Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process.This process starts with a series of mutations in colonic epithelial cells,continues with their detachment from the lar...Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process.This process starts with a series of mutations in colonic epithelial cells,continues with their detachment from the large intestine,dissemination through the blood and/or lymphatic circulation,attachment to the hepatic sinusoids and interactions with the sinusoidal cells,such as sinusoidal endothelial cells,Kupffer cells,stellate cells and pit cells.The metastatic sequence terminates with colorectal cancer cell invasion,adaptation and colonisation of the hepatic parenchyma.All these events,termed the colorectal cancer invasion-metastasis cascade,include multiple molecular pathways,intercellular interactions and expression of a plethora of chemokines and growth factors,and adhesion molecules,such as the selectins,the integrins or the cadherins,as well as enzymes including matrix metalloproteinases.This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting.展开更多
Systematic analysis of the epidermal growth factor receptor(EGFR)pathway revealed that biomarkers could be used to predict the response to and outcome of antiEGFR therapies in patients affected by metastatic colorecta...Systematic analysis of the epidermal growth factor receptor(EGFR)pathway revealed that biomarkers could be used to predict the response to and outcome of antiEGFR therapies in patients affected by metastatic colorectal cancer.We have conducted a review on the most recent findings and advances on this topic.To this aim,we searched the PubMed database for articles devoted to predictive and prognostic biomarkers for patients administered cetuximab-and panitumumab-based therapies.Here we review the state of the art and the controversies about the molecular factors known to be predictors of the efficacy of anti-EGFR therapy,namely,KRAS,BRAF,NRAS,PI3KCA and PTEN,and we discuss their prognostic value in colorectal cancer patients.展开更多
AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal ...AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal carcinoma patients. The patients were re-grouped according to the presence or absence of LI and lymph node metastasis. Forty-three cancer-free subjects without any metabolic disturbances were included into the control group. Serum neopterin was measured by enzyme linked immunosorbent assay. Urinary neopterin and biopterin, serum tryptophan (Trp) and kynurenine (Kyn) concentrations of all patients were determined by high performance liquid chromatography. Kyn/Trp was calculated and its correlation with serum neopterin was determined to estimate the serum indoleamine 2,3-dioxygenase activity. Tissue sections from the studied tumors were re-examined histopathologically and were stained by immunohistochemistry with indoleamine-2,3-dioxygenase antibodies.RESULTS: Neither serum nor urinary neopterin was significantly different between the patient and control groups (both P > 0.05). However, colorectal carcinoma patients showed a significant positive correlation between the serum neopterin levels and Kyn/Trp (r = 0.450, P < 0.01). Urinary biopterin was significantly higher in cancer cases (P < 0.05). Serum Kyn/Trp was significantly higher in colorectal carcinoma patients (P < 0.01). Lymphatic invasion was present in 23 of 44 patients, of which only 12 patients had lymph node metastasis. Eleven patients with LI had no lymph node metastasis. Indoleamine-2,3-dioxygenase intensity score was significantly higher in LI positive cancer group (44.56% ± 6.11%) than negative colorectal cancer patients (24.04% ± 6.90%), (P < 0.05). Indoleamine 2,3-dioxygenase expression correlated both with the presence of LI and lymph node metastasis (P < 0.01 and P < 0.05, respectively). A significant difference between the accuracy of diagnosis by using either 展开更多
We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma （HCC） metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms ...We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma （HCC） metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography （CT） revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging （HR/） disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced HRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations, Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.展开更多
BACKGROUND: We commonly encounter fractures secondary to trauma on and off in our daily practice. While it is not uncommon to see fractures due to underlying pathology, we need to be on the alert when patients present...BACKGROUND: We commonly encounter fractures secondary to trauma on and off in our daily practice. While it is not uncommon to see fractures due to underlying pathology, we need to be on the alert when patients present atypically because the treatment for pathological fractures is far different from that for simple fractures.METHODS: We presented a case of left clavicle fracture secondary to minor trauma, in which the initial X-ray shows suspicious lesion around the fracture site and further investigation reveals multiple myeloma. The patient received treatment at the clinical oncology department upon diagnosis. Since he was relatively young and fi t, he was started on the induction therapy of VTD, which was followed by high dose melphalan and autologous stem cell transplant.RESULTS: He is currently free from symptoms and on maintenance thalidomide.CONCLUSIONS: Though multiple myeloma is not commonly encountered in emergency practice, earlier identification of relatively subtle symptoms can allow early treatment. Missing this diagnosis will delay treatment and produce severe outcome to the patient. We should be on the alert for such important condition.展开更多
AIM: To define the rational extent of regional lymphadenectomy for gallbladder cancer and to clarify its effect on long-term survival. METHODS: A total of 152 patients with gallbladder cancer who underwent a minimum o...AIM: To define the rational extent of regional lymphadenectomy for gallbladder cancer and to clarify its effect on long-term survival. METHODS: A total of 152 patients with gallbladder cancer who underwent a minimum of "extended" portal lymph node dissection (defined as en bloc removal of the first-and second-echelon nodes) from 1982 to 2010 were retrospectively analyzed. Based on previous studies, regional lymph nodes of the gallbladder were divided into first-echelon nodes (cystic duct or pericholedochal nodes), second-echelon nodes (node groups posterosuperior to the head of the pancreas or around the hepatic vessels), and more distant nodes. RESULTS: Among the 152 patients (total of 3352 lymph nodes retrieved, median of 19 per patient), 79 patients (52%) had 356 positive nodes. Among nodepositive patients, the prevalence of nodal metastasis was highest in the pericholedochal (54%) and cystic duct (38%) nodes, followed by the second-echelon node groups (29% to 19%), while more distant node groups were only rarely (5% or less) involved. Disease-specific survival after R0 resection differed according to the nodal status (P < 0.001): most node-negative patients achieved long-term survival (median, not reached; 5-year survival, 80%), whereas among nodepositive patients, 22 survived for more than 5 years (median, 37 mo; 5-year survival, 43%). CONCLUSION: The rational extent of lymphadenectomy for gallbladder cancer should include the first-and second-echelon nodes. A considerable proportion of node-positive patients benefit from such aggressive lymphadenectomy.展开更多
Colorectal cancer (CRC) is one of the commonest cancers with 1.2 million new cases diagnosed each year in the world. It remains the fourth most common cause of cancer-related mortality in the world and accounts for &a...Colorectal cancer (CRC) is one of the commonest cancers with 1.2 million new cases diagnosed each year in the world. It remains the fourth most common cause of cancer-related mortality in the world and accounts for > 600000 cancer-related deaths each year. There have been significant advances in treatment of metastatic CRC in last decade or so, due to availability of new active targeted agents and more aggressive approach towards the management of CRC, particularly with liver-only-metastases; however, these drugs work best when combined with conventional chemotherapy agents. Despite these advances, there is a lack of biomarkers to inform us about the accurate management of the patients with metastatic CRC. It is therefore imperative to carefully select the patients with comprehensive multi-disciplinary team input in order to optimise the management of these patients. In this review we will discuss various treatment options available in management of colorectal liver metastases with potential guidance on how and when to choose these options along with consideration on future directions in management of this disease.展开更多
文摘Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process.This process starts with a series of mutations in colonic epithelial cells,continues with their detachment from the large intestine,dissemination through the blood and/or lymphatic circulation,attachment to the hepatic sinusoids and interactions with the sinusoidal cells,such as sinusoidal endothelial cells,Kupffer cells,stellate cells and pit cells.The metastatic sequence terminates with colorectal cancer cell invasion,adaptation and colonisation of the hepatic parenchyma.All these events,termed the colorectal cancer invasion-metastasis cascade,include multiple molecular pathways,intercellular interactions and expression of a plethora of chemokines and growth factors,and adhesion molecules,such as the selectins,the integrins or the cadherins,as well as enzymes including matrix metalloproteinases.This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting.
文摘Systematic analysis of the epidermal growth factor receptor(EGFR)pathway revealed that biomarkers could be used to predict the response to and outcome of antiEGFR therapies in patients affected by metastatic colorectal cancer.We have conducted a review on the most recent findings and advances on this topic.To this aim,we searched the PubMed database for articles devoted to predictive and prognostic biomarkers for patients administered cetuximab-and panitumumab-based therapies.Here we review the state of the art and the controversies about the molecular factors known to be predictors of the efficacy of anti-EGFR therapy,namely,KRAS,BRAF,NRAS,PI3KCA and PTEN,and we discuss their prognostic value in colorectal cancer patients.
基金Supported by Gazi UniversityScientific Research Projects DivisionNo.01/2007-62
文摘AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal carcinoma patients. The patients were re-grouped according to the presence or absence of LI and lymph node metastasis. Forty-three cancer-free subjects without any metabolic disturbances were included into the control group. Serum neopterin was measured by enzyme linked immunosorbent assay. Urinary neopterin and biopterin, serum tryptophan (Trp) and kynurenine (Kyn) concentrations of all patients were determined by high performance liquid chromatography. Kyn/Trp was calculated and its correlation with serum neopterin was determined to estimate the serum indoleamine 2,3-dioxygenase activity. Tissue sections from the studied tumors were re-examined histopathologically and were stained by immunohistochemistry with indoleamine-2,3-dioxygenase antibodies.RESULTS: Neither serum nor urinary neopterin was significantly different between the patient and control groups (both P > 0.05). However, colorectal carcinoma patients showed a significant positive correlation between the serum neopterin levels and Kyn/Trp (r = 0.450, P < 0.01). Urinary biopterin was significantly higher in cancer cases (P < 0.05). Serum Kyn/Trp was significantly higher in colorectal carcinoma patients (P < 0.01). Lymphatic invasion was present in 23 of 44 patients, of which only 12 patients had lymph node metastasis. Eleven patients with LI had no lymph node metastasis. Indoleamine-2,3-dioxygenase intensity score was significantly higher in LI positive cancer group (44.56% ± 6.11%) than negative colorectal cancer patients (24.04% ± 6.90%), (P < 0.05). Indoleamine 2,3-dioxygenase expression correlated both with the presence of LI and lymph node metastasis (P < 0.01 and P < 0.05, respectively). A significant difference between the accuracy of diagnosis by using either
文摘We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma （HCC） metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography （CT） revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging （HR/） disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced HRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations, Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.
文摘BACKGROUND: We commonly encounter fractures secondary to trauma on and off in our daily practice. While it is not uncommon to see fractures due to underlying pathology, we need to be on the alert when patients present atypically because the treatment for pathological fractures is far different from that for simple fractures.METHODS: We presented a case of left clavicle fracture secondary to minor trauma, in which the initial X-ray shows suspicious lesion around the fracture site and further investigation reveals multiple myeloma. The patient received treatment at the clinical oncology department upon diagnosis. Since he was relatively young and fi t, he was started on the induction therapy of VTD, which was followed by high dose melphalan and autologous stem cell transplant.RESULTS: He is currently free from symptoms and on maintenance thalidomide.CONCLUSIONS: Though multiple myeloma is not commonly encountered in emergency practice, earlier identification of relatively subtle symptoms can allow early treatment. Missing this diagnosis will delay treatment and produce severe outcome to the patient. We should be on the alert for such important condition.
基金Supported by A grant from the Ministry of Education, Culture,Sports, Science and Technology in Japan, Grant-in-Aid for Scientific Research, No. 23592004
文摘AIM: To define the rational extent of regional lymphadenectomy for gallbladder cancer and to clarify its effect on long-term survival. METHODS: A total of 152 patients with gallbladder cancer who underwent a minimum of "extended" portal lymph node dissection (defined as en bloc removal of the first-and second-echelon nodes) from 1982 to 2010 were retrospectively analyzed. Based on previous studies, regional lymph nodes of the gallbladder were divided into first-echelon nodes (cystic duct or pericholedochal nodes), second-echelon nodes (node groups posterosuperior to the head of the pancreas or around the hepatic vessels), and more distant nodes. RESULTS: Among the 152 patients (total of 3352 lymph nodes retrieved, median of 19 per patient), 79 patients (52%) had 356 positive nodes. Among nodepositive patients, the prevalence of nodal metastasis was highest in the pericholedochal (54%) and cystic duct (38%) nodes, followed by the second-echelon node groups (29% to 19%), while more distant node groups were only rarely (5% or less) involved. Disease-specific survival after R0 resection differed according to the nodal status (P < 0.001): most node-negative patients achieved long-term survival (median, not reached; 5-year survival, 80%), whereas among nodepositive patients, 22 survived for more than 5 years (median, 37 mo; 5-year survival, 43%). CONCLUSION: The rational extent of lymphadenectomy for gallbladder cancer should include the first-and second-echelon nodes. A considerable proportion of node-positive patients benefit from such aggressive lymphadenectomy.
基金Supported by the National Institute for Health Research(NIHR)Biomedical Research Centre(BRC)at the Royal Marsden NHS Foundation Trust and Institute of Cancer Research and the Robert McAlpine Charity(partly,for Khurum Khan)
文摘Colorectal cancer (CRC) is one of the commonest cancers with 1.2 million new cases diagnosed each year in the world. It remains the fourth most common cause of cancer-related mortality in the world and accounts for > 600000 cancer-related deaths each year. There have been significant advances in treatment of metastatic CRC in last decade or so, due to availability of new active targeted agents and more aggressive approach towards the management of CRC, particularly with liver-only-metastases; however, these drugs work best when combined with conventional chemotherapy agents. Despite these advances, there is a lack of biomarkers to inform us about the accurate management of the patients with metastatic CRC. It is therefore imperative to carefully select the patients with comprehensive multi-disciplinary team input in order to optimise the management of these patients. In this review we will discuss various treatment options available in management of colorectal liver metastases with potential guidance on how and when to choose these options along with consideration on future directions in management of this disease.
