Evaluation of Orbital Lymphoproliferative and Inflammatory Disorders by Gene Expression Analysis.

Non-specific orbital inflammation (NSOI) and IgG4-related orbital disease (IgG4-ROD) are often challenging to differentiate. Furthermore, it is still uncertain how chronic inflammation, such as IgG4-ROD, can lead to mucosa-associated lymphoid tissue (MALT) lymphoma. Therefore, we aimed to evaluate the diagnostic value of gene expression analysis to differentiate orbital autoimmune diseases and elucidate genetic overlaps. First, we established a database of NSOI, relapsing NSOI, IgG4-ROD and MALT lymphoma patients of our orbital center (2000−2019). In a consensus process, three typical patients of the above mentioned three groups (mean age 56.4 ± 17 years) at similar locations were selected. Afterwards, RNA was isolated using the RNeasy FFPE kit (Qiagen) from archived paraffin-embedded tissues. The RNA of these 12 patients were then subjected to gene expression analysis (NanoString nCounter®), including a total of 1364 target genes. The most significantly upregulated and downregulated genes were used for a machine learning algorithm to distinguish entities. This was possible with a high probability (p < 0.0001). Interestingly, gene expression patterns showed a characteristic overlap of lymphoma with IgG4-ROD and NSOI. In contrast, IgG4-ROD shared only altered expression of one gene regarding NSOI. To validate our potential biomarker genes, we isolated the RNA of a further 48 patients (24 NSOI, 11 IgG4-ROD, 13 lymphoma patients). Then, gene expression pattern analysis of the 35 identified target genes was performed using a custom-designed CodeSet to assess the prediction accuracy of the multi-parameter scoring algorithms. They showed high accuracy and good performance (AUC ROC: IgG4-ROD 0.81, MALT 0.82, NSOI 0.67). To conclude, genetic expression analysis has the potential for faster and more secure differentiation between NSOI and IgG4-ROD. MALT-lymphoma and IgG4-ROD showed more genetic similarities, which points towards progression to lymphoma.

Conjunctival and uveal melanoma: Survival and risk factors following orbital exenteration.

PURPOSE: This study aims to analyse disease-free survival, overall survival and risk factors after orbital exenteration in patients with conjunctival and uveal melanoma. METHODS: Patients who underwent orbital exenteration due to conjunctival and uveal melanoma were included in this retrospective study (March 2000 to March 2018). RESULTS: A total of 76 patients were enrolled in this study: 60 patients had a conjunctival melanoma and 16 had a uveal melanoma. In conjunctival melanoma, the mean age was 68.4 years. The overall survival rate was 82% after 1 year and 52% after 5 years. Univariate analysis of overall survival found that the following parameters were predictive of a worse prognosis: gender, extent of the primary tumour, lymph node metastases, distant metastases, adjuvant chemotherapy or radiotherapy and relapse. In multivariate analysis, relapse and adjuvant radiotherapy appeared to contribute to a significantly worse prognosis. In uveal melanoma, the mean age was 63.6 years. Eleven patients died during follow-up (mean follow up 30.7 months). The overall survival and disease-free survival rates after 1 year were 62% and 57%, respectively. An analysis of risk factors was not possible due to the small number of cases. CONCLUSION: Orbital exenterations in conjunctival and uveal melanoma are rarely necessary, but can be performed as an ultima ratio treatment with curative intent. Disease-free survival and overall survival are significantly lower for both groups due to the advanced stage of the disease compared to patients treated without exenteration in the literature. If a recurrence occurs after exenteration, the prognosis is poor in both groups.

Orbital exenteration: Symptoms, indications, tumour localizations, pathologies, reconstruction, complications and survival.

OBJECTIVE: This study aims to evaluate malignant and benign diseases that lead to orbital exenteration. PATIENTS: From December 1999 to September 2017, patients undergoing orbital exenteration were included in this retrospective study. All of them were evaluated on clinical symptoms, indications, tumour localizations, pathologies, reconstruction techniques, complications, recurrences, and survival. RESULTS: Of the 205 patients enrolled in this study, 94 had a carcinoma, 73 melanoma, 9 a sarcoma, 14 some other malignant disease, and 15 a benign medical condition. Sixteen patients underwent reconstruction using a local eyelid skin flap (7.8%), 6 with a split-thickness graft (2.9%), 144 with a local flap (70.2%), and 25 with a microvascular graft (12.2%), whereas 14 patients did not undergo reconstruction (6.8%). The most common complications were wound dehiscences (25 cases), pain (17 cases), and partial flap necroses (13 cases). Moreover, 62% of the patients were treated with different facial prostheses or artificial eyes. Given these results, it appears that lymph nodes and distant metastases, as well as lymphatic invasion into vessels, perineural invasion, and non-cleared resection margins, seem to affect overall survival after orbital exenteration. CONCLUSION: Different reconstruction techniques can be used to provide the patient with maximum functionality and aesthetics after orbital exenteration. Individual concepts should be discussed at the beginning of the treatment. Using primary reconstruction and providing osseointegrated implant-retained prostheses remain the gold standard.

Reconstruction of Orbital Exenteration Defects with Cheek Rotation Flaps: Indications, Technique, Complications, Rehabilitation, and Survival.

The objective of this study was to examine the role of cheek rotation flaps in the reconstruction of orbital defects after exenteration. From January 2000 to August 2018, patients undergoing orbital exenteration and reconstruction with cheek rotation flaps were enrolled in this retrospective study. All patients were evaluated for wound complications, orbital rehabilitation, tumor relapse, and survival. Thirty patients completed the study. Fourteen complications allocated to 11 patients were assessed. The most common complications were seroma (13%), temporary facial nerve weakness (13%), and partial necrosis of the flap (10%). A major complication occurred in a total of two patients (7%), so that surgical correction was necessary. Eleven patients had a relapse; 15 patients died as part of the follow-up. Fifteen patients were treated with facial prostheses. The overall survival rate was 61% after 1 year and 42% after 5 years. Follow-up periods ranged from 6 to 95 months. Cheek rotation flap reconstruction after exenteration is a reliable method with a low rate of major complications. It is indicated when an approach to the parotid gland or the neck region is necessary because of suspected lymph node metastasis and in elderly patients because of their skin's laxity. It can be performed as primary or secondary reconstruction. Good esthetic results can be achieved, especially after endosseous implantation.

Periorbital, conjunctival and primary intraorbital carcinomas: Survival and risk factors after orbital exenteration.

OBJECTIVES: This study aimed to analyse the disease-free survival (DFS), overall survival (OS) and risk factors after orbital exenteration in patients with periorbital, conjunctival and primary intraorbital carcinomas. METHODS: Patients undergoing orbital exenteration due to a primary carcinoma between March 2000 and March 2018 were included in this retrospective study. Risk factors in all the patients were evaluated using univariate and multivariate analyses. RESULTS: In total, 97 patients were enroled in this study. The most common tumours were conjunctival carcinoma (35 cases), squamous cell carcinoma of the skin (27 cases) and basal cell carcinoma (20 cases). The median follow-up period was 36 months. The average age of the patients was 67.3 years (range, 29-93 years). In all the patients, OS was 85% after 1 year and 69% after 5 years, while DFS was 71% after 1 year and 55% after 5 years. Univariate analysis of OS revealed that the following parameters were predictive of a poor prognosis: localisation, neck dissection, lymph node metastases, lymphatic invasion, perineural invasion, resection margins and immunosuppression. Multivariate analysis revealed resection margins as the only independent risk factor. CONCLUSION: Orbital exenteration is rarely necessary in patients with periorbital, conjunctival and primary intraorbital carcinomas; however, it can be performed as an ultima ratio treatment with a curative intent. Clear margins can be achieved in most cases. OS and DFS are not significantly different in the subgroups. In most cases, recurrence occurs within the first 2 years.

Modified types of orbital exenteration, survival, and reconstruction.

PURPOSE: This study aims to analyse the various modifications of orbital exenteration. METHODS: Patients undergoing orbital exenteration from March 1978 to October 2019 were included in this retrospective study. The patients were evaluated on the basis of the indication, type of exenteration, reconstruction technique, overall survival (OS), and disease-free survival (DFS). RESULTS: In total, 300 patients were enrolled in this study. As many as 24 patients had lid and conjunctiva sparing anterior exenteration, 16 had lid sparing anterior exenteration, 83 had anterior exenteration, 14 had lid and conjunctiva sparing total exenteration, seven had lid sparing total exenteration, 44 had total exenteration, one had lid and conjunctiva sparing extended exenteration, 23 had lid sparing extended exenteration, and 88 had extended exenteration. As many as 39 patients had a primary wound closure. Six patients underwent reconstruction with a split-thickness skin graft, 177 patients with a local or regional flap, and 40 patients with a microvascular flap. A total of 38 patients did not undergo reconstruction. The mean follow-up was 40 months (range 6-216 months). The OS rate was 82.2% after 1 year, 58.5% after 5 years, and 49% after 10 years for all patients with malignant tumours. The DFS rate was 67.7% after 1 year, 45.6% after 5 years, and 31.7% after 10 years. CONCLUSION: Individual types of orbital exenteration allow patient-adapted therapies. The preservation of uninvolved orbital tissue facilitates orbital reconstruction. The type of exenteration did not have any influence on overall survival.

Treatment of odontogenic abscesses: comparison of primary and secondary removal of the odontogenic focus and antibiotic therapy.

PURPOSE: To examine the time of removal of the odontogenic focus, antibiotic therapy and risk factors in odontogenic abscesses. PATIENTS: From January 2012 to December 2015, inpatients undergoing incision due to odontogenic abscesses were identified in a retrospective study. All the patients were evaluated for time of removal of the odontogenic focus, antibiotic therapy, germ spectrum, complications and risk factors. RESULTS: Two hundred ten patients completed the study. In 89 cases (42.4%), the odontogenic focus was removed as part of the abscess treatment (group A). In 121 cases (57.6%), the focus was secondarily removed (group B). On average, 2 ± 4 teeth were removed in group A, and 6 ± 5 teeth in group B (p < 0.0001). An average of 1.2 ± 0.4 surgical interventions were performed in group A, and 2 ± 0.2 operations in group B (p < 0.0001). Microbiological examination was positive in one-third of the cases (70 cases). Most commonly, streptococci (27%) were isolated. A resistance screening was possible in 57 of the detected germs (68.7%). In 89% of these patients, the combination of ampicillin-sulbactam was effective. The hospital stay was 4.8 ± 2 days for group A and 7.6 ± 3 days for group B (p < 0.0001). The clinical evaluation revealed 12 intermediate (5.7%) and three long-term (1.4%) complications. The long-term complications included a recurrence in two cases (1%) and an osteomyelitis in one case (0.5%). A logistic regression analysis identified no significant risk factor in relation to these complications. CONCLUSION: The study shows that a primary removal of the odontogenic focus may have advantages over a secondary removal: (1) fewer operations, (2) shorter hospital stay and (3) shorter antibiotic therapy. Broad-spectrum penicillins in combination with beta-lactamase inhibitors are a possible, sufficient antibiotic regimen. Long-term complications are rare. No risk factors are identified in relation to these complications.

Autologous dermis-fat grafts in head and neck patients: Indications and evaluation in reconstructive surgery.

PURPOSE: The aim of this study was to examine the indications and results of autologous dermis-fat grafts in the reconstruction of maxillofacial soft-tissue defects. MATERIALS AND METHODS: A total of 93 patients with dermis-fat graft reconstruction due to a soft tissue defect in the head and neck region were enrolled in this retrospective clinical study between March 2002 and January 2017. They were classified into the subgroups 'parotid surgery', 'orbital surgery', and 'facial surgery'. All the patients were evaluated for wound complications, and the general indications were discussed. RESULTS: In all, 96 dermis-fat grafts were performed in 93 patients. A total of 34 complications that arose in 30 patients were assessed. The dermis-fat graft was primarily transplanted in 50 cases and secondarily in 46. Of the patients, 90 showed well-integrated dermis-fat grafts. A major complication occurred in three patients. CONCLUSION: Dermis-fat grafts for the reconstruction of maxillofacial soft-tissue defects represent a reliable method with a low rate of major complications. The graft can be used as a primary as well as secondary transplant. Especially in parotid and orbital surgery, the dermis-fat graft appears to be a transplant of choice. It can also be used as an alternative in facial surgery, lip enhancement, and special individual cases.

Metastases from distant primary tumours on the head and neck: clinical manifestation and diagnostics of 91 cases.

PURPOSE: The aim of this study was to evaluate which primary tumours metastasize on the head and neck region, identify the kind of clinical manifestation, the types of diagnostics that should be performed, and prove that the therapy appears possible and useful. PATIENTS: As many as 91 patients with a distant metastasis on the head and neck were enrolled in this retrospective clinical study from January 2004 to September 2016. All the patients were evaluated for clinical symptoms, primary tumour, localization, diagnostics, and surgical procedure. RESULTS: A total of 31 patients had asymptomatic swelling, 27 patients had symptomatic swelling, and nine experienced isolated pain without swelling. Most other symptoms were organ-specific. The most frequent localizations were the orbit (44 metastases), mandible (19), neck region (9), and skin (7). The most common primary tumours were breast carcinoma (44), bronchial carcinoma (12), and renal carcinoma (9). A biopsy was performed on 38 patients, a partial resection was done on 28 patients, extirpation on six patients, and a radical resection on 19 patients. CONCLUSION: Distant metastases on the head and neck are rare and, therefore, pose a challenge for the oncologist and other involved disciplines. Most distant metastases occur within the first five years. Late metastases, especially in breast carcinoma, are still possible after 20 years. A surgical examination should be carried out if the findings are not clear due to multiple differential diagnoses. In particular, surgical options under palliative aspects should be examined.

Autologous dermis - Fat grafts as primary and secondary orbital transplants before rehabilitation with artificial eyes.

OBJECTIVE: The aim of this study was to examine the role of autologous dermis-fat grafts in the reconstruction of orbital soft-tissue defects. PATIENTS: Thirty-six patients (3-84 years) were enrolled in this retrospective study from 2002 to 2014. The dermis-fat graft was primarily transplanted in seven cases, and secondarily in 29 patients. All the patients were evaluated for complications, adequate prosthetic cavity, possibility of artificial eye supply and movement, as well as cosmetic results. Follow-up periods ranged from 25 to 144 months. RESULTS: All the patients could be supplied with an artificial eye in the long term after dermis-fat transplantation. The clinical evaluation revealed 17 complications allocated to 11 patients. A major complication occurred in three patients (8.3%) so that a surgical correction was necessary. Thirty-three patients (91.7%) showed an aesthetically stable long-term outcome. CONCLUSION: Dermis-fat grafts for reconstruction of anophthalmic orbit represent a reliable method with a low complication rate and good cosmetic and functional results. The graft can be used as primary and secondary transplants. The stable long-term results and high aesthetic satisfaction lead us to recommend this method as a routine operation.

Correction of whistle deformity using autologous free fat grafting: first results of a pilot study and review of the literature.

PURPOSE: Whistle deformities are frequent sequelae after surgical correction of cleft lip, trauma, or tumor excision. The aim of this study was to examine the role of autologous free fat grafting in the reconstruction of whistle deformity. PATIENTS: Fifteen patients with whistle deformity were enrolled in this pilot study. The mean follow-up period was 19 months. Liposuction was done followed by the replantation of an average of 2.2 ml autologous fat per patient (range 0.7-4 ml). An overcorrection was performed in all patients. RESULTS: All the patients showed improvements in whistle deformity. The mean resorption rate was 53% (range 30-80%). Three patients (20%) were not satisfied with the postoperative result. Six complications were assessed (4× feeling of pressure [27%], one hematoma [7%], one recurrent pain [7%]), but a major complication did not occur. REVIEW: We also present a review of the literature with different techniques that were described in the last 20 years. CONCLUSION: Autologous free fat graftings for reconstruction of whistle deformity represent a reliable method with a low complication rate. However, the resorption rate is unpredictable. If necessary, several autologous fat transplantations should be conducted at an interval of at least 6 months.

Use of dermis-fat grafts in the prevention of Frey's syndrome after parotidectomy.

OBJECTIVE: To examine the role of dermis-fat grafts in preventing gustatory sweating and in the reconstruction of facial contour defects after parotidectomy. PATIENTS: Twenty-three patients with tumours of the parotid gland were enrolled in this prospective clinical study from January 2006 to February 2014. All of them were evaluated for wound complications, Frey's syndrome, satisfaction, and tumour relapse. Follow-up periods ranged from 6 to 72 months. RESULTS: Nineteen patients completed the study. Nine complications observed in six patients were assessed (two haematomas [10%], one seroma [5%], one sialocele [5%], and recurrent pain in five patients [26%]). None revealed Frey's syndrome. Satisfactory results were found in relation to scar, facial contour, and overall outcomes. CONCLUSION: Dermis-fat grafts appear to be an effective method of preventing Frey's syndrome after parotidectomy. The stable long-term results and high patient satisfaction lead to the application of this operation technique in daily routine.