Statistical controversies in clinical research: building the bridge to phase II-efficacy estimation in dose-expansion cohorts.

BACKGROUND: Regulatory agencies and others have expressed concern about the uncritical use of dose expansion cohorts (DECs) in phase I oncology trials. Nonetheless, by several metrics-prevalence, size, and number-their popularity is increasing. Although early efficacy estimation in defined populations is a common primary endpoint of DECs, the types of designs best equipped to identify efficacy signals have not been established. METHODS: We conducted a simulation study of six phase I design templates with multiple DECs: three dose-assignment/adjustment mechanisms multiplied by two analytic approaches for estimating efficacy after the trial is complete. We also investigated the effect of sample size and interim futility analysis on trial performance. Identifying populations in which the treatment is efficacious (true positives) and weeding out inefficacious treatment/populations (true negatives) are competing goals in these trials. Thus, we estimated true and false positive rates for each design. RESULTS: Adaptively updating the MTD during the DEC improved true positive rates by 8-43% compared with fixing the dose during the DEC phase while maintaining false positive rates. Inclusion of an interim futility analysis decreased the number of patients treated under inefficacious DECs without hurting performance. CONCLUSION: A substantial gain in efficiency is obtainable using a design template that statistically models toxicity and efficacy against dose level during expansion. Design choices for dose expansion should be motivated by and based upon expected performance. Similar to the common practice in single-arm phase II trials, cohort sample sizes should be justified with respect to their primary aim and include interim analyses to allow for early stopping.

Safety, efficacy, and long-term follow-up evaluation of perioperative epirubicin, Cisplatin, and capecitabine chemotherapy in esophageal resection for adenocarcinoma.

BACKGROUND: Perioperative epirubicin, cisplatin, and capecitabine (ECC) chemotherapy was evaluated in patients who underwent esophageal resection for adenocarcinoma of the esophagus or gastroesophageal junction (GEJ). METHODS: A cohort of 93 consecutive patients was analyzed. The median follow-up period was 60 months. Source data verification of adverse events was performed by two independent observers. RESULTS: All three planned preoperative chemotherapy cycles were administered to 65 patients (69.9 %). Only 27 % of the patients completed both pre- and postoperative chemotherapy. The reasons for not receiving postoperative adjuvant chemotherapy could be separated in two main problems: toxicity of the preoperative chemotherapy and postoperative problems involving difficulty in recovery and postoperative complications. Finally, 25 patients (27 %), completed three preoperative and three postoperative cycles. Grades 3 and 4 nonhematologic adverse events of preoperative chemotherapy mainly consisted of thromboembolic events (16.2 %) and cardiac complications (7.5 %). A history of cardiac and vascular disease was independently associated with discontinuation of preoperative chemotherapy and the occurrence of grade 3 or higher adverse events. Surgery was performed for 94 % of all the patients who started with ECC chemotherapy. A radical resection (R0) was achieved in 93 % of the patients. A complete pathologic response was observed in 8 % of the patients. During a median follow-up period of 60 months, the median disease-free survival time was 28 months, and the median overall survival time was 36 months. The 3-year overall survival rate was 50 %, and the 5-year overall survival rate was 42 %. CONCLUSION: For patients with adenocarcinoma of the esophagus or GEJ, six cycles of ECC-based perioperative chemotherapy is associated with a relatively high number of adverse events. Although this toxicity did not affect the esophageal resectability rate, this regimen should be used with caution in this patient population.

European consensus meeting of ARM-Net members concerning diagnosis and early management of newborns with anorectal malformations.

The ARM-Net (anorectal malformation network) consortium held a consensus meeting in which the classification of ARM and preoperative workup were evaluated with the aim of improving monitoring of treatment and outcome. The Krickenbeck classification of ARM and preoperative workup suggested by Levitt and Peña, used as a template, were discussed, and a collaborative consensus was achieved. The Krickenbeck classification is appropriate in describing ARM for clinical use. The preoperative workup was slightly modified. In males with a visible fistula, no cross-table lateral X-ray is needed and an anoplasty or (mini-) posterior sagittal anorectoplasty can directly be performed. In females with a small vestibular fistula (Hegar size <5 mm), a primary repair or colostomy is recommended; the repair may be delayed if the fistula admits a Hegar size >5 mm, and in the meantime, gentle painless dilatations can be performed. In both male and female perineal fistula and either a low birth weight (<2,000 g) or severe associated congenital anomalies, prolonged preoperative painless dilatations might be indicated to decrease perioperative morbidity caused by general anesthesia. The Krickenbeck classification is appropriate in describing ARM for clinical use. Some minor modifications to the preoperative workup by Levitt and Peña have been introduced in order to refine terminology and establish a comprehensive preoperative workup.

[Treatment of a fractured endodontical instrument in the root canal]. / Behandeling van een gefractureerd endodontisch instrument in het wortelkanaal.

A 53-year-old woman with continuing pain coming from a lower first molar was diagnosed with apical periodontitis, with a retained fractured instrument in the root canal. There are a variety of treatment options for dealing with a corpus alienum in a root canal. In this case it was decided to treat the tooth endodontically, and leave the fractured instrument fragment in situ. The selection of this treatment option was made on the basis of knowledge of the original diagnosis and the success rates of the various treatment options as described in the relevant literature, weighed against the possible risks and their effects on the prognosis. This suggested that the use of a dental operating microscope has a positive impact on the success rates of endodontic treatment The prognosis for endodontic treatment when a fractured instrument fragment is left within the root canal, as in this case, is not significantly reduced. The presence of preoperative periapical pathology, however, is a more clinically significant prognostic indicator.

Sensitivity of the Boston criteria version 2.0 in Dutch-type hereditary cerebral amyloid angiopathy.

BACKGROUND AND AIM: The revised Boston criteria v2.0 for cerebral amyloid angiopathy (CAA) add two radiological markers to the existing criteria: severe visible perivascular spaces in the centrum semiovale and white matter hyperintensities (WMHs) in a multispot pattern. This study aims to determine the sensitivity of the updated criteria in mutation carriers with Dutch-type hereditary CAA (D-CAA) in an early and later disease stage. METHODS: In this cross-sectional study, we included presymptomatic and symptomatic D-CAA mutation carriers from our prospective natural history study (AURORA) at the Leiden University Medical Center between 2018 and 2021. 3-Tesla scans were assessed for CAA-related magnetic resonance imaging (MRI) markers. We compared the sensitivity of the Boston criteria v2.0 to the previously used modified Boston criteria v1.5. RESULTS: We included 64 D-CAA mutation carriers (mean age 49 years, 55% women, 55% presymptomatic). At least one white matter (WM) feature was seen in 55/64 mutation carriers (86%: 74% presymptomatic, 100% symptomatic). Fifteen (23%) mutation carriers, all presymptomatic, showed only WM features and no hemorrhagic markers. The sensitivity for probable CAA was similar between the new and the previous criteria: 11/35 (31%) in presymptomatic mutation carriers and 29/29 (100%) in symptomatic mutation carriers. The sensitivity for possible CAA in presymptomatic mutation carriers increased from 0/35 (0%) to 15/35 (43%) with the new criteria. CONCLUSION: The Boston criteria v2.0 increase the sensitivity for detecting possible CAA in presymptomatic D-CAA mutation carriers and, therefore, improve the detection of the early phase of CAA.

Leflunomide as part of the treatment for multidrug-resistant cytomegalovirus disease after lung transplantation: case report and review of the literature.

Treatment of cytomegalovirus (CMV) disease in transplant patients is challenging and, with antiviral resistance to first-line drugs, it remains uncertain which treatment algorithm to follow. Some data suggest that leflunomide, a pyrimidine synthesis inhibitor, can be used to treat resistant CMV infections. We report a 57-year-old CMV immunoglobulin-G (IgG)-seronegative woman, who received a bilateral lung transplant (LuTx) from a CMV IgG-positive donor with CMV primary disease. The CMV strain was genotypically resistant to ganciclovir, foscarnet, and cidofovir. After starting leflunomide as add-on therapy to a multidrug anti-CMV regimen, viral load declined substantially in 2 months without adverse events. This experience is discussed against the background of existing literature on the use of leflunomide as an anti-CMV agent in LuTx recipients.

Diffusion MRI correlation with p16 status and prediction for tumor progression in locally advanced head and neck cancer.

Purpose: To investigate p16 effects on diffusion image metrics and associations with tumor progression in patients with locally advanced head and neck cancers. Methods: Diffusion images pretreatment and after 20 Gy (2wk) of RT were analyzed in patients with cT4/N3 p16+ oropharynx cancer (OPSCC) (N=51) and locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) (N=28), enrolled onto a prospective adaptive RT trial. Mean ADC values, subvolumes with ADC <1.2 um2/ms (TVLADC), and peak values of low (µL) and high (µH) components of ADC histograms in primary and total nodal gross tumor volumes were analyzed for prediction of freedom from local, distant, or any progression (FFLP, FFDP or FFLRDP) using multivariate Cox proportional-hazards model with clinical factors. P value with false discovery control <0.05 was considered as significant. Results: With a mean follow up of 36 months, 18 of LAHNSCC patients and 16 of p16+ OPSCC patients had progression. After adjusting for p16, small µL and ADC values, and large TVLADC of primary tumors pre-RT were significantly associated with superior FFLRDP, FFLP and FFDP in the LAHNSCC (p<0.05), but no diffusion metrics were significant in p16+ oropharynx cancers. Post ad hoc analysis of the p16+ OPSCC only showed that large TVLADC of the total nodal burden pre-RT was significantly associated with inferior FFDP (p=0.05). Conclusion: ADC metrics were associated with different progression patterns in the LAHNSCC and p16+ OPSCC, possibly explained by differences in cancer biology and morphology. A deep understanding of ADC metrics is warranted to establish imaging biomarkers for adaptive RT in HNSCC.

Shockwave treatment for medial tibial stress syndrome in athletes; a prospective controlled study.

Objective The purpose of this study was to describe the results of two treatment regimens for medial tibial stress syndrome (MTSS); a graded running programme and the same running programme with additional shockwave therapy (extracorporeal shockwave therapy; ESWT). Design A prospective observational controlled trial. Setting Two different sports medicine departments. Participants 42 athletes with MTSS were included. Intervention Patients from one hospital were treated with a graded running programme, while patients from the other hospital were treated with the same graded running programme and focused ESWT (five sessions in 9 weeks). Main Outcome Measures Time to full recovery (the endpoint was being able to run 18 min consecutively without pain at a fixed intensity). Results The time to full recovery was significantly faster in the ESWT group compared with the patients who only performed a graded running programme, respectively 59.7±25.8 and 91.6±43.0 days (p=0.008). Conclusions This prospective observational study showed that MTSS patients may benefit from ESWT in addition to a graded running programme. ESWT as an additional treatment warrants further investigation in a prospective controlled trial with the addition of randomisation and double blinding.

CD34+ cells augment endothelial cell differentiation of CD14+ endothelial progenitor cells in vitro.

Neovascularization by endothelial progenitor cells (EPC) for the treatment of ischaemic diseases has been a topic of intense research. The CD34(+) cell is often designated as EPC, because it contributes to repair of ischaemic injuries through neovascularization. However, incorporation of CD34(+) cells into the neovasculature is limited, suggesting another role which could be paracrine. CD14(+) cells can also differentiate into endothelial cells and contribute to neovascularization. However, the low proliferative capacity of CD14(+) cell-derived endothelial cells hampers their use as therapeutic cells. We made the assumption that an interaction between CD34(+) and CD14(+) cells augments endothelial differentiation of the CD14(+) cells. In vitro, the influence of CD34(+) cells on the endothelial differentiation capacity of CD14(+) cells was investigated. Endothelial differentiation was analysed by expression of endothelial cell markers CD31, CD144, von Willebrand Factor and endothelial Nitric Oxide Synthase. Furthermore, we assessed proliferative capacity and endothelial cell function of the cells in culture. In monocultures, 63% of the CD14(+)-derived cells adopted an endothelial cell phenotype, whereas in CD34(+)/CD14(+) co-cultures 95% of the cells showed endothelial cell differentiation. Proliferation increased up to 12% in the CD34(+)/CD14(+) co-cultures compared to both monocultures. CD34-conditioned medium also increased endothelial differentiation of CD14(+) cells. This effect was abrogated by hepatocyte growth factor neutralizing antibodies, but not by interleukin-8 and monocyte chemoattractant protein-1 neutralizing antibodies. We show that co-culturing of CD34(+) and CD14(+) cells results in a proliferating population of functional endothelial cells, which may be suitable for treatment of ischaemic diseases such as myocardial infarction.

Medical oncology patients' preferences with regard to health care: development of a patient-driven questionnaire.

BACKGROUND: To improve quality of care for cancer patients, it is important to have an insight on the patient's view on health care and on their specific wishes, needs and preferences, without restriction and without influence of researchers and health care providers. The aim of this study was to develop a questionnaire assessing medical oncology patients' preferences for health care based on their own input. PATIENTS AND METHODS: Items were generated using 10 focus group interviews with 51 cancer patients. A preliminary questionnaire was handed out to 681 patients of seven Dutch departments of medical oncology. Explorative factor analysis was carried out on the 386 returned questionnaires (response 57%). RESULTS: Focus group interviews resulted in a preliminary questionnaire containing 136 items. Explorative factor analysis resulted in a definitive questionnaire containing 123 items (21 scales and eight single items). Patients rated expertise, safety, performance and attitude of physicians and nurses as the most important issues in cancer care. CONCLUSION: This questionnaire may be used to assess preferences of cancer patients and to come to a tailored approach of health care that meets patients' wishes and needs.

Robot-assisted thoracoscopic oesophagectomy for cancer.

BACKGROUND: Thoracoscopic oesophagectomy was introduced to reduce the morbidity of transthoracic oesophagectomy. The aim was to assess the short- and mid-term results of robot-assisted thoracoscopic oesophagectomy for oesophageal cancer. METHODS: Between October 2003 and May 2007, 47 patients with resectable oesophageal cancer underwent robot-assisted thoracoscopic oesophagectomy. Clinical data were collected prospectively. RESULTS: Conversion to thoracotomy was necessary in seven patients. Median operating time was 450 min and median blood loss 625 ml. Median postoperative ventilation time was 1 day, intensive care stay 3 days and hospital stay 18 days. Twenty-one of 47 patients had pulmonary complications. Three patients died in hospital. A median of 29 (range 8-68) lymph nodes was dissected and R0 resection was achieved in 36 patients. Twenty-three patients had stage IVa disease. After a median follow-up of 35 months, median disease-free survival was 15 (95 per cent confidence interval 12 to 18) months. CONCLUSION: Robot-assisted thoracoscopic oesophagectomy was oncologically acceptable. Operating time, blood loss and pulmonary complications might decrease with further experience.

High prevalence of esophageal involvement in lichen planus: a study using magnification chromoendoscopy.

BACKGROUND AND STUDY AIMS: The first cases of squamous cell carcinoma in esophageal lichen planus were recently described. We performed a study to establish the prevalence of endoscopic and histopathologic abnormalities consistent with lichen planus and (pre-) malignancy in a cohort of patients with lichen planus. PATIENTS AND METHODS: A total of 24 patients with lichen planus were prospectively studied using high-magnification chromoendoscopy. Focal esophageal abnormalities were mapped, classified, and biopsied. Biopsies were also taken from normal-appearing esophageal mucosa at three levels (proximal, middle, and distal). The presence of a lymphohistiocytic interface inflammatory infiltrate and Civatte bodies (i. e. apoptotic basal keratinocytes) at histopathologic examination was considered diagnostic for esophageal lichen planus. Symptoms were assessed using validated questionnaires. RESULTS: A total of 38 focal abnormalities were biopsied. These consisted of: layers of mucosa peeling off, hyperemic lesions, papular lesions, submucosal plaques/papules, a flat polypoid lesion, and segments of cylindrical epithelium. No endoscopic signs of dysplasia were present. Esophagitis consistent with gastroesophageal reflux disease was noted in 12 / 24 patients. Histopathology showed chronic inflammation of the esophageal mucosa in the majority (18 / 24) of patients. In 50 % (12 / 24), the diagnosis of esophageal lichen planus was made. Dysplasia was not present. There were no differences in symptoms between patients with and without esophageal lichen planus. CONCLUSIONS: At screening endoscopy a high prevalence (50 %) of esophageal lichen planus was found in patients with orocutaneous lichen planus. No dysplasia was found.

An extensive screen of the HLA region reveals an independent association of HLA class I and class II with susceptibility for systemic lupus erythematosus.

OBJECTIVES: The association of systemic lupus erythematosus (SLE) with the human leucocyte antigen (HLA) region is well known. In this study, we analysed the involvement of the HLA region in susceptibility for SLE in a stable founder, Caucasian population of SLE patients. METHODS: We performed an extensive screen of the entire HLA region on 103 SLE patients and family-based controls. Both single locus association analysis and haplotype sharing analysis were performed. The Additional Disease Locus Test (ADLT) was applied to examine the nature of the observed associations and to distinguish true causal associations from associations due to linkage disequilibrium (LD). RESULTS: Significant associations were observed at markers in the HLA class I, class II, and class III regions using both haplotype sharing and single locus methods. The haplotype sharing methods revealed the most significant difference at marker D6S1666 in the HLA class II region (p(HSS) = 0.00037, p(CROSS) = 1.7 x 10(-5)). The most significant result for single locus association was shown at marker D6S265 in the HLA class I region (p = 0.00019). The ADLT demonstrated that these markers represent independent associations. CONCLUSION: HLA class I, class II, and class III are associated with SLE, but only class I and class II contribute independently to increased risk of SLE.

High frequency of early colorectal cancer in inflammatory bowel disease.

BACKGROUND AND AIMS: To detect precancerous dysplasia or asymptomatic cancer, patients suffering from inflammatory bowel disease often undergo colonoscopic surveillance based on American or British guidelines. It is recommended that surveillance is initiated after 8-10 years of extensive colitis, or after 15-20 years for left-sided disease. These starting points, however, are not based on solid scientific evidence. Our aim was to assess the time interval between onset of inflammatory bowel disease (IBD) and colorectal carcinoma (CRC), and subsequently evaluate how many patients developed cancer before their surveillance was recommended to commence. METHODS: A nationwide automated pathology database (PALGA) was consulted to identify patients with IBD-associated colorectal carcinoma in seven university medical centres in The Netherlands between January 1990 and June 2006. Data were collected retrospectively from patient charts. Time intervals between onset of disease and cancer diagnosis were calculated in months. RESULTS: 149 patients were identified with confirmed diagnoses of IBD and CRC (ulcerative colitis n = 89/Crohn's disease n = 59/indeterminate colitis n = 1). Taking date of diagnosis as the entry point, 22% of patients developed cancer before the 8 or 15 year starting points of surveillance, and 28% if surveillance was commenced 10 or 20 years after diagnosis for extensive or left-sided disease, respectively. Using onset of symptoms to calculate the time interval, 17-22% of patients would present with cancer prior to the surveillance starting points. CONCLUSIONS: These results show that the diagnosis of colorectal cancer is delayed or missed in a substantial number of patients (17-28%) when conducting surveillance strictly according to formal guidelines.

A mid-treatment break and reassessment maintains tumor control and reduces toxicity in patients with hepatocellular carcinoma treated with stereotactic body radiation therapy.

BACKGROUND AND PURPOSE: Patients with hepatocellular carcinoma (HCC) commonly have underlying liver dysfunction with variable tolerance to liver stereotactic body radiation therapy (SBRT). We hypothesized that insertion of a 1-month mid-treatment break would allow us to adapt treatment to the individual patient response, thereby reducing toxicity without compromising local control (LC). MATERIALS AND METHODS: We analyzed HCC patients receiving 3-5 fraction SBRT at our institution from 2005 to 2017. Over this time, patients were offered enrollment on prospective trials assessing individualized adaptive SBRT. Based on normal tissue complication probability and modeling of changes in liver function following a 1-month treatment break between fractions 3 and 4, patients could receive a total of 3 or 5 fractions. Patients not on trial received 3 or 5 fractions without a break. Toxicity was defined as a ≥2 point rise in Child-Pugh (CP) score within 6 months of SBRT. RESULTS: 178 patients were treated with SBRT to 263 HCCs. Median follow-up was 23 months. 86 treatments had a 1-month break. 1-Year LC was 95.4%; this was not different between patients treated with or without a break (p = 0.14). Controlling for tumor size and dose a break was not associated with inferior LC (HR: 0.58, 95%CI: 0.1-3.34, p = 0.54). 54 patients experienced a ≥2 point rise in CP score. Controlling for the number of prior liver directed therapies and mean liver dose, a treatment break reduced the odds of toxicity (OR: 0.42, 95% CI: 0.17-1.03, p = 0.06). CONCLUSION: A one-month mid-treatment break and reassessment may reduce the odds of treatment related toxicity without compromising LC.

T cells in cardiac allograft vasculopathy are skewed to memory Th-1 cells in the presence of a distinct Th-2 population.

Cardiac allograft vasculopathy (CAV) in heart transplantation (HTx) patients remains the major complication for long-term survival, due to concentric neointima hyperplasia induced by infiltrating mononuclear cells (MNC). Previously, we showed that activated memory T-helper-1 (Th-1) cells are the major component of infiltrating MNC in coronary arteries with CAV. In this study, a more detailed characterization of the MNC in human coronary arteries with CAV (n = 5) was performed and compared to coronary arteries without CAV (n = 5), by investigating MNC markers (CD1a, DRC-1, CD3, CD20, CD27, CD28, CD56, CD68, CD69, FOXP3 and HLA-DR), cytokines (IL-1A, 2, 4, 10, 12B, IFN-gamma, and TGF-beta1), and chemokine receptors (CCR3, CCR4, CCR5, CCR7, CCR8, CXCR3 and CX3CR1) by immunohistochemical double-labeling and quantitative PCR on mRNA isolated from laser microdissected layers of coronary arteries. T cells in the neointima and adventitia of CAV were skewed toward an activated memory Th-1 phenotype, but in the presence of a distinct Th-2 population. FOXP3 positive T cells were not detected and production of most cytokines was low or absent, except for IFN-gamma, and TGF-beta. This typical composition of T-helper cells and especially production of IFN-gamma and TGF-beta may play an important role in the proliferative CAV reaction.

The effect of azygos vein preservation on mediastinal lymph node harvesting in thoracic esophagolymphadenectomy.

The standard surgical procedure for esophageal cancer is transthoracic esophagectomy with en bloc resection of the azygos vein, thoracic duct and mediastinal lymph nodes. To reduce morbidity of esophago-lymphadenectomy, minimally invasive techniques are increasingly being applied. In (robot-assisted) thoracoscopic esophagolymphadenectomy, the azygos vein is generally left in place, as the scopic ligation of the numerous intercostal veins is technically difficult and time-consuming. This could affect the extent of mediastinal lymph node dissection. Therefore, in this study, the effect of azygos vein preservation during thoracic esophagectomy on mediastinal lymph node harvesting was assessed. In 15 human cadavers, a right-sided thoracotomy was performed, followed by esophagectomy with mediastinal lymph node dissection after ligation of the azygos arch (representing the situation in robot-assisted thoracoscopic esophagolymphadenectomy). Subsequently, the remaining azygos vein with surrounding tissue was resected. The number of lymph nodes in both specimens was determined. A mean of 17.3 (95% Poisson CI 15.3-19.6) lymph nodes was dissected en bloc with the esophagus, and 0.67 (95% Poisson CI 0.32-1.23) around the separately resected azygos vein. The additional azygos vein resection did not add to the number of lymph nodes dissected in 60% (9/15) of cadavers. In conclusion, the extent of mediastinal lymph node dissection was not substantially affected by leaving the azygos vein in situ . Time-sparing azygos vein preservation in (robot-assisted) thoracoscopic esophagolymphadenectomy may therefore be considered justified.

Robot-assisted thoracoscopic esophagectomy for a giant upper esophageal leiomyoma.

This is the first report of a thoracoscopic esophagectomy for a giant leiomyoma of the upper esophagus aided by a robotic system. A 37-year-old man presented with progressive dysphagia and nocturnal aspiration. Endoscopic ultrasound and CT scan of the chest revealed an upper esophageal tumor of 9 x 4 cm arising from the muscularis mucosae. A fine needle aspiration showed clustering of mesenchymal cells, confirming the diagnosis of a stromal cell tumor. A mesenchymal malignancy was suspected because the tumor was located in the upper esophagus and was arising from the muscularis mucosae, both uncommon for a leiomyoma. Moreover, tumor size, an indicator of potential malignancy if >3 cm, was 9 cm. Therefore, an esophagectomy was performed thoracoscopically with the formation of a gastric conduit via laparotomy and a hand-sewn end-to-side cervical anastomosis. The thoracoscopic phase was performed with support of the da Vincitrade mark robotic system, which allowed for an excellent 3-dimensional view and a precise dissection of the esophagus along the vital mediastinal structures. The duration of the thoracoscopic part was 115 min and that of the total procedure was 270 min. Blood loss during the thoracoscopic phase was 50 mL; total blood loss was 200 mL. The patient was ventilated for 1 day; his total intensive care stay was 2 days. He left the hospital in good condition on the 11th postoperative day. Histopathological examination combined with immunohistochemistry revealed a leiomyoma of 9.0 x 5.0 x 2.5 cm. After 3 years of follow-up, the patient is in good health.

Assessment of mandibular invasion of squamous cell carcinoma by various modes of imaging: constructing a diagnostic algorithm.

The aim of this study was to determine the optimal combination of preoperative examination methods to predict mandibular invasion by squamous cell carcinoma of the oral cavity. Data were gathered prospectively but evaluated retrospectively. The preoperative results of clinical examination, conventional radiography, bone single photon emission computed tomography (SPECT), computed tomography and magnetic resonance imaging were compared to the histological results of resection specimens from 67 patients with tumours, adjacent or fixed to the mandible, histologically confirmed as squamous cell carcinoma. The examination methods with acceptable sensitivity and specificity were selected and diagnostic algorithms were constructed using all possible combinations. The preferred diagnostic algorithm was found to be either computed tomography or magnetic resonance imaging, followed by a bone SPECT in cases where the first scan is negative. A negative bone SPECT rules out mandibular invasion (100% sensitivity). This algorithm accurately predicted mandibular invasion in 85% of the patients, without yielding false negative results. In this study group, application of such an algorithm would have resulted in a reduction of the number of unnecessary mandibular resections by 50%. The suggested, preferred, diagnostic algorithm shortens the preoperative screening process, avoiding unnecessary costs, as well as considerably reducing the number of unnecessary mandibular resections.