Exploring the Need and Strategy for Intraoperative Freezing to Identify Metastatic Adenocarcinoma of the Lungs

Objective: To explore the necessity and strategy of intraoperative freezing to identify primary and metastatic adenocarcinoma of the lung. Methods: This study retrospectively analyzes the impact of failing to make a definitive diagnosis of metastatic adenocarcinoma of the lung on the clinical surgical approach in four cases of intraoperative freezing. It also examines the reasons for this failure and reviews the relevant literature. Results: All 4 cases of intraoperative freezing were diagnosed as invasive adenocarcinoma, and none of them made a definitive diagnosis of metastatic adenocarcinoma. Conclusion: It is difficult to confirm the diagnosis of metastatic adenocarcinoma of the lung by intraoperative frozen section, and the combination of patient history, rapid immunohistochemistry, and histological morphology of intraoperative frozen section for its identification can guide the surgeon to adjust the surgical approach in time and provide evidence for the establishment of surgical protocols for reference.

Scoring system for prediction of metastatic spine tumor prognosis

Assessing the prognosis before treatment for metastatic spine tumor is extremely important in therapy selection.Therefore,we review some prognostic scoring systems and their outcomes.Articles with combinations of two keywords among"metastatic spine tumor"and"prognosis","score","scoring system","predicting",or"life expectancy"were searched for in Pub Med.As a result,236 articles were extracted.Those referring to representative scoring systems about predicting the survival of patients with metastatic spine tumors were used.The significance and limits of these scoring systems,and the future perspectives were described.Tokuhashi score,Tomita score,Baur score,Linden score,Rades score,and Katagiri score were introduced.They are all scoring systems prepared by combining factors that affect prognosis.The primary site of cancer and visceral metastasis were common factors in all of these scoring systems.Other factors selected to influence the prognosis varied.They were useful to roughly predict thesurvival period,such as,"more than one year or not"or"more than six months or not".In particular,they were utilized for decision-making about operative indications and avoidance of excessive medical treatment.Because the function depended on the survival period in the patients with metastatic spine tumor,it was also utilized in assessing functional prognosis.However,no scoring system had more than 90%consistency between the predicted and actual survival periods.Future perspectives should adopt more oncological viewpoints with adjustment of the process of treatment for metastatic spine tumor.

Differential study of DCE-MRI parameters in spinal metastatic tumors, brucellar spondylitis and spinal tuberculosis

Objective： In the present study, spinal metastatic tumors, brucellar spondylitis and spinal tuberculosis werequantitatively analyzed using dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI） to assess thevalue of DCE-MRI in the differential diagnosis of these diseases.Methods： Patients with brucellar spondylitis, spinal tuberculosis or a spinal metastatic tumor （30 cases of each）received conventional MRI and DCE-MRI examination. The volume transfer constant （Ktrans）, rate constant （Kep）,extravascular extracellular volume fraction （Ve） and plasma volume fraction （Vp） of the diseased vertebral bodieswere measured on the perfusion parameter map, and the differences in these parameters between the patients werecompared.Results： For pathological vertebrae in cases of spinal metastatic tumor, brucellar spondylitis and spinaltuberculosis, respectively, the Ktrans values （median ＋ quartile pitch） were 0.989±0.014, 0.720±0.011 and0.317±0.005 min-1; the Kep values were 2.898±0.055, 1.327±0.017 and 0.748±0.006 min-1; the Ve values were0.339±0.008, 0.542±0.013 and 0.428±0.018; the Vp values were 0.048±0.008, 0.035±0.004 and 0.028±0.009; thecorresponding H values were 50.25 （for Ktrans）, 52.47 （for Kep）, 48.33 （for Ve） and 46.56 （for Vp）, and all differenceswere statistically significant （two-sided P〈0.05）.Conclusions： The quantitative analysis of DCE-MRI has a certain value in the differential diagnosis of spinalmetastatic tumor, brucellar spondylitis and spinal tuberculosis.

Complications of high intensity focused ultrasound in patients with recurrent and metastatic abdominal tumors

AIM： To analyze the local and systemic complications of high intensity focused ultrasound （HIFU） for patients with recurrent and metastatic abdominal tumors. METHODS： From Aug 2001 to Aug 2004, 17 patients with recurrent and metastatic abdominal tumors were enrolled in this study. Real-time sonography was taken, and vital signs, liver and kidney function, skin burns, local reactions, and systemic effects were observed and recored before, during, and after HIFU. CT and MR/were also taken before and after HIFU. RESULTS： All 17 patients had skin burns and pain in the treatment region; the next common complication was neurapraxia of the stomach and intestines to variable degrees. The other local and systemic complications were relatively rare. Severe complications were present in two patients; one developed a superior mesenteric artery infarction resulting in necrosis of the entire small intestines, and the other one suffered from a perforation in terminal ileum due to HIFU treatment. CONCLUSION： Although HIFU is a one of noninvasive treatments for the recurrent and metastatic abdominal tumors, there are still some common and severe complications which need serious consideration.

Significance of postoperative follow-up of patients with metastatic colorectal cancer using circulating tumor DNA

BACKGROUND One of the most notable applications for circulating tumor DNA(ctDNA)detection in peripheral blood of patients with metastatic colorectal cancer(mCRC)is a long-term postoperative follow-up.Sometimes referred to as a“liquid(re)biopsy”it is a minimally invasive procedure and can be performed repeatedly at relatively short intervals(months or even weeks).The presence of the disease and the actual extent of the tumor burden(tumor mass)within the patient’s body can be monitored.This is of particular importance,especially when evaluating radicality of surgical treatment as well as for early detection of disease progression or recurrence.AIM To confirm the radicality of surgery using ctDNA and compare available methods for detection of recurrence in metastatic colorectal cancer.METHODSA total of 47 patients with detected ctDNA and indications for resection of mCRC were enrolled in the multicenter study involving three surgical centers.Standard postoperative follow-ups using imaging techniques and the determination of tumor markers were supplemented by ctDNA sampling.In addition to the baseline ctDNA testing prior to surgery,a postoperative observation was conducted by evaluating ctDNA presence up to a week after surgery and subsequently at approximately three-month intervals.The presence of ctDNA was correlated with radicality of surgical treatment and the actual clinical status of the patient.RESULTS Among the monitored patients,the R0(curative)resection correlated with postoperative ctDNA negativity in 26 out of 28 cases of surgical procedures(26/28,93%).In the remaining cases of R0 surgeries that displayed ctDNA,both patients were diagnosed with a recurrence of the disease after 6 months.In 7 patients who underwent an R1 resection,4 ctDNA positivities(4/7,57%)were detected after surgery and associated with the confirmation of early disease recurrence(after 3 to 7 months).All 15 patients(15/15,100%)undergoing R2 resection remained constantly ctDNA positive during the entire follow-up period.In 22 cases of recurrence,ctDNA positivity was detected 22 times(22/22,100%)compared to 16 positives(16/22,73%)by imaging methods and 15 cases(15/22,68%)of elevated tumor markers.CONCLUSION ctDNA detection in patients with mCRC is a viable tool for early detection of disease recurrence as well as for confirmation of the radicality of surgical treatment.

Macrophage inflammatory protein-2 contributes to liver resection-induced acceleration of hepatic metastatic tumor growth

AIM： To study the role of macrophage inflammatory protein （HIP）-2 in liver resection-induced acceleration of tumor growth in a mouse model of hepatic metastasis. METHODS： After a 50% hepatectomy, 1×10^5 CT26.WT cells were implanted into the left liver lobe of syngeneic balb/c mice （PHx）. Additional animals were treated with a monoclonal antibody （HAB452） neutralizing HIP-2 （PHx＋mAB）. Non-resected and non-mAB-treated mice （Con） served as controls. After 7 d, tumor angiogenesis and microcirculation as well as cell proliferation, tumor growth, and CXCR-2 expression were analyzed using in- travital fluorescence microscopy, histology, immunohisto- chemistry, and flow cytometry. RESULTS： Partial hepatectomy increased （P〈0.05）the expression of the HIP-2 receptor CXCR-2 on tumor cells when compared with non-resected controls, and markedly accelerated （P〈 0.05） angiogenesis and metastatic tumor growth. Neutralization of HIP-2 by HAB452 treatment significantly （P〈 0.05） depressed CXCR-2 expression. Further, the blockade of MIP-2 reduced the angiogenic response （P〈 0.05） and inhibited tumor growth （P〈 0.05）. Of interest, liver resection-induced hepatocyte proliferation was not effected by anti-HIP-2 treatment. CONCLUSION： HIP-2 significantly contributes to liver resection-induced acceleration of colorectal CT26.WT hepatic metastasis growth.

Metastatic tumors to the stomach: Clinical and endoscopicfeatures

AIM: To evaluate the clinical and endoscopic patterns in a large series of patients with metastatic tumors in the stomach. METHODS: A total of 64 patients with gastric meta- stases from solid malignant tumors were retros- pectively examined between 1990 and 2005. The clinicopathological findings were reviewed along with tumor characteristics such as endoscopic pattern, location, size and origin of the primary sites. RESULTS: Common indications for endoscopy were anemia, bleeding and epigastric pain. Metastases presented as solitary (62.5%) or multiple (37.5%) tumors were mainly located in the middle or upper third of stomach. The main primary metastatic tumors were from breast and lung cancer and malignant melanoma. CONCLUSION: As the prognosis of cancer patients has been improving gradually, gastrointestinal (GI) metastases will be encountered more often. Endoscopic examinations should be conducted carefully in patients with malignancies, and endoscopic biopsies and information on the patient’s clinical history are useful for correct diagnosis of gastric metastases.

Rectal neuroendocrine tumor with uncommon metastatic spread:A case report and review of literature

Neuroendocrine tumors of the gastrointestinal tract are rare neoplasms. Rectal neuroendocrine tumors consist approximately the 5%-14% of all neuroendocrine neoplasms in Europe. These tumors are diagnosed in relatively young patients,with a mean age at diagnosis of 56 years. Distant metastases from rectal neuroendocrine tumors are not very common. Herein we describe a case of a rectal neuroendocrine tumor which metastasized to the lung,mediastinum and orbit. This case underscores the importance of early identification and optimal management to improve patient's prognosis. Therefore,the clinical significance of this case is the necessity of physicians' awareness and education regarding neuroendocrine tumors' diagnosis and management.

Metastatic colon cancer treated using traditional Chinese medicine combined with chemotherapy:A case report

BACKGROUND Colon cancer(CC)is one of the leading causes of cancer-related morbidity and mortality worldwide.Traditional Chinese medicine(TCM)is widely used in the treatment of various chronic diseases.CC easily metastasizes and results in high morbidity and mortality rates.CASE SUMMARY A 71-year-old man with a 12-year history of old myocardial infarction and a 7-year history of type 2 diabetes mellitus was diagnosed with CC and underwent right hemicolectomy 1 year ago.Tumor biopsy revealed moderately poorly differentiated adenocarcinoma.Subsequently,chemotherapy with oxaliplatin and paclitaxel was administered.Anastomosis recurrence and pelvic metastasis were noted 37 d later.The patient received eight 21-d cycles of adjuvant chemotherapy with oxaliplatin and capecitabine after recurrence.However,the tumor persisted,and chemotherapy-related liver damage developed gradually.Thus,he was advised to take TCM for the recurrence and pelvic metastasis.The patient’s metastatic CC was cured after receiving TCM combined with long-term chemotherapy.CONCLUSION TCM may be an effective adjunct therapy in the treatment of patients with metastatic CC.

Influence of primary tumor location and resection on survival in metastatic colorectal cancer

BACKGROUND Patients with right sided colorectal cancer are known to have a poorer prognosis than patients with left sided colorectal cancer, whatever the cancer stage. To this day, primary tumor resection(PTR) is still controversial in a metastatic, non resectable setting.AIM To explore the survival impact of PTR in patients with metastatic colorectal cancer(mCRC) depending on PTL.METHODS We retrospectively collected data from all consecutive patients treated for mCRC at the Centre Georges Francois Leclerc Hospital. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of PTR on survival. We then evaluated the association between PTL and overall survival among patients who previously underwent or did not undergo PTR. A propensity score was performed to match cohorts.RESULTS Four hundred and sixty-six patients were included. A total of 153(32.8%) patients had unresected synchronous mCRC and 313(67.2%) patients had resected synchronous mCRC. The number of patients with right colic cancer, left colic cancer and rectal cancer was respectively 174(37.3%), 203(43.6%) and 89(19.1%). In the multivariate analysis only PTL, PTR, resection of hepatic and or pulmonary metastases and the use of oxaliplatin, EGFR inhibitors or bevacizumab throughout treatment were associated to higher overall survival rates. Survival evaluation depending on PTR and PTL found that PTR improved the prognosis of both left and right sided mCRC. Results were confirmed by using a weighted propensity score.CONCLUSION In mCRC, PTR seems to confer a higher survival rate to patients whatever the PTL.

Focal peliosis hepatis in a colon cancer patient resembling metastatic liver tumor

Peliosis hepatis(PH) is a rare benign condition characterized by the presence of multiple,randomly distributed,blood filled cystic areas of variable size within the liver parenchyma.PH is difficult to recognize and may be mistaken for neoplasm,metastases or multiple abscesses.A 75-year-old female with a previous history of colon cancer was admitted when a liver mass in the right liver lobe was found 11 mo after surgery during the follow-up period.Computed tomography and magnetic resonance imaging scan of the abdomen were performed.The initial possible diagnosis was metastatic hepatocellular carcinoma.The patient underwent excision of the hepatic segment where the nodule was located.The pathological diagnosis of the surgical specimen was PH.PH should be considered in the differential diagnosis of new liver lesions in patients whose clinical settings do not clearly favor metastasization.Clinicians and radiologists must recognize these lesions to minimize the probability of misdiagnosis and inappropriate treatment.

Prognostic tumor microenvironment gene and the relationship with immune infiltration characteristics in metastatic breast cancer

The aim of this study was to reveal genes associated with breast cancer metastasis,to investigate their intrinsic relationship with immune cell infiltration in the tumor microenvironment,and to screen for prognostic biomarkers.Gene expression data of breast cancer patients and their metastases were downloaded from the GEO,TCGA database.R language package was used to screen for differentially expressed genes,enrichment analysis of genes,PPI network construction,and also to elucidate key genes for diagnostic and prognostic survival.Spearman’s r correlation was used to analyze the correlation between key genes and infiltrating immune cells.We screened 25 hub genes,FN1,CLEC5A,ATP8B4,TLR7,LY86,PTGER3 and other genes were differentially expressed in cancer and paraneoplastic tissues.However,patients with higher expression of CD1C,IL-18 breast cancer had a better prognosis in the 10 years survival period,while patients with high expression of FN1,EIF4EBP1 tumors had a worse prognosis.In addition,TP53 and HIF1 genes are closely related to the signaling pathway of breast cancer metastasis.In this study,gene expression of ATP8B4 and CD1C were correlated with cancer tissue infiltration of CD8^(+)T lymphocytes,while GSE43816,GSE62327 and TCGA databases showed that CD8^(+)T lymphocytes were closely associated with breast cancer progression.Functional enrichment analysis of genes based on expression differences yielded key genes of prognostic value in the breast cancer microenvironment.

SURGICAL TREATMENT OF METASTATIC SPINAL TUMOR

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Palliative primary tumor resection provides survival beneits for the patients with metastatic colorectal cancer and low circulating levels of dehydrogenase and carcinoembryonic antigen

Background: It remains controversial whether palliative primary tumor resection(PPTR) can provide survival benefits to the patients with metastatic colorectal cancer(m CRC) who have unresectable metastases. The aim of this study was to evaluate whether PPTR could improve the survival of patients with m CRC.Methods: We conducted a retrospective study on consecutive m CRC patients with unresectable metastases who were diagnosed at Sun Yat?sen University Cancer Center in Guangzhou, Guangdong, China, between January 2005 and December 2012. Overall survival(OS) and progression?free survival(PFS) after first?line chemotherapy failure were compared between the PPTR and non?PPTR patient groups.Results: A total of 387 patients were identified, including 254 who underwent PPTR and 133 who did not. The median OS of the PPTR and non?PPTR groups was 20.8 and 14.8 months(P < 0.001), respectively. The median PFS after first?line chemotherapy was 7.3 and 4.8 months(P < 0.001) in the PPTR and non?PPTR groups, respectively. A larger proportion of patients in the PPTR group(219 of 254, 86.2%) showed local progression compared with that of patients in the non?PPTR group(95 of 133, 71.4%; P < 0.001). Only patients with normal lactate dehydrogenase(LDH) levels and with carcinoembryonic antigen(CEA) levels <70 ng/m L benefited from PPTR(median OS, 22.2 months for the PPTR group and 16.2 months for the non?PPTR group; P < 0.001).Conclusions: For m CRC patients with unresectable metastases, PPTR can improve OS and PFS after first?line chemo?therapy and decrease the incidence of new organ involvement. However, PPTR should be recommended only for patients with normal LDH levels and with CEA levels <70 ng/m L.

APPLICATION VALUE OF MAGNETIC RESONANCE SEQUENCES IN DIAGNOSIS OF EARLY SPINAL METASTATIC TUMOR

Objective To investigate the clinical value of different magnetic resonance (MR) pulse sequences in diagnosis of spinal metastatic tumor. Methods Fifteen patients with clinically suspected spinal metastatic tumor were included in this study. These patients were with documented primary tumors. Four MR pulse sequences, T1-weighted spin echo (T1WI SE), T2-weighted fast spin echo (T2WI FSE), short time inversion recovery (STIR), and gradient echo 2-D multi echo data imaging combination (GE Me-2D) were used to detect spinal metastasis. Results Fifteen vertebral bodies were entire involvement, 38 vertebral bodies were section involvement, and totally 53 vertebral bodies were involved. There were 19 focal infections in pedicle of vertebral arch, 15 metastases in spinous process and transverse process. Fifty-three vertebral bodies were abnormal in T1WI SE and GE Me-2D, 35 vertebral bodies were found abnormal in T2WI FSE, and 50 vertebral bodies were found abnormal in STIR. The verges of focal signal of involved vertebral bodies were comparatively clear in T1WI SE, comparatively clear or vague in T2WI FSE, vague in STIR, and clear in GE Me-2D.Conclusions GE Me-2D may be the most sensitive technique to detect metastases. So three sequences (T1WI SE, T2WI FSE, GE Me-2D) can demonstrate the early changes of spinal metastasis roundly.

Hepatic metastatic disease in pediatric and adolescent solid tumors

The management of hepatic metastatic disease from solid tumors in adults has been extensively described and resection of metastatic liver lesions from colorectal adenocarcinoma, renal adenocarcinoma, breast cancer, testicular cancer, and neuroendocrine tumors(NET) havedemonstrated therapeutic benefits in select patients. However, there are few reports in the literature on the management of hepatic metastatic disease in the pediatric and adolescent populations and the effectiveness of hepatic metastasectomy. This may be due to the much lower incidence of pediatric malignancies and the higher chemosensitivity of childhood tumors which make hepatic metastasectomy less likely to be required. We review liver involvement with metastatic disease from the main pediatric solid tumors, including neuroblastoma and Wilms tumor focusing on the management and treatment options. We also review other solid malignant tumors which may have liver metastases including germ cell tumors, gastrointestinal stromal tumors, osteosarcoma, desmoplastic small round cell tumors and NET. However, these histological subtypes are so rare in the pediatric and adolescent populations that the exact incidence and best management of hepatic metastatic disease are unknown and can only be extrapolated from adult series.

Analysis of therapeutic efficacy of Aredia in treating pain caused by advanced malignant metastatic bone tumors

Objective To study therapeutic efficacy of Aredia in treating malignant metastatic bone tumors. Method 60～90 mg Aredia was administrated iv in 31 cases with malignant metastatic tumors,once each week. Results Pain in 12 cases was significantly relieved.14 cases acquired relif.Total effective rate was 83.9%.Activity ability was improved by 80.6%.No apparent toxicological and adverse effects as well as fever and cold symptoms were observed.Conclusion Aredia is a kind of ideal drugs for treatment of pain caused by malignant metastatic bone tumors.It is convenient in use and could be endured by patients.

Expression of the Tumor Metastatic Suppressor Gene in Mouse Melanoma Model: Inverse Association to Metastatic Potential

Data obtained in experimental cutaneous melanomas have suggested that the nm23 gene may function as a metastasis suppressor gene. The nm23 level in 8 human cutaneous melanoma cell lines and 2 murine melanoma cell lines were examined. Each melanoma cell line was transplanted subcutaneously into the flank of nude mice, and the metastatic behavior was evaluated by counting lung tumor fool and by determining host survival time. It was found that expression of 'm23 mRNA in human melanomas is correlated closely with reduced metastatic behavior in experimental animals and may serve as a sensitive prognostic indicator of malignancy and survival in patients with melanomas.

Observation of the therapeutic efficacy of stereotactic radiotherapy in 44 cases of retroperitoneal metastatic tumor

Objective: To investigate the therapeutic effects of stereotactic radiotherapy for retroperitoneal metastatic tumor. Methods: From August 1997 to October 2004, 44 patients with retroperitoneal metastatic tumors were treated with stereotactic radiotherapy. The planning target volume was encompassed by 90%–95% isodose line. Fractional dose was from 6 Gy to 8 Gy, and they were treated 2–3 times per-week and 4–8 times in all. The total radiation doses of PTV were from 32 Gy to 48 Gy. Re- sults: After the radiotherapy, the pain was obviously relieved in 81.8% patients. Three months after completion of radiotherapy passed and then, abdominal CT was performed to evaluate the results. The whole effective rate was 81.8% [CR 27.7% (12/44) and PR 54.5% (24/44)], and six months after radiotherapy, CR was 27.7% (12/44) and PR was 59.1% (26/44). The middle survival time was 12 months. Conclusion: It is suggested that stereotactic radiotherapy for retroperitoneal metastatic tumor is a safe and effective method.

Clnical Study of the Treatment of Patients with a Metastatic Spinal Tumor by Percutaneous Vertebroplasty under the Guidance of DSA

OBJECTIVE To explore the clinical effect in patients with metastatic spinal tumors treated by percutaneous vertebroplasty （PVP） under the guidance of digital subtraction angiography （DSA）. METHODS A total of 110 cases with a metastatic spinal tumor were di- vided into 55 cases in the treatment group （group A ） and 55 cases in the control group （group B ）. The general clinical data were statistically analyzed before treatment with the parameters showing no differences. Group A was treated by PVP and chemotherapy as well. Group B was treated by the regular chemotherapy and regular radiation therapy. The same chemotherapy program was used for the same type of disease. All cases were provided with a follow-up survey for 12 months. During the follow-up survey, changes in the quality of life, in evaluation of bone pain and in vertebral column stability as well as adverse reactions were observed. RESULTS The statistics showed a significant difference between the 2 groups, specifically changes in the quality of life and evaluation of bone pain （P〈0.05, t1=2.74, t2=9.02）. During the follow-up survey, 5 cases in group A died of other organ complilcations, the death rate being 9.1% （5 out of 55）, but all survived more than 3 months following PVP. The vertebral columns of the survivors were kept stable, with no pathological fractures occurring in the vertebral bodies filled with bone cement, there were no obvious adverse reactions, and no paraplegia occurred. Thirteen cases died in group B with a death rate of 23.6% （13 out of 55）. Pathological compression fractures in the vertebral bodies occurred in 30 cases, and 12 cases of complicated paraplegia were noted. The incident rate of paraplegia was 21.8% （12 out of 55）. CONCLUSION PVP is a simple operation causing only small wounds and few complications. It can effectively alleviate pain of metastatic spinal tumors in patients, improve quality of life and reduce the incidence rate of paraplegia.