Mutational analysis of PI3K/AKT and RAS/RAF pathway activation in malignant salivary gland tumours with a new mutation of PIK3CA.

The phosphoinositide 3-kinase (PIK3)/v-akt murine thymoma (AKT) oncogene pathway and the RAS/RAF pathway are involved in regulating the signalling of multiple biological processes, including apoptosis, metabolism, cell proliferation, and cell growth. Mutations in the genes within these pathways are frequently found in several tumours. The aim of this study was to investigate the frequency of mutations in the PIK3CA, BRAF, and KRAS genes in cases of malignant salivary gland tumours. Mutational analysis of the PIK3CA, KRAS, and BRAF genes was performed by direct sequencing of material from 21 patients with malignant salivary gland tumours who underwent surgery between 1992 and 2001. No mutations were found in the KRAS exon 2, BRAF exon 15, or PIK3CA exon 9 genes. However, an unpublished mutation of the PIK3CA gene in exon 20 (W1051 stop mutation) was found in one case of adenocarcinoma NOS. The impact of this mutation on the biological behaviour of the tumour has yet to be explored, however the patient with adenocarcinoma NOS harbouring this mutation has survived for over 20 years following surgery despite a high stage at presentation. Further studies with more homogeneous patient cohorts are needed to address whether this mutation reflects a different clinical presentation and may benefit from targeted treatment strategies.

Clinical factors associated with readmission for postpartum hypertension in women with pregnancy-related hypertension: a nested case control study.

OBJECTIVE: To evaluate the association between mode of delivery and length of labor on readmission for postpartum hypertension in women with pregnancy-related hypertension. STUDY DESIGN: Nested case control study within a cohort of 99 women with pregnancy-related hypertension who delivered at our institution between 2005 and 2009. Data were abstracted for clinical and labor information. Mode of delivery and length of labor were compared between women with previously diagnosed pregnancy-related hypertension readmitted within 4 weeks post partum (25 cases) and those not readmitted (74 controls). Categorical and continuous variables were compared using χ(2) and T-tests, respectively. Multivariable logistic regression controlled for confounders. RESULT: Hypertension readmission was not associated with mode of delivery (cases: 10(40%) spontaneous vaginal delivery, 15(60%) cesarean delivery; controls: 38(51%) spontaneous vaginal delivery, 36(49%) cesarean delivery, P=0.33). Length of labor appeared longer in cases, with a trend toward significance (median: 15.5 [7,28] h vs 10.75 [5.8,15.9] h, P=0.12) and was significantly associated with readmission after controlling for delivery mode, induction and parity (adjusted odds ratio=1.06 [1 to 1.12], P=0.048). Readmitted patients were less likely to have initially been started on antihypertensive medications after controlling for age, race and chronic hypertension (adjusted odds ratio=0.23 [0.06 to 0.88], P=0.03). CONCLUSION: Postpartum readmission for hypertension in women with known pregnancy-related hypertension is not associated with mode of delivery, appears increased in those with longer length of labor and decreased in those initially started on antihypertensive medications. This provides targets for future research to continue to improve transitions of care and reduce preventable readmissions.

Programmed cell removal biomarkers calreticulin and CD47 implicated in oral lichen planus.

OBJECTIVES: To investigate the expression of the programmed cell removal markers, calreticulin (CRT) and CD47, known to be involved in various autoimmune diseases, in patients with oral lichen planus (OLP), and to investigate the association with clinical behavior. MATERIALS AND METHODS: Biopsies of 78 patients with OLP were included. The clinical data were collected from patients' charts. The expression of CRT and CD47 was immunomorphometrically analyzed in the epithelial (CRTep, CD47ep) and inflammatory cells (CRTinf, CD47inf), and the results were correlated with the clinical presentation. RESULTS: The epithelial and inflammatory cells expressed CRT (2.83 ± 6.62 and 5.13 ± 3.72) and CD47 (7.92 ± 4.6 and 10.7 ± 7.16). The expressions of CD47ep and CD47inf were associated (R = 0.64, P < 0.0005) with one another. The expressions of CRTinf and CD47ep were higher in atrophic erosive forms (A/ELP) than in the keratotic form of patients with OLP (6.46 ± 0.76 and 9.38 ± 0.87 vs 4.2 ± 0.61 and 6.84 ± 0.91, respectively, P = 0.002 and P = 0.021). The expression of CRTep was associated with more localized lesions (P < 0.009) and more abundant in males (P = 0.049), and the expression of CRTinf was associated with the presence of skin lesions and symptoms (P < 0.034 and P = 0.047, respectively). Only in A/ELP patients, the expression of CRTep was associated with high expression of CD47ep (R = 0.6, P = 0.004), where both CD47ep and CD47inf were associated with lower age of the patients (R = -0.48, P = 0.03 and R = -0.54, P = 0.01). CONCLUSIONS: The pattern of expression of CRT and CD47 in OLP suggests a general programmed cell removal response in OLP. Symptomatic patients may benefit from CRT/CD47 targeted therapy in the future.

Diffusion Reflection: A Novel Method for Detection of Oral Cancer.

Intraoperative detection of residual disease in oral cancer may reduce the high rate of recurrences. The aim of the present study was to evaluate the detection sensitivity of diffusion reflection (DR) measurements of bioconjugated gold nanorods (GNRs) to cancerous sites in a rat model of oral squamous cell carcinoma. We used hyperspectral spectroscopy and DR measurements of GNRs bioconjugated to slide specimens of rat tongues where squamous carcinoma was induced by 4NQO (4-nitroquinoline-N-oxide). Wistar-derived male rats were used: 6 were sacrificed at wk 32 to 37 following 4NQO administration (experimental rats), as were 2 control rats at wk 32 and 36. The detection results were compared with histopathology: 19 sites of cancerous changes were identified microscopically (11 invasive cancer and 8 carcinoma in situ [CIS]). The GNRs attached selectively to areas of carcinomatous changes with an intensity exceeding 17 intensity units at 780 nm (overall specificity, 97%; overall sensitivity, 87%) when the hyperspectral spectroscopy system was used. The resulting DR slopes of the reflected intensity showed an increase of >80% in areas of invasive cancer and an increase of >30% in the CIS sites. The resulting intensity units of the hyperspectral spectroscopy system in the invasive cancer significantly exceed those of the CIS (t test, p = .0002; Mann-Whitney, p = .0024). The results demonstrate a great potential of the direct DR scanning as a new and simple tool for detecting residual disease intraoperatively.

HIF-1α, VEGF, and EGFR: contributing factors in the pathogenesis of necrotizing sialometaplasia.

OBJECTIVES: Necrotizing sialometaplasia (NS) is an uncommon reactive lesion involving the minor salivary glands. This study aimed to investigate the expression of hypoxia-inducible factor alpha (HIF-1α), vascular endothelial growth factor (VEGF), and epithelial growth factor receptor (EGFR) in the pathogenesis of NS. METHODS: Paraffin-embedded tissue sections from 10 cases of NS were immunohistochemically stained for HIF-1α, VEGF, and EGFR. A semiquantitative morphometric analysis was performed and compared with normal palatal salivary glands and traumatic ulcerations. RESULTS: Hypoxia-inducible factor alpha staining was observed in most elements of the affected area, the acini and ducts of the involved salivary glands as well as in the inflammatory infiltrate, the endothelial cells, and stromal cells. HIF-1α was almost absent in the control glands (P < 0.0001). VEGF staining was positive in the stromal capillaries and in the inflammatory infiltrate. The expression was higher in cases of NS compared with the normal salivary glands (P < 0.001). EGFR was expressed in the surface epithelium, the pseudo-epitheliomatous hyperplasia, and the islands of squamous metaplasia. VEGF expression in traumatic ulcerations was lower than that in cases of NS. CONCLUSION: This study provides molecular evidence to the role of hypoxia in NS; HIF-1α, the main regulator of hypoxia, was expressed in the infarcted salivary glands, EGFR in the metaplastic epithelium and VEGF in the stromal capillaries, all three components are the key factors induced by hypoxia.

Chromosomal numerical aberrations in oral lichen planus.

The malignant potential of oral lichen planus (OLP) has been a matter of serious controversy. We aimed to detect chromosomal numerical aberrations in cells of brush samples collected from affected mucosa. The samples were simultaneously analyzed for morphology and fluorescent in situ hybridization (FISH) with chromosomes 2 and 8 centromeric probes. We analyzed 57 persons with OLP and 33 control individuals. A cut-off value of aneuploid cells was determined as 1.1%. Aneuploid cells were found in 16 persons with OLP (28.1%); in 10 individuals (17.5%), over 5% of the cells were aneuploid. Aneuploid cells were also detected in normal-looking mucosa of seven persons with OLP. One person with OLP developed squamous cell carcinoma; 10% of the cells examined were aneuploid. OLP carries an increased risk for chromosomal instability. Identifying aneuploid cells in a brush sample and the combined morphological and FISH analysis can increase the specificity in predicting the malignant potential of OLP.

Glandular odontogenic cyst: a challenge in diagnosis and treatment.

The present review analyzes the accumulated data from all cases of glandular odontogenic cyst (GOC) reported in the English language literature. In the 20 years since it was first described, 111 cases have been reported, an incidence of 0.2% of odontogenic cysts. The age range is 14-75, mean 45.7, with a M/F ratio of 1.3:1. GOC has a predilection for the mandible (70%), affecting both anterior and posterior areas. It is typically radiolucent, well defined, either unilocular (53.8%) or multilocular (46.2%). Frequent perforation (61%) and of thinning of cortical plates (24.4%) indicate aggressiveness. Sufficient follow-up indicates that 30% of cases can recur. Treatment by enucleation or curettage carries the highest risk for recurrence, especially in large and multilocular lesions. Peripheral osteoectomy or marginal resection can eliminate the risk. Defined criteria for microscopic diagnosis are described, which in addition to Ki67 and p53 can help in differentiating GOC from lesions with histological similarities (cysts with mucous metaplasia, botryoid and surgical ciliated cysts, low-grade mucoepidermoid carcinoma). Definite diagnosis may not be possible in small incisional biopsies due to the focal presentation of characteristic features required for diagnosis. There is now evidence to support an odontogenic rather than a sialogenic origin.

Prevalence, diameter and course of the maxillary intraosseous vascular canal with relation to sinus augmentation procedure: a radiographic study.

The aim of the study was to characterize the prevalence, diameter and course of intraosseous anastomosis between the posterior superior alveolar artery and the infraorbital artery (bony canal) involved in the sinus floor augmentation procedure. Data from 208 sinuses were analyzed from reconstructed computed tomography (CT) images. The presence of the intraosseous anastomosis in the lateral antral wall was detected using sagittal plane sections, in addition, the intraosseous course and the diameter of the bony canal were examined. The bony canal was identified in 114 (55%) of the 208 maxillary sinuses, with a mean distance of 16.9 mm from the alveolar ridge. From the examined canals, in 7% the diameter was 2-3 mm wide, in 22% 1-2 mm and in 26% it was less than 1 mm wide. Because only in 50% of cases the vessel was large enough to be detected by a CT scan, it is recommended, to place the superior border of the osteotomy up to 15 mm from the alveolar crest in A to C type ridges to avoid penetration of the artery.

Early definitive closure of the open abdomen: a quiet revolution.

Contrary to the management strategy recommended only 2-3 years ago, temporarily covering the open abdomen with an absorbable mesh or a plastic sheath without preserving the peritoneal space is no longer considered in the patient's best interest. The use of the vacuum pack, in conjunction with vacuum-assisted wound management and new biological prostheses now offer patients with an open abdomen a better and simpler alternative to the giant "planned ventral hernia". With very few exceptions in the most critically ill patients, the survivors of damage control surgery or infected pancreatic necrosis should not be sent home with a huge defect only to undergo a complex reconstruction a year later. Simpler and better alternatives exist. The new concepts and technologies presented in this review, when widely adopted, will rapidly translate into safer and better management of the patient with an open abdomen.

Peripheral odontogenic tumours--differential diagnosis in gingival lesions.

Peripheral odontogenic tumours (POT) are rare benign focal overgrowths of the oral soft tissue, usually occurring in the gingiva. Between 1996-2000, 6 out of 406 excised gingival lesions were diagnosed as POT (1.5%). Tumours included peripheral odontogenic fibroma (2 patients), peripheral calcifying odontogenic cyst (2 patients), peripheral ameloblastoma (1 patient), and peripheral calcifying epithelial odontogenic tumour (1 patient). Review of the literature reveals that peripheral odontogenic fibroma and peripheral ameloblastoma were the most common POT. The purpose of this article was to analyse the clinical data of these tumours according to the presented cases and the literature review, to elucidate typical features of each tumour type and enhance easy identification.

[Mass casualties after an explosion]. / Der Massenanfall an Verletzten nach Explosion.

Because of the intifada, the Israeli-Palestinian conflict has become characterized by violence against civilians on both sides. Since the early 1990s, this conflict has seen directed operations performed by suicide attackers, whose goal is to kill civilians who are not direct participants in the confrontation. For urban and local hospitals this means that they must always be aware of being confronted with limited multiple-casualty incidents. This has required a restructuring of emergency plans at the scene and in the hospital. At the scene the incident is classified according to the number and degree of injury of the victims. The accumulation of such incidents made it necessary in Israel to change views of the system of triage, which has essential differences from the central European system. Apart from changing preclinical and clinical management algorithms, the surgeons specialized in casualties must be prepared for a new quality of injuries. Barotrauma of the lung and multiple, seemingly superficial injuries often only emerge later as life-threatening and lead to the paralysis of intensive care and surgical capacity.

[Update review on prevention and early diagnosis in oral cancer].

Oral cancer is a major health problem in some parts of the world, especially in developing countries. Worldwide, the annual incidence exceeds 3,000,000 new cases. The main risk factors are tobacco and alcohol. However, dietary factors, viruses and possibly genetic predisposition have also been associated with oral cancer. Several oral lesions such as leukoplakia, erythroplakia and lichen planus carry an increased risk for malignant transformation in the oral cavity. Prognosis of oral cancer differs significantly between specific oral locations, with cancer of the lip for example having a much better prognosis than at the base of tongue or on the gingiva. Prognosis of intra-oral cancer is generally poor, with a five-year survival less than 50 percent. Local recurrences as well as lymph node metastases occur in a significant percentage of patients, while distant metastases are less frequent. Prognosis correlates mainly with the size of the lesion and the nodal status at the time of diagnosis, therefore early detection of small, stage-1 oral cancer can reduce mortality and morbidity. Oral lesions can be easily observed by direct visualization, however, knowledge of the differential diagnosis of oral lesions is mandatory for early diagnosis of malignant and pre-malignant lesions in the oral cavity. Use of screening and detection aids such as vital stains and Oral CDX can increase the number of cases diagnosed at an early stage, or even in the pre-malignant stage. Development of molecular markers can improve the early diagnosis and can help in predicting treatment response. New treatment modalities including tumor specific antibodies and gene therapy are emerging, giving more hope for patients with oral cancer. There is an important role for the dentist in both early diagnosis of pre-malignant and malignant lesions, and in prevention by educating the patients of the risks associated with tobacco, alcohol and dietary factors.

Early reoperation for perirectal abscess: a preventable complication.

PURPOSE: The aim of this study was to analyze failures in the operative management of perirectal abscesses resulting in early reoperation. METHODS: This was a retrospective case study of 500 consecutive patients who underwent 627 drainage procedures for a perirectal abscess. RESULTS: Forty-eight patients (7.6 percent of all drainage procedures) required reoperation within ten days of the original procedure. The main factors leading to reoperation were incomplete drainage (23 patients), missed loculations within a drained abscess (15 patients), missed abscesses (4 patients), and postoperative bleeding (3 patients). Incomplete drainage was more common with simple perirectal abscesses, whereas most overlooked collections were located posteriorly. Horseshoe abscesses were associated with a particularly high rate (50 percent) of operative failures. Neither preexisting perianal pathology nor systemic immunosuppressive disease contributed to early failures. CONCLUSION: Surgical errors are the leading cause of early failures in the surgical treatment of perianal abscesses. These errors occur in a limited number of typical patterns and can therefore be identified and taught with an aim to decrease their occurrence.

Military, civilian, and rural application of the damage control philosophy.

Damage control surgery is a useful salvage strategy for the most critically injured patients. Conceptually, this approach to individual patients can be extrapolated to situations such as military field surgery, civilian mass casualty events, and long-range transfers from rural areas. The logistic realities of Army forward surgery teams are addressed with regard to typical damage control maneuvers and evacuation. Specific areas requiring improvement through directed research are identified. Initial civilian mass casualty strategies are discussed, and a plan to prevent transfer delays of rural trauma patients is presented. By transferring the lessons learned from individual damage control patients to military, civilian mass casualty, and rural casualty events, resource utilization is optimized. The concept of minimal acceptable care rather than optimal trauma care can be applied to these three seemingly different situations.

Hospital trauma care in multiple-casualty incidents: a critical view.

During a multiple-casualty incident, a large casualty caseload adversely affects the quality of trauma care given to individual patients. From a trauma care perspective, the goal of the hospital emergency plan is to provide severely injured patients with a level of care that approximates the care given to similar patients under normal conditions. Therefore, the realistic admitting capacity of the hospital is determined primarily by the number of trauma teams that the hospital can recruit. Effective triage of these casualties is often not straightforward, with high overtriage rates. Simplified triage algorithms may be a practical alternative to more elaborate schemes. The concept of minimal acceptable care is the key to a staged management approach during a mass-casualty incident. Discrete-event computer simulation and war game tabletop exercises for key personnel are 2 new modalities that are supplementing the traditional mock disaster drill as effective planning and training tools.

Thoracic aortic and thoracic vascular injuries.

Patients with thoracic vascular injuries fall into two groups: those who are exsanguinating and require an empiric operation with a high mortality and those with contained injuries that permit preoperative evaluation. The unstable group requires judgment to determine the appropriate empiric position, exposure, and operation. Unlike abdominal trauma, which is addressed by way of a midline incision, there are multiple thoracic incisions that can be used to access thoracic vascular injuries. Thus, the stable group may benefit from preoperative imaging, which then can suggest a patient position, incision, and operative approach. Avoiding overaggressive resuscitation, obtaining appropriate imaging studies, choosing an operative strategy to achieve proximal and distal control, and using adjuncts based on the injury can make the care of these patients a rewarding but challenging activity.

Two cases of Munchausen's syndrome presenting as acute respiratory distress.

We present two cases of factitious disorder that presented as acute respiratory distress. The presentation was extreme to the point that the patients were intubated. Both patients were employed in an ancillary health care profession.