Diagnostic performance of response assessment FDG-PET/CT in patients with head and neck squamous cell carcinoma treated with high-precision definitive (chemo)radiation

Purpose

To prospectively assess diagnostic performance of response assessment fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with HNSCC treated with high-precision definitive (chemo)radiation.

Methods

Fifty-seven patients treated on a prospective clinical trial having post-treatment response assessment FDG-PET/CT scans were included. Clinico-pathologic findings and follow-up information was considered as reference standard.

Results

First response assessment FDG-PET/CT was done at a median of 9 weeks (inter-quartile range 8-10 weeks) from completion of treatment. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of first response assessment FDG-PET/CT for identifying residual disease at primary site was 50%, 91.8%, 50%, 91.8%, and 86%. The corresponding figures for the neck were 62.5%, 98%, 83.3%, 94.1%, and 93%. With a median follow-up of 26 months (range 7-45 months), the 3-year loco-regional control (83.9% vs 58.3%, p = 0.001) and overall survival (68.8% vs 58.3%, p = 0.063) was significantly better in patients with negative response assessment scans.

Conclusion

The overall diagnostic accuracy of response assessment FDG-PET/CT is good, but its sensitivity and PPV is somewhat low, particularly for primary site. A negative response assessment FDG-PET/CT scan is highly suggestive of absence of viable disease that could be used to guide decision-making.     

Homocysteinethiolactone and Paraoxonase: Novel markers of diabetic retinopathy

OBJECTIVE

Paraoxonase (PON) exhibits esterase activity (PON-AREase) and lactonase activity (PON-HCTLase), which prevent LDL oxidation and detoxify homocysteine thiolactone (HCTL). The role of HCTL and PON-HCTLase as a risk factor for the microvascular complication in diabetic retinopathy at the level of vitreous has not been investigated.

RESEARCH DESIGN AND METHODS

Undiluted vitreous from patients with proliferative diabetic retinopathy (PDR) (n = 13) and macular hole (MH) (n = 8) was used to determine PON-HCTLase and PON-AREase activity spectrophotometrically. HCTL levels were detected by liquid chromatography–tandem mass spectrometry. In vitro studies were done in primary cultures of bovine retinal capillary endothelial cells (BRECs) to determine the dose- and time-dependent effect of HCTL and homocysteine (Hcys) on PON-HCTLase activity, as well as to determine mRNA expression of PON by RT-PCR.

RESULTS

A significant increase in HCTL and PON-HCTLase activity was observed in PDR compared with MH (P = 0.036, P = 0.001), with a significant positive correlation between them (r = 0.77, P = 0.03). The in vitro studies on BRECs showed a dose- and time-dependent increase in the PON-HCTLase activity and mRNA expression of PON2 when exposed to HCTL and Hcys.

CONCLUSIONS

This is the first study showing elevated levels of vitreous HCTL and PON-HCTLase activity in PDR. These elevations are probably a protective effect to eliminate HCTL, which mediates endothelial cell dysfunction. Thus, vitreous levels of HCTL and PON activity can be markers of diabetic retinopathy. The bioinformatics analysis reveals that the structure and function of PON that can be modulated by hyperhomocysteinemia in PDR can affect the dual-enzyme activity of PON.Hyperhomocysteinemia is a well-established independent risk factor for the development of macrovascular and microvascular diseases (1). Recent reports show that increased homocysteine thiolactone (HCTL) levels are associated with diabetic macrovasculopathy (2). HCTL is formed in all cell types as a result of error-editing met-tRNA synthetase when there is excess homocysteine (Hcys). The interaction of HCTL with proteins leads to protein homocysteinylation and loss of function (3). Therefore, detoxification of HCTL is crucial. This is possible by the lactonase (HCTLase) activity of paraoxonase (PON) (4). The enzyme PON is a calcium-dependent 45-kDa protein coded by chromosome 7q21-22. The PON gene family in humans has three members: PON1, PON2, and PON3. Whereas PON1 and PON3 are associated with serum HDL (5), PON2 is ubiquitously expressed in tissues (6). PON1 exhibits antioxidant properties, thereby preventing the accumulation of oxidized LDL, and PON2 acts mainly at the cellular level (7). Lipid oxidation plays a role not only in macrovascular diseases but also in microvascular dysfunction, and serum PON1 activity was decreased in patients with diabetic retinopathy (8). While elevated Hcys in the vitreous of patients with proliferative diabetic retinopathy (PDR) was reported by us and others (9,10), there are no reports on HCTL levels and PON activity. This study aims to detect the vitreous levels of HCTL, PON-HCTLase, and esterase (PON-AREase) activity in PDR case subjects and in in vitro studies in bovine retinal capillary endothelial cells (BRECs).     

Pulmonary arteriovenous malformations

Pulmonary arteriovenous malformations rarely present in childhood. Two cases are presented in this report. Both the cases presented clinically with cyanosis and clubbing without a cardiac murmur. The second case had cerebral abscess in addition. Both the cases underwent a contrast-enhanced echocardiography which suggested the presence of pulmonary arteriovenous malformations. The first case also underwent^99mTc radionuclide scan and pulmonary angiography. The cases are being reported for their characteristic clinical features and for emphasizing the role of non-invasive modalities like contrast-enhanced echocardiography and radionuclide scan in reaching the diagnosis.     

Integrated microfluidic biophotonic chip for laser induced fluorescence detection

Integrated Lab-on-a-Chip or Micro-Total Analysis Systems offer several advantages for the detection of active chemical and biological species. In this work, an integrated microfluidic biophotonic chip is proposed for carrying out laser induced fluorescence detection. A Spectrometer-on-Chip device, specifically designed for multiple fluorescence detections at different emission wavelengths is integrated with the opto-microfluidic chip fabricated on Silicon-Polymer hybrid platform. The input fiber from the laser source, and output fiber coupled with a Spectrometer-on-Chip were integrated with the microfluidic channel so as to make a robust setup. Fluorescence detection was carried out using Alexafluor 647 tagged antibody particles. The experimental results show that the proposed biophotonic microfluidic device is highly suitable for high throughput detection of chemical and biological specimens.     

Laparoscopic appendectomy for mucocele of the appendix: Report of 8 cases.

Mucocele of the appendix is an aseptic dilatation secondary to obstruction. Surgical excision is the treatment of choice in benign mucocele. The incidence of mucocele of the appendix in our center is 0.15%, of a total of 6000 appendectomies over 8 years. We operated on 9 cases; laparoscopic appendectomy was done in 8 of them. One patient had pseudomyxoma peritonei, so open surgery was done. Other organs were also examined as there is a possibility of concurrent tumors. As there is risk of malignancy of the appendix leading to port-site metastasis we used a non-permeable bag to remove the resected specimen.     

Severe transplant‐associated thrombotic microangiopathy in patients with hemoglobinopathies

Incidence and severity of transplant‐associated thrombotic microangiopathy (TA‐TMA) in patients with hemoglobinopathies receiving hematopoietic cell transplant is unknown. We report the outcomes for two patients with TA‐TMA who received eculizumab. A 2.5‐year‐old male with sickle cell disease developed TA‐TMA‐associated pericardial tamponade, severe hypertension, and acute kidney injury 2 months after transplant. A 7‐year‐old female with β‐thalassemia major developed TA‐TMA‐related acute kidney injury, severe hypertension, and seizures at 6 months after transplant. Both patients progressed to chronic kidney disease (CKD). In patients with hemoglobinopathies, preexisting endothelial dysfunction may place them at a greater risk for TA‐TMA and subsequent CKD.