Hyperbaric Oxygen Therapy and Tissue Regeneration: A Literature Survey.

By addressing the mechanisms involved in transcription, signaling, stress reaction, apoptosis and cell-death, cellular structure and cell-to-cell contacts, adhesion, migration as well as inflammation; HBO upregulates processes involved in repair while mechanisms perpetuating tissue damage are downregulated. Many experimental and clinical studies, respectively, cover wound healing, regeneration of neural tissue, of bone and cartilage, muscle, and cardiac tissue as well as intestinal barrier function. Following acute injury or in chronic healing problems HBO modulates proteins or molecules involved in inflammation, apoptosis, cell growth, neuro- and angiogenesis, scaffolding, perfusion, vascularization, and stem-cell mobilization, initiating repair by a variety of mechanisms, some of them based on the modulation of micro-RNAs. HBO affects the oxidative stress response via nuclear factor erythroid 2-related factor 2 (Nrf2) or c-Jun N-terminal peptide and downregulates inflammation by the modulation of high-mobility group protein B1 (HMGB-1), toll-like receptor 4 and 2 (TLR-4, TLR-2), nuclear factor kappa-B (NFκB), hypoxia-inducible factor (HIF-1α) and nitric oxide (NO•). HBO enhances stem-cell homeostasis via Wnt glycoproteins and mammalian target of rapamycin (mTOR) and improves cell repair, growth, and differentiation via the two latter but also by modulation of extracellular-signal regulated kinases (ERK) and the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway. The HBO-induced downregulation of matrix metalloproteinases-2 and 9 (MMP-2/-9), rho-associated protein kinase (ROCK) and integrins improve healing by tissue remodeling. Interestingly, the action of HBO on single effector proteins or molecules may involve both up- or downregulation, respectively, depending on their initial level. This probably mirrors a generally stabilizing potential of HBO that tends to restore the physiological balance rather than enhancing or counteracting single mechanisms.

Excised melanocytic lesions in children and adolescents - a 10-year survey.

BACKGROUND: Early recognition and prompt excision is to date the only available strategy for reducing mortality from melanoma. Little is known about the accuracy of melanoma detection in children and adolescents. OBJECTIVES: To assess the accuracy of melanoma detection in a paediatric population. METHODS: From the Department of Dermatology, Medical University of Graz, Austria, we reviewed the dermatopathology reports of naevi and melanomas excised in patients younger than 20 years over a 10-year period (1998-2007). Patients were subdivided into four age groups: 0-4, 5-9, 10-14 and 15-19 years. RESULTS: Accuracy in melanoma detection was tested using the number needed to excise (NNE) value that is obtained by dividing the total number of excised lesions by the number of melanomas. A total of 22564 lesions were reviewed, disclosing 22526 naevi and 38 melanomas, for an overall NNE value of 593.8. Five melanomas were excised in children aged 10-14 years (NNE 1141) and 33 in children aged 15-19 years (NNE 479.8), whereas no melanomas were found among 1026 lesions excised in children younger than 10 years. In children aged 0-4 years, congenital and Spitz/Reed naevi accounted for 34.5% and 20% of lesions, respectively. These percentages decreased progressively when moving to older age groups (P<0.0001). In contrast, the percentage of dermal and compound naevi rose in direct proportion with age, being 3.4% and 20.7%, respectively, in the youngest age group, and 36.7% and 31.9%, respectively, among the oldest patients (P<0.0001). CONCLUSIONS: The overall NNE value in paediatric patients over the 10-year study period was 593.8, meaning that about 594 lesions were excised to find one melanoma. This value is 20 times higher than the rates found in adult patients.

In vivo reflectance confocal microscopy: automated diagnostic image analysis of melanocytic skin tumours.

BACKGROUND: In vivo reflectance confocal microscopy (RCM) has been shown to be a valuable imaging tool in the diagnosis of melanocytic skin tumours. However, diagnostic image analysis performed by automated systems is to date quite rare. OBJECTIVES: In this study, we investigated the applicability of an automated image analysis system using a machine learning algorithm on diagnostic discrimination of benign and malignant melanocytic skin tumours in RCM. METHODS: Overall, 16,269 RCM tumour images were evaluated. Image analysis was based on features of the wavelet transform. A learning set of 6147 images was used to establish a classification tree algorithm and an independent test set of 10, 122 images was applied to validate the tree model (grouping method 1). Additionally, randomly generated 'new' learning and test sets, tumour images only and different skin layers were evaluated (grouping method 2, 3 and 4). RESULTS: The classification tree analysis correctly classified 93.60% of the melanoma and 90.40% of the nevi images of the learning set. When the classification tree was applied to the independent test set 46.71 ± 19.97% (range 7.81-83.87%) of the tumour images in benign melanocytic skin lesions were classified as 'malignant', in contrast to 55.68 ± 14.58% (range 30.65-83.59%; t-test: P < 0.036) in malignant melanocytic skin lesions (grouping method 1). Further investigations could not improve the results significantly (grouping method 2, 3 and 4). CONCLUSIONS: The automated RCM image analysis procedure holds promise for further investigations. However, to date our system cannot be applied to routine skin tumour screening.

Follow-up of actinic keratoses after shave biopsy by in-vivo reflectance confocal microscopy--a pilot study.

BACKGROUND: Monitoring of treatment efficacy after shave biopsy of actinic keratoses (AK) is often difficult, as clinical and dermoscopic features may not be reliable. OBJECTIVES: We investigated the applicability of in-vivo reflectance confocal microscopy (RCM) for the follow-up of AK after shave biopsy. METHODS: A total of 10 lesions were investigated by RCM before shave biopsy, after 3 and 12 months by two observers in agreement blinded to location, patients and time interval. RESULTS: At baseline all lesions showed typical clinical, dermoscopic and RCM criteria of AK. Three months after shave biopsy, all lesions presented clinically as normal skin (NS), but two lesions showed features suspicious for AK by RCM. After 12 months, one lesion of these two lesions changed into NS in RCM, whereas the other lesion progressed into clinical visible AK. At baseline, the two observers diagnosed 10 of 10 lesions correctly in RCM, after 3 months eight of 10 lesions and after 12 months all lesions were diagnosed correctly. CONCLUSIONS: Our results suggest that RCM might be a useful tool in the follow-up of AK after shave biopsy and might be used in inconclusive clinical and dermoscopic presentations of lesions after surgery or other treatment modalities.

Reflectance confocal microscopy of facial lentigo maligna and lentigo maligna melanoma: a preliminary study.

BACKGROUND: Facial lentigo maligna (LM) and lentigo maligna melanoma (LMM) may be difficult to diagnose clinically and dermoscopically. Reflectance confocal microscopy (RCM) enables the in vivo assessment of equivocal skin lesions at a cellular level. OBJECTIVES: To assess cytomorphological and architectural RCM features of facial LM/LMM. METHODS: Four women and eight men aged 58-88 years presenting with facial skin lesions suspicious of LM/LMM were included. In total, 17 lesion areas were imaged by RCM before biopsy. The histopathological diagnosis of LM was made in 15 areas; the other two were diagnosed as early LMM. RESULTS: A focal increase of atypical melanocytes and nests surrounding adnexal openings, sheets of mainly dendritic melanocytes, cord-like rete ridges at the dermoepidermal junction (DEJ) and an infiltration of adnexal structures by atypical melanocytes were found to be characteristic RCM features of facial LM/LMM. Areas with a focal increase of atypical melanocytes and nests surrounding adnexal openings were observed at the basal layer in three cases. The remaining cases displayed these changes at suprabasal layers above sheets of mainly dendritic melanocytes. Cord-like rete ridges at the DEJ and an infiltration of adnexal structures by atypical melanocytes were observed in all cases. Previously described criteria for RCM diagnosis of melanoma, such as epidermal disarray, pleomorphism of melanocytes and pagetoid spreading of atypical melanocytes, were additionally observed. CONCLUSIONS: We observed a reproducible set of RCM criteria in this case series of facial LM/LMM.

Confocal laser scanning microscopy-guided surgery for neurofibroma.

The neurofibromatoses comprise at least two separate genetic disorders with variable clinical features and an unpredictable course. The most common type, neurofibromatosis 1, is characterized by > or = 6 café-au-lait spots and the occurrence of neurofibromas, which may present as cutaneous, subcutaneous or plexiform lesions. Normally, excision of neurofibromas is only indicated in the presence of neurological symptoms, suspicion of malignancy or for exceptional cosmetic reasons. For a good functional and aesthetic result with the least danger of recurrence, the surgeon's goal is to excise as much tissue as necessary and as little tissue as possible. One of the main issues during the surgical procedure is to distinguish between neurofibroma and surrounding tissue. We report for the first time the use of confocal laser scanning microscopy to differentiate between neurofibroma and healthy skin.

In vivo confocal laser scanning microscopy in the diagnosis of melanocytic skin tumours.

Melanoma of the skin represents one of the greatest challenges in early or preventive detection. Whereas surgical excision in early stages of melanoma development is almost always curative, delayed recognition puts the patient at risk for destructive growth and death from disease once the tumour has progressed to competence for metastasis. The worldwide introduction of dermoscopy has led to improved diagnostic accuracy for melanocytic skin tumours. Whereas dermoscopy has probably reached the method's inherent potential diagnostic accuracy because of the lack of cellular level evaluation, further improvements could be expected by in vivo confocal laser scanning microscopy. In vivo confocal microscopy represents a novel imaging tool that allows the noninvasive examination of skin cancer morphology in real time at a 'quasihistopathological' resolution viewing microanatomical structures and individual cells. Numerous morphological confocal features of melanocytic skin tumours have been described and histopathological correlates of confocal structures have been previously elucidated. Recently, several studies have evaluated the diagnostic accuracy of in vivo confocal microscopy for melanocytic skin tumours, investigating approximately 50,000 tumour images. Remarkably, sensitivity superior to the diagnostic accuracy achieved with dermoscopy could be reached by this imaging modality. These studies represent a significant contribution to the body of research necessary for the evaluation and implementation of in vivo confocal microscopy in clinical practice to avoid many currently unnecessary biopsies. In vivo confocal microscopy probably augurs a sea change in the way we evaluate melanocytic skin tumours in the future and will ultimately move the art of histological diagnosis closer to the bedside.

Onychomycosis: a new emerging infectious disease in childhood population and adolescents. Report on treatment experience with terbinafine and itraconazole in 36 patients.

BACKGROUND: Onychomycosis is a rare disease in children with an estimated prevalence ranging from 0% to 2.6%. Thus far, only limited experience with itraconazole and terbinafine treatment in children with onychomycosis is available in the literature. AIM OF THE STUDY: Evaluation of treatment experience with itraconazole or terbinafine in childhood onychomycosis. SUBJECTS: Thirty-six children and adolescents (aged 4-17 years, 18 males and 18 females) with clinical and mycologically proven onychomycosis were enrolled in the present study. METHODS AND OUTCOME: In 27 of 36 patients, the causative agent (Trichophyton rubrum in 26 cases and Trichophyton interdigitale in one patient) could be identified by means of cultivation. Nineteen patients were treated with itraconazole 200 mg once daily for 12 weeks, and 17 patients were treated with terbinafine for 12 weeks in a dosage according to their body weight, respectively. Clinical cure was achieved within 1 to 5 months after discontinuation in all patients treated with itraconazole and in all but two patients after cessation of terbinafine treatment. Neither in the itraconazole nor in the terbinafine group were serious adverse events reported. Clinical cure was achieved within 1 to 5 months after discontinuation in all patients treated with itraconazole and in all but two patients after cessation of terbinafine treatment. Neither in the itraconazole nor in the terbinafine group were serious adverse events reported. CONCLUSION: To our experience, a mycological and clinical cure appears in children in a shorter time after treatment discontinuation (average 2-5 months) compared with adults. Itraconazole and terbinafine seem to be safe and effective in childhood onychomycosis; therefore, these antifungals seem to be potential alternatives to griseofulvin.

In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images.

BACKGROUND: In vivo confocal laser scanning microscopy (CLSM) represents a novel imaging tool that allows the noninvasive examination of skin cancer morphology in real time at a 'quasi-histopathological' resolution viewing microanatomical structures and individual cells. OBJECTIVES: To validate diagnostic confocal examination of melanocytic skin tumours using unselected tumour images. METHODS: In the present study, we used a total of 3709 unselected CLSM tumour images obtained from 20 malignant melanomas and 50 benign naevi. The entire set of images derived from each tumour was evaluated by independent observers. Classification tree analysis based on a subsample of 857 tumour images was performed to develop a diagnostic algorithm. RESULTS: Overall, sensitivity and specificity of 97.5% and 99% could be achieved by the independent observers (positive predictive value 97.5%, negative predictive value 99%). Classification tree analysis yielded a three-step algorithm based on only three morphological CLSM features, facilitating a correct classification in 92.4% of the benign naevus images and 97.6% of melanoma images. CONCLUSIONS: In vivo CLSM augurs a sea change in the way we will view skin tumour processes clinically at the bedside and merits application for use as a screening tool in skin oncology.

Automatic identification of diagnostic significant regions in confocal laser scanning microscopy of melanocytic skin tumors.

OBJECTIVES: Confocal laser scanning microscopy (CLSM) is used for quick medical checkups. The aim of this study is to check the discrimination power of texture features for the automatic identification of diagnostic significant regions in CLSM views of skin lesions. METHODS: In tissue counter analysis (TCA) the images are dissected in equal square elements, where different classes of features are calculated out. Features defined in the spatial domain are based on histogram (grey level distribution) and co-occurrence matrix (grey level combinations). The features defined in the frequency domain are based on spectral properties of the wavelet Daubechie 4 transform (texture exploration at different scales) and the Fourier transform (global texture properties are localized in the spectrum). Hundred cases of benign common nevi and malignant melanoma were used as the study set. Classification was done with CART (Classification and Regression Trees) analysis which splits the set of square elements into homogenous terminal nodes and generates a set of splitting rules. RESULTS: Features based on the wavelet transform provide the best results with 96.0% of correctly classified elements from benign common nevi and 97.0% from malignant melanoma. The classification results are relocated to the images by use of the splitting rules as diagnostic aid. The discriminated square elements are highlighted in the images, showing tissue with features in good accordance with typical diagnostic CLSM features. CONCLUSION: Square elements with more than 80% of discrimination power enable the identification of diagnostic highly significant parts in confocal microscopic views of malignant melanoma.

Influence of route of gastric transposition on oxygen supply at cervical oesophagogastric anastomoses.

BACKGROUND: The microcirculation and oxygen supply at the oesophagogastric anastomosis are crucial factors that influence anastomotic healing after oesophagectomy. METHODS: Twenty-nine patients (mean age 61.7 years) underwent gastric transposition via an orthotopic (14) or retrosternal (15) route. Interstitial partial pressure of oxygen (PO2) of the stomach in the anastomotic region was measured during oesophagectomy and in the intensive care unit. Interstitial PO2 values were determined after ligation of the short gastric vessels, after ligation of the left gastric artery, after forming the conduit and after gastric transposition. Postoperative measurements were recorded during endotracheal intubation, while breathing oxygen by mask or through the nose, and while breathing air. RESULTS: Interstitial PO2 levels were significantly higher before ligation of the left gastric artery than after ligation (mean 76.1 (95 per cent confidence interval 54.9 to 103.1) versus 44.9 (24.6 to 77.1) mmHg; P = 0.001). Levels were also higher following orthotopic transposition compared with the retrosternal route (68.2 (44.0 to 118.8) versus 24.6 (10.7 to 39.4) mmHg; P = 0.001) and during each postoperative measurement period. No differences were found between the various oxygen supply systems. CONCLUSION: Oxygen supply at the anastomosis of the gastric conduit reaches higher levels after orthotopic than retrosternal gastric transposition.

The use of confocal laser-scanning microscopy in microsurgery for invasive squamous cell carcinoma.

BACKGROUND: Ex-vivo confocal laser-scanning microscopy offers rapid imaging of excised tissue specimens without conventional histotechnical procedures. As vertical sections are prepared, morphological features can be assessed according to standard criteria used in conventional histopathology. OBJECTIVES: To validate the diagnostic confocal examination of squamous cell carcinoma (SCC) in microscopy-guided surgery. METHODS: Four independent observers received standardized instructions about diagnostic confocal microscopy features of SCC. Subsequently, 120 confocal images of fresh excisions from SCC or normal skin, imaged using a commercially available, near-infrared, reflectance confocal laser-scanning microscope, were evaluated by each observer. RESULTS: General morphology, such as location, size and shape of the cancer area could be visualized by the imaging system. Furthermore, densely packed and irregularly organized nuclei and nuclear atypia could be delineated. Overall, a sensitivity of 95% and a specificity of 96.25% were achieved by the four observers (positive predictive value 96.25%, negative predictive value 95.23%). CONCLUSIONS: This study provides a set of well-described morphological criteria with obvious diagnostic impact which should be used in further investigations. In the future, confocal laser-scanning microscopy may guide microsurgery of any skin cancer.

Vascular pattern of the palms--a clinical feature of atopic skin diathesis.

BACKGROUND: Atopic skin diathesis is a clinical term to describe skin atopics with previous, present or future atopic eczema/dermatitis syndrome (AEDS). In clinical practice, an unequivocal assessment of atopic skin diathesis in non-eczematous patients may be difficult. The majority of the known clinical features included in diagnostic scores are characteristic, but not specific markers of atopy. Especially, the vasoreactivity of atopic skin is disturbed. This is manifested by white dermographism, an irregular vascular response to thermal stimuli, and paradoxic skin reactions to histamine, cholinergic agents, and nicotinates. OBJECTIVE: The aims of our study were to investigate the clinical morphology of palmar vascular reactions in skin atopic and non-atopic individuals, and to determine whether this abnormal vascular reaction is more pronounced in skin atopic individuals. METHODS: Forty persons, 20 of them skin atopics, assessed by the Erlangen Atopy Score and an elevated serum IgE level (>150 U/ml), were included in a prospective single-centre study. Standardized digital photographs of the palms were presented in a blinded manner to five dermatologists in random order by means of the computerized imaging analysis system KS400 3.0. RESULTS: Evaluation of the original rgb (red, green, blue) color images and modified gray-level images showed that a pronounced reticular pattern of erythema of the palms was significantly (P < 0.0001) more common in skin atopics (72% and 69.6%, respectively). CONCLUSION: The gross vascular pattern of the palm might be an additional diagnostic feature of atopy, and further studies are needed to establish its exact prevalence.

[Safety and efficacy of interferon alfa-2b in the adjuvant treatment of uveal melanoma]. / Verträglichkeit und Wirksamkeit einer adjuvanten Interferon-alfa-2b-Behandlung beim Aderhautmelanom.

PURPOSE: In this manuscript, the safety and efficacy of adjuvant interferon alfa 2b treatment of uveal melanoma is described. PATIENTS AND METHODS: A total of 39 patients (23 male and 16 female, mean age 56.5 years, range 35-78 years) with uveal melanoma were treated with interferon alfa 2b, 3 million units three times a week subcutaneously for 1 year after therapy of the primary tumor. In all patients age, gender, primary melanoma data, therapeutic interventions, treatment side effects and outcome were documented. RESULTS: Of the 39 patients, 31 (80%) finished the treatment as scheduled after 1 year. In 18 patients (46%) the initial dose had to be reduced due to leucopenia, thrombopenia, cardiac symptoms, elevated of liver function or vertigo (WHO grade I-III). In eight patients, therapy had to be withdrawn because of serious side effects (five patients) and the appearance of metastases (three patients). Neither a univariate approach nor a multivariate approach could show a protective effect of interferon treatment on survival. CONCLUSIONS: Adjuvant treatment of uveal melanoma with interferon alfa should be abandoned until the question of dose and administration for cutaneous melanoma is solved.

Neurotological and neuroanatomical changes in the connexin-26-related HID/KID syndrome.

The phenotype of the HID (hystrix-like ichthyosis, deafness)/KID (keratitis, ichthyosis, deafness) syndrome is primarily characterized by skin changes. However, the connexin 26 (Cx 26) autosomal dominant mutation underlying this syndrome is of special neurotological interest. In the present paper, the clinical pattern, audiovestibular and neuroimaging findings and the detailed genetic analysis of 4 patients with identical HID/KID-associated mutation D50N of Cx 26 are reported. The audiological test results demonstrated profound sensorineural hearing loss in all of the patients. Neurotological testing revealed inconsistent abnormalities in dynamic posturography (sensory organization test), but the vestibular ocular reflex upon caloric irrigation was normal in all patients. Vestibular-evoked myogenic potential testing for otolith function (saccule) showed a regular response in 1 patient and pathologic responses in 3 patients, while subjective haptic vertical (utricular function) testing was normal in all of the patients. CCT showed an extended (in length), but very thin (in diameter) bony lining between the basal portion of the internal auditory canal and the vestibule in the 3 scanned patients. Our study provides evidence for functionally intact semicircular canals and normal utricular function in subjects with the autosomal dominant D50N mutation of Cx 26, in contrast to saccular function which was generally compromised and hearing loss which was profound.

Organ- and treatment-specific local response rates to systemic and local treatment modalities in stage IV melanoma.

BACKGROUND: Metastatic melanoma shows different local response rates in organs to systemic or local treatment modalities. Whereas skin, soft tissue, lymph node and lung metastases seem to have better local response rates, the local response of metastases localized in the liver, brain and bone seems to be low. OBJECTIVES: The organ-specific response rate, local response rate of each therapeutic measure and survival of 68 patients with stage IV disease were evaluated. METHODS: Four hundred and ten treatment periods (1-18 per patient) in 17 different organs of 43 men and 25 women (mean age 55 years, range 19-79) with measurable, widespread, surgically incurable disease were analysed. Chemotherapy was given in 405 of 410 treatment periods with dacarbazine, fotemustine, vindesine, carboplatin and temozolomide in different schedules. Local treatment modalities comprising radiotherapy, gamma knife radiosurgery and local hyperthermia were given in 71 of 410 treatment periods. RESULTS: Local response (complete or partial local remission) was achieved in 52 treatment periods (12.7%). When local treatment modalities, either combined with systemic therapy or not, were compared with systemic therapeutic modalities alone, a local response of 24% was achieved with local measures, compared with 10% in systemic treatment only (P = 0.003). When a spontaneous remission rate of less than 5% is considered, however, local as well as systemic treatments had a significant effect (P < 0.001). Organ-specific response rates to local therapies showed no statistically significant differences between the various organs involved. When systemic treatments without local measures were taken into account, lung metastases, cutaneous/subcutaneous metastases and adrenal metastases performed significantly better than liver metastases. When different treatment modalities were considered, there was no significant difference between the three local measures applied (radiotherapy, gamma knife radiosurgery and hyperthermia). Among the systemic therapies, dacarbazine high dose and carboplatin monochemotherapy were superior to combined regimens using fotemustine. A local response, irrespective of the mode of therapy, was significantly associated with longer survival (median 16 months) compared with no local response or local progressive disease (median 7 months; P < 0.0001). When the first treatment period of each patient was considered, local response was no longer a significant predictor. CONCLUSIONS: The study shows that local therapeutic measures are superior in inducing a local response than systemic therapies alone. Induction of remission may be associated with longer survival. Chemotherapy, despite limited local response rates, is still statistically superior to an estimated spontaneous remission rate.

The acute coronary syndrome--pre-hospital diagnostic quality.

BACKGROUND AND OBJECTIVE: In the Austrian emergency medical service (EMS), emergency medical technician-staffed and physician-staffed vehicles are in operation. Patients with suspected acute coronary syndromes (ACS) are treated in the pre-hospital phase and transported to the hospital by an emergency physician (EP). This study evaluates the diagnostic performance of EPs in ACS and the impact of this emergency system on the outcome of ACS in an urban area. DESIGN: Retrospective case control study. METHODS: All protocol sheets from the emergency physicians were searched for the diagnosis of ACS. The database of the emergency department (ED) was searched for patients with ACS as an admission diagnosis or ACS as discharge diagnosis. For patients admitted to an intensive care unit (ICU), the medical history from the ICU was reviewed. According to the diagnosis and the aggressiveness of therapy, patients were divided in five categories of severity at each stage of care (pre-hospital category, ED category, ICU category). RESULTS: A total of 3585 patients was analysed. Only 17.8% of the patients with ACS as the admission diagnosis and 20.3% of the patients with ACS as the discharge diagnosis were transported by an EP. 46.8% of the ACS diagnosis by EPs were confirmed in hospital. Patients transported by EPs showed a higher all-cause mortality in hospital (1.6% vs. 0.6%; p=0.011). There was no significant correlation between the pre-hospital category of patients treated by EPs and the ED category. When a 12-lead-electrocardiogram was recorded, the correlation improved slightly (rho: 0.139; p=0.006). CONCLUSIONS: The percentage of ACS patients transported to hospital by an EP is very low, and EPs seem to be "over-aware" in the diagnosis of ACS.

Early enteral feeding compared with parenteral nutrition after oesophageal or oesophagogastric resection and reconstruction.

After resective and reconstructive surgery in the gastrointestinal tract, oral feeding is traditionally avoided in order to minimize strain to the anastomoses and to reduce the inherent risks of the postoperatively impaired gastrointestinal motility. However, studies have given evidence that the small bowel recovers its ability to absorb nutrients almost immediately following surgery, even in the absence of peristalsis, and that early enteral feeding would preserve both the integrity of gut mucosa and its immunological function. The aim of this study was to investigate the impact of early enteral feeding on the postoperative course following oesophagectomy or oesophagogastrectomy, and reconstruction. Between May 1999 and November 2002, forty-four consecutive patients (thirty-eight males and six females; mean age 62, range 30-82) with oesophageal carcinoma (stages I-III), who had undergone radical resection and reconstruction, entered this study (early enteral feeding group; EEF). A historical group of forty-four patients (thirty-seven males and seven females; mean age 64, range 41-79; stages I-III) resected between January 1997 and March 1999 served as control (parenteral feeding group; PF). The duration of both postoperative stay in the Intensive Care Unit (ICU) and the total hospital stay, perioperative complications and the overall mortality were compared. Early enteral feeding was administered over the jejunal line of a Dobhoff tube. It started 6 h postoperatively at a rate of 10 ml/h for 6 h with stepwise increase until total enteral nutrition was achieved on day 6. In the controls oral enteral feeding was begun on day 7. If compared to the PF group, EEF patients recovered faster considering the duration of both stay in the ICU and in the hospital. There was a significant difference in the interval until the first bowel movements. No difference in overall 30 d mortality was identified. A poor nutritional status was a significant prognostic factor for an increased mortality. Early enteral feeding significantly reduces the duration of ICU treatment and total hospital stay in patients who undergo oesophagectomy or oesophagogastrectomy for oesophageal carcinoma. The mortality rate is not affected.

Erythroderma with lichenoid granulomatous features induced by erythropoietin.

The increasing use of new drugs in cancer therapy, especially growth factors, hormones, and chemotherapies resulted in several reports of unusual skin eruptions. We studied a patient with erythroderma who had received erythropoietin because of myeloma with tumor anemia. The histological features were characterized by a lichenoid, focally granulomatous infiltrate with predominance of histiocytes. It is important for dermatopathologists to recognize this interesting pattern induced by erythropoietin.

Temozolomide and interferon alpha 2b in metastatic melanoma stage IV.

BACKGROUND: A multicentre, centrally randomized, open-labelled study with temozolomide and interferon (IFN)-alpha 2b was carried out to study the therapeutic effect in patients with metastatic melanoma stage IV. OBJECTIVES: The response rate, efficacy, side-effects, reasons for discontinuation of therapy and survival rate of 47 patients treated with temozolomide in combination with two different dosing regimens of IFN-alpha 2b were documented. PATIENTS/METHODS: Twenty-nine male and 18 female patients (mean age 57.6 years, range 34-74) were centrally randomized to two different arms: 20 patients received a treatment schedule with temozolomide 150 mg m(-2) on days 1-5 orally every 28 days in combination with IFN-alpha 2b 10 MIU m(-2) every other day and 27 patients received temozolomide 150 mg m(-2) on days 1-5 every 28 days in combination with IFN-alpha 2b in a fixed dose of 10 MIU every other day. RESULTS: We observed an overall response rate of 27.6% comprising five complete remissions (10.6%: one patient group A, four patients group B), in two of these five patients at the last follow-up in the study (4.3%, both in group B); and eight partial remissions (17%: six patients in group A, two patients in group B), in three of these eight patients at the last follow-up in the study (6.4%, two patients in group A, one patient in group B). Three patients showed stable disease (6.4%: one patient in group A, two patients in group B). Mean survival was 14.5 months [95% confidence interval (CI) 10-19] with no significant differences between treatment groups. However, there was a significant correlation with response after three cycles (log rank test, P < 0.03). Within the 32 patients who completed at least three cycles of therapy, seven patients (three in group A and four in group B) with a partial or complete response showed a significantly better mean survival of 30.6 months (95% CI 19.1-42) compared with 25 patients who did not respond (13.7 months 95% CI 9.2-18.3). In total, patients with at least one complete remission showed the longest survival (37.1 months 95% CI 26.3-47.9), followed by patients with at least one partial response (17.4 95% CI 10.9-23.9). Major side-effects of the treatment were nausea, vomiting, headache, leucopenia, thrombopenia, elevation of liver function parameters and neurological symptoms. In five patients, the side-effects led to a discontinuation of treatment: neurological symptoms (two patients), sepsis (one patient), brain haemorrhage (one patient) and exanthema (one patient). There were no treatment-related deaths. CONCLUSIONS: The combination of temozolomide and IFN-alpha 2b can easily be administered and shows tolerable toxicity. When an objective response occurs after three cycles, it indicates a significant survival advantage.