Prognostic significance of programmed cell death-1-positive cells in follicular lymphoma patients may alter in the rituximab era.

Programmed cell death-1 (PD-1) is involved in one of the inhibitory pathways of the B7-cluster of differentiation (CD) 28 family; this pathway is known to be involved in the attenuation of T-cell responses and promotion of T-cell tolerance. PD-1 is known to negatively regulate T-cell receptor-mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Although several studies have shown that high levels of PD-1-positive cells in follicular lymphoma (FL) patients influence their prognosis, those studies included patients treated without rituximab, and the prognostic impact of PD-1 positivity in the rituximab era (R-era) has not yet been elucidated. We retrospectively studied 82 patients with FL uniformly treated with standard R-CHOP therapy at six institutions between 2001 and 2009 (median follow-up for survivors: 55 months). We also collected and examined biopsy specimens for diagnosis with respect to PD-1 positivity. The PD-1 positivity was significantly higher in male patients and patients with high beta-2 microglobulin (B2M ≥ 3.0) (P = 0.03 and 0.003, respectively). Three-year progression free survival (PFS) and overall survival (OS) were 60% and 86%, respectively. By univariate analysis, elevated LDH (P = 0.07) worsened PFS. Male gender (P = 0.03), high FLIPI score (P = 0.05), and high B2M levels (P = 0.08) worsened OS. Multivariate analysis detected no significant prognostic factors, including PD-1 positivity. However, in male subgroup, high levels of PD-1-positive cells were found to be a prognostic factor for PFS. Addition of rituximab might have altered the prognostic impact of PD-1-positive cells.

Malignant paraganglioma of the retroperitoneum with lung metastases: a 13-year survivor after radical surgery.

We present a 23-year-old patient with extra-adrenal retroperitoneal paraganglioma with lung metastases who was successfully treated by complete removal of the tumour. Lung metastases were the first manifestation of the disease, and an abdominal computed tomography scan showed a large mass in the retroperitoneum with marked contrast enhancement. Angiography demonstrated a hypervascular mass with many feeding arteries, but vascular invasion was not apparent. The retroperitoneal tumour was resected completely followed by resection of lung metastases after 1 month of observation. The patient was disease free for 13 years after this radical surgery. The survival rate in patients with retroperitoneal paraganglioma with lung metastasis is low, and this case represents the longest surviving period reported in the literature. These tumours are usually large and located in the para-aortic region, and hence resection is sometimes challenging. We believe that a complete and meticulous surgical procedure is a prerequisite for long survival from this rare disease.

The preserved expression of neuropilin (NRP) 1 contributes to a better prognosis in colon cancer.

Vascular endothelial growth factor A (VEGF-A) plays an essential role in tumor progression through stromal neovascularization in malignant solid tumors. Neuropilin (NRP) is considered to be the specific receptor for limited types of VEGF-A isoform, VEGF165. The clinicopathological implications of NRP are not well understood in colon cancer, while almost all colon cancers overexpressed VEGF-A. We examined the expression levels of NRP1 and NRP2 genes in 54 colon cancer cases and paired extraneoplastic tissue with quantitative real-time polymerase chain reaction. The gene expression levels of NRP1 in the tumor (0.431+/-0.583) were significantly decreased compared to those in the extraneoplastic tissue (0.754+/-0.799) (paired t-test, p=0.0208). On the other hand, the gene expression levels of NRP2 in the tumor (0.763+/-0.791) were not decreased compared to those in the extraneoplastic tissue (0.508+/-0.386) (paired t-test, p=0.0511). Twenty cases, with preserved expression of the NRP1 gene in the tumor, showed a better prognosis as compared to the 34 cases with decreased NRP1 expression (p=0.0258, log-rank test). No significant relationship was noted between NRP2 gene expression and prognosis. The results suggested that preserved NRP1 expression provides colon cancer patients with a better prognosis.

Fine-needle aspiration cytology of breast lesions: a review of cytological analysis using smooth muscle actin (SMA) immunostaining.

We reviewed fine-needle aspiration (FNA) cytology cases for breast lesions in order to improve the reliability of cytological diagnoses. We analyzed the results of 1,019 FNA cytology cases of patients with breast lesions for five years in our hospital. One hundred and ninety-seven (19.3%) of the 1,019 cases were examined using histological sections, in addition to cytological specimens, and included 27 cytologically suspicious cases. Of the 1,019 cytology cases, 606 (59.5%) were benign, 41 (4.0%) suspicious, 149 (14.6%) malignant and 223 (21.9%) inadequate/nondiagnostic. We also performed immunostaining against smooth muscle actin (SMA), using 19 cytological specimens and 88 histological specimens. We observed myoepithelial cells positive for SMA, which were valuable for cytological or histological diagnosis. To improve the reliability of cytological diagnoses and decrease the false-positive and false-negative cases, it is very important to obtain sufficient aspirates and to understand the cytological characteristics of various benign and malignant breast lesions.

Expression of CD44 in primary lung carcinomas using histological and cytological analyses.

CD44 is a family of transmembrane glycoproteins expressed in hematopoietic and epithelial cells, and associated with diverse physiological functions such as cell-cell and cell-matrix interactions. CD44 exists in a standard form, CD44s, and in multiple isoforms which are produced by alternative splicing of the variant exons (exon v1 to exon v10) encoding parts of the extracellular domain. Recently, CD44 was shown to play a role in the invasive and metastatic properties of tumor cells. In this study, we demonstrated CD44 immunoreactivities in 74 primary lung carcinomas. CD44s was noted in 38% (28 out of 74) of primary lung carcinomas. CD44v3 (38%, 28 out of 74) and CD44v6 (41%, 30 out of 74) were less frequently expressed in the primary lung carcinomas, compared with non-neoplastic lung tissues (CD44v3, 100%, p < 0.001; CD44v6, 73%, p < 0.05), respectively. CD44v3 and CD44v6 were more frequently found in squamous cell carcinomas than the other histological types (p < 0.05. CD44s, CD44v3 and CD44v6 were noted in 33% (6 out of 18), 44% (8 out of 18) and 33% (6 out of 18) of cytology-positive cases, and in 46% (6 out of 13), 38% (5 out of 13) and 31% (4 out of 13) of cytology-negative cases, respectively. It is suggested that decreased CD44v3 and CD44v6 might be correlated with sputum cytology-negative cases of lung adenocarcinoma.

[Continuous epidural administration of droperidol to prevent postoperative nausea and vomiting].

This randomized double-blind trial was designed to evaluate the antiemetic effect of continuous epidural analgesia with droperidol mixed with bupivacaine and buprenorphine. We studied 78 patients for abdominal gynecological surgery under general-epidural anesthesia. After recovery from anesthesia, they received epidural administration of 0.25% bupivacaine 40 ml and buprenorphine 0.4 mg with or without droperidol 2.5-5.0 mg at a rate of 2 ml.h-1 for 24 hours. The addition of droperidol 5.0 mg led to serious undesirable effects. Droperidol 2.5 mg, however, showed not only significant antiemetic effect without any adverse action, but also the reduction of rescue analgesics. We conclude that the addition of a small dose of droperidol to epidural analgesics reduces the incidence of postoperative emesis and the requirement of rescue analgesics.