Optimal Diagnostic Workup Research Articles

Management of lymph node metastases from an unknown primary site to the head and neck (Review).

Cancer of unknown primary site (CUP) is an intriguing clinical phenomenon found in ~3-9% of all head and neck cancers. It has not yet been determined whether CUP forms a distinct biological entity with specific genetic and phenotypic characteristics, or whether it is the clinical presentation of metastasis in patients with an undetected primary tumor and no visible clinical signs. The treatment of patients with cervical lymph node metastases from CUP remains controversial, due to the lack of randomized clinical trials comparing different treatment options. Consequently, treatment is currently based on non-randomized data and institutional policy. In the present review, the range and limitations of diagnostic procedures are summarized and an optimal diagnostic work-up is recommended. The initial preferred diagnostic procedures include fine-needle aspiration biopsy (FNAB) and imaging. Although neck dissection followed by postoperative radiotherapy is the the most generally accepted approach, other curative options may be used in certain patients, such as neck dissection alone, nodal excision followed by postoperative radiotherapy, or radiotherapy alone. There remains controversy regarding target radiation volumes, ranging from ipsilateral neck irradiation to prophylactic irradiation of all the potential mucosal sites and both sides of the neck. When no primary lesion is identified with imaging and endoscopy in patients without history of smoking and alcohol abuse, molecular profiling of an FNAB sample for human papillomavirus and/or Epstein-Barr virus is required.

Cost-effectiveness of diagnostic strategies for the management of abnormal uterine bleeding (heavy menstrual bleeding and post-menopausal bleeding): a decision analysis.

Heavy menstrual bleeding (HMB) and post-menopausal bleeding (PMB) together constitute the commonest gynaecological presentation in secondary care and impose substantial demands on health service resources. Accurate diagnosis is of key importance to realising effective treatment, reducing morbidity and, in the case of PMB, reducing mortality. There are many tests available, including transvaginal scan (TVS), endometrial biopsy (EBx), saline infusion sonography and outpatient hysteroscopy (OPH); however, optimal diagnostic work-up is unclear. To determine the most cost-effective diagnostic testing strategy for the diagnosis and treatment of (i) HMB and (ii) PMB. Parameter inputs were derived from systematic quantitative reviews, individual patient data (IPD) from existing data sets and focused searches for specific data. In the absence of data estimates, the consensus view of an expert clinical panel was obtained. Two clinically informed decision-analytic models were constructed to reflect current service provision for the diagnostic work-up of women presenting with HMB and PMB. The model-based economic evaluation took the form of a cost-effectiveness analysis from the perspective of the NHS in a contemporary, 'one-stop' secondary care clinical setting, where all indicated testing modalities would be available during a single visit. Two potentially cost-effective testing strategies for the initial investigation of women with HMB were identified: OPH alone or in combination with EBx. Although a combination testing strategy of OPH + EBx was marginally more effective, the incremental cost-effectiveness ratio (ICER) was approximately £21,000 to gain one more satisfied patient, whereas for OPH it was just £360 when compared with treatment with the levonorgestrel intrauterine system (LNG-IUS) without investigation. Initial testing with OPH was the most cost-effective testing approach for women wishing to preserve fertility and for women with symptoms refractory to empirical treatment with a LNG-IUS. For the investigation of PMB, selective use of TVS based on historical risk prediction for the diagnostic work-up of women presenting with PMB generated an ICER compared with our reference strategy of 'no initial work-up' of £129,000 per extra woman surviving 5 years. The ICERs for the two other non-dominated testing strategies, combining history and TVS or combining OPH and TVS, were over £2M each. In the absence of IPD, estimates of accuracy for test combinations presented some uncertainty where test results were modelled as being discordant. For initial investigation of women presenting to secondary care with HMB who do not require preservation of their fertility, our research suggests a choice between OPH alone or a combination of OPH and EBx. From our investigation, OPH appears to be the optimal first-line diagnostic test used for the investigation of women presenting to secondary care with HMB wishing to preserve their fertility or refractory to previous medical treatment with the LNG-IUS. We would suggest that the current recommendation of basing the initial investigation of women with PMB on the universal TVS measurement of endometrial thickness at a 5-mm threshold may need to be replaced by a strategy of restricting TVS to women with risk factors (e.g. increasing age-raised body mass index, diabetes or nulliparity), obtained from the preceding clinical assessment. The National Institute for Health Research Health Technology Assessment programme.

Correlation of histomorphologic prognostic markers and proliferative index with loss of heterozygosity 1p/19q and MGMT status in diffusely infiltrating gliomas

BackgroundLoss of heterozygosity (LOH)1p/19q, and epigenetic silencing of O6-methylguanine-DNAmethyltransferase (MGMT) gene, displayed promising role as predictive and prognostic markers in brain tumours. The present study correlated both with conventional histomorphologic prognostic markers and proliferative index in diffusely infiltrating gliomas (DIG). MethodsTissues from 45 patients were evaluated for LOH1p/19q using polymerase chain reaction based microsatellite analysis; and for MGMT using immunohistochemistry. Results were correlated with age, histologic type, WHO grade, and proliferation index. ResultsMean MIB-1 LI showed significant correlation with tumour grade. MGMT-staining in grade II and IV tumours were 31.1% and 16.8%, respectively, while in DA and GBM it was 88.2% and 19.0%, respectively, which were statistically significant. Sixteen cases showed LOH 1p and/or 19q of which 10 (5 oligodendroglial, 3 GBM, AA, DA) had combined LOH; while three each showed 1p (all GBM) and 19q (2 DA and GBM) loss. In the MIB-1LI ≤ 5% and >5% groups LOH 1p and/or 19q was encountered in 6 and 10 cases, respectively. A significant inverse association was noted between LOH with MGMT. ConclusionsLOH1p/19q and MGMT shows good correlation with conventional histomorphologic and proliferation markers, and should constitute part of the optimal diagnostic workup of DIG.

Contemporary management of lymph node metastases from an unknown primary to the neck: I. A review of diagnostic approaches

In an era of advanced diagnostics, metastasis to cervical lymph nodes from an occult primary tumor is a rare clinical entity and accounts for approximately 3% of head and neck malignancies. Histologically, two thirds of cases are squamous cell carcinomas (SCCs), with other tissue types less common in the neck. With modern imaging and tissue examinations, a primary tumor initially undetected on physical examination is revealed in >50% of patients and the site of the index primary can be predicted with a high level of probability. In the present review, the range and limitations of diagnostic procedures are summarized and the optimal diagnostic workup is proposed. Initial preferred diagnostic procedures are a fine-needle aspiration biopsy (FNAB) and imaging. This allows directed surgical biopsy (such as tonsillectomy), based on the preliminary findings, and prevents misinterpretation of postsurgical images. When no primary lesion is suggested after imaging and panendoscopy, and for patients without a history of smoking and alcohol abuse, molecular profiling of an FNAB sample for human papillomavirus (HPV) and/or Epstein-Barr virus (EBV) is important.

7th Biennial Congress of the Mediterranean Society of Coloproctology (MSCP), Thessaloniki, Greece, April 22–24, 2010

I attended a well-organized meeting, with the participation of many speakers from Greece, from the Mediterranean area and from several European countries, despite the ashes of the Icelandic volcano. Topics included the most relevant aspects of coloproctological research. A friendly but frank atmosphere has characterized the comprehensive discussion in every session. The optimal diagnostic work-up of rectal cancer was stressed. Endorectal ultrasound can accurately predict T stage in more than 90% of cases, but it is poor at identifying the N stage. CT is useful for locally advanced tumors in identifying adjacent organ involvement, but it cannot accurately evaluate the T stages. MRI is able to accurately predict T stage in 50–90% of patients but is the most reliable tool to detect the circumferential margin involvement. Accuracy in identifying peritoneal tumor perforation and venous invasion is up to 80 and 83%, respectively (M.G. Pramateftakis, I. Kanellos). Total mesorectal excision is the gold standard in the treatment of rectal cancer. Additionally, high ligation of colonic arteries and complete mesocolon excision was presented as the optimal surgical technique of right hemicolectomy for colon cancer (M.G. Pramateftakis). Minimally invasive local excision techniques can be applied for early T1 and T2 rectal tumors smaller than 4 cm, involving less than 40% of the lumen circumference, in patients with significant comorbidities to undergo a radical procedure, in symptomatic patients with multi-organ distant metastatic disease and in well-informed patients denying a radical procedure or a stoma (K. Tepetes). Leakage of colonic anastomosis is the most serious complication after colon resection. Early diagnosis and treatment is imperative; minor leaks can be treated conservatively with parenteral nutrition and antibiotics, while operative treatment is needed for major leaks defined by symptoms of peritonitis and septicemia (D. Kanellos). Loco-regional recurrences of colon cancer (tumor bed, regional nodes, adjoining structures or organs, anastomosis, peritoneum, retroperitoneum, pelvis and surgical scars) after curative colon cancer range between 11 and 40% and are responsible for 30% of deaths. The ideal treatment is the complete resection of the recurrence tumor to achieve R0 operation that provides significant long-term survival (A.N. Machairas). GISTs are the most common mesenchymal gastrointestinal tumors. The most common sites are the stomach and the small bowel. Colorectal GISTs represent 5–10% of the cases, with rectum being the most common site. Segmental colectomy is the mainstay of treatment for resectable nonmetastatic primary colorectal GIST. Since GIST do not metastasize through lymphatics, lymphadenectomy and mesorectal excision are not necessary. Unresectable tumors could be downstaged with neoadjuvant treatment and restaged for respectability (A. Amato). Firstand second-degree hemorrhoids should be treated conservatively. Stapled hemorrhoidopexy is indicated for third-degree hemorrhoids. The technique is questionable for fourth-degree hemorrhoids, showing a higher long-term recurrence rates than excisional surgery (I. Kanellos, X. Delgadillo). Obstructed defecation affects nearly 50% of constipated patients. Symptoms include incomplete and frequent evacuations, straining at stool, self-digitation, perineal and pelvic heaviness, long time spent in toilette. Rectocele and rectal mucosal prolapse are the most common findings, E. Yiannakopoulou (&) Faculty of Health and Caring Professions, Technological Educational Institute of Athens, Athens, Greece e-mail: nyiannak@teiath.gr

Upper gastrointestinal bleeding from the endoscopist’s view

Bleeding from the upper gastrointestinal tract is a frequent cause for emergency hospital admission that concerns both the endoscopist and general surgeon. Regarding the cause, peptic ulcers are the most frequent source of bleeding. Regarding severity, they range from simply a small episode to severe life-threatening hemorrhage. The aim of this article is to present current trends regarding optimal diagnostic work-up and therapeutic procedures for patients with upper gastrointestinal bleeding, especially those with severe haemorrhage, by a comprehensive review of the current literature.

Lymph Node Metastases from an Unknown Head and Neck Primary Site: Evaluating the Diagnostic Work-up

Despite an adequate diagnostic workup, 2% to 3% of neck node metastases from a primary head-and-neck tumor cannot be detected. There is no general consensus on the optimal diagnostic workup, and its timing, for carcinomas of an unknown primary (CUP). The purpose of our study is to describe the detection rate and identification of the location of the primary after a conventional workup and panendoscopy with or without a tonsillectomy and with or without an 18-F-FDG positron emission tomography (PET) or PET/computed tomography (CT) scan.

CT Coronary Angiography in Patients Suspected of Having Coronary Artery Disease: Decision Making from Various Perspectives in the Face of Uncertainty

To determine the cost-effectiveness of computed tomographic (CT) coronary angiography as a triage test, performed prior to conventional coronary angiography, by using a Markov model. A Markov model was used to analyze the cost-effectiveness of CT coronary angiography performed as a triage test prior to conventional coronary angiography from the perspective of the patient, physician, hospital, health care system, and society by using recommendations from the United Kingdom, the United States, and the Netherlands for cost-effectiveness analyses. For CT coronary angiography, a range of sensitivities (79%-100%) and specificities (63%-94%) were used to help diagnose significant coronary artery disease (CAD). Optimization criteria (ie, outcomes considered) were: revised posttest probability of CAD, life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Extensive sensitivity analysis was performed. For a prior probability of CAD of less than 40%, the probability of CAD after CT coronary angiography with negative results was less than 1%. The Markov model calculations from the patient/physician perspective suggest that CT coronary angiography maximizes life-years respectively in 60-year-old men and women at a prior probability of less than 38% and 24% and maximizes QALYs at a prior probability of less than 17% and 11%. From the hospital/health care perspective, CT coronary angiography helps reduce health care and direct nonhealth care-related costs (according to UK/U.S. recommendations), regardless of prior probability, and lowers all costs, including production losses (Netherlands recommendations) at a prior probability of less than 87%-92%. Analysis performed from a societal perspective by using a willingness-to-pay threshold level of euro 80,000/QALY suggests that CT coronary angiography is cost-effective when the prior probability is lower than 44% and 37% in men and women, respectively. Sensitivity analyses showed that results changed across the reported range of sensitivity of CT coronary angiography. The optimal diagnostic work-up depends on the optimization criterion, prior probability of CAD, and the diagnostic performance of CT coronary angiography.

The diagnosis of food allergy in children

To give an update about the optimal diagnostic work-up for children with suspected food allergy. Food allergy has become a very severe health problem not only for many children and parents, but also for the entire medical and paramedical community. The financial and social costs related to these conditions are increasing, but, contemporarily, basic and clinical research are deeply involved in the search of possible solutions to facilitate the management of these patients. Food allergy is defined as an abnormal immunological reaction to food proteins, which causes an adverse clinical reaction. Over 90% of food allergies in childhood are caused by eight foods: cow's milk, hen's egg, soy, peanuts, tree nuts, wheat, fish and shellfish. The evaluation of a child with suspected food allergy includes detailed medical history, physical examination, screening tests and response to elimination diet and to oral food challenge. None of the screening tests, alone or in combination, can definitely diagnose or exclude it. The main principle of food allergy management is avoidance of the offending antigen. An incorrect diagnosis is likely to result in unnecessary dietary restrictions, which, if prolonged, may adversely affect the child's nutritional status and growth.

Catamenial hemoptysis from endobronchial endometriosis in a child with type 1 von Willebrand disease

Catamenial hemoptysis is a rare condition characterized by cyclic pulmonary hemorrhage, synchronous with menses and associated with the presence of intrapulmonary or endobronchial endometrial tissue. Because of the paucity of cases reported in the literature, information regarding the natural history is limited and also the optimal diagnostic workup and management of these patients are not well defined. In this report, we present a case of endobronchial endometriosis in a 12-year-old female diagnosed by bronchoscopy and immunocytochemical assay, associated with type 1 von Willebrand disease.

Drug-resistant temporal lobe epilepsy due to cavernous malformations

Supratentorial cavernous angiomas may be associated with drug-resistant focal epilepsy. Surgical removal of the malformation may result in seizure control in a number of patients, although in most studies a long history and high frequency of attacks have been recognized as indicators of unfavorable seizure outcome. In the literature, there are no clear indications regarding the optimal diagnostic presurgical workup and the surgical strategy for this particular subgroup of patients with symptomatic epilepsy. In this paper the authors focus on the preoperative workup and the surgical management of the disease in eight consecutive patients undergoing surgery for drug-resistant temporal lobe epilepsy (TLE) due to cavernous malformations (CMs), and the relevant literature on this issue is also reviewed. Preoperatively, all patients were assessed using a noninvasive protocol aimed at localizing the epileptogenic zone on the basis of anatomical, electrical, and clinical criteria. The presurgical assessment yielded an indication for lesionectomy in two cases, lesionectomy plus anteromesial temporal lobectomy in four cases, and lesionectomy plus extended temporal lobectomy in two cases. At follow-up examinations, seizure, neuropsychological, and psychiatric outcomes were all evaluated. Seven patients were categorized in Engel Class IA (seizure free), and one was categorized in Engel Class IB (occasional auras only). No adverse effects on neuropsychological or psychosocial functioning were observed. Epilepsy surgery can be performed with excellent results in patients with intractable TLE caused by CMs. Noninvasive presurgical evaluation of these patients may enable a tailored approach, providing complete seizure relief in most cases.

Low-grade T a (noninvasive) urothelial carcinoma of the bladder

This article discusses the development of international guidelines for the diagnosis, treatment, follow-up, and prevention of low-grade Ta urothelial carcinoma of the bladder. The authors, who are experts in this field from 3 continents and 7 countries, reviewed the English language literature through September 2004. The results of the authors’ deliberations are presented here as a consensus document. The objective of this study was to determine the optimal diagnostic workup, treatment, follow-up, and prevention of low-grade, Ta urothelial carcinoma of the bladder. A consensus conference convened by the World Health Organization (WHO) and the Société Internationale d’Urologie (SIU) met to critically review the literature on the diagnosis and treatment of low-grade Ta urothelial carcinoma of the bladder. Research was conducted using Medline; this search engine also was used to identify additional works not detected at the initial search. Evidence-based recommendations for diagnosis and management of the disease were made with reference to a 4-point scale. Low-grade Ta urothelial carcinoma of the bladder is a well-studied subject with many level 1 and 2 evidence references that support clinical practice. Findings from 135 reviewed citations are summarized. Many grade A and B recommendations on the diagnostic workup and management of this disease can be given with level 1 and 2 evidence based on prospective randomized clinical trials of sufficient statistical power. This should improve the quality of the treatment of this disease.

Rational diagnosis and surgical treatment of solitary thyroid nodules

Few subjects in endocrine surgery have generated as much controversy as the management of thyroid nodule. The controversial issues include evaluation of laboratory findings and imaging diagnostic procedures in the patient with solitary thyroid nodule. The major issue in relation to controversies is choice of optimal diagnostic workup.

Radiologic Diagnosis of Nonsquamous Tumors of the Head and Neck

Nonsquamous cell tumors of the head and neck can be reliably identified and often accurately diagnosed by proper state of the art radiologic assessment. For optimal diagnostic and preoperative work-up of head and neck lesions, complete radiologic analysis is now essential.

Computer-Aided Diagnostic Strategy Selection

Determination of the optimal diagnostic work-up strategy for the patient is becoming a major concern for the practicing physician. Overlap of the indications for various diagnostic procedures, differences in their invasiveness or risk, and high costs have made physicians aware of the need to consider the choice of procedure carefully, as well as its relation to management actions available. In this article, the author discusses research approaches that aim toward development of formal decision analytic methods to allow the physician to determine optimal strategy; clinical algorithms or rules as guides to physician decisions; improved measures for characterizing the performance of diagnostic tests; educational tools for increasing the familiarity of physicians with the concepts underlying these measures and analytic procedures; and computer-based aids for facilitating the employment of these resources in actual clinical practice.