Shiksha Kedia

The value of the pretreatment neutrophil lymphocyte ratio vs. platelet lymphocyte ratio in predicting the long-term survival in colorectal cancer

BACKGROUND The neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) have been well studied as inflammatory markers and predictors for outcomes in colorectal cancer patients. Our aim was to determine the predictive value of both above ratios in colorectal cancer patients. METHODS This is a longitudinal retrospective study of a prospectively maintained database, included 580 patients, who had a complete blood count recorded before treatment (surgery or chemotherapy). We excluded patients presented with obstruction, infection, active hematological disease or those receiving steroid. The primary outcome (4-year cancer-related mortality) was obtained from our cancer registry. RESULTS The 4-year cancer-related mortality rate in the 3rd tertile of NLR was 37% in comparison with 13% and 19% in lower tertiles, P value < 0.001. Similarly the 3rd tertile of PLR was 32% with 18% and 19% in lower tertiles, P value < 0.0005. In the multivariate survival analyses, elevated NLR was associated with higher mortality (a hazard ratio of 2.31(1.4-3.8) for the highest tertile and 5% increase in mortality for each unit increase in NLR, p < 0.001). Similarly, elevated NLR was a significant predictor for a worse disease-free survival. However, PLR was not significant predictor of mortality when adjusted for other confounding variables. CONCLUSION Elevated pretreatment NLR is an independent predictor of both worse overall and disease free survival in colorectal cancer, whereas PLR was not after adjusting for confounding variables.

Brain Metastasis in Patients With Non–Small-Cell Lung Cancer and Epidermal Growth Factor Receptor Mutations

TO THE EDITOR: Welsh et al report a 52.9% prevalence of epidermal growth factor receptor (EGFR) mutations in a small subset of patients who had non–small-cell lung cancer (NSCLC) with newly diagnosed brain metastasis and known EGFR status (n 17) who were enrolled onto a phase II trial of erlotinib and concurrent wholebrain radiation therapy. The prevalence is considerably higher than the expected 10% of the white population. Although the study by Welsh et al was not primarily designed to assess the incidence of EGFR mutation and confounders may be in play, this observation merits further exploration. Paez et al found EGFR mutations to be more frequent in women compared with men (20% v 9%), more frequent in adenocarcinomas compared with other NSCLCs (21% v 2%), and more frequent in East Asians compared with North Americans (26% v 2%). Not surprisingly, the prevalence of an EGFR mutation was highest in Japanese women with adenocarcinoma (57%). Pham et al have shown the incidence of EGFR mutations to be higher in never-smokers than former or current smokers (51% v 19% v 4%, respectively). The likelihood of an EGFR mutation seems to vary with the history of smoking pack-year numbers and smoke-free years. A study to assess the difference in the prevalence of EGFR mutations in patients with NSCLC with and without brain metastases requires a sufficiently large sample adjusted for sex, smoking status, ethnicity, and histology. In the study by Welsh et al, the EGFR mutation–positive group consisted predominantly of non-Asian patients (100%) with adenocarcinoma (100%) who were women (78%), and never-smokers (55.6%) or former smokers (33.3%). Although no differences between EGFR mutation–positive and EGFR mutation–negative groups in terms of histology, sex, and smoking status were observed, the small sample size was not adequately powered to detect the differences. In any case, the possibility of more frequent EGFR mutations in patients with NSCLC and brain metastasis is intriguing and has been suggested by previous studies (Table 1). Although these studies also included a greater preponderance of women never-smokers with adenocarcinoma in the EGFR mutation–positive groups, this is the patient population most likely to undergo screening for EGFR mutations. All patients in these studies had brain metastasis. There were no comparisons with control groups without brain metastasis to help determine whether patients with NSCLC and EGFR mutations are more likely to experience metastasis to the brain. Mutation of the EGFR gene seems to be an early event in the development of NSCLC, and heterogeneous distribution of an EGFR mutation between primary and metastatic lesions or between primary and recurrent cancer is extremely rare. Conversely, EGFR amplification occurs relatively late in the disease course and is more frequent in metastatic lesions, possibly contributing to the development of a metastatic phenotype. In one study, patients with NSCLC and EGFR amplification in the primary tumor developed brain metastases earlier than those without, and the metastatic tumor cells had a higher expression of phosphorylated forms of EGFR and human epidermal growth factor receptor 3 proteins compared with the primary site. Although the EGFR pathway seems to play an important role in the metastasis of NSCLC, whether EGFR mutations are more frequent in NSCLC with brain metastasis is not clear. Given the therapeutic implications of this finding, research that is specifically designed to answer this question is required. Data are emerging to indicate the usefulness of gefitinib and erlotinib in NSCLC with brain metastasis. Promising results of the study by Welsh et al provide grounds for continued exploration of the role of an EGFR tyrosine kinase inhibitor (TKI) alone or with radiation for these patients. The potential role of high-dose erlotinib for brain metastasis that is refractory to standard-dose erlotinib should also be assessed. Finally, although an EGFR mutation is the best predictor for response to an EGFR TKI, high EGFR gene copy numbers and high levels of EGFR protein expression also correlate, although to a lesser extent, with sensitivity to EGFR TKIs. In one instance, EGFR protein overexpression, EGFR gene high polysomy, and EGFR mutation correlated with three subsequent responses to EGFR TKIs. Given the association of brain metastasis with EGFR amplification and human epidermal growth factor receptor 3 overexpression, correlative studies to evaluate the potential role of EGFR overexpression and amplification as a predictive biomarker in NSCLC with brain metastasis could prove valuable.

Antiphospholipid Syndrome: Multiple Manifestations in a Single Patient—A High Suspicion Is Still Needed

Antiphospholipid Syndrome (APS) is an autoimmune disorder with clinical and laboratory features of vascular thrombosis, pregnancy loss, and persistent antiphospholipid antibodies (aPLs). The pathophysiology is thought to involve the activation of endothelial cells, monocytes, platelets, and complement by aPLs. Disease can range from asymptomatic to rapidly fatal catastrophic APS. We present a case of a 34-year-old male referred for pancytopenia and splenomegaly. On examination, he had decreased sensation and 4/5 power in the left upper extremity. A lacy, purplish rash was noted on the trunk and upper extremity. MRI of brain showed acute/subacute lacunar infarctions. Laboratory studies revealed an elevated lactate dehydrogenase level, bilirubin and ferritin, decreased haptoglobin, and positive Coombs test. Antinuclear antibody test was negative and antiphospholipid antibody panel revealed positivity for anti-cardiolipin IgG and IgM, antiphosphatidylserine IgG, and anti-β2-glycoprotein IgG. The patient was diagnosed with primary APS. Pancytopenia is relatively rare in primary APS and is more often seen in secondary APS. Our patient demonstrated involvement of multiple organ systems as well as livedo reticularis and autoimmune-related findings such as Raynaud phenomenon and Coombs positive hemolytic anemia. We discuss the various clinical and laboratory findings in patients with APS that aid in diagnosis, as well as important management considerations.

Long-term Survival in a Patient with Recurrent Pulmonary Metastases from Uterine Leiomyosarcoma

Chemotherapy is the standard of care for disseminated uterine leiomyosarcoma; however, long-term survival is rarely achieved with this aggressive disease. We report a patient with recurrent pulmonary metastatic disease from uterine leiomyosarcoma who is doing well without significant disease nine years after her initial diagnosis. We discuss her clinical course, the treatment modalities she received, and the clinical evidence supporting these.

Acute mesenteric ischemia: a sequela of abdominal aortography.

The use of abdominal angiography and transcatheter embolization has increased rapidly in the last few decades. Although improvement in angiographic techniques has made the procedure safe, ischemic colitis is a rare but potentially dreadful complication. We report a case of a 51-year-old woman who developed ischemic colitis following aortography, demonstrating that such angiographic studies may produce substantial morbidity.

Composite Diffuse Large B-cell and Mantle Cell Lymphoma: A Case Report

Composite lymphoma is an extremely rare clinical entity and is characterized by the presence of two different subtypes of lymphoma in the same lymph node. We report a case of composite lymphoma in a 57-year-old male presenting with leg and groin pain. The right inguinal lymph node biopsy showed large and small cells. Immunohistochemistry was consistent with large cells staining for diffuse large B-cell lymphoma (DLBCL) and small cells positive for mantle cell lymphoma (MCL). Polymerase chain reaction (PCR) analysis of immunoglobulin heavy (IGH) chain and immunoglobulin kappa (IGK) light chain gene rearrangements confirmed that the two were clonally unrelated neoplasms. There are only two reported cases of composite lymphoma with this combination in the published English literature. We report the third such case and discuss the pathology, diagnostic challenges and management of composite lymphoma.

Soft tissue myoepithelial carcinoma of the neck with spinal invasion

Soft tissue myoepithelial neoplasms are a rare yet diverse group of tumors, ranging from benign to malignant lesions. Their presentation in the head and neck region is uncommon and represents a challenging diagnosis. Early identification of myoepithelial carcinoma is crucial given its more aggressive course compared to its benign counterpart, although the histopathological distinction between the two can be difficult. EWSR1 gene rearrangement is found in half the cases and has a speculative role in pathogenesis. Complete excision remains the treatment of choice. The roles of chemotherapy and radiation are unclear. We report the hospital course of a 33-year-old female who presented to our institution with a posterior neck mass with spinal invasion, diagnosed as myoepithelial cancer. A literature review of these rare tumors is discussed here.

Stage IV EGFR Mutation-Negative and ALK Mutation-Negative Lung Adenocarcinoma: Long-Term Survival is Possible

Lung cancer is the leading cause of cancer death in the United States with a five-year survival of 16.8% for all stages and median survival of four months for Stage IV disease. We report a case of a 54-year-old male with a seven-year survival after being diagnosed with Stage IV epidermal growth factor receptor (EGFR) mutation-negative and anaplastic lymphoma kinase (ALK) mutation-negative adenocarcinoma of the lung, demonstrating an exceptional response to treatment.

Reversible bone marrow aplasia induced by pegylated interferon-α-2a therapy in a patient with primary myelofibrosis

Interferon has been widely used in the management of patients with hematological malignancies such as polycythemia vera, myelofibrosis, chronic myeloid leukemia and viral infections such as chronic hepatitis C. Hematological adverse effects such as cytopenias have been observed, particularly in patients who receive a combination of interferon-α-2a and ribavirin for hepatitis C. Mild myelosuppression can be seen with pegylated interferon; however, bone marrow aplasia in patients with myelofibrosis has not been reported. It is important to be aware of such a serious complication since persistent bone marrow aplasia can be fatal. We describe a case of pegylated interferon-induced reversible bone marrow aplasia in a patient with primary myelofibrosis.