Pain from a Bullet Lingers on: An Uncommon Case of Lead Toxicity

Lead toxicity from a retained bullet as a cause for abdominal pain is rarely considered. Given its unpredictable latent period and nonspecific clinical symptoms, such cases are difficult to diagnose but may be fatal if unrecognized. We present the case of a 48-year-old man who presented with complaints of abdominal pain, weight loss and constipation. His past history was significant for a gunshot wound to the left hip about 20 years before. Radiographic studies confirmed the same with the presence of numerous intra-articular bullet fragments and a calcified hemarthrosis surrounding the left femoral head. Blood lead levels were elevated following which the patient was started on chelation therapy with succimer which resulted in symptomatic improvement. The aim of this paper is to highlight the importance of considering lead toxicity from a retained bullet as a cause of abdominal pain and to review the relevant literature

Concurrent chemoradiotherapy with low dose weekly gemcitabine in stage III non-small cell lung cancer

BACKGROUND: Combined chemoradiotherapy (CRT) is the treatment of choice for stage III NSCLC. Gemcitabine (G) is a novel deoxycitidine analogue that has been proven to be a potent radiosensitizer. Twenty-two consecutive patients were treated with concurrent CRT to demonstrate the tolerability and efficacy of low dose G given weekly as radiosensitizer in stage III NSCLC. METHODS: Patients with KPS ≥70, adequate bone marrow reserve, with no prior radiotherapy (RT) and surgery were included. Eighteen patients had received prior induction chemotherapy (CT). G (75 mg/m(2)/week) was infused over 1 hour for 6 weeks. Thoracic RT was given two hours later over 6 weeks at 1.8 Gy/day fractions (total dose of 61.2 Gy). Pulmonary toxicity was evaluated with computed tomography scans in 6 weeks. RESULTS: Median age was 60 years (range, 48–75), median follow-up was 15 months (range, 2–40). Sixty-eight percent of patients were male and median KPS score was 90. Conformal 3D-RT planning was used in 64% of patients. G was given for a median of 5 weeks (range 1–9). Twelve patients (54.6%) received all planned CT. G was stopped because of intolerance in 6 and death in 2 patients. Seven patients (31.8%) had radiation pneumonitis. Twenty patients were evaluated for overall response, 1 patient (4.5%) had clinical CR, 81.8% had PR while 9.5% had SD. Median overall survival (OS) was 14 ± 5 months (95% CI 3–25). One- and 2-year OS rates were 55% and 38%. Sixteen patients died of disease-related events (6 with progression of primary tumor, 8 due to metastatic disease), 2 patients died of other causes. One- and 2-year progression-free survival and local control rates were 56%, 27% and 79%, 51%, respectively. CONCLUSION: G might be used as radiosensitizer for patients with stage III NSCLC who could not receive full doses CT with concurrent RT

TNF autovaccination induces self anti-TNF antibodies and inhibits metastasis in a murine melanoma model

TNF is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases, but also in metastasis in certain types of cancer. In terms of therapy, TNF is targeted by anti-TNF neutralising monoclonal antibodies or soluble TNF receptors. Recently, a novel strategy based on the generation of self anti-TNF antibodies (TNF autovaccination) has been developed. We have previously shown that TNF autovaccination successfully generates high anti-TNF antibody titres, blocks TNF and ameliorates collagen-induced arthritis in DBA/1 mice. In this study, we examined the ability of TNF autovaccination to generate anti-TNF antibody titres and block metastasis in the murine B16F10 melanoma model. We found that immunisation of C57BL/6 mice with TNF autovaccine produces a 100-fold antibody response to TNF compared to immunisation with phosphate-buffered saline vehicle control and significantly reduces both the number (P<0.01) and size of metastases (P<0.01) of B16F10 melanoma cells. This effect is also observed when an anti-TNF neutralising monoclonal antibody is administered, confirming the essential role TNF plays in metastasis in this model. This study suggests that TNF autovaccination is a cheaper and highly efficient alternative that can block TNF and reduce metastasis in vivo and trials with TNF autovaccination are already underway in patients with metastatic cancer

Exploiting inflammation for therapeutic gain in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with <5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC

In-Vivo Biodistribution and Safety of 99mTc-LLP2A-HYNIC in Canine Non-Hodgkin Lymphoma

Theranostic agents are critical for improving the diagnosis and treatment of non-Hodgkin Lymphoma (NHL). The peptidomimetic LLP2A is a novel peptide receptor radiotherapy candidate for treating NHL that expresses the activated α4β1 integrin. Tumor-bearing dogs are an excellent model of human NHL with similar clinical characteristics, behavior, and compressed clinical course. Canine in vivo imaging studies will provide valuable biodistribution and affinity information that reflects a diverse clinical population of lymphoma. This may also help to determine potential dose-limiting radiotoxicity to organs in human clinical trials. To validate this construct in a naturally occurring model of NHL, we performed in-vivo molecular targeted imaging and biodistribution in 3 normal dogs and 5 NHL bearing dogs. 99mTc-LLP2A-HYNIC-PEG and 99mTc-LLP2A-HYNIC were successfully synthesized and had very good labeling efficiency and radiochemical purity. 99mTc-LLP2A-HYNIC and 99mTc-LLP2A-HYNIC-PEG had biodistribution in keeping with their molecular size, with 99mTc-LLP2A-HYNIC-PEG remaining longer in the circulation, having higher tissue uptake, and having more activity in the liver compared to 99mTc-LLP2A-HYNIC. 99mTc-LLP2A-HYNIC was mainly eliminated through the kidneys with some residual activity. Radioactivity was reduced to near-background levels at 6 hours after injection. In NHL dogs, tumor showed moderately increased activity over background, with tumor activity in B-cell lymphoma dogs decreasing after chemotherapy. This compound is promising in the development of targeted drug-delivery radiopharmaceuticals and may contribute to translational work in people affected by non-Hodgkin lymphoma

Prophylactic cranial irradiation in locally advanced non-small cell lung cancer: outcome of recursive partitioning analysis group 1 patients

<p>Abstract</p> <p>Background</p> <p>Prophylactic cranial irradiation (PCI) has been demonstrated to reduce or delay the incidence of brain metastases (BM) in locally advanced non-small cell lung carcinoma (LA-NSCLC) patients with various prognostic groups. With this current cohort we planned to evaluate the potential usefulness of prophylactic cranial irradiation (PCI) specifically in recursive partitioning analysis (RPA) Group 1, which is the most favorable group of LA-NSCLC patients.</p> <p>Methods</p> <p>Between March 2007 and February 2008, 62 patients in RPA group 1 were treated with sequential chemoradiotherapy and PCI for stage IIIB NSCLC. The induction chemotherapy consisted of 3 courses of cisplatin (80 mg/m²) and docetaxel (80 mg/m²); each course was given every 21 days. Thoracic radiotherapy (TRT) was given at a dose of 60 Gy using 3-D conformal planning. All patients received a total dose of 30 Gy PCI (2 Gy/fr, 5 days a week), beginning on the first day of the TRT. Then, all patients received 3 further courses of the same chemotherapy protocol.</p> <p>Results</p> <p>Six (9.7%) patients developed brain metastases during their clinical course. Only one (2%) patient developed brain metastasis as the site of first treatment failure. Median brain metastasis-free survival, overall survival, and progression free survival were 16.6, 16.7, and 13.0 months, respectively. By univariate analysis, rates of BM were significantly higher in patients younger than 60 years of age (p = 0.03). Multivariate analysis showed no significant difference in BM-free survival according to gender, age, histology, and initial T- and N-stage.</p> <p>Conclusion</p> <p>The current finding of almost equal bone metastasis free survival and overall survival in patients with LA-NSCLC in RPA group 1 suggests a longer survival for patients who receive PCI, and thereby have a reduced risk of BM.</p

Risk factors associated with fatal pulmonary hemorrhage in locally advanced non-small cell lung cancer treated with chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to identify the risk factors associated with fatal pulmonary hemorrhage (PH) in patients with locally advanced non-small cell lung cancer (NSCLC), treated with chemoradiotherapy.</p> <p>Methods</p> <p>The medical records of 583 patients with locally advanced NSCLC, who were treated with chemoradiotherapy between July 1992 and December 2009 were reviewed. Fatal PH was defined as PH leading to death within 24 h of its onset. Tumor cavitation size was defined by the cavitation diameter/tumor diameter ratio and was classified as minimum (< 0.25), minor (≥ 0.25, but < 0.5), and major (≥ 0.5).</p> <p>Results</p> <p>Of the 583 patients, 2.1% suffered a fatal PH. The numbers of patients with minimum, minor, and major cavitations were 13, 11, and 14, respectively. Among the 38 patients with tumor cavitation, all 3 patients who developed fatal PH had major cavitations. On multivariate analysis, the presence of baseline major cavitation (odds ratio, 17.878), and a squamous cell histology (odds ratio, 5.491) proved to be independent significant risk factors for fatal PH. Interestingly, all patients with fatal PH and baseline major cavitation were found to have tumors with squamous cell histology, and the occurrence of fatal PH in patients having both risk factors was 33.3%.</p> <p>Conclusions</p> <p>Patients at high risk of fatal PH could be identified using a combination of independent risk factors.</p