Gemcitabine and Erlotinib with or without Oxaliplatin in Previously Untreated Advanced Pancreatic Cancer: A Randomized Phase II Trial

Purpose@#Erlotinib has been the only targeted agent to show significantly improved outcomes in pancreatic adenocarcinoma when combined with gemcitabine. We aimed to evaluate whether the addition of oxaliplatin to a combination gemcitabine/erlotinib treatment conferred a clinical benefit in patients with locally advanced unresectable or metastatic pancreatic cancer. @*Materials and Methods@#Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T [gemcitabine 1000 mg/m2 and oxaliplatin 50 mg/m2 on day 1 (D1) and D8 plus erlotinib 100 mg daily for 3 weeks] or GT (gemcitabine 1000 mg/m2 on D1 and D8 plus erlotinib 100 mg daily for 3 weeks). The primary endpoint was the overall response rate (ORR). @*Results@#Between 2013 and 2016, 65 patients were assigned to a treatment group (33 in the GEMOX-T arm, 32 in the GT arm). The ORR was 18.2% [95% confidence interval (CI), 8.82–27.58] in the GEMOX-T arm and 6.2% (95% CI, 0.34–12.06) in the GT arm (p=0.051). The disease control rate was significantly superior in the GEMOX-T arm compared to the GT arm (72.7% vs. 43.8%, p=0.019). After a median follow-up of 19.7 months, the median progression-free survival (PFS) was 3.9 months for the GEMOX-T arm and 1.4 months for the GT arm (p=0.033). However, this did not translate to an improvement in overall survival. The most common grade 3 or higher hematologic adverse events were neutropenia (16.9%) and anemia (13.8%). @*Conclusion@#The addition of oxaliplatin to a first-line gemcitabine/erlotinib regimen demonstrated higher response rates and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.

Gemcitabine and Erlotinib with or without Oxaliplatin in Previously Untreated Advanced Pancreatic Cancer: A Randomized Phase II Trial

Purpose@#Erlotinib has been the only targeted agent to show significantly improved outcomes in pancreatic adenocarcinoma when combined with gemcitabine. We aimed to evaluate whether the addition of oxaliplatin to a combination gemcitabine/erlotinib treatment conferred a clinical benefit in patients with locally advanced unresectable or metastatic pancreatic cancer. @*Materials and Methods@#Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T [gemcitabine 1000 mg/m2 and oxaliplatin 50 mg/m2 on day 1 (D1) and D8 plus erlotinib 100 mg daily for 3 weeks] or GT (gemcitabine 1000 mg/m2 on D1 and D8 plus erlotinib 100 mg daily for 3 weeks). The primary endpoint was the overall response rate (ORR). @*Results@#Between 2013 and 2016, 65 patients were assigned to a treatment group (33 in the GEMOX-T arm, 32 in the GT arm). The ORR was 18.2% [95% confidence interval (CI), 8.82–27.58] in the GEMOX-T arm and 6.2% (95% CI, 0.34–12.06) in the GT arm (p=0.051). The disease control rate was significantly superior in the GEMOX-T arm compared to the GT arm (72.7% vs. 43.8%, p=0.019). After a median follow-up of 19.7 months, the median progression-free survival (PFS) was 3.9 months for the GEMOX-T arm and 1.4 months for the GT arm (p=0.033). However, this did not translate to an improvement in overall survival. The most common grade 3 or higher hematologic adverse events were neutropenia (16.9%) and anemia (13.8%). @*Conclusion@#The addition of oxaliplatin to a first-line gemcitabine/erlotinib regimen demonstrated higher response rates and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.

Evaluating the recent developments in palliative chemotherapy for metastatic colorectal cancer

The incidence of colorectal cancer (CRC) has increased. CRC is the third most common cancer and the fourth most common cause of cancer-related deaths in Korea. Palliative chemotherapy can be used to shrink tumors and ease symptoms caused by the cancer when cure is not possible. It is important to identify chemotherapeutic agents that can be used to effectively treat metastatic CRC (mCRC) and thus improve the survival and quality of life of patients with mCRC. This review aimed to evaluate the recent developments in palliative chemotherapy for mCRC and the biological or targeted agents used based on genetic alterations.

Epigenetic inactivation of RUNX3 in colorectal cancer

PURPOSE: Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC. METHODS: Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining. RESULTS: Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363). CONCLUSION: Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

The incidence of venous thromboembolism is not lowin Korean patients with advanced pancreatic cancer

BACKGROUND: Pancreatic cancer is among the most common malignancies associated with venous thromboembolism (VTE). Asian patients are known to have a lower incidence of VTE compared to Caucasian patients. However, few studies have investigated the incidence of VTE in Asian patients with pancreatic cancer. METHODS: This retrospective review of medical records was performed on 505 patients with histopathologically proven advanced stage pancreatic cancer, from January 2006 to December 2012, at Soonchunhyang University Hospitals. RESULTS: Ninety-four patients (18.6%) had at least one pulmonary embolism (PE), deep vein thrombosis (DVT), or splanchnic vein thrombosis (SVT); 38 patients had isolated SVT; and 56 patients (11.1%) had at least one classic VTE (PE and/or DVT of lower extremities). Patients with more advanced stages of pancreatic cancer (distant metastatic stage, recurrence) or who had received chemotherapy had a higher incidence of classic VTE. Patients who were simultaneously diagnosed with pancreatic cancer and classic VTE had a poorer prognosis than patients with subsequent VTEs. There was a significant difference in overall survival (OS) between the presence and absence of a concurrent classic VTE diagnosis (median: OS, 2.1 mo vs. 10.7 mo; P < 0.001). Even when VTE included SVT, the result was similar (P < 0.001). CONCLUSION: In Korean patients with advanced pancreatic cancer, the incidence of VTEs is comparable to that of Caucasian patients. We also found that pancreatic cancer patients with concurrent VTEs had a poor prognosis compared to patients who developed VTEs later.

Medical Treatment of Cancer Pain: Drug Therapy according to Guidelines Will Improve the Quality of Life of Cancer Patients / 대한내과학회지

Cancer pain is the most common and troublesome symptom for cancer patients. The more the cancer patient gets to the end of the life, the worse the pain. There are many clinical practice guidelines for cancer pain, and most pain can be controlled with appropriate medication by guideline. We would like to summarize various domestic and foreign clinical practice guidelines relatively simply. According to the clinical practice guidelines, medical treatment including opioids will greatly improve the quality of life of cancer patients.

Association Between c-Met and Lymphangiogenic Factors in Patients With Colorectal Cancer

PURPOSE: Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC. METHODS: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed. RESULTS: Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found. CONCLUSION: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.

CORRIGENDUM: Correction of funding statement in ACKNOWLEDGEMENTS section: Epigenetic inactivation of RUNX3 in colorectal cancer

Correction of funding statement in ACKNOWLEDGEMENTS section.

Expressions and Clinical Significances of Angiopoietin-1, Angiopoietin-2, and Tie-2 Receptor in Patients With Colorectal Cancer

PURPOSE: Angiopoietin-1 (Ang-1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor, Tie-2. Increased levels of Ang-2 have been shown to be correlated with abnormal tumor angiogenesis in several malignancies. Hence, we estimated the increased expression of Ang-2 relative to Ang-1 in patients with colorectal cancer and correlated our finding with prognosis in order to investigate the relationships between the expressions of Ang-1/Ang-2/Tie-2 receptor and the clinical parameters or overall survival of such patients. METHODS: We retrospectively analyzed 114 tissue samples from patients with colorectal cancer by using immunohistochemistry (IHC) to examine Ang-1, Ang-2, and Tie-2 expressions and to investigate the relationship between those expressions and clinical parameters or overall survival of such patients. A Western blot analysis was used for Ang-2 expression. RESULTS: IHC staining showed a link between Ang-1 and Tie-2 (P = 0.018), as well as meaningful correlations between Ang-2 and Tie-2 receptor (P = 0.022) and between lymph-node metastasis and Ang-2 (P = 0.025). The stronger the IHC staining for Ang-2 expression was, the shorter the cumulative survival was (P = 0.016). CONCLUSION: A relationship was found to exist between Ang-2 and Tie-2 expressions. The Ang-2 was correlated with lymph-node metastasis, and high expression of Ang-2 was indicative of poor overall survival. These findings suggest that Ang-2 is a useful prognostic marker in the management of patients with colorectal cancer. In addition, we suggest that Ang/Tie-2 signaling plays an important role in the progression of colorectal cancer.

Clinicopathologic and Prognostic Significance of Transducin-Like Enhancer of Split 1 Protein Expression in Invasive Breast Cancer / 한국유방암학회지

PURPOSE: Transducin-like enhancer of split 1 (TLE1) is a member of the TLE family of transcriptional co-repressors that control the transcription of a wide range of genes. We investigated the prognostic significance of TLE1 protein expression in breast cancers by using immunohistochemistry and explored the relationship of TLE1 with clinicopathological parameters. METHODS: Immunohistochemistry was performed on 456 cases of breast cancer tiled on tissue microarrays. The relationship between TLE1 expression in normal breast specimens and ductal carcinoma in situ (DCIS) was also analyzed. RESULTS: TLE1 was highly expressed in 57 of 456 (12.5%) carcinoma samples. TLE1 was more frequently expressed in DCIS and invasive breast cancers than in normal breast tissue (p=0.002). High expression of TLE1 significantly correlated with negative lymph node (LN) metastasis (p=0.007), high histologic grade (p<0.001), estrogen receptor negativity (p<0.001), progesterone receptor negativity (p<0.001), human epidermal growth factor receptor 2 (HER2) positivity (p<0.001), and high Ki-67 proliferation index (p<0.001). Based on intrinsic subtypes, high TLE1 expression was strongly associated with HER2+ and triple-negative breast cancers (TNBC) (p<0.001). Survival analysis demonstrated no significant association between TLE1 expression and disease-free survival (DFS) (p=0.167) or overall survival (OS) (p=0.286). In subgroup analyses, no correlation was found between TLE1 expression and DFS or OS according to LN status or intrinsic subtype. CONCLUSION: High TLE1 expression is significantly associated with the HER2+ and TNBC subtypes. This is the first study documenting immunohistochemical expression of TLE1 in invasive breast cancer and its association with clinicopathological parameters, prognosis, and intrinsic subtype.

Expression of Programmed Death Receptor Ligand 1 with High Tumor-Infiltrating Lymphocytes Is Associated with Better Prognosis in Breast Cancer / 한국유방암학회지

PURPOSE: The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis. METHODS: PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas. RESULTS: High PD-L1 expression was demonstrated in 63 of 465 tumors (13.5%). High PD-L1 expression was significantly associated with high histologic grade (p<0.001), negative lymph nodes (p=0.011), early pathologic stage (p=0.025), high tumor-infiltrating lymphocyte (TIL) (p<0.001) counts, negative estrogen receptor (p<0.001) and progesterone receptor (p=0.002) expression, positive human epidermal growth factor receptor 2 (HER2) (p=0.003), cytokeratin 5/6 (p=0.011), epidermal growth factor receptor (p<0.001), and p53 (p<0.001) expression, and high Ki-67 proliferating index (p<0.001). Based on intrinsic subtypes, high PD-L1 expression and high TIL counts were significantly associated with the HER2 and triple-negative basal type (p<0.001). PD-L1 expression was significantly associated with better disease-free survival (DFS) (p=0.041) and overall survival (OS) (p=0.026) in the univariate analysis, but not in the multivariate analysis. Higher TIL levels was an independent prognostic factor for decreased disease progression (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.284–4.445; p=0.006) and overall death (HR, 3.666; 95% CI, 1.561–8.607; p=0.003). CONCLUSION: PD-L1 protein expression in breast cancer is associated with better DFS and OS, but is not an independent prognostic factor. High PD-L1 expression was significantly associated with high TIL levels. This finding has important implications for antibody therapies targeting the PD-1/PD-L1 signaling mechanism in breast cancer.

Intrathecal Trastuzumab Treatment in Patients with Breast Cancer and Leptomeningeal Carcinomatosis / Journal of the Korean Cancer Association, 대한암학회지

Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis.

Intrathecal Trastuzumab Treatment in Patients with Breast Cancer and Leptomeningeal Carcinomatosis / Journal of the Korean Cancer Association, 대한암학회지

Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis.

High EZH2 Protein Expression Is Associated with Poor Overall Survival in Patients with Luminal A Breast Cancer / 한국유방암학회지

PURPOSE: The enhancer of zeste homologue 2 (EZH2) is a catalytic subunit of the polycomb repressive complex 2, a highly conserved histone methyltransferase. EZH2 overexpression has been implicated in various malignancies, including breast cancer, where is associated with poor outcomes. This study aims to clarify nuclear EZH2 expression levels in breast cancers using immunohistochemistry (IHC) and correlate these findings with clinicopathologic variables, including prognostic significance. METHODS: IHC was performed on tissue microarrays of 432 invasive ductal carcinoma (IDC) tumors. Associations between EZH2 expression, clinicopathologic characteristics, and molecular subtype were retrospectively analyzed. The relationship between EZH2 protein expression in normal breast tissue and ductal carcinoma in situ (DCIS) was also assessed. RESULTS: High EZH2 expression was demonstrated in 215 of 432 tumors (49.8%). EZH2 was more frequently expressed in DCIS and IDC than in normal breast tissue (p=0.001). High EZH2 expression significantly correlated with high histologic grade (p<0.001), large tumor size (p=0.014), advanced pathologic stage (p=0.006), negative estrogen receptor status (p<0.001), positive human epidermal growth factor receptor 2 (HER2) status (p<0.001), high Ki-67 staining index (p<0.001), positive cytokeratin 5/6 status (p=0.003), positive epidermal growth factor receptor status (p<0.001), and positive p53 status (p<0.001). Based on molecular subtypes, high EZH2 expression was significantly associated with HER2-negative luminal B, HER2-positive luminal B, and HER2 type and triple-negative basal cancers (p<0.001). In patients with luminal A, there was a significant trend toward shorter overall survival for those with tumors having high EZH2 expression compared to those with tumors having low EZH2 expression (p=0.045). CONCLUSION: EZH2 is frequently upregulated in breast malignancies, and it may play an important role in cancer development and progression. Furthermore, EZH2 may be a prognostic marker, especially in patients with luminal A cancer.

Idiopathic erythrocytosis in a patient on chronic hemodialysis

A 78-year-old man on hemodialysis presented to our hospital with erythrocytosis. He had started hemodialysis 4 years previously, with a hemoglobin level of 9.8 g/dL, and was administered erythropoiesis stimulating agents and ferrous sulfate. Two years previously, his hemoglobin level increased to 14.5 g/dL and the treatment for anemia was discontinued. He continued hemodialysis thrice weekly; however, the hemoglobin level had increased to 17.0 g/dL at the time of presenting to our hospital. His serum erythropoietin level was 31.4 mIU/mL (range, 3.7-31.5 mIU/mL), carboxyhemoglobin level was 0.6% (range, 0-1.5%), and oxygen saturation in ambient air was 95.4%. The JAK2 V617F mutation was not observed and other bone marrow abnormalities were not identified. The patient was diagnosed with bladder cancer and a transurethral resection was performed. Eight months after the treatment of bladder cancer, his hemoglobin level was 15.1 g/dL, and he was diagnosed with idiopathic erythrocytosis.

Loss of Tumor Suppressor ARID1A Protein Expression Correlates with Poor Prognosis in Patients with Primary Breast Cancer / 한국유방암학회지

PURPOSE: Somatic mutations of the chromatin remodeling AT-rich interactive domain 1A (SWI-like) gene (ARID1A) have been identified in many human cancers, including breast cancer. The purpose of this study was to evaluate the nuclear expression of ARID1A in breast cancers by immunohistochemistry (IHC) and to correlate the findings to clinicopathologic variables including prognostic significance. METHODS: IHC was performed on tissue microarrays of 476 cases of breast cancer. Associations between ARID1A expression and clinicopathologic characteristics and molecular subtype were retrospectively analyzed. RESULTS: Low expression of ARID1A was found in 339 of 476 (71.2%) cases. Low expression of ARID1A significantly correlated with positive lymph node metastasis (p=0.027), advanced pathologic stage (p=0.001), low Ki-67 labeling index (p=0.003), and negative p53 expression (p=0.017). The ARID1A low expression group had significantly shorter disease-free and overall survival than the ARID1A high expression group (p<0.001 and p<0.001, respectively). Multivariate analysis demonstrated that low expression of ARID1A was a significant independent predictive factor for poor disease-free and overall survival in patients with breast cancer (disease-free survival: hazard ratio, 0.38, 95% confidence interval [CI], 0.20-0.73, p=0.004; overall survival: hazard ratio, 0.11, 95% CI, 0.03-0.46, p=0.003). In patients with luminal A type disease, patients with low ARID1A expression had significantly shorter disease-free and overall survival rates than patients with high ARID1A expression (p=0.022 and p=0.018, respectively). CONCLUSION: Low expression of ARID1A is an independent prognostic factor for disease-free and overall survival in breast cancer patients and may be associated with luminal A type disease. Although the biologic function of ARID1A in breast cancer remains unknown, low expression of ARID1A can provide valuable prognostic information.

Second-Line Chemotherapy in Advanced Biliary Tract Cancer: A Retrospective Analysis

OBJECTIVE: The evidence of 2nd line chemotherapy has not been validated. We investigated the treatment outcomes of 2nd line palliative chemotherapy in patients with biliary tract cancer (BTC) and analyzed the factors affecting response or survival. METHODS: We retrospectively reviewed and analyzed the outcomes in advanced BTC patients who underwent 2nd line chemotherapy in Soonchunhyang Universitiy Hospitals (Bucheon, Seoul, and Cheonan). RESULTS: From December 2004 to May 2014, 65 patients were enrolled. The median age was 56 years (range, 40 to 76 years) and the ratio of cholangiocarcinoma (intrahepatic or extrahepatic), gall bladder cancer, and ampulla of Vater cancer was 41 (63.1%):18 (27.7%):6 (9.25%). Half of the patients (33 patients, 50.8%) were treated with gemcitabine-based and 28 patients (43.1%) with 5-fluorouracil- based therapy. The response rate was 3.0% and disease control rate was 21.5% in intention-to-treat analysis. Median overall survival (OS) was 7.2 months (95% confidence interval [CI], 3.9 to 10.5 months) and median progression free survival (PFS) was 3.7 months (95% CI, 2.5 to 4.9 months). In multivariate analysis, patients with good performance status (PS) (P=0.001) and chemo-sensitive tumor to 2nd line chemotherapy (P=0.000) had longer PFS as compared to the others. In addition, patients with good PS (P=0.003), chemo-sensitive tumor to 1st line (P=0.046), and 2nd line chemotherapy (P=0.004) were good prognostic factors for OS. CONCLUSION: The effect of 2nd line chemotherapy in advanced BTC was modest and maybe beneficial in select patients.

Hereditary hemorrhagic telangiectasia treated with low dose intravenous bevacizumab

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that leads to mucocutaneous telangiectasias, epistaxis, and gastrointestinal bleeding. Depending on the severity and manifestation of the disease, various therapeutic modalities have been used, from local bleeding control to surgery or concomitant drug therapy. Several articles under review have presented guidelines for treatment of HHT with bevacizumab as a direct anti-angiogenesis strategy. Still, neither the exact optimal dose nor the minimum effective dose of intravenous bevacizumab in patients with severe HHT has been reported. A 55-year-old man presented with long-standing epistaxis, recent melena, dizziness, and a three-generation family history of chronic epistaxis, anemia, and regular blood transfusions. Treatment with argon plasma coagulation (APC) for the gastrointestinal bleeding failed to raise hemoglobin levels, we considered using the bevacizumab. We report a patient with severe HHT, who was treated with low-dose bevacizumab (2 mg/kg) and improved substantially.

Expression of Secreted Protein Acidic and Rich in Cysteine in the Stroma of a Colorectal Carcinoma is Associated With Patient Prognosis

PURPOSE: Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin or basement-membrane-40 (BM-40), is a member of a family of matricellular proteins, whose functions are to modulate cell-matrix interactions, growth and angiogenesis in colorectal cancer. In this study, the expression of SPARC was evaluated and its correlations with clinicopathological parameters were investigated. METHODS: The researchers analyzed the expression patterns of SPARC by using immunohistochemistry in 332 cases of colorectal cancer of tissue microarray. The clinicopathological characteristics were defined by using the TNM criteria of the Union for International Cancer Control. Clinicopathological factors such as age, sex, histologic type of the tumor, pathologic tumor stage, TNM stage, and lymphovascular invasion were evaluated according to the SPARC expression. RESULTS: The hazard ratios expressing SPARC in tumor cells, in the stroma, and in both tumor cells and the stroma were 2.10 (P = 0.036), 3.27 (P = 0.003) and 2.12 (P = 0.038), respectively. Patient survival was decreased in patient expressing SPARC in the stroma, and this result showed statistical significance (P = 0.016). CONCLUSION: These findings suggest that SPARC expression in a tumor and in the stroma correlates with disease progression and may be used as a prognostic marker for colorectal cancer.

Expression of Secreted Protein Acidic and Rich in Cysteine in the Stroma of a Colorectal Carcinoma is Associated With Patient Prognosis

PURPOSE: Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin or basement-membrane-40 (BM-40), is a member of a family of matricellular proteins, whose functions are to modulate cell-matrix interactions, growth and angiogenesis in colorectal cancer. In this study, the expression of SPARC was evaluated and its correlations with clinicopathological parameters were investigated. METHODS: The researchers analyzed the expression patterns of SPARC by using immunohistochemistry in 332 cases of colorectal cancer of tissue microarray. The clinicopathological characteristics were defined by using the TNM criteria of the Union for International Cancer Control. Clinicopathological factors such as age, sex, histologic type of the tumor, pathologic tumor stage, TNM stage, and lymphovascular invasion were evaluated according to the SPARC expression. RESULTS: The hazard ratios expressing SPARC in tumor cells, in the stroma, and in both tumor cells and the stroma were 2.10 (P = 0.036), 3.27 (P = 0.003) and 2.12 (P = 0.038), respectively. Patient survival was decreased in patient expressing SPARC in the stroma, and this result showed statistical significance (P = 0.016). CONCLUSION: These findings suggest that SPARC expression in a tumor and in the stroma correlates with disease progression and may be used as a prognostic marker for colorectal cancer.