Barrington et al., Eur J Nucl Med Mol Imaging 37:1824–1833, 2010). PET/CT status was compared with prospectively recorded patient outcomes.

Results

Central evaluation was performed on 119 scans. At diagnosis, 58 of 59 were recorded as positive, with a mean maximum standardized uptake value (SUV_max) of 11.7 (range 4.6–35.6). There was no significant association between baseline SUV_max and progression-free survival (PFS). Sixty post-induction scans were interpreted using both the IHP criteria and 5PS. Post-induction PET-positive status failed to predict progression when applying the IHP criteria [p?=?0.14; hazard ratio (HR) 1.9; 95 % confidence interval (CI) 0.8–4.6] or 5PS with a cut-off ≥3 (p?=?0.12; HR 2.0; 95 % CI 0.8–4.7). However, when applying the 5PS with a cut-off ≥4, there was a significantly inferior 42-month PFS in PET-positive patients of 25.0 % (95 % CI 3.7–55.8 %) versus 61.4 % (95 % CI 45.4–74.1 %) in PET-negative patients (p?=?0.01; HR 3.1; 95 % CI 1.2–7.8). The positive predictive value (PPV) of post-induction PET with this liver cut-off was 75 %. The 42-month PFS for patients remaining PET-positive by local assessment was 31.1 % (95 % CI 10.2–55.0 %) vs 64.6 % (95 % CI 47.0–77.6 %) for PET-negative patients (p?=?0.002; HR 3.3; 95 % CI 1.5–7.4), with a PPV of 66.7 %.

Conclusion

We confirm that FDG PET/CT status when applying the 5PS with a cut-off ≥4 is strongly predictive of outcome after first-line immunochemotherapy for FL. Further efforts to refine the criteria for assessing minimal residual FDG uptake in FL should provide a reproducible platform for response assessment in future prospective studies of a PET-adapted approach.     

Gastric wall necrosis owing to its incarceration through a rupture of the diaphragm into the left thoracic cavity

A 73 year-old female patient was admitted to the 3rd Medical Department of Semmelweis University with a painful haematoma in the left loin and respiratory disorders. Her general condition was getting progressively worse. Chest X-ray demonstrated a left sided hemopneumothorax caused by a fractured rib. Thoracic drainage was planned, but the tube introduced on the usual place into the left thoracic cavity perforated the stomach which was incarcerated in the chest. After this an urgent operation was carried out. We found an incarcerated, twisted stomach prolapsing through a rupture of the diaphragm. It was partially necrotic. Excision of the stomach wall with suturing the diaphragm, lavage and drainage of the thoracic and abdominal cavity was carried out. Despite the operation multi-organ failure developed as a result of sepsis, and the patient'died. We discuss the literature in connection with the presentation of this rare and interesting case. In the past 15 years we could not find similar case in the Hungarian surgical literature.     

Bilateral testicular epidermoid cyst in a pediatric patient with Klinefelter syndrome

Epidermoid cysts of the testis are rare in children (3% of all the testicular tumors). Bilateral appearance has only been described in the pediatric age in 2 cases and none associated to Klinefelter's syndrome. We present, for our knowledge, the first case of bilateral epidermoid testicular cyst associated to klinefelter's syndrome in a boy, highlighting its management and therapeutic approach. We analyze the different kinds of treatment.     

Assessment of non-small cell lung cancer viability and necrosis with three radiopharmaceuticals

Assessment of tumor viability and necrosis of non-small cell lung cancer and detection of distant metastases are important for diagnosis, staging, monitoring the response to treatment and planning long-term management. We performed scintigraphy on patients with non-small cell lung cancer to determine the utility of three tumor targeting tracers for diagnosing primary lung cancer, for differentiating viable from necrotic tumor tissue and for detecting distant bone and soft tissue metastases. Our patients were divided into groups. Group A consisted of 27 patients, 25 male and 2 female, mean age 59 years, range from 35 to 72 years. These patients underwent radioimmunoscintigraphy (RIS) using monoclonal antibody against human milk fat globule labeled with technetium-99m ((99m)Tc). Group B consisted of 23 patients, 21 male and 2 female, mean age 56 years, range: 37 to 70 years. Group C consisted of 24 patients, 20 male and 4 female, mean age 58 years, range: 35 to 74 years. Both Groups B and C underwent chest and whole-body scintigraphy with 555 MBq of (99m)Tc-sestamibi ((99m)Tc-S) and 111 MBq of thallium-201 chloride ((201)TlCl), respectively. Tumor to non-tumor ratio was calculated. Our findings show that RIS had 52% sensitivity in detecting primary non-small cell lung cancer. In contrast, the sensitivity of (99m)Tc-S and of (201)Tl scintigraphy was 87% and 88%, respectively. High uptake of all three radiopharmaceuticals was found in 6 patients with distant soft tissue and bone tissue metastases and in 1 patient with brain metastasis. Mean tumor to non-tumor ratios were similar: for RIS 1.7+/-0.4, for (99m)Tc-S 1.6+/-0.3 and for (201)Tl 1.6+/-0.2. In conclusion: (99m)Tc-S and (201)Tl scintigraphy are superior to RIS for detecting non-small primary lung cancers and potentially clinically useful methods for detecting primary lung cancer as above, as well as bone and soft tissue metastases.     

Effect of prenatal glucocorticoids and postnatal nitric oxide inhalation on survival of newborn rats with nitrofen-induced congenital diaphragmatic hernia

Background/Purpose: Pulmonary hypertension and pulmonary hypoplasia account for the high mortality rate associated with congenital diaphragmatic hernia (CDH). In animal models of CDH, postnatal nitric oxide (NO) inhalation resulted in significantly better survival rates and antenatal glucocorticoid administration in improved lung compliance. The objective of this study was to evaluate the combined effect of prenatal glucocorticoid administration and postnatal NO inhalation on the survival rate of newborn rats with nitrofen-induced CDH. Methods: Right-sided CDH was induced by maternal administration of a single oral dose (100 mg, intraperitoneally) of nitrofen on day 11.5 of pregnancy. Dexamethasone (DEX, 0.25 mg/kg) was given in groups III and IV by maternal intraperitoneal injection on day 18.5 and 19.5 of pregnancy. Control animals (groups I and II) received vehicle alone. After spontaneous delivery, the newborn animals were exposed to either NO (80 ppm; groups II and IV) or room air (groups I and III). Vitality (Rat-Score), sO₂ and survival were monitored continuously for 12 hours until animals were killed. Hernia size was estimated as percentage of total thoracic content. Results: Right-sided CDH was observed in 392 of 491 newborn rats (81%). Animals with large hernias ([gt ]50%) died within 4 hours after birth, irrespective of treatment. Hernias with less than 50% of the thoracic volume were considered clinically relevant hernias. In this category, 12.5% of animals without treatment (group I) survived compared with 63.6% after NO treatment alone (group II; P [lt ] .01). Survival rate after DEX treatment alone (group III) was 69.4% (group III v I; P [lt ] .01). In group IV (DEX and NO) 95.2% of the animals survived (group IV v I; P [lt ] .001). In contrast to DEX alone, NO administration resulted in significantly better sO₂(group II and IV) compared with group I (P [lt ] .05). Conclusion: Combination of prenatal maternal glucocorticoids and postnatal NO inhalation significantly improved survival rate of newborn rats with nitrofen-induced CDH.     

Indications, results and techniques of permanent prostate brachytherapy for localized prostate cancer

Introduction and objectiveProstate brachytherapy is a first-line therapeutic approach for localized prostate cancer in selected patients. We present our experience in brachytherapy and a thorough review of the literature.Materials and MethodsA review of the literature and evaluation of patient’s selection was done. Furthermore the implantation technique, oncological results according to the different risk groups and acute and chronic complications were also analyzed.ResultsThe biochemical relapse-free 10 year survival rate was 87-96% in low risk tumours and 63-86% in intermediate risk tumours. A total of 3-24% underwent urinary retention that required TURP in 0-8,7%. Other complications were urinary incontinence in 0-6,7%, proctitis in 0-15,5%, erectile dysfunction in 6,3-30%, rectal ulcer/fistula in 0-5,4%.ConclusionsProstate brachytherapy is a safe and effective treatment in low and intermediate risk patients with prostate cancer.