Neutrophils from chronic lymphocytic leukemia patients exhibit an increased capacity to release extracellular traps (NETs)

Abstract

Chronic lymphocytic leukemia (CLL) is characterized by immune defects that contribute to a high rate of infections and autoimmune cytopenias. Neutrophils are the first line of innate immunity and respond to pathogens through multiple mechanisms, including the release of neutrophil extracellular traps (NETs). These web-like structures composed of DNA, histones, and granular proteins are also produced under sterile conditions and play important roles in thrombosis and autoimmune disorders. Here we show that neutrophils from CLL patients are more prone to release NETs compared to those from age-matched healthy donors (HD). Increased generation of NETs was not due to higher levels of elastase, myeloperoxidase, or reactive oxygen species production. Instead, we found that plasma from CLL patients was able to prime neutrophils from HD to generate higher amounts of NETs upon activation. Plasmatic IL-8 was involved in the priming effect since its depletion reduced plasma capacity to enhance NETs release. Finally, we found that culture with NETs delayed spontaneous apoptosis and increased the expression of activation markers on leukemic B cells. Our study provides new insights into the immune dysregulation in CLL and suggests that the chronic inflammatory environment typical of CLL probably underlies this inappropriate neutrophil priming.

http://ift.tt/2dTWF0y

A panel of four genes accurately differentiates benign from malignant thyroid nodules

Abstract

Background

Clinicians are confronted with an increasing number of patients with thyroid nodules. Reliable preoperative diagnosis of thyroid nodules remains a challenge because of inconclusive cytological examination of fine-needle aspiration biopsies. Although molecular analysis of thyroid tissue has shown promise as a diagnostic tool in recent years, it has not been successfully applied in routine clinical use, particularly in Chinese patients.

Methods

Whole-transcriptome sequencing of 19 primary papillary thyroid cancer (PTC) samples and matched adjacent normal thyroid tissue (NT) samples were performed. Bioinformatics analysis was carried out to identify candidate diagnostic genes. Then, RT-qPCR was performed to evaluate these candidate genes, and four genes were finally selected. Based on these four genes, diagnostic algorithm was developed (training set: 100 thyroid cancer (TC) and 65 benign thyroid lesions (BTL)) and validated (independent set: 123 TC and 81 BTL) using the support vector machine (SVM) approach.

Results

We discovered four genes, namely fibronectin 1 (FN1), gamma-aminobutyric acid type A receptor beta 2 subunit (GABRB2), neuronal guanine nucleotide exchange factor (NGEF) and high-mobility group AT-hook 2 (HMGA2). A SVM model with these four genes performed with 97.0 % sensitivity, 93.8 % specificity, 96.0 % positive predictive value (PPV), and 95.3 % negative predictive value (NPV) in training set. For additional independent validation, it also showed good performance (92.7 % sensitivity, 90.1 % specificity, 93.4 % PPV, and 89.0 % NPV).

Conclusions

Our diagnostic panel can accurately distinguish benign from malignant thyroid nodules using a simple and affordable method, which may have daily clinical application in the near future.

http://ift.tt/2feZZsZ

Tripartite motif containing 62 is a novel prognostic marker and suppresses tumor metastasis via c-Jun/Slug signaling-mediated epithelial-mesenchymal transition in cervical cancer

Abstract

Background

TRIM62 (tripartite motif containing 62) has been found to act as a tumor suppressor of several cancers. However, its precise biological role and related mechanism remain unknown in cervical cancer (CC).

Methods

Quantitative Real-time PCR and western blot were adopted to detect the mRNA and protein expression level of TRIM62 in both human CC cell lines and tissues. Immunohistochemistry was used to measure the TRIM62 expression in 30 normal cervical and 189 CC tissues. Univariate and multivariate Cox regression analyses and Kaplan–Meier survival analyses performed to investigate the association between TRIM62 expression and CC patients' prognosis. The effect of TRIM62 on CC growth and metastasis was studied in vitro and in vivo. Multi-pathway reporter array were utilized to identify the potential signaling manipulated by TRIM62.

Results

TRIM62 was frequently down-regulated in both human CC cells and tissues. Low expression of TRIM62 in CC tissues was associated with aggressive clinicopathological features of CC patients. In addition, TRIM62 was also an independent poor prognostic factor for overall and disease-free survival of CC patients after surgery. Moreover, enforced expression of TRIM62 in CC cells significantly inhibited their abilities of proliferation, migration and invasion in vitro. Besides, subcutaneous xenograft tumor model and xenograft mouse metastatic model respectively displayed that TRIM62 impeded the growth and metastasis of CC in vivo. Furthermore, mechanism study exhibited that TRIM62 could suppress epithelial-mesenchymal transition (EMT) by inhibiting c-Jun/Slug signaling. The inhibitory role of TRIM62 in tumor proliferation might be through regulating cell cycle related proteins CyclinD1 and P27 by targeting c-Jun.

Conclusion

TRIM62 is a potential prognostic biomarker in CC and suppresses metastasis of CC via inhibiting c-Jun/Slug signaling-mediated EMT.

http://ift.tt/2eY7q3R

Neutrophils from chronic lymphocytic leukemia patients exhibit an increased capacity to release extracellular traps (NETs)

Abstract

Chronic lymphocytic leukemia (CLL) is characterized by immune defects that contribute to a high rate of infections and autoimmune cytopenias. Neutrophils are the first line of innate immunity and respond to pathogens through multiple mechanisms, including the release of neutrophil extracellular traps (NETs). These web-like structures composed of DNA, histones, and granular proteins are also produced under sterile conditions and play important roles in thrombosis and autoimmune disorders. Here we show that neutrophils from CLL patients are more prone to release NETs compared to those from age-matched healthy donors (HD). Increased generation of NETs was not due to higher levels of elastase, myeloperoxidase, or reactive oxygen species production. Instead, we found that plasma from CLL patients was able to prime neutrophils from HD to generate higher amounts of NETs upon activation. Plasmatic IL-8 was involved in the priming effect since its depletion reduced plasma capacity to enhance NETs release. Finally, we found that culture with NETs delayed spontaneous apoptosis and increased the expression of activation markers on leukemic B cells. Our study provides new insights into the immune dysregulation in CLL and suggests that the chronic inflammatory environment typical of CLL probably underlies this inappropriate neutrophil priming.

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Targeted Next Generation Sequencing Enables Reliable Detection of HER2 (ERBB2) Status in Breast Cancer and Provides Ancillary Information of Clinical Relevance

Abstract

HER2-positive breast cancers are a heterogeneous group of tumors, which share amplification and overexpression of HER2. In routine diagnostics, the HER2 (ERBB2) status is currently assessed by immunohistochemistry (IHC) and in-situ hybridization (ISH). Data on targeted next-generation sequencing (NGS) approaches that could be used to determine the HER2 status are sparse. Employing two breast cancer-related gene panels, we performed targeted NGS of 41 FFPE breast cancers for which full pathological work-up including ISH and IHC results were available. Selected cases were analyzed by qPCR. Of the 41 cases, the HER2 status of the 4 HER2-positive and 6 HER2-negative tumors was independently detected by our NGS approach achieving a concordance rate of 100%. The remaining 31 cases were equivocal HER2 cases by IHC of which 5 showed amplification of HER2 by ISH. Our NGS approach classified all non-amplified cases correctly as HER2-negative and corroborated all but one of the 5 cases with amplified HER2 as detected by ISH. For the overall cohort, concordance between the gold standard and NGS was 97.6% (sensitivity 88.9%, specificity 100%). Additionally, we observed mutations in PIK3CA (44%), HER2 (8%), and CDH1 (6%) among others. Amplifications were found in CCND1 (12%), followed by MYC (10%) and EGFR (2%) and deletions in CDKN2A (10%), MAP2K4 and PIK3R1 (2% each). We here show that targeted NGS data can be used to interrogate the HER2 status with high specificity and high concordance with gold standard methods. Moreover, this approach identifies additional genetic events that may be clinically exploitable. This article is protected by copyright. All rights reserved.

http://ift.tt/2eDMkJV

Neutrophils from chronic lymphocytic leukemia patients exhibit an increased capacity to release extracellular traps (NETs)

Abstract

Chronic lymphocytic leukemia (CLL) is characterized by immune defects that contribute to a high rate of infections and autoimmune cytopenias. Neutrophils are the first line of innate immunity and respond to pathogens through multiple mechanisms, including the release of neutrophil extracellular traps (NETs). These web-like structures composed of DNA, histones, and granular proteins are also produced under sterile conditions and play important roles in thrombosis and autoimmune disorders. Here we show that neutrophils from CLL patients are more prone to release NETs compared to those from age-matched healthy donors (HD). Increased generation of NETs was not due to higher levels of elastase, myeloperoxidase, or reactive oxygen species production. Instead, we found that plasma from CLL patients was able to prime neutrophils from HD to generate higher amounts of NETs upon activation. Plasmatic IL-8 was involved in the priming effect since its depletion reduced plasma capacity to enhance NETs release. Finally, we found that culture with NETs delayed spontaneous apoptosis and increased the expression of activation markers on leukemic B cells. Our study provides new insights into the immune dysregulation in CLL and suggests that the chronic inflammatory environment typical of CLL probably underlies this inappropriate neutrophil priming.

http://ift.tt/2dTWF0y

A panel of four genes accurately differentiates benign from malignant thyroid nodules

Clinicians are confronted with an increasing number of patients with thyroid nodules. Reliable preoperative diagnosis of thyroid nodules remains a challenge because of inconclusive cytological examination of f...

from Cancer via ola Kala on Inoreader http://ift.tt/2dPc6fe
via IFTTT

Tripartite motif containing 62 is a novel prognostic marker and suppresses tumor metastasis via c-Jun/Slug signaling-mediated epithelial-mesenchymal transition in cervical cancer

TRIM62 (tripartite motif containing 62) has been found to act as a tumor suppressor of several cancers. However, its precise biological role and related mechanism remain unknown in cervical cancer (CC).

from Cancer via ola Kala on Inoreader http://ift.tt/2ej9JgG
via IFTTT

Targeted Next Generation Sequencing Enables Reliable Detection of HER2 (ERBB2) Status in Breast Cancer and Provides Ancillary Information of Clinical Relevance

Abstract

HER2-positive breast cancers are a heterogeneous group of tumors, which share amplification and overexpression of HER2. In routine diagnostics, the HER2 (ERBB2) status is currently assessed by immunohistochemistry (IHC) and in-situ hybridization (ISH). Data on targeted next-generation sequencing (NGS) approaches that could be used to determine the HER2 status are sparse. Employing two breast cancer-related gene panels, we performed targeted NGS of 41 FFPE breast cancers for which full pathological work-up including ISH and IHC results were available. Selected cases were analyzed by qPCR. Of the 41 cases, the HER2 status of the 4 HER2-positive and 6 HER2-negative tumors was independently detected by our NGS approach achieving a concordance rate of 100%. The remaining 31 cases were equivocal HER2 cases by IHC of which 5 showed amplification of HER2 by ISH. Our NGS approach classified all non-amplified cases correctly as HER2-negative and corroborated all but one of the 5 cases with amplified HER2 as detected by ISH. For the overall cohort, concordance between the gold standard and NGS was 97.6% (sensitivity 88.9%, specificity 100%). Additionally, we observed mutations in PIK3CA (44%), HER2 (8%), and CDH1 (6%) among others. Amplifications were found in CCND1 (12%), followed by MYC (10%) and EGFR (2%) and deletions in CDKN2A (10%), MAP2K4 and PIK3R1 (2% each). We here show that targeted NGS data can be used to interrogate the HER2 status with high specificity and high concordance with gold standard methods. Moreover, this approach identifies additional genetic events that may be clinically exploitable. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2eDMkJV
via IFTTT

Neutrophils from chronic lymphocytic leukemia patients exhibit an increased capacity to release extracellular traps (NETs)

Abstract

Chronic lymphocytic leukemia (CLL) is characterized by immune defects that contribute to a high rate of infections and autoimmune cytopenias. Neutrophils are the first line of innate immunity and respond to pathogens through multiple mechanisms, including the release of neutrophil extracellular traps (NETs). These web-like structures composed of DNA, histones, and granular proteins are also produced under sterile conditions and play important roles in thrombosis and autoimmune disorders. Here we show that neutrophils from CLL patients are more prone to release NETs compared to those from age-matched healthy donors (HD). Increased generation of NETs was not due to higher levels of elastase, myeloperoxidase, or reactive oxygen species production. Instead, we found that plasma from CLL patients was able to prime neutrophils from HD to generate higher amounts of NETs upon activation. Plasmatic IL-8 was involved in the priming effect since its depletion reduced plasma capacity to enhance NETs release. Finally, we found that culture with NETs delayed spontaneous apoptosis and increased the expression of activation markers on leukemic B cells. Our study provides new insights into the immune dysregulation in CLL and suggests that the chronic inflammatory environment typical of CLL probably underlies this inappropriate neutrophil priming.

from Cancer via ola Kala on Inoreader http://ift.tt/2dTWF0y
via IFTTT

Assessing Short-term Deterioration in Maintenance-naïve Patients with COPD Receiving Umeclidinium/Vilanterol and Tiotropium: A Pooled Analysis of Three Randomized Trials

Abstract

Introduction

Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy. The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.

Methods

This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747). Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis. The primary endpoint was trough forced expiratory volume in 1 s (FEV₁). St George's Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV₁, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.

Results

UMEC/VI improved trough FEV₁ versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102–189) and ITT: 95 ml (71–118); both P < 0.001]. Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO. UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51–0.85); ITT: 0.62 (0.54–0.71), both P ≤ 0.001]. Adverse events were similar across both populations and treatments.

Conclusions

Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.

Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).

Funding: This study was funded by GSK.

http://ift.tt/2eMYMEZ

Diagnostic revision of 206 adult gliomas (including 40 oligoastrocytomas) based on ATRX, IDH1/2 and 1p/19q status

Abstract

The diagnosis of 206 low and high grade adult gliomas, including 40 oligoastrocytomas, was revised based on the immunohistochemical reactivity for the ATRX protein, IDH1/2 mutation status and 1p/19q chromosomal status. All oligodendrogliomas kept the initial diagnosis. Astrocytomas did not change diagnosis in 30 of 36 cases (83.3 %); four of 36 (11.1 %) cases were reclassified as oligodendroglioma, one (2.8 %) as DNT and the other (2.8 %) as reactive gliosis. Oligoastrocytomas changed diagnosis in 35 of 40 (87.5 %) cases, being reclassified 22 of 40 (55 %) as astrocytoma, 11 of 40 (27.5 %) as oligodendroglioma and two of 40 (5 %) as reactive gliosis. Four (10 %) remained unclassifiable. In one case only (2.5 %), the diagnosis of oligoastrocytoma could not be excluded since tumor astrocytes and tumor oligodendrocytes coexisted in mixed tumor areas. In the GBM tumor subgroup, GBMO disappeared because they were not substantiated by molecular genetics. Pilocytic astrocytomas retained ATRX expression. Loss of nuclear ATRX protein expression was strongly associated to IDH1/2 mutations (p = 0.0001) and mutually exclusive with total 1p/19q co-deletion (p = 0.0001). In astrocytic tumors, loss of immunoreactivity for the ATRX protein was significantly associated to the ALT phenotype (p = 0.0003). The constitutive ATRX expression in microglia/macrophages may be misleading, especially in the identification of an oligodendroglial tumor infiltration. Of paramount importance in the recognition of oligodendroglial and astrocytic tumor cells were the double immunostainings for ATRX/GFAP, ATRX/IDH1^R132H, ATRX/Iba-1 and ATRX/CD68.

http://ift.tt/2eMU763

Assessing Short-term Deterioration in Maintenance-naïve Patients with COPD Receiving Umeclidinium/Vilanterol and Tiotropium: A Pooled Analysis of Three Randomized Trials

Abstract

Introduction

Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy. The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.

Methods

This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747). Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis. The primary endpoint was trough forced expiratory volume in 1 s (FEV₁). St George's Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV₁, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.

Results

UMEC/VI improved trough FEV₁ versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102–189) and ITT: 95 ml (71–118); both P < 0.001]. Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO. UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51–0.85); ITT: 0.62 (0.54–0.71), both P ≤ 0.001]. Adverse events were similar across both populations and treatments.

Conclusions

Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.

Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).

Funding: This study was funded by GSK.

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Diffuse 18F-fluorodeoxyglucose accumulation in the bone marrow of a patient with haemophagocytic lymphohistiocytosis due to Hodgkin lymphoma

Description

A 53-year-old man was referred to our hospital due to malaise with intermittent high fever. Thoracoabdominal CT scan revealed abdominal lymphadenopathy with splenomegaly. Hepatic disorder (aspartate transaminase 47 IU/L; alanine transaminase 53 IU/L), peripheral blood cytopaenia (red blood cell count 370x10⁴/μL; haemoglobin 11.0 g/dL; haematocrit 32.9%; platelet count 7.9x10⁴/μL), hypertriglyceridaemia (184 mg/dL), hyperferritinaemia (4111 ng/mL) and an increased serum soluble interleukin-2 receptor level (4450 U/mL) were observed. Bone marrow (BM) aspiration showed erythrocyte phagocytosis by macrophages (figure 1A). However, no atypical cells were detected. Additional BM trephine biopsy was not performed. Pathological examination of a laparoscopic lymph node biopsy revealed Reed-Sternberg cells (figure 1B), and atypical cells were positive for CD30 but not for CD3, CD20 or CD79a indicating nodular sclerosis Hodgkin lymphoma (HL). A diagnosis of lymphoma-associated haemophagocytic lymphohistiocytosis (LA-HLH) was established. ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) performed for the staging showed splenic and multiple abdominal lymph node...

http://ift.tt/2eZD8wl

Diagnostic revision of 206 adult gliomas (including 40 oligoastrocytomas) based on ATRX, IDH1/2 and 1p/19q status

Abstract

The diagnosis of 206 low and high grade adult gliomas, including 40 oligoastrocytomas, was revised based on the immunohistochemical reactivity for the ATRX protein, IDH1/2 mutation status and 1p/19q chromosomal status. All oligodendrogliomas kept the initial diagnosis. Astrocytomas did not change diagnosis in 30 of 36 cases (83.3 %); four of 36 (11.1 %) cases were reclassified as oligodendroglioma, one (2.8 %) as DNT and the other (2.8 %) as reactive gliosis. Oligoastrocytomas changed diagnosis in 35 of 40 (87.5 %) cases, being reclassified 22 of 40 (55 %) as astrocytoma, 11 of 40 (27.5 %) as oligodendroglioma and two of 40 (5 %) as reactive gliosis. Four (10 %) remained unclassifiable. In one case only (2.5 %), the diagnosis of oligoastrocytoma could not be excluded since tumor astrocytes and tumor oligodendrocytes coexisted in mixed tumor areas. In the GBM tumor subgroup, GBMO disappeared because they were not substantiated by molecular genetics. Pilocytic astrocytomas retained ATRX expression. Loss of nuclear ATRX protein expression was strongly associated to IDH1/2 mutations (p = 0.0001) and mutually exclusive with total 1p/19q co-deletion (p = 0.0001). In astrocytic tumors, loss of immunoreactivity for the ATRX protein was significantly associated to the ALT phenotype (p = 0.0003). The constitutive ATRX expression in microglia/macrophages may be misleading, especially in the identification of an oligodendroglial tumor infiltration. Of paramount importance in the recognition of oligodendroglial and astrocytic tumor cells were the double immunostainings for ATRX/GFAP, ATRX/IDH1^R132H, ATRX/Iba-1 and ATRX/CD68.

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Non-traumatic trans-diaphragmatic intercostal hernia and cor pulmonale in a patient with poorly controlled obstructive sleep apnoea

Trans-diaphragmatic intercostal hernia is a rare entity. Patient with multiple medical comorbidities, including obstructive sleep apnoea, presents with shortness of breath, leg oedema and a bulging swelling through the right chest wall. CT shows partial herniation of the right lung and liver through intercostal space and an echocardiogram reveals right heart failure. He was treated initially with continuous positive airway pressure with poor response and subsequently treated with adaptive servo ventilation with much better symptomatic relief and treatment tolerance.

http://ift.tt/2e4LZiV

Pulmonary air leak syndrome associated with traumatic nasopharyngeal suctioning

We describe a healthy 7-month-old female infant who developed spontaneous pneumomediastinum (PM) and subcutaneous emphysema after traumatic nasopharyngeal suctioning (NPS) while hospitalised for respiratory syncytial virus bronchiolitis. To the best of our knowledge, this is the first reported case of pulmonary air leak syndrome associated with traumatic NPS in a healthy infant affected by bronchiolitis. Although NPS is currently the mainstay of treatment in patients admitted with bronchiolitis in the USA, currently there are minimal data regarding the safety and effectiveness of the procedure in patients with bronchiolitis. Physicians should consider the possibility of pulmonary air leak as a complication of NPS and have high suspicion in a decompensating infant after suctioning who is afflicted with bronchiolitis.

http://ift.tt/2eZplGr

A unique presentation of a complex haemorrhagic adrenal pseudocyst

A man aged 33 years presented with a 3-day history of left-sided testicular discomfort. Clinical examination revealed a large left-sided varicocele. He was referred for a testicular ultrasound, which demonstrated a moderate left-sided varicocele and an associated large suprarenal mass. An urgent (CT) scan was arranged which confirmed this, with associated compression of adjacent structures, including the left kidney and left renal vessels. The patient was admitted 1 week following the CT scan with features of sepsis. An inpatient adrenal MRI scan suggested the presence of a large left-sided haemorrhagic adrenal cyst. This was removed surgically through a left subcostal incision. Histology confirmed there was no malignancy. The patient was discharged and a follow-up CT scan at 6 months showed complete resolution of the cyst with no further testicular discomfort. This is the first known case of an adrenal cyst presenting with a varicocele.

http://ift.tt/2e4KhxX

Example of the drug interaction between ciclosporin and orlistat, resulting in relapse of Evan's syndrome

A man aged 35 years with a history of Evan's syndrome presented to the clinic with jaundice and shortness of breath, with further testing indicating a relapse of his previously well-controlled condition, for which he was taking ciclosporin. This followed shortly after he had started taking orlistat to prevent weight gain from a course of steroids, and once the orlistat was stopped, his platelets began to rise. The patient required 4 months of steroid treatment before his platelet levels finally stabilised and he could be put back on his regular medicine regime.

http://ift.tt/2eZpMjW

True brachial artery aneurysm in a child aged 2 years

Congenital brachial artery true aneurysms are exceedingly rare. Most are pseudoaneurysms secondary to trauma or infection. We report a boy aged 2 years who presented with painless, pulsatile swelling on the medial aspect of the right arm, 4 cm above the elbow joint that had been present since birth. Spiral CT angiography showed a fusiform aneurysm of the distal right brachial artery with a peripheral crescent-shaped thrombus. Distal arteries were normally opacified. There was no evidence of abnormal dilation or stenosis in any other artery. The aneurysm was surgically resected, with vascularisation re-established using a reversed great saphenous vein graft. His postoperative course was uneventful. Early surgery should be performed for moderately sized to large aneurysms that recently increased in size, exhibited luminal thrombus formation or caused neurovascular distal limb compromise. Early surgery could prevent complications such as a ruptured aneurysm, thromboembolism or limb ischaemia or loss.

http://ift.tt/2e4Hepu

Dementia, epilepsy and polyneuropathy in a mercury-exposed patient: investigation, identification of an obscure source and treatment

We present a patient aged 54 years with early onset of dementia, epilepsy and peripheral polyneuropathy. A mercury intoxication was diagnosed in 2010, chelation therapy with 2,3-dimercaptopropane-1-sulfonate had failed. A source of exposure could not be identified. MRI showed unspecific hyperintense brain lesions in 2015. She was referred for diagnosis and treatment. Neuropsychological testing indicated severe memory loss and nerve conduction speed measurements showed chronic neurogenically changed potentials. Mercury levels in blood and urine and neuron-specific enolase (NSE) were elevated. A detailed patient history revealed a daily application of mercury-containing skin lightening creams for 6 years. Treatment with 2,3-dimercaptosuccinic acid (DMSA) was started, blood mercury levels were falling during treatment. She was discharged with DMSA prescriptions. A renewed MRI revealed unchanged brain lesions. Blood and urine mercury levels and NSE were falling. Memory function had improved qualitatively and quantitatively.

http://ift.tt/2eZoKo8

Unilateral fusion of the scaphoid and the trapezium

Fusion of the carpal bones is a rare anatomical abnormality, caused by a defect in the separation and cavitation during embryonic development. It has a prevalence of about 0.1% and most of the time, patients do not present with symptoms. Symptoms are usually caused by wear and tear of the ligaments attached to the fused carpal fragments. We present a case in which a woman aged 36 years experiences pain caused by a lunato-triquetral instability which in turn is caused by a unilateral complete fusion of the scaphoid and the trapezium. A unilateral complete fusion of the scaphoid and trapezium has not been reported before.

http://ift.tt/2e4FLzx

Sequential adjuvant chemoradiotherapy-induced diffuse alveolar haemorrhage in a patient with breast cancer successfully treated with corticosteroid plus recombinant human soluble thrombomodulin

The effective treatment for corticosteroid (CS)-refractory sequential chemoradiotherapy (CRT)-induced lung injury has not been established. We report a case of sequential CRT-induced diffuse alveolar haemorrhage (DAH) successfully treated with CS therapy plus recombinant human soluble thrombomodulin (rhTM). A 69-year-old woman was treated with sequential adjuvant CRT for early-stage breast cancer. After sequential CRT, she suffered from progressive dyspnoea. Chest CT scan showed consolidations in the irradiation field and diffuse ground-glass attenuations in the non-irradiation regions. We suspected sequential CRT-induced DAH because of increased haemosiderin-laden macrophages in bronchoalveolar lavage fluid. Her clinical conditions did not improve with high-dose CS therapy. Therefore, rhTM was added, and her disease and serum high-mobility group box-1 levels improved rapidly. Therefore, rhTM plus CS might be a safe and effective treatment for sequential CRT-induced lung injury, although further study is necessary to validate these findings.

http://ift.tt/2eZpXLZ

Unilateral macrostomia in the newborn: a rare congenital anomaly of the oral commissure

Macrostomia is a rare medical condition, defined as an enlargement of the mouth at the oral commissure. The incidence varies between 1 in 60 000 to 1 in 300 000 live births. Macrostomia is a form of a facial cleft. Macrostomia can present as a unilateral or bilateral anomaly with a partial or complete cleft. Associated anomalies of the surrounding bone, muscle and soft tissue can also be present with or without the presence of a syndrome. Macrostomia results in aesthetic disharmony and also in functional problems. In both cases surgery is the treatment of choice. In cases of macrostomia, additional investigations should be performed to rule out accompanying cardiac and renal anomalies and associated syndromes. A multidisciplinary approach and good collaboration between healthcare providers is essential for optimal care of these patients.

http://ift.tt/2e4KxNh

Takotsubo cardiomyopathy with use of salbutamol nebulisation and aminophylline infusion in a patient with acute asthma exacerbation

Takotsubo cardiomyopathy, apical ballooning syndrome or stress-induced cardiomyopathy is characterised by transient left ventricular dysfunction, mimicking myocardial infarction in the absence of obstructive coronary artery disease or acute plaque rupture on coronary angiography. The exact mechanism of myocardial dysfunction in Takotsubo cardiomyopathy is unknown; however, due to its association with physical and emotional stress, it is postulated that catecholamines play a central role in its pathogenesis. We present a case of a patient who was admitted with acute asthma exacerbation and was treated with β-2 agonist nebulisation and intravenous aminophylline. During her hospital stay she developed Takotsubo cardiomyopathy.

http://ift.tt/2eZqI7V

Transcervical approach to the removal of a deep-seated giant submandibular calculus and the submandibular gland

Sialolithiasis is among the most common disease affecting the major salivary glands whereby the submandibular gland or its duct is affected in the majority of cases. We report a case of the surgical removal of a giant sialolith along with the submandibular gland using the transcervical approach and its clinical outcome.

http://ift.tt/2e4H4yl

Adult necrotising enterocolitis--pig-bel disease: a Pacific disease in London

Adult necrotising enterocolitis secondary Clostridium perfringens type C—pig-bel disease—is rarely seen outside of Pacific populations, with the highest incidence being in Papau New Guinea. We present the first reported case of pig-bel disease in a previously well patient without diabetes following food poisoning since 1996. In this case, the enterotoxin-induced disease necessitated emergency laparotomy and bowel resection following the failure of medical treatment and worsening septic shock. We hypothesise that obstruction secondary to a sigmoid diverticular stricture complicated by infection-related oedema led to colonic stasis and rapid progression of disease and bowel loss. Following bowel resection, several parenteral antibiotic agents and prolonged intensive care, this patient survived this severe infective process and was discharged home.

http://ift.tt/2e4KeSN

Unusual case of hyperpigmentation secondary to irinotecan

Description

A 62-year-old Caucasian woman was referred to dermatology by oral medicine regarding intra and extraoral hyperpigmentation which had developed gradually over the past year. Her only significant medical history was stage 4 colorectal carcinoma diagnosed 8 years previously. It was initially surgically managed with adjuvant chemo and radiotherapy, however hyperpigmentation had since recurred and was now being treated with irinotecan (topoisomerase 1 inhibitor) and cetuximab (an epidermal growth factor receptor inhibitor) for the past 1 year. She had no family history of oral or cutaneous pigmentation disorders.

On examination she was normotensive with no postural drop. Cutaneous examination revealed mild hyperpigmentation of the dorsum of her hands and fingernails bilaterally (figure 1). There were also pigmented macules on her forehead, but no pigmentation of the palmar creases. Intraoral examination showed multiple brown pigmented macules on the dorsum of the tongue and hard palate (figures 2

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Metastatic lung cancer presenting as gastric outlet obstruction: diagnosis and management with laparoscopic gastric bypass: a novel technique

Metastatic tumours of the duodenum are relatively rare. Here we present a case of a 64-year-old Caucasian male who presented with a 3-week history of postprandial vomiting, weight-loss and epigastric discomfort. Imaging and biopsy revealed that the patient had a primary lung tumour in his right upper lung lobe as well as a duodenal metastasis leading to gastric outlet obstruction (GOO). The patient was stabilised and subsequently underwent a laparoscopic gastric bypass to palliate the gastric outlet obstruction. Appropriate management of metastatic GOO involves accurate diagnosis and treatment with either enteral stenting or laparoscopic gastric bypass. It is suggested that the decision whether to stent or surgically bypass the obstruction can be based on the patient's life expectancy and performance status. Regardless of the approach, palliating metastatic GOO can improve the quality of life of carefully chosen symptomatic patients. We describe a technique of laparoscopic palliative gastric bypass which has not been reported previously in the literature.

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Spontaneous mediastinal haematoma

Description

A healthy man aged 32 years, with no notable family or medical history and no history of trauma, reported of sudden severe back pain on stretching and holding his breath while working at his desk. Apart from tachypnoea, his vital signs and physical examination were normal. A chest radiograph showed mediastinal widening (figure 1). Results of laboratory tests, including coagulation tests—prothrombin time, activated partial thromboplastin time and erythrocyte sedimentation rate—were all within normal limits. Contrast-enhanced CT revealed a mediastinal haematoma surrounding the descending aorta, with no aortic dissection or extravasation (figure 2). Contrast oesophagography detected no oesophageal rupture. Intercostal artery catheter angiography demonstrated no extravasation or aneurysm. Given his haemodynamic stability, conservative management was initiated. On day 2, repeat CT showed some haematoma absorption. One month postadmission, the haematoma had resolved.

Figure 1

Chest X-ray showed widening of the right paraspinal line (arrowhead)...

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Pseudohyperglycaemia in a comatose patient after picking cherries

We report a case of pseudohyperglycaemia on a capillary blood glucose measurement taken from fingers stained with sugar (fructose). A 76-year-old patient with type 1 diabetes received emergency attention at home because of a coma. The first capillary blood glucose measurement collected from a finger revealed a concentration higher than the reference limits, misleading the clinician. After starting symptomatic treatment, a second blood glucose measurement was taken. This measurement, taken at the earlobe, revealed profound hypoglycaemia (0.89 mmol/L), which prompted the administration of appropriate treatment. The elevated initial capillary blood glucose measurement was linked to the presence of fructose on the fingers of the patient from picking cherries just before the patient fainted. After intravenous administration of glucose, the patient regained normal consciousness and had no sequelae despite the severity of the hypoglycaemia and delayed diagnosis. Pseudohyperglycaemia is rare, and delayed diagnosis frequently results in severe sequelae or death.

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Central odontogenic fibromyxoma of mandible: an aggressive odontogenic pathology

Myxoma of the jaws which was first described by Thoma and Goldman in 1947 is a rare neoplasm and its rate of prevalence and incidence is not available. Myxoma term, according to 1992 WHO classification, is used along with odontogenic myxoma (OM) and myxofibroma. There are two forms of myxomas or fibromyxomas that are recognised in head and neck region: one is derived from the facial skeleton and the other is derived from the soft tissue. Most of the OM are located intraosseously, but peripheral ones are also recognised. OM behaves differently from myxomatous tumours of long bones, which recur more often and may transform into malignancy. A majority of these lesions occur between 2nd and 4th decade. In the pathogenesis of OM, dental papilla, dental follicle and periodontal ligament tissues have been implicated as possible 'germ centres'. This case describes an uncommon finding of central odontogenic fibromyxoma, throwing light on its epidemiology, clinical, histopathology, molecular and treatment aspects.

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Subcellular localisation of pMEK has a different prognosis in locally advanced head and neck cancer treated with concomitant radiochemotherapy

Abstract

Background

MEK1 (MAP2K1) and MEK2 (MAP2K2) are closely related dual-specificity protein kinases which function by phosphorylating both serine/threonine and tyrosine residues of their substrates ERK1 and ERK2, controlling fundamental cellular processes that include cell growth and proliferation. To investigate the prognostic significance of pMEK expression in the nucleus and cytoplasm among patients with locally advanced head and neck cancer treated with concurrent radiochemotherapy.

Methods

Immunohistochemistry was performed on the retrieved archival tissue of 96 patients to detect pMEK, p53 and Ki-67.

Results

Sixty-six percent of patients were positive for pMEK expression in the nucleus and 41 % in cytoplasm. On univariate analysis, high nuclear pMEK was predictive of worse 5y-DFS and 5y-OS, with a trend to significance (26 % vs. 41 %, p = 0.09; 36 % vs. 47 %, p = 0.07). High cytoplasmic pMEK was predictive of better 5-y OS and 5-y DFS outcomes (61 % vs. 27 %, p = 0.01; 46 % vs. 22 %, p = 0.02). On multivariate analysis, low cytoplasmic pMEK and high nuclear pMEK predicted worse DFS and OS (p = 0.01; p = 0.04 and p = 0.02; p = 0.02 respectively).

Conclusions

Subcellular localisation of pMEK has different prognosis in locally advanced head and neck cancer treated with radiochemotherapy.

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Invasive myoepithelial carcinoma ex pleomorphic adenoma of the major salivary gland: two case reports

Abstract

Background

Myoepithelial carcinoma (MEC) is a rare salivary gland tumor. Its long-term prognosis remains unknown because of the paucity of reported cases with long-term follow-up. Although some case series exist, the clinical features of MEC vary considerably depending on the site of origin. Therefore, accumulation of these rare cases is important.

Case presentation

Case 1: An 89-year-old man presented with a 10-year history of a mass originating from the right parotid gland and involving the neck. The mass grew rapidly for 3 months, reaching approximately 8 cm. There was no facial paralysis. MEC ex pleomorphic adenoma (PA) was suspected. Superficial parotid gland resection was performed in 2013; the tumor grade was pT3N0M0, and the resection margins were free of carcinoma. Because of several high-risk factors for metastasis (i.e., invasive carcinoma ex PA, high MIB1 index, and mutant p53 protein positivity), radiotherapy and chemotherapy were recommended as adjuvant therapy. Although the patient refused adjuvant therapy, he was recurrence-free at 36 months after surgery.

Case 2: A 54-year-old woman presented with a >10-year history of a right submandibular mass, which grew rapidly for 1 year, reaching approximately 6 cm. Preoperative diagnosis was PA of the right submandibular gland. Submandibular gland resection was performed in 2013. Pathological analysis revealed invasive MEC ex PA, pT3N0M0; in addition, the carcinoma portion had an extra capsule and had invaded the platysma muscle close to the margin. An MIB1 index of 40 % and mutant p53 protein positivity indicated a high risk for metastasis. Additional resection and right neck dissection revealed no residual carcinoma. The patient refused adjuvant chemotherapy. One year after surgery, metastasis to the right pulmonary hilar node and both lungs were detected. Chemotherapy prevented recurrent growth of the lesion and extended survival. The patient was alive with cancer 30 months after the first surgery.

Conclusions

High expression of the Ki67 labeling index might reflect prognosis of these cases. Chemotherapy for distant metastasis was effective, as expected. Further accumulation of cases and long follow-up data are needed to elucidate the pathophysiology and prognosis of MEC ex PA.

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Epidemiological study of HER-2 mutations among EGFR wild-type lung adenocarcinoma patients in China

Abstract

Background

Human epidermal growth factor receptor (HER)-2 is a driver gene in non-small cell lung cancer (NSCLC). The present study evaluated the mutation rate of HER-2 within the wild-type epidermal growth factor receptor (EGFR) lung adenocarcinoma population in China.

Methods

Formalin-fixed, paraffin-embedded samples from 456 patients with wild-type EGFR lung adenocarcinoma were analyzed for HER-2 mutations by amplification-refractory mutation system (ARMS), and HER-2 protein expression was evaluated by immunohistochemistry. All samples positive for HER-2 mutation underwent direct sequencing for further verification.

Results

HER-2 mutation was detected in 22/456 cases (4.8 %); the rate was 6.7 % among 331 triple-negative samples (i.e., wild-type EGFR, anaplastic lymphoma kinase, and ROS proto-oncogene 1). Direct sequencing confirmed that the results were consistent with those obtained by ARMS analysis in 19 cases. The positive rate was 15.4 % by immunohistochemical analysis of HER-2 expression; this was not correlated with mutation rate. HER-2 mutation and positivity were not correlated with gender, age, smoking status, disease stage, or histological subtype. The 22 cases of HER-2 mutations occurred only in acinar (36.4 %), papillary (36.4 %), minimally invasive (13.6 %), solid (9.2 %), and invasive mucinous (4.5 %) subtypes. Disease-free and overall survival were not associated with HER-2 mutation or HER-2 protein overexpression.

Conclusion

The HER-2 mutation rate was 4.8 % among EGFR wild-type lung adenocarcinoma patients in China, and 6.7 % among driver genes, triple-negative lung adenocarcinoma. The incidence of HER-2 mutation varied among different lung adenocarcinoma subtypes, occurring mainly in acinar and papillary predominant subtypes. 15.4 % of EGFR wild-type lung adenocarcinoma patients showed HER-2 protein overexpression, but this was not correlated to HER-2 mutation. Existing follow-up data did not show a correlation between HER-2 mutation with DFS or OS.

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The American Society of Peritoneal Surface Malignancies Multi-Institution evaluation of 1,051 advanced ovarian cancer patients undergoing cytoreductive surgery and HIPEC: An introduction of the peritoneal surface disease severity score

Background

Standard treatment for ovarian epithelial cancer (OEC) consists of cytoreductive surgery (CRS) and a platinum–taxane chemotherapy combination. There is increasing interest in evaluating hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with stage IIIC/IV disease. The peritoneal surface disease severity score (PSDSS) was introduced as a basis to improve patient selection for this therapy in OEC.

Methods

The charts of 1,051 patients with advanced OEC who underwent CRS/HIPEC were retrospectively evaluated using the following preoperatively obtained criteria: symptoms, peritoneal dissemination, and tumor histology. Overall survival was analyzed according to PSDSS as well as the timings and agents used during CRS/HIPEC.

Results

Median survival for all 1,051 patients was 73.4 months. PSDSS information was available for 553 patients. Survival correlated negatively with PSDSS (P < 0.001). Furthermore, combining PSDSS scores into I/II and III/IV described two distinct patient populations with vastly different outcomes, 100 versus 55 months, respectively (P < 0.001). Multivariate analysis failed to describe any differences between timings of HIPEC or chemotherapy agents used.

Conclusion

PSDSS was capable of identifying a better surviving patient population in advanced-stage OEC. While randomized trials to evaluate the benefit of HIPEC are needed, the PSDSS may be a useful tool for selecting and stratifying OEC patients in clinical trials. J. Surg. Oncol. 2016;114:779–784. © 2016 2016 Wiley Periodicals, Inc.

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The prognostic implications of primary colorectal tumor location on recurrence and overall survival in patients undergoing resection for colorectal liver metastasis

Background and Objectives

The prognostic impact of primary colorectal cancer (CRC) location following resection of colorectal liver metastasis (CRLM) remains largely unknown. We sought to characterize the prognostic implications of primary tumor location among patients who underwent curative-intent hepatectomy for CRLM.

Methods

Tumors of the cecum, ascending, and transverse colon were defined as right-sided; tumors of the sigmoid flexure, descending, and sigmoid colon were defined as left-sided. Clinicopathologic and long-term survival data were collected and assessed using univariable and multivariable analyses.

Results

About 475 patients who underwent CRLM resection at a single institution were included; most patients had left-sided tumors (n = 284). Median and 5-year RFS was 20.2 months and 28.0%, respectively. Patients who had a left-sided primary tumor had a shorter RFS compared with patients who had a right-sided tumor (P = 0.01). Although site of and time to recurrence did not differ between the two groups (P > 0.05), patients with right-sided primary tumors were more likely to recur with advanced disease (i.e., ≥4 recurrent lesions) (P < 0.01). In turn, patients with right-sided tumors had both worse OS (P = 0.03) and worse survival after recurrence (P = 0.01).

Conclusion

While patients with right-sided tumors experienced longer RFS, when these patients did recur following CRLM resection, disease extent was more advanced. In turn, OS following recurrence was shorter among patients with right-sided CRC. J. Surg. Oncol. 2016;114:803–809. © 2016 2016 Wiley Periodicals, Inc.

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The American Society of Peritoneal Surface Malignancies Multi-Institution evaluation of 1,051 advanced ovarian cancer patients undergoing cytoreductive surgery and HIPEC: An introduction of the peritoneal surface disease severity score

Background

Standard treatment for ovarian epithelial cancer (OEC) consists of cytoreductive surgery (CRS) and a platinum–taxane chemotherapy combination. There is increasing interest in evaluating hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with stage IIIC/IV disease. The peritoneal surface disease severity score (PSDSS) was introduced as a basis to improve patient selection for this therapy in OEC.

Methods

The charts of 1,051 patients with advanced OEC who underwent CRS/HIPEC were retrospectively evaluated using the following preoperatively obtained criteria: symptoms, peritoneal dissemination, and tumor histology. Overall survival was analyzed according to PSDSS as well as the timings and agents used during CRS/HIPEC.

Results

Median survival for all 1,051 patients was 73.4 months. PSDSS information was available for 553 patients. Survival correlated negatively with PSDSS (P < 0.001). Furthermore, combining PSDSS scores into I/II and III/IV described two distinct patient populations with vastly different outcomes, 100 versus 55 months, respectively (P < 0.001). Multivariate analysis failed to describe any differences between timings of HIPEC or chemotherapy agents used.

Conclusion

PSDSS was capable of identifying a better surviving patient population in advanced-stage OEC. While randomized trials to evaluate the benefit of HIPEC are needed, the PSDSS may be a useful tool for selecting and stratifying OEC patients in clinical trials. J. Surg. Oncol. 2016;114:779–784. © 2016 2016 Wiley Periodicals, Inc.

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The prognostic implications of primary colorectal tumor location on recurrence and overall survival in patients undergoing resection for colorectal liver metastasis

Background and Objectives

The prognostic impact of primary colorectal cancer (CRC) location following resection of colorectal liver metastasis (CRLM) remains largely unknown. We sought to characterize the prognostic implications of primary tumor location among patients who underwent curative-intent hepatectomy for CRLM.

Methods

Tumors of the cecum, ascending, and transverse colon were defined as right-sided; tumors of the sigmoid flexure, descending, and sigmoid colon were defined as left-sided. Clinicopathologic and long-term survival data were collected and assessed using univariable and multivariable analyses.

Results

About 475 patients who underwent CRLM resection at a single institution were included; most patients had left-sided tumors (n = 284). Median and 5-year RFS was 20.2 months and 28.0%, respectively. Patients who had a left-sided primary tumor had a shorter RFS compared with patients who had a right-sided tumor (P = 0.01). Although site of and time to recurrence did not differ between the two groups (P > 0.05), patients with right-sided primary tumors were more likely to recur with advanced disease (i.e., ≥4 recurrent lesions) (P < 0.01). In turn, patients with right-sided tumors had both worse OS (P = 0.03) and worse survival after recurrence (P = 0.01).

Conclusion

While patients with right-sided tumors experienced longer RFS, when these patients did recur following CRLM resection, disease extent was more advanced. In turn, OS following recurrence was shorter among patients with right-sided CRC. J. Surg. Oncol. 2016;114:803–809. © 2016 2016 Wiley Periodicals, Inc.

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Subcellular localisation of pMEK has a different prognosis in locally advanced head and neck cancer treated with concomitant radiochemotherapy

Abstract

Background

MEK1 (MAP2K1) and MEK2 (MAP2K2) are closely related dual-specificity protein kinases which function by phosphorylating both serine/threonine and tyrosine residues of their substrates ERK1 and ERK2, controlling fundamental cellular processes that include cell growth and proliferation. To investigate the prognostic significance of pMEK expression in the nucleus and cytoplasm among patients with locally advanced head and neck cancer treated with concurrent radiochemotherapy.

Methods

Immunohistochemistry was performed on the retrieved archival tissue of 96 patients to detect pMEK, p53 and Ki-67.

Results

Sixty-six percent of patients were positive for pMEK expression in the nucleus and 41 % in cytoplasm. On univariate analysis, high nuclear pMEK was predictive of worse 5y-DFS and 5y-OS, with a trend to significance (26 % vs. 41 %, p = 0.09; 36 % vs. 47 %, p = 0.07). High cytoplasmic pMEK was predictive of better 5-y OS and 5-y DFS outcomes (61 % vs. 27 %, p = 0.01; 46 % vs. 22 %, p = 0.02). On multivariate analysis, low cytoplasmic pMEK and high nuclear pMEK predicted worse DFS and OS (p = 0.01; p = 0.04 and p = 0.02; p = 0.02 respectively).

Conclusions

Subcellular localisation of pMEK has different prognosis in locally advanced head and neck cancer treated with radiochemotherapy.

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Invasive myoepithelial carcinoma ex pleomorphic adenoma of the major salivary gland: two case reports

Abstract

Background

Myoepithelial carcinoma (MEC) is a rare salivary gland tumor. Its long-term prognosis remains unknown because of the paucity of reported cases with long-term follow-up. Although some case series exist, the clinical features of MEC vary considerably depending on the site of origin. Therefore, accumulation of these rare cases is important.

Case presentation

Case 1: An 89-year-old man presented with a 10-year history of a mass originating from the right parotid gland and involving the neck. The mass grew rapidly for 3 months, reaching approximately 8 cm. There was no facial paralysis. MEC ex pleomorphic adenoma (PA) was suspected. Superficial parotid gland resection was performed in 2013; the tumor grade was pT3N0M0, and the resection margins were free of carcinoma. Because of several high-risk factors for metastasis (i.e., invasive carcinoma ex PA, high MIB1 index, and mutant p53 protein positivity), radiotherapy and chemotherapy were recommended as adjuvant therapy. Although the patient refused adjuvant therapy, he was recurrence-free at 36 months after surgery.

Case 2: A 54-year-old woman presented with a >10-year history of a right submandibular mass, which grew rapidly for 1 year, reaching approximately 6 cm. Preoperative diagnosis was PA of the right submandibular gland. Submandibular gland resection was performed in 2013. Pathological analysis revealed invasive MEC ex PA, pT3N0M0; in addition, the carcinoma portion had an extra capsule and had invaded the platysma muscle close to the margin. An MIB1 index of 40 % and mutant p53 protein positivity indicated a high risk for metastasis. Additional resection and right neck dissection revealed no residual carcinoma. The patient refused adjuvant chemotherapy. One year after surgery, metastasis to the right pulmonary hilar node and both lungs were detected. Chemotherapy prevented recurrent growth of the lesion and extended survival. The patient was alive with cancer 30 months after the first surgery.

Conclusions

High expression of the Ki67 labeling index might reflect prognosis of these cases. Chemotherapy for distant metastasis was effective, as expected. Further accumulation of cases and long follow-up data are needed to elucidate the pathophysiology and prognosis of MEC ex PA.

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Epidemiological study of HER-2 mutations among EGFR wild-type lung adenocarcinoma patients in China

Abstract

Background

Human epidermal growth factor receptor (HER)-2 is a driver gene in non-small cell lung cancer (NSCLC). The present study evaluated the mutation rate of HER-2 within the wild-type epidermal growth factor receptor (EGFR) lung adenocarcinoma population in China.

Methods

Formalin-fixed, paraffin-embedded samples from 456 patients with wild-type EGFR lung adenocarcinoma were analyzed for HER-2 mutations by amplification-refractory mutation system (ARMS), and HER-2 protein expression was evaluated by immunohistochemistry. All samples positive for HER-2 mutation underwent direct sequencing for further verification.

Results

HER-2 mutation was detected in 22/456 cases (4.8 %); the rate was 6.7 % among 331 triple-negative samples (i.e., wild-type EGFR, anaplastic lymphoma kinase, and ROS proto-oncogene 1). Direct sequencing confirmed that the results were consistent with those obtained by ARMS analysis in 19 cases. The positive rate was 15.4 % by immunohistochemical analysis of HER-2 expression; this was not correlated with mutation rate. HER-2 mutation and positivity were not correlated with gender, age, smoking status, disease stage, or histological subtype. The 22 cases of HER-2 mutations occurred only in acinar (36.4 %), papillary (36.4 %), minimally invasive (13.6 %), solid (9.2 %), and invasive mucinous (4.5 %) subtypes. Disease-free and overall survival were not associated with HER-2 mutation or HER-2 protein overexpression.

Conclusion

The HER-2 mutation rate was 4.8 % among EGFR wild-type lung adenocarcinoma patients in China, and 6.7 % among driver genes, triple-negative lung adenocarcinoma. The incidence of HER-2 mutation varied among different lung adenocarcinoma subtypes, occurring mainly in acinar and papillary predominant subtypes. 15.4 % of EGFR wild-type lung adenocarcinoma patients showed HER-2 protein overexpression, but this was not correlated to HER-2 mutation. Existing follow-up data did not show a correlation between HER-2 mutation with DFS or OS.

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The American Society of Peritoneal Surface Malignancies Multi-Institution evaluation of 1,051 advanced ovarian cancer patients undergoing cytoreductive surgery and HIPEC: An introduction of the peritoneal surface disease severity score

Background

Standard treatment for ovarian epithelial cancer (OEC) consists of cytoreductive surgery (CRS) and a platinum–taxane chemotherapy combination. There is increasing interest in evaluating hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with stage IIIC/IV disease. The peritoneal surface disease severity score (PSDSS) was introduced as a basis to improve patient selection for this therapy in OEC.

Methods

The charts of 1,051 patients with advanced OEC who underwent CRS/HIPEC were retrospectively evaluated using the following preoperatively obtained criteria: symptoms, peritoneal dissemination, and tumor histology. Overall survival was analyzed according to PSDSS as well as the timings and agents used during CRS/HIPEC.

Results

Median survival for all 1,051 patients was 73.4 months. PSDSS information was available for 553 patients. Survival correlated negatively with PSDSS (P < 0.001). Furthermore, combining PSDSS scores into I/II and III/IV described two distinct patient populations with vastly different outcomes, 100 versus 55 months, respectively (P < 0.001). Multivariate analysis failed to describe any differences between timings of HIPEC or chemotherapy agents used.

Conclusion

PSDSS was capable of identifying a better surviving patient population in advanced-stage OEC. While randomized trials to evaluate the benefit of HIPEC are needed, the PSDSS may be a useful tool for selecting and stratifying OEC patients in clinical trials. J. Surg. Oncol. 2016;114:779–784. © 2016 2016 Wiley Periodicals, Inc.

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The prognostic implications of primary colorectal tumor location on recurrence and overall survival in patients undergoing resection for colorectal liver metastasis

Background and Objectives

The prognostic impact of primary colorectal cancer (CRC) location following resection of colorectal liver metastasis (CRLM) remains largely unknown. We sought to characterize the prognostic implications of primary tumor location among patients who underwent curative-intent hepatectomy for CRLM.

Methods

Tumors of the cecum, ascending, and transverse colon were defined as right-sided; tumors of the sigmoid flexure, descending, and sigmoid colon were defined as left-sided. Clinicopathologic and long-term survival data were collected and assessed using univariable and multivariable analyses.

Results

About 475 patients who underwent CRLM resection at a single institution were included; most patients had left-sided tumors (n = 284). Median and 5-year RFS was 20.2 months and 28.0%, respectively. Patients who had a left-sided primary tumor had a shorter RFS compared with patients who had a right-sided tumor (P = 0.01). Although site of and time to recurrence did not differ between the two groups (P > 0.05), patients with right-sided primary tumors were more likely to recur with advanced disease (i.e., ≥4 recurrent lesions) (P < 0.01). In turn, patients with right-sided tumors had both worse OS (P = 0.03) and worse survival after recurrence (P = 0.01).

Conclusion

While patients with right-sided tumors experienced longer RFS, when these patients did recur following CRLM resection, disease extent was more advanced. In turn, OS following recurrence was shorter among patients with right-sided CRC. J. Surg. Oncol. 2016;114:803–809. © 2016 2016 Wiley Periodicals, Inc.

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