Extensive screening for occult malignant disease in idiopathic venous thromboembolism: a prospective randomized clinical trial.

Patients with symptomatic idiopathic venous thromboembolism and apparently cancer-free have an approximate 10% incidence of subsequent cancer. Apparently cancer-free patients with acute idiopathic venous thromboembolism were randomized to either the strategy of extensive screening for occult cancer or to no further testing. Patients had a 2-year follow-up period. Of the 201 patients, 99 were allocated to the extensive screening group and 102 to the control group. In 13 (13.1%) patients, the extensive screening identified occult cancer. In the extensive screening group, a single (1.0%) malignancy became apparent during follow-up, whereas in the control group a total of 10 (9.8%) malignancies became symptomatic [relative risk, 9.7 (95% CI, 1.3-36.8; P < 0.01]. Overall, malignancies identified in the extensive screening group were at an earlier stage and the mean delay to diagnosis was reduced from 11.6 to 1.0 months (P < 0.001). Cancer-related mortality during the 2 years follow-up period occurred in two (2.0%) of the 99 patients of the extensive screening group vs. four (3.9%) of the 102 control patients [absolute difference, 1.9% (95% CI, -5.5-10.9)]. Although early detection of occult cancers may be associated with improved treatment possibilities, it is uncertain whether this improves the prognosis.     

JAK2V617F mutation screening as part of the hypercoagulable work-up in the absence of splanchnic venous thrombosis or overt myeloproliferative neoplasm: assessment of value in a series of 664 consecutive patients

The JAK2V617F mutation is recurrent in polycythemia vera and essential thrombocythemia, which are myeloproliferative neoplasms (MPNs) frequently associated with arterial and/or venous thromboembolism. More recently, the JAK2V617F mutation has been identified as a surrogate marker for subclinical or "occult" clonal myeloproliferation in patients with splanchnic venous thrombosis. However, information is limited regarding JAK2V617F-associated thrombosis outside the splanchnic district in patients without overt MPN. To address this issue, we retrospectively studied a consecutive series of 664 such patients who experienced thrombotic events characteristic of an MPN (500 with venous thromboembolism, 136 with stroke, and 28 with myocardial infarction at a young age). The JAK2V617F mutation was detected in only 6 (<1.0%) patients (5 with recurrent venous thromboembolism and 1 with stroke), and the mutant allele burden was low in all instances (range, 2.2%-7.5%). None of these 6 patients developed either overt MPN or recurrent thrombosis after a median follow-up of 40 months. We conclude that the prevalence of the JAK2V617F mutation in patients with nonsplanchnic venous thrombosis in the absence of MPN is too low to warrant mutation screening as part of the hypercoagulable work-up. Our study also suggests that the natural history of a JAK2V617F-positive "occult" MPN might be different from that of a typical MPN.     

Ultrasonographic detection of occult cancer in patients after surgical therapy for breast cancer.

OBJECTIVE: The purpose of this study was to investigate the efficacy of ultrasonography in detecting an occult malignancy after surgery for breast cancer and to assess the imaging and clinical findings associated with a recurrence. METHODS: During a 4-year period, 3329 bilateral whole-breast ultrasonographic examinations were performed to detect occult malignancies clinically and mammographically in 1968 asymptomatic patients after breast cancer surgery. All questionable lesions were confirmed with ultrasonographically guided intervention. This study reviewed ultrasonographic findings and pathologic results of the questionable lesions along with the clinical parameters of the patients. We searched for false-negative cases from the hospital database. RESULTS: Among the 1968 patients, ultrasonography revealed questionable lesions in 57 (2.9%). The questionable lesions were lymph nodes in 42 and masses in 15; of these lesions, 24 were malignant (true-positive) and 33 were benign (false-positive). Ten false-negative cases were identified. The sensitivity and specificity were 70.6% and 98.3%, respectively. The locations of the recurrent lesions were the regional lymph nodes in 14 cases (4, axillary fossa; 4, interpectoral; 4, internal mammary; and 2, supraclavicular lymph nodes) and the breast and mastectomy bed in 7 cases. The mean size of the malignant lymph nodes was larger than that of the benign lymph nodes. Among those with positive examination results, the clinical parameters in the recurrent and nonrecurrent groups were similar. CONCLUSIONS: Postoperative follow-up ultrasonography showed occult malignancies clinically and mammographically in 1.2% of the patients who had been treated for breast cancer. Familiarity with the common location of a tumor recurrence is essential for making an accurate ultrasonographic evaluation in these patients.     

The safety of dosing dalteparin based on actual body weight for the treatment of acute venous thromboembolism in obese patients.

Data evaluating the safety of using weight-based low-molecular-weight heparin in the treatment of obese patients with acute venous thromboembolism are limited. The product monograph of dalteparin suggests the maximum dose should be limited to 18,000 U subcutaneously once daily. There are no specific data regarding the risk of recurrence or bleeding in patients given dalteparin in a weight-based dose of 200 IU kg(-1). We report a retrospective chart review of 193 obese patients who weighed more than 90 kg and who received dalteparin at or near to 200 IU kg(-1) actual body weight for 5-7 days for acute venous thromboembolism with 90 day follow-up information. Of the patients, 77% had idiopathic venous thromboembolism, 16% had an underlying malignancy, and 7% had a transient risk factor. Warfarin was initiated within 2 days with a target International Normalized Ratio range of 2.0-3.0. All patients were followed for 12 weeks post diagnosis. Only two patients had a major hemorrhage, 4 and 8 weeks from diagnosis. This study supports the safety of dosing dalteparin based on actual body weight in obese patients.     

Optimizing breast cancer follow-up: diagnostic value and costs of additional routine breast ultrasound

A total of 2,546,325 breast cancer survivors are estimated to live in the United States. The organized breast cancer follow-up programs do not generally include breast ultrasound in asymptomatic women. The purpose of our prospective study was to investigate the efficacy of breast ultrasound in detecting previously occult recurrences. A total of 735 eligible patients with a history of breast cancer were recruited. We assessed the same patient population before (routine follow-up program) and after (study follow-up program) the introduction of an additional ultrasound examination. In the routine follow-up program 245 of 735 patients (33.3% [95% confidence-interval (CI): 29.9-36.7]) had an ultrasound due to abnormal local or mammographic findings. 490 of 735 patients (66.7% [95% CI: 63.3-70.1]) were initially considered asymptomatic and received an additional ultrasound exclusively within the study follow-up program.All positive examination results were followed by accelerated core needle biopsy. The routine follow-up program led to a biopsy in 66 of 735 patients (9.0%) revealing a recurrent cancer in 27 cases (3.7%). The study follow-up program with the additional ultrasound led to another 21 biopsies raising the total number of patients who had to undergo a biopsy from 9.0% (95% CI: 6.9-11.1) to 11.8% (95% CI: 9.5-14.2). Finally, we diagnosed a previously occult malignant lesion in an additional six patients following this protocol. Therefore, the rate of detected recurrences rose from 3.7% (95% CI: 2.3-5.0) in the routine follow-up program to 4.5% (95% CI: 3.0-6.0) in the study follow-up program (p = 0.041). Negative side effects were the additional costs (the costs per detected malignancy in the routine follow-up program were $2455.69; the costs for each additionally detected malignancy in the study follow-up program were $7580.30), the higher overall biopsy rate (9.0 vs. 11.8%) and the elevated benign biopsies rate (59.1% vs. 71.4%). Regarding these results, the advantages and disadvantages of additional breast ultrasound must be discussed for every follow-up patient individually even today, as we can detect a significantly higher number of previously occult malignancies. (E-mail s@wojcinski.de)     

Is extensive screening for cancer in idiopathic venous thromboembolism warranted?

Summary. Background: Patients with a first episode of idiopathic venous thromboembolism (IVTE) have an estimated 10% incidence of cancer within 12 months after diagnosis. However, the utility of screening for cancer in this population is controversial. Methods: In this prospective concurrently controlled cohort study, limited and extensive cancer screening strategies were compared. All 630 patients underwent baseline screening consisting of history, physical examination, basic laboratory tests and chest X‐ray. In the extensive screening group abdominal and chest CT scan and mammography were added. Outcomes were incidence and curability of cancer, and cancer‐related and overall mortality. Results: In 12 of the 342 (3.5%) patients in the extensive screening group malignancy was diagnosed at baseline compared with 2.4% (seven of 288 patients) in the limited screening group. Extensive screening detected six additional cancers (2.0%; 95% CI, 0.74–4.3), of which three were potentially curable. During a median 2.5 years of follow‐up, cancer was diagnosed in 3.7% and 5.0% in the extensive and limited screening groups, respectively. In the extensive screening group 26 patients (7.6%) died compared with 24 (8.3%) in the limited screening group; adjusted hazard ratio 1.22 (95% CI, 0.69–2.22). Of these deaths 17 (5.0%) in the extensive screening group and 8 (2.8%) in the limited screening group were cancer related; adjusted hazard ratio 1.79 (95% CI, 0.74–4.35). Conclusions: The low yield of extensive screening and lack of survival benefit do not support routine screening for cancer with abdominal and chest CT scan and mammography in patients with a first episode of IVTE.     

Differential value of risk factors and clinical signs for diagnosing pulmonary embolism according to age

INTRODUCTION: The diagnostic value of clinical presentation of pulmonary embolism (PE) is uncertain in the elderly, who often have concomitant cardiopulmonary diseases that may mimic PE. The aim of our study was to assess the differential value of risk factors, symptoms and clinical signs of venous thromboembolism, results of electrocardiogram and chest X-ray for the diagnosis of PE in suspected patients according to age. METHODS: We analyzed data from two outcome studies which enrolled 1721 consecutive patients presenting in the emergency department with clinically suspected PE defined as acute onset of new or worsening shortness of breath or chest pain without any other obvious etiology. All patients underwent a sequential diagnostic work-up and a 3-month follow-up. RESULTS: The proportion of confirmed PE was 24.2% (416 of 1721). Strength of the association with PE did not differ according to age group for history of venous thromboembolism (VTE), recent surgery, tachypnea at admission or right ventricular strain on electrocardiogram. Active malignancy, hemoptysis, tachycardia, hemidiaphragmatic elevation and pleural effusion at chest X-ray were no more associated with PE in the patients aged of 75 years or more. Finally, symptoms and signs of deep venous thrombosis, and an alternative diagnosis less probable than PE were associated with PE in all age groups, but the strength of this association decreased significantly with advancing age. CONCLUSION: Some risk factors, symptoms and signs of VTE are less strongly or even not at all associated with PE in the elderly. Physicians should take this into account when attending elderly patients suspected of PE and when assessing their clinical probability of PE.     

Incidental detection of breast apocrine carcinoma via endometrial cytology

Breast apocrine carcinoma is a rare malignancy characterized histologically by a predominance of acidophilic tumor cells exhibiting apocrine metaplasia. Apocrine tumors represent only about 0.4% of all breast cancers. Many cases are diagnosed at stage I or II; thus, the prognosis is better than that for other types of breast cancer. Here we present a 57-year-old female patient with primary apocrine breast carcinoma that was incidentally discovered by endometrial cytology. The patient had undergone routine uterine cancer screening at the age of 56 with resulting positive endometrial cytology. Subsequent histological examination of an endometrial biopsy revealed suspected metastatic uterine adenocarcinoma. Further evaluation revealed a 3-cm mass in the left breast, which was histopathologically diagnosed as breast cancer. Dual procedures were performed at the departments of gynecology and breast surgery. The patient underwent a modified radical mastectomy of the left breast and left axillary lymph node dissection. Laparotomy revealed multiple adhesions throughout the peritoneal cavity that suggested invasive metastatic cancer, and a right adnexectomy was performed. Histopathological examination of the resected left breast and right ovary tissues revealed apocrine carcinoma. Thus, stage IV breast cancer was diagnosed. The patient finished 6 cycles of paclitaxel and is now under observation on an outpatient basis. In this patient, breast cancer was discovered incidentally through a detailed work-up after a positive result of endometrial cytology. Uterine cancer screening has the potential, although rare, to detect metastatic cancer originating elsewhere. This should be taken into consideration during the work-up due to positive endometrial cytology.     

Decision analysis for cancer screening in idiopathic venous thromboembolism

BACKGROUND: The SOMIT trial randomized patients with idiopathic venous thromboembolism (IVTE) and without signs of cancer at routine medical examination, to extensive screening for cancer plus 2 years of follow-up or to just 2-year follow-up. METHODS: The data of the SOMIT-trial were used to perform a decision analysis. The screening tests were divided in several possible strategies. The number of detected cancer patients and the number of patients investigated further for an eventually benign condition were calculated for each strategy. The total costs for the screening strategy and for each detected cancer patient were determined. Based on the tumor type, stage, age and gender of the individual cancer patient, the difference in live years gained (LYG) was calculated between the two study groups. RESULTS: Computed tomography (CT) of the abdomen combined with sputum cytology and mammography detected 12 of the 14 patients with cancer and had one false-positive result. In general, screening strategies including abdominal/pelvic ultrasonography (US) or tumor markers yielded a higher number of patients needed to screen in comparison with those using abdominal/pelvic CT. Furthermore, the strategies which included colonoscopy, tumor markers, and abdominal/pelvic US were significantly more costly, had inferior LYG and higher costs per LYG, when compared with strategies using abdominal/pelvic CT. CONCLUSIONS: Despite the limitations of this analysis, the screening for cancer with a strategy including abdominal/pelvic CT with or without mammography and/or sputum cytology appears potentially useful for cancer screening in patients with IVTE. The cost-effectiveness analysis of this strategy needs confirmation in a large trial.     

Accuracy of clinical decision rule, D-dimer and spiral computed tomography in patients with malignancy, previous venous thromboembolism, COPD or heart failure and in older patients with suspected pulmonary embolism

BACKGROUND: The diagnostic work-up of patients with suspected pulmonary embolism (PE) has been optimized and simplified by the use of clinical decision rules (CDR), D-dimer (DD) testing and spiral computed tomography (s-CT). Whether this strategy is equally safe and efficient in specific subgroups of patients is evaluated in this study. METHODS: A diagnostic strategy including a CDR, DD test and s-CT was evaluated in patients with malignancy, previous venous thromboembolism (VTE), chronic obstructive pulmonary disease or heart failure and in older patients. PE was ruled out by either an unlikely CDR and a normal DD or a s-CT negative for PE. The safety of these tests was assessed by the 3-month incidence rate of symptomatic VTE in those without PE at baseline. The efficiency was evaluated by calculating the numbers needed to test for the different subgroups. RESULTS: The venous thromboembolic incidence rate after the combination of an unlikely CDR and a normal DD varied from 0% (95% CI: 0-7.9%) in the 482 patients older than 75 years of age to 2% (95% CI: 0.05-10.9%) in the 474 patients with a malignancy. For s-CT these incidences varied from 0.3% to 1.8%. The number needed to test in order to rule out one patient from PE with the studied strategy was highest in cancer patients and in the elderly patients (approximately 10). CONCLUSION: It appears to be safe to rule out PE by either the combination of an unlikely CDR and a normal DD or by a negative s-CT in various subgroups of patients with suspected PE. However, the clinical usefulness of the CDR in combination with the DD as the initial step in the diagnostic process varied among these patient groups.     

Venous thromboembolism in patients undergoing rehabilitation for stroke.

OBJECTIVE: To determine the incidence of venous thromboembolism during rehabilitation for stroke and to identify factors that alter its risk. DESIGN: Cohort. SETTING: Tertiary care stroke rehabilitation program. PATIENTS: 102 consecutive patients undergoing rehabilitation for stroke. INTERVENTIONS: Impedance plethysmography (IPG) as routine screening and in patients with symptoms of deep venous thrombosis (DVT). MAIN OUTCOME MEASURES: DVT, pulmonary embolism (PE), death from PE. RESULTS: Venous thromboembolism was documented in 11 patients (11%) an average of 60 days after stroke onset (range 14-138 days); 2 patients (2%) died from PE. DVT was found on routine IPG screening in six patients and verified by IPG in two clinically symptomatic patients. The odds of developing venous thromboembolism was 17.6 (95% confidence interval: 2.2-143.5) in patients who were bedridden or wheelchair-bound at the time of admission. CONCLUSIONS: The incidence of venous thromboembolism is high and greatest in bedridden or wheelchair-bound patients undergoing stroke rehabilitation; randomized trials evaluating the safety and efficacy of screening and/or prophylaxis in such patients are required.     

Reintervention in C-cell carcinoma

Cervical re-exploration in persistent medullary thyroid cancer usually fails to normalize serum calcitonin levels, which is the most sensitive criterion of tumour-free status (2 out of 21 patients in our re-exploration series). Positive lymph nodes - even at an early tumour stage - seem much more important (postoperative normal serum calcitonin: 86% in the occult tumour group, 71% in patients with palpable primary tumour and negative lymph nodes, as opposed to only 18% with a palpable cervical mass and positive lymph nodes). However, local re-exploration in case of persistent medullary thyroid cancer seems to offer a possible curative chance for the control of recurrence, especially after inadequate primary surgery. In cases without visible distant metastases a marked reduction in serum calcitonin level may be expected (21% of the preoperative level for stages N1 and N2 and 16% for stage N3 on average). In patients with elevated calcitonin levels after stimulation as sole indicator of persistent tumour the indication for reoperation should be handled cautiously. Thus, in 3 out of 5 patients with occult medullary thyroid cancer diagnosed only on the basis of venous sampling who were subjected to multiple cervical re-explorations, distant metastases were subsequently found during follow-up.     

Clinical uses of tumor markers: a critical review.

Tumor markers are molecules that indicate the presence of malignancy. They are potentially useful in cancer screening, aiding diagnosis, assessing prognosis, predicting in advance a likely response to therapy, and monitoring patients with diagnosed disease. Because of the low prevalence of most cancers in the general population and the limited sensitivity and specificity of available markers, these tests alone are generally of little value in screening for cancer in healthy subjects. Currently, however, PSA in combination with digital rectal examination and CA 125 together with ultrasound are undergoing evaluation as screening modalities for prostate and ovarian cancer, respectively. Again, because of a lack of sensitivity and specificity, markers are rarely of use in the early diagnosis of cancer. As prognostic indicators, markers may provide information that is independent of traditionally used factors or within subgroups defined by traditional criteria, for example, urokinase plasminogen activator in node-negative breast cancer. At present, the best available marker for predicting response to therapy is the estrogen receptor for selecting hormone-sensitive breast cancers. Many different markers can be used in the surveillance of patients with diagnosed malignancies, the most useful of these being HCG in trophoblastic disease and both AFP and HCG for nonseminomatous testicular germ cell tumors. In general, the currently available tumor markers lack sensitivity for early cancer and specificity for malignancy. The goal of future research should be to develop more sensitive and specific markers, especially for the common cancers.     

Controversies in venous ultrasound

Ultrasound is the principal method used for diagnosing deep venous thrombosis in the United States, and its accuracy and limitations are well known. As venous ultrasound examination has matured, several controversial issues, primarily clinical, have arisen concerning the application of this diagnostic method. This article addresses some of the more noteworthy and vexing issues, including, but not limited to (a) the need to examine both legs in patients with unilateral symptoms; (b) the role of venous ultrasound in patients with bilateral leg swelling; (c) the necessary extent of the venous ultrasound examination; (d) the importance of calf vein thrombosis; (e) the significance of negative leg veins in a patient with possible pulmonary embolus; and (f) deep venous thrombosis in patients with occult malignancy. Technical aspects of the venous ultrasound examination, and diagnostic accuracy are not described.     

Use of spiral computed tomography contrast angiography and ultrasonography to exclude the diagnosis of pulmonary embolism in the emergency department

Spiral computed tomography (CT) contrast angiography is a promising imaging modality for the diagnosis of pulmonary embolism but the negative predictive value of this test remains controversial. We performed a multi-center prospective cohort study to determine the safety of relying on a negative spiral CT contrast angiography scan to exclude pulmonary embolism. Patients presenting to the Emergency Departments of three tertiary care institutions with clinically suspected pulmonary embolism were potentially eligible for the study. Patients underwent a clinical evaluation to categorize pretest probability into low, moderate, and high categories, and had D-dimer testing performed. Patients at low pretest probability with normal D-dimer were considered to have pulmonary embolism excluded. The remaining patients underwent spiral CT contrast angiography scan of the pulmonary arterial circulation and bilateral venous ultrasound of the proximal leg veins. Patients who were confirmed to have pulmonary embolism or deep vein thrombosis were treated with anticoagulant therapy. Patients in whom the diagnosis of pulmonary embolism was excluded did not receive anticoagulant therapy and were followed for a 3-month period for the development of venous thromboembolic complications. Eight hundred fifty-eight (858) patients were enrolled in this study. Three-hundred sixty-nine (369) patients had low pretest probability and negative D-dimer results and no further diagnostic tests were performed. None of these patients subsequently developed venous thromboembolic complications (0%, 95% confidence interval [CI] 0% to 1.0%). The remaining 489 were referred for spiral CT contrast angiography scan and ultrasound. Sixty-seven patients were confirmed to have pulmonary embolism and an additional 15 patients with negative CT scans had proximal deep vein thrombosis (DVT) on ultrasound for a total prevalence of venous thromboembolism of 82/489 (16.8%). Two of 409 patients who had pulmonary embolism excluded in the initial evaluation phase developed proximal venous thromboembolism (0.5%; 95% CI 0% to 1.8%) in the 3-month follow-up period. These findings suggest that the combination of a negative spiral CT contrast angiography scan and normal venous ultrasound imaging safely excludes the diagnosis of pulmonary embolism in the Emergency Department setting.     

Microsatellite analysis of pleural supernatants could increase sensitivity of pleural fluid cytology

Pleural effusions may result from various inflammatory, hemodynamic, or neoplastic conditions. A common diagnostic problem lies in distinguishing malignant from benign pleural effusions using routine cytological evaluation. We studied pleural fluid samples obtained from 14 patients with histologically confirmed malignancy and from 6 patients with benign pleural effusions using 12 microsatellite markers from 8 different chromosomal regions. Supernatants and cellular sediments of all 20 pleural fluid samples were analyzed. Routine cytological examination was 100% specific for malignancy but was only 57% sensitive. Microsatellite analyses of pleural fluid supernatants showed genetic alterations in tumor patients only. However, 50% of pleural effusions that were considered negative for malignancy by routine cytological analysis showed either loss of heterozygosity or microsatellite instability. The sensitivity of pleural fluid examination rose to 79% when routine cytological assessment was supplemented by molecular studies. Our data suggest that microsatellite analysis increases the sensitivity of cytological pleural fluid examination in assessing potential malignancy and that combining cytological and molecular methods may improve yield and certainty in diagnostically challenging cases.     

30岁以下妇科恶性肿瘤的临床分析

目的探讨30岁以下妇科恶性肿瘤的病例特征及合理的治疗措施。方法回顾性分析2000年1月至2009年12月间在我院住院诊治的30岁以下的妇科恶性肿瘤患者的临床资料,以及随访部分患者的月经生育情况等,进行统计分析总结。结果我院10年期间共收治妇科恶性肿瘤患者721例,30岁以下的患者56例,占7．77％,发生率排位分别为卵巢癌、恶性滋养细胞肿瘤、宫颈癌和子宫体恶性肿瘤。子宫体恶性肿瘤前5年收治数为0,后5年的收治数为3;宫颈癌收治比例从前5年的7．7％上升到后5年的23．3％,差异有统计学意义（P〈0．05）。30岁以下患者妇科恶性肿瘤的Ⅰ期诊断率分别为卵巢癌76．7％,宫体恶性肿瘤100％,恶性滋养细胞肿瘤35．7％,宫颈癌66．7％。14例卵巢癌患者行了保留生育功能的手术,12例恶性滋养细胞肿瘤只用化疗,1例宫颈原位癌患者行了宫颈锥切术。电话随访成功的10例卵巢恶性生殖细胞肿瘤患者,月经均基本正常,获得总妊娠数4例,其中3人各育1人;随访成功的9例恶性滋养细胞肿瘤患者中,月经均能恢复基本正常,共有2个妊娠,已出生一活胎;1例宫颈原位癌患者行了宫颈锥切术尚在随访1年中,无妊娠记录。结论30岁以下年轻女性的妇科恶性肿瘤发生率排位分别为卵巢癌、恶性滋养细胞肿瘤、宫颈癌和子宫体恶性肿瘤,而宫颈癌和子宫内膜癌的发病率有上升的趋势。各种保留生育功能或保留卵巢功能的治疗方法在不断地探讨总结中并形成规范。     

Recurrent venous thromboembolism

A previous venous thromboembolism is the most important risk factor for predicting recurrence of the condition. Several studies have shown that routine testing for inherited thrombophilias is not helpful in predicting the risk of recurrence or altering treatment decisions, and therefore is not cost-effective. Updated practice guidelines from the American College of Chest Physicians shift the focus away from laboratory testing and place stronger emphasis on identifying clinical factors when making treatment decisions. The major determinants for treatment duration are whether the deep venous thrombosis was located in a distal or proximal vein, whether the thrombotic episode was an initial or recurrent event, and whether transient risk factors were present. Persistent elevations on the D-dimer test or the presence of residual thrombosis may provide further information to predict recurrence risk and determine treatment duration. Screening for antiphospholipid syndrome and/or malignancy should be considered in patients presenting with arterial thrombosis, thrombosis at an unusual site, or recurrent pregnancy loss. Patients with venous thromboembolism and a known malignancy should be treated with low-molecular-weight heparin rather than oral anticoagulation as long as the cancer is active. All patients with recurrent, unprovoked venous thromboembolism should be considered for long-term treatment.     

Diagnosis and management of colorectal cancer

Colorectal cancer is an important disease with high mortality. Clinical features are usually nonspecific and vary with the location of the tumor. Diagnosis depends on colonic investigations initiated by a high index of clinical suspicion. Rectal examination, sigmoidoscopy, air-contrast barium enema, and colonoscopy are the crucial diagnostic tools. Clinical judgment dictates the extent of work-up in individual symptomatic patients. Screening of asymptomatic middle-aged and elderly persons is widely advised but less widely practiced. More evidence is needed to clarify the value of screening, especially by occult blood testing. CEA testing is unsuitable for screening and of only limited value for monitoring patients with known colorectal cancer. Surgical resection is the mainstay of treatment. Radiotherapy is useful for palliation of rectal cancer and may delay postoperative tumor recurrence. Chemotherapy for disseminated disease generally gives disappointing results, since only a minority of tumors respond and survival benefit is marginal. Periodic colonic surveillance is important after tumor resection, primarily to detect premalignant new growths.