• Title/Summary/Keyword: metastatic colorectal cancer

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Endothelial Cell Proliferation and Vascular Endothelial Growth Factor Expression in Primary Colorectal Cancer and Corresponding Liver Metastases

  • Raluca, Balica Amalia;Cimpean, Anca Maria;Cioca, Andreea;Cretu, Octavian;Mederle, Ovidiu;Ciolofan, Alexandru;Gaje, Pusa;Raica, Marius
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4549-4553
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    • 2015
  • Background: Colorectal carcinoma (CRC) is one of the major causes of cancer death worldwide. Data from the literature indicate differences between the proliferation rate of endothelial cells relative to the morphology growth type, possibly due to origin of specimens (autopsy material, surgery fragments) or quantification methods. Vascular endothelial growth factor (VEGF) is a factor that stimulates the proliferation of endothelial cells. It is expressed in more than 90% of cases of metastatic CRC. Aim: The aim of this study was to evaluate the endothelial cell proliferation and VEGF expression in primary tumors and corresponding liver metastases. Materials and Methods: Our study included 24 recent biopsies of primary tumors and corresponding liver metastases of CRC cases. CD34/Ki67 double immunostaining and RNA scope assay for VEGF were performed. Results: In the primary tumors analysis of VEGFmRNA expression indicated no significant correlation with differentiation grade, proliferative and non-proliferative vessels in the intratumoral and peritumoral areas. In contrast, in the corresponding liver metastases, VEGFmRNA expression significantly correlated with the total number of non-proliferative vessels and total number of vessels. CD34/Ki67 double immunostaining in the cases with poorly differentiated carcinoma indicated a high number of proliferating endothelial cells in the peritumoral area and a low number in the intratumoral area for the primary tumor. Moderately differentiated carcinomas of colon showed no proliferating endothelial cells in the intratumoral area in half of the cases included in the study, for both, primary tumor and liver metastasis. In well differentiated CRCs, in primary tumors, a high proliferation rate of endothelial cells in the intratumoral area and a lower proliferation rate in the peritumoral area were found. A low value was found in corresponding liver metastasis. Conclusions: The absence of proliferative endothelial cells in half of the cases for the primary tumors and liver metastases in moderately differentiated carcinoma suggest a vascular mimicry phenomenon. The mismatch between the total number of vessels and endothelial proliferation in primary tumors indicate that a functional vascular network is already formed or the existence of some mechanisms influenced by other angiogenic factors.

Verification of the Correlation between Progression-free Survival and Overall Survival Considering Magnitudes of Survival Post-progression in the Treatment of Four Types of Cancer

  • Liu, Li-Ya;Yu, Hao;Bai, Jian-Ling;Zeng, Ping;Miao, Dan-Dan;Chen, Feng
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.1001-1006
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    • 2015
  • Background: With development and application of new and effective anti-cancer drugs, the median survival post-progression (SPP) is often prolonged, and the role of the median SPP on surrogacy performance should be considered. To evaluate the impact of the median SPP on the correlation between progression-free survival (PFS) and overall survival (OS), we performed simulations for treatment of four types of cancer, advanced gastric cancer (AGC), metastatic colorectal cancer (MCC), glioblastoma (GBM), and advanced non-small-cell lung cancer (ANSCLC). Materials and Methods: The effects of the median SPP on the statistical properties of OS and the correlation between PFS and OS were assessed. Further, comparisons were made between the surrogacy performance based on real data from meta-analyses and simulation results with similar scenarios. Results: The probability of a significant gain in OS and HR for OS was decreased by an increase of the SPP/OS ratio or by a decrease of observed treatment benefit for PFS. Similarly, for each of the four types of cancer, the correlation between PFS and OS was reduced as the median SPP increased from 2 to 12 months. Except for ANSCLC, for which the median SPP was equal to the true value, the simulated correlation between PFS and OS was consistent with the values derived from meta-analyses for the other three kinds of cancer. Further, for these three types of cancer, when the median SPP was controlled at a designated level (i.e., < 4 months for AGC, < 12 months for MCC, and <6 months for GBM), the correlation between PFS and OS was strong; and the power of OS reached 34.9% at the minimum. Conclusions: PFS is an acceptable surrogate endpoint for OS under the condition of controlling SPPs for AGC, MCC, and GBM at their limit levels; a similar conclusion cannot be made for ANSCLC.

Digestive Neuroendocrine Tumor Distribution and Characteristics According to the 2010 WHO Classification: a Single Institution Experience in Lebanon

  • Kourie, Hampig Raphael;Ghorra, Claude;Rassy, Marc;Kesserouani, Carole;Kattan, Joseph
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.5
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    • pp.2679-2681
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    • 2016
  • Background: Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) are relatively rare tumors, not equally distributed in gastro-intestinal system. In 2010, a revised version of the WHO classification of GEP-NENs was published. This study reports for the first time the distribution and characteristics of GEP-NEN in a Lebanese population. Materials and Methods: This descriptive retrospective study concerns all the digestive neuroendocrine tumors with their characteristics diagnosed in $H\hat{o}tel$ Dieu de France in Beirut, Lebanon from 2001 to 2012, all the pathology reports being reanalyzed according to the latest WHO 2010 classification. The characteristics and features of GEP-NEN analyzed in this study were age, gender, grade and site. Results: A total of 89 GEP-NENs were diagnosed, representing 28.2% of all neuroendocrine tumors. The mean age of GEP-NEN patients was 58.7 years and the M/F sex ratio was 1.2. The primary localization was as follows: 21.3%(19) pancreatic, 18% (16) gastric, 15.7% (14) duodenal, 11.2% (10) appendix, 10.1% (9) intestinal, 10.1% (9) colorectal (7.9% colonic and 2.2% rectal), 5.6% (4) hepatic, 2.2% (2) ampulla, 1.1% (1) esophageal and 7.9%(5) NOS digestive (metastatic with unknown primary). Of the 89 patients with GEP-NEN, 56.2% (50) were diagnosed as grade I, 11.2% (10) as grade II, 20.2% (18) as grade III and 12.4% (11) were considered as mixed adeno-neuroendocrine carcinomas (MANEC). Conclusions: This study, one of the rare examples based on the 2010 WHO classification of neuroendocrine tumors in the literature, indicates that in the Lebanese population, all duodenal and appendicular tumors are G1 and the majority of MANEC tumors are gastric and pancreatic tumors. Moreover, more duodenal tumors and fewer rectal tumors were encountered in our study compared to European reports.

Preoperative Detection of Hepatic Metastases from the colorectal Cancers: Comparison of Dual-phase CT scan, Mn-DPDP enhanced MRI, and combination of CT and MRI (대장암의 간 전이 진단: 이중시기 CT, Mn-DPDP 조영증강 MRI, 그리고 CT-MRI 종합 판독의 비교)

  • Shin, Kyung-Min;Kim, Jong-Yeol;Choi, Gyu-Seok;Kim, Hye-Jeong;Lee, Jong-Min;Chang, Yong-Min;Kim, Yong-Seon;Kang, Duk-Sik;Ryeom, Hun-Kyu
    • Investigative Magnetic Resonance Imaging
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    • v.9 no.2
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    • pp.109-116
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    • 2005
  • Purpose : To determine the usefulness of additional Mn-DPDP MRI for preoperative evaluation of the patients with colorectal cancers by comparison of dual-phase CT scan, Mn-DPDP enhanced MRI and combination of CT and MRI. Materials and Methods : Fifty-three colorectal cancer patients with 92 metastatic nodules underwent dualphase (arterial and portal) helical CT scan and Mn-DPDP MRI prior to surgery. The indication of MRI was presence or suspected of having metastatic lesions at CT scan and/or increased serum carcinoembryonic antigen (CEA) levels (10 ng/mL or more). The diagnosis was established by the combination of findings at surgery, intraoperative ultrasonography, and histopathologic examination. Two radiologists interpreted CT, MRI, and combination of CT-MRI at discrete sessions and evaluated each lesion for location, size, and intrinsic characteristics. The lesions were divided into three groups according to their diameter; 1cm<, 1-2 cm, and >2 cm. Diagnostic accuracy was evaluated using the alternative-free response receiver operating characteristic method. Detection and false positive rate were also evaluated. Results : In the lesions smaller than 1 cm, detection rate of combined CT-MRI was superior to CT or MRI alone (82%, p=0.036). The mean accuracy (Az values) of combined CT and MRI was significantly higher than that of CT in the lesions smaller than 2 cm (1 cm<, p=0.034; 1-2 cm, p=0.045). However, there was no significant difference between MRI and combined CT-MRI. The false positive rate of CT was higher than those of combined CT-MR in the lesions smaller than 1 cm (28%, p=0.023). Conclusion : Additional MRI using Mn-DPDP besides routine CT scan was helpful in differentiating the hepatic lesions (<2 cm) and could improve detection of the small hepatic metastases (<1 cm) from colorectal carcinoma.

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Hepatic Resection in Patients with Liver Metastasis from Gastric Cancer (위암의 간전이에 대한 간 절제 수술)

  • Jun, Kyong-Hwa;Chin, Hyung-Min
    • Journal of Gastric Cancer
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    • v.9 no.1
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    • pp.14-17
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    • 2009
  • The clinical significance of hepatic resection for gastric metastases is controversial, even though hepatic resection has been widely accepted as a modality for colorectal metastases. Very few patients with gastric hepatic metastases are good candidates for hepatic resection because of multiple bilateral metastases, extrahepatic disease, or advanced cancer progression, such as peritoneal dissemination or extensive lymph node metastases. Therefore, several authors have reported the clinical significance of hepatic resection for gastric metastases in a small number of patients. Considering the present results with previous reports. The number and distribution of tumors in hepatic metastases from gastric cancer was considered based on the present and previous reports. Several authors have reported significantly better survival in patients with metachronous metastasis than in those with synchronous disease. However, metachronous hepatic resection necessitates the dissection of adhesions between the pancreas, liver, and residual stomach to prepare for Pringle's maneuver. Patients with unilobar liver metastasis, and/or metastatic tumors <4 cm in diameter may be good candidates for hepatic resection. Synchronous metastasis is not a contraindication for hepatic resection. Most of the long-term survivors underwent anatomic hepatic resection with a sufficient resection margin. After hepatic resection, the most frequent site of recurrence was the remaining liver, which was associated with a high frequency of mortality within 2 years. A reasonable strategy for improvement in survival would be to prevent recurrence by means of adjuvant chemotherapy and careful follow-up studies.

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Current Status and Future Perspective of PET (PET 이용 현황 및 전망)

  • Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.36 no.1
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    • pp.1-7
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    • 2002
  • Positron Emission Tomography (PET) is a nuclear medicine imaging modality that consists of systemic administration to a subject of a radiopharmaceutical labeled with a positron-emitting radionuclide. Following administration, its distribution in the organ or structure under study can be assessed as a function of time and space by (1) defecting the annihilation radiation resulting from the interaction of the positrons with matter, and (2) reconstructing the distribution of the radioactivity from a series of that used in computed tomography (CT). The nuclides most generally exhibit chemical properties that render them particularly desirable in physiological studies. The radionuclides most widely used in PET are F-18, C-11, O-15 and N-13. Regarding to the number of the current PET Centers worldwide (based on ICP data), more than 300 PET Centers were in operation in 2000. The use of PET technology grew rapidly compared to that in 1992 and 1996, particularly in the USA, which demonstrates a three-fold rise in PET installations. In 2001, 194 PET Centers were operating in the USA. In 1994, two clinical and research-oriented PET Centers at Seoul National University Hospital and Samsung Medical Center, was established as the first dedicated PET and Cyclotron machines in Korea, followed by two more PET facilities at the Korea Cancer Center Hospital, Ajou Medical Center, Yonsei University Medical Center, National Cancer Center and established their PET Center. Catholic Medical School and Pusan National University Hospital have finalized a plan to install PET machine in 2002, which results in total of nine PET Centers in Korea. Considering annual trends of PET application in four major PET centers in Korea in Asan Medical Center recent six years (from 1995 to 2000), a total of 11,564 patients have been studied every year and the number of PET studies has shown steep growth year upon year. We had 1,020 PET patients in 1995. This number increased to 1,196, 1,756, 2,379, 3,015 and 4,414 in 1996,1997,1998,1999 and 2000, respectively. The application in cardiac disorders is minimal, and among various neuropsychiatric diseases, patients with epilepsy or dementia can benefit from PET studios. Recently, we investigated brain mapping and neuroreceptor works. PET is not a key application for evaluation of the cardiac patients in Korea because of the relatively low incidence of cardiac disease and less costly procedures such as SPECT can now be performed. The changes in the application of PET studios indicate that, initially, brain PET occupied almost 60% in 1995, followed by a gradual decrease in brain application. However, overall PET use in the diagnosis and management of patients with cancer was up to 63% in 2000. The current medicare coverage policy in the USA is very important because reimbursement policy is critical for the promotion of PET. In May 1995, the Health Care Financing Administration (HCFA) began covering the PET perfusion study using Rubidium-82, evaluation of a solitary pulmonary nodule and pathologically proven non-small cell lung cancer. As of July 1999, Medicare's coverage policy expanded to include additional indications: evaluation of recurrent colorectal cancer with a rising CEA level, staging of lymphoma and detection of recurrent or metastatic melanoma. In December of 2001, National Coverage decided to expand Medicare reimbursement for broad use in 6 cancers: lung, colorecctal, lymphoma, melanoma, head and neck, and esophageal cancers; for determining revascularization in heart diseases; and for identifying epilepsy patients. In addition, PET coverage is expected to further expand to diseases affecting women, such as breast, ovarian, uterine and vaginal cancers as well as diseases like prostate cancer and Alzheimer's disease.

Comparison of Stereotactic Radiosurgery and Whole Brain Radiotherapy in Patients with Four or More Brain Metastases (4개 이상의 다발성 전이성 뇌종양의 정위적 방사선수술과 전뇌 방사선조사의 비교)

  • Kim, Cheol-Jin;Baek, Mi-Young;Park, Sung-Kwang;Ahn, Ki-Jung;Cho, Heung-Lae
    • Radiation Oncology Journal
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    • v.27 no.3
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    • pp.163-168
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    • 2009
  • Purpose: This study was a retrospective evaluation of the efficacy of stereotactic radiosurgery (SRS) in patients with >4 metastases to the brain. Materials and Methods: Between January 2004 and December 2006, 68 patients with $\geq$4 multiple brain metastases were included and reviewed retrospectively. Twenty-nine patients received SRS and 39 patients received whole brain radiotherapy (WBRT). Patients with small cell lung cancers and melanomas were excluded. The primary lesions were non-small cell lung cancer (69.0%) and breast cancer (13.8%) in the SRS group and non-small cell lung cancer (64.1%), breast cancer (15.4%), colorectal cancer (12.8%), esophageal cancer (5.1%) in the WBRT group. SRS involved gamma-knife radiosurgery and delivered 10~20 Gy (median, 16 Gy) in a single fraction with a 50% marginal dose. WBRT was delivered daily in 3 Gy fractions, for a total of 30 Gy. After completion of treatment, a follow-up brain MRI or a contrast-enhanced brain CT was reviewed. The overall survival and intracranial progression-free survival were compared in each group. Results: The median follow-up period was 5 months (range, 2~19 months) in the SRS group and 6 months (range, 4~23 months) in the WBRT group. The mean number of metastatic lesions in the SRS and WBRT groups was 6 and 5, respectively. The intracranial progression-free survival and overall survival in the SRS group was 5.1 and 5.6 months, respectively, in comparison to 6.1 and 7.2 months, respectively, in the WBRT group. Conclusion: SRS was less effective than WBRT in the treatment of patients with >4 metastases to the brain.