Facial Cutaneous Metastases of Gastric Signet-ring Cell Carcinoma: Resection and Reconstruction as a Palliative Surgical Treatment Option.

BACKGROUND: Cutaneous metastases of gastric signet-ring cell gastric carcinoma are very rare. Our following case report highlights the need for careful clinical examination and skin biopsy of newly developing scar-like or erythematous skin lesions in patients with a known history of malignant disease in order to prevent diagnostic and therapeutic delay. CASE REPORT: A 68-year-old male patient presented with two slightly painful, erythematous, facial skin lesions (chin and forehead) 2 years after gastrectomy for a signet-ring cell gastric carcinoma. The patient complained of intermittent neuropathic pain in the area of the mental nerve. A biopsy of both skin lesions demonstrated metastasis of signet-ring cell gastric carcinoma. Following discussion within the multidisciplinary tumor board, palliative surgical excision was recommended for this patient. Both skin lesions were resected and the large defect in the chin region was primarily closed by a cervical skin transposition flap. CONCLUSION: The presented case report of a patient with a known history of malignancy illustrates that newly developing erythematous skin lesions may be suspicious for cutaneous metastases. Palliative surgical interventions may play a role even in an advanced disease stage.

Current concepts in cleft care: A multicenter analysis.

The current surgical techniques used in cleft repair are well established, but different centers use different approaches. To determine the best treatment for patients, a multi-center comparative study is required. In this study, we surveyed all craniofacial departments registered with the German Society of Maxillofacial Surgery to determine which cleft repair techniques are currently in use. Our findings revealed much variation in cleft repair between different centers. Although most centers did use a two-stage approach, the operative techniques and timing of lip and palate closure were different in every center. This shows that a retrospective comparative analysis of patient outcome between the participating centers is not possible and illustrates the need for prospective comparative studies to establish the optimal technique for reconstructive cleft surgery.

Defining the surgical margins of adenoid cystic carcinoma and their impact on outcome: An international collaborative study.

BACKGROUND: The mainstay of treatment in adenoid cystic carcinoma (ACC) of the head and neck is surgical resection with negative margins. The purpose of this study was to define the margin status that associates with survival outcomes of ACC of the head and neck. METHODS: We conducted univariate and multivariate analyses of international data. RESULTS: Data of 507 patients with ACC of the head and neck were analyzed; negative margins defined as ≥5 mm were detected in 253 patients (50%). On multivariate analysis, the hazard ratios (HRs) of positive margin status were 2.68 (95% confidence interval [CI], 1.2-6.2; p = .04) and 2.63 (95% CI, 1.1-6.3; p = .03) for overall survival (OS) and disease-specific survival (DSS), respectively. Close margins had no significant impact on outcome, with HRs of 1.1 (95% CI, 0.4-3.0; p = .12) and 1.07 (95% CI, 0.3-3.4; p = .23) for OS and DSS, respectively, relative with negative margins. CONCLUSION: In head and neck ACC, positive margins are associated with the worst outcome. Negative or close margins are associated with improved outcome, regardless of the distance from the tumor. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1008-1014, 2017.

Nomograms for predicting survival and recurrence in patients with adenoid cystic carcinoma. An international collaborative study.

BACKGROUND: Due to the rarity of adenoid cystic carcinoma (ACC), information on outcome is based upon small retrospective case series. The aim of our study was to create a large multiinstitutional international dataset of patients with ACC in order to design predictive nomograms for outcome. METHODS: ACC patients managed at 10 international centers were identified. Patient, tumor, and treatment characteristics were recorded and an international collaborative dataset created. Multivariable competing risk models were then built to predict the 10 year recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and cancer specific mortality (CSM). All predictors of interest were added in the starting full models before selection, including age, gender, tumor site, clinical T stage, perineural invasion, margin status, pathologic N-status, and M-status. Stepdown method was used in model selection to choose predictive variables. An external dataset of 99 patients from 2 other institutions was used to validate the nomograms. FINDINGS: Of 438 ACC patients, 27.2% (119/438) died from ACC and 38.8% (170/438) died of other causes. Median follow-up was 56 months (range 1-306). The nomogram for OS had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N-status and M-status) with a concordance index (CI) of 0.71. The nomogram for CSM had the same variables, except margin status, with a concordance index (CI) of 0.70. The nomogram for RFP had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N status and perineural invasion) (CI 0.66). The nomogram for DRFP had 6 variables (gender, clinical T stage, tumor site, pathologic N-status, perineural invasion and margin status) (CI 0.64). Concordance index for the external validation set were 0.76, 0.72, 0.67 and 0.70 respectively. INTERPRETATION: Using an international collaborative database we have created the first nomograms which estimate outcome in individual patients with ACC. These predictive nomograms will facilitate patient counseling in terms of prognosis and subsequent clinical follow-up. They will also identify high risk patients who may benefit from clinical trials on new targeted therapies for patients with ACC. FUNDING: None.

Elective neck dissection in patients with head and neck adenoid cystic carcinoma: an international collaborative study.

BACKGROUND: Adenoid cystic carcinoma (ACC) accounts for 3-5 % of all head and neck malignancies. Investigations of outcomes from elective neck dissection (END) for patients with ACC are sparse. This study aimed to assess the impact of END on the survival of patients with ACC. METHODS: This retrospective multicentered study investigated 270 patients who underwent neck dissection. A multivariate analysis assessed associations of clinical and histopathologic characteristics with survival outcomes. RESULTS: The primary tumor sites included the oral cavity in 250 patients (55 %), the major salivary glands in 133 patients (29 %), the sinonasal mucosa in 68 patients (15 %), and the larynx in six patients (1 %). The overall rate of occult nodal metastases among the patients who underwent END was 17 % (38/226). The highest incidence of occult nodal metastases was with the oral cavity (66 %). The 5-year overall survival (72 and 79 % for patients with or without END, respectively) and disease-specific survival (74 and 81 % for patients with or without END, respectively) were similar in the two groups. The subgroup analysis of patients according to the primary site showed no significant impact of END on outcome. In the multivariate analysis, primary site, T classification, and N classification were the only variables associated with outcome. CONCLUSIONS: The incidence of occult neck metastases among patients with ACC is 17 %. The highest incidence of occult metastases is with the oral cavity. Statistical analysis showed no survival advantage for patients who underwent END compared with those who did not.

Incidence of cervical lymph node metastasis and its association with outcomes in patients with adenoid cystic carcinoma. An international collaborative study.

BACKGROUND: The patterns of regional metastasis in adenoid cystic carcinoma (ACC) of the head and neck and its association with outcome is not established. METHODS: We conducted a retrospective multicentered multivariate analysis of 270 patients who underwent neck dissection. RESULTS: The incidence rate of neck metastases was 29%. The rate observed in the oral cavity is 37%, and in the major salivary glands is 19% (p = .001). The rate of occult nodal metastases was 17%. Overall 5-year survival rates were 44% in patients undergoing therapeutic neck dissections, and 65% and 73% among those undergoing elective neck dissections, with and without nodal metastases, respectively (p = .017). Multivariate analysis revealed that the primary site, nodal classification, and margin status were independent predictors of survival. CONCLUSION: Our findings support the consideration of elective neck treatment in patients with ACC of the oral cavity.

International collaborative validation of intraneural invasion as a prognostic marker in adenoid cystic carcinoma of the head and neck.

BACKGROUND: The purpose of this study was to characterize the incidence, pattern of spread, and prognostic correlation of nerve invasion in patients with adenoid cystic carcinoma (ACC). METHODS: Using 3 different pathological categories of perineural invasion, intraneural invasion, and perineural inflammation, we investigated the prognostic value of nerve invasion in a total of 495 ACCs from 9 international patient cohorts with median follow-up 90 months (range, 12-288 months). RESULTS: Of 239 patients (48%) with nerve invasion, 174 (73%) had perineural invasion, 65 (27%) intraneural invasion, and 37 (15%) perineural inflammation. Multivariate Cox regression analysis identified tumor site (p = .008; hazard ratio [HR] = 1.8; 95% confidence interval [CI] = 0.07-3.7) and intraneural invasion (p < .001; HR = 5.9; 95% CI = 0.8-12.3) as independent prognostic markers for both overall survival (OS) and disease-specific survival (DSS), but not of distant metastases. CONCLUSION: Although perineural invasion has no impact on survival, intraneural invasion is an independent predictor of poor prognosis. Recognition of intraneural invasion may help optimize treatment of patients with head and neck ACC.

Analysis of failure in patients with adenoid cystic carcinoma of the head and neck. An international collaborative study.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a locally aggressive tumor with a high prevalence of distant metastases. The purpose of this study was to identify independent predictors of outcome and to characterize the patterns of failure. METHODS: An international retrospective review was conducted of 489 patients with ACC treated between 1985 and 2011 in 9 cancer centers worldwide. RESULTS: Five-year overall-survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 76%, 80%, and 68%, respectively. Independent predictors of OS and DSS were: age, site, N classification, and presence of distant metastases. N classification, age, and bone invasion were associated with DFS on multivariate analysis. Age, tumor site, orbital invasion, and N classification were independent predictors of distant metastases. CONCLUSION: The clinical course of ACC is slow but persistent. Paranasal sinus origin is associated with the lowest distant metastases rate but with the poorest outcome. These prognostic estimates should be considered when tailoring treatment for patients with ACC.

Functional features of cancer stem cells in melanoma cell lines.

BACKGROUND: Recent evidence suggests a subset of cells within a tumor with "stem-like" characteristics. These cells are able to transplant tumors in immunodeficient hosts. Distinct from non-malignant stem cells, cancer stem cells (CSC) show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumor cells, and resistance to chemotherapy or radiation. They are often characterized by elevated expression of stem cell surface markers, in particular CD133, and sets of differentially expressed stem cell-associated genes. CSC are usually rare in clinical specimens and hardly amenable to functional studies and gene expression profiling. In this study, a panel of heterogenous melanoma cell lines was screened for typical CSC features. METHODS: Nine heterogeneous metastatic melanoma cell lines including D10 and WM115 were studied. Cell lines were phenotyped using flow cytometry and clonogenic assays were performed by limiting dilution analysis on magnetically sorted cells. Spheroidal growth was investigated in pretreated flasks. Gene expression profiles were assessed by using real-time rt-PCR and DNA microarrays. Magnetically sorted tumor cells were subcutaneously injected into the flanks of immunodeficient mice. Comparative immunohistochemistry was performed on xenografts and primary human melanoma sections. RESULTS: D10 cells expressed CD133 with a significantly higher clonogenic capacity as compared to CD133- cells. Na8, D10, and HBL cells formed spheroids on poly-HEMA-coated flasks. D10, Me39, RE, and WM115 cells expressed at least 2 of the 3 regulatory core transcription factors SOX2, NANOG, and OCT4 involved in the maintenance of stemness in mesenchymal stem cells. Gene expression profiling on CD133+ and CD133- D10 cells revealed 68 up- and 47 downregulated genes (+/-1.3 fold). Two genes, MGP and PROM1 (CD133), were outstandingly upregulated. CD133+ D10 cells formed tumors in NSG mice contrary to CD133- cells and CD133 expression was detected in xenografts and primary human melanoma sections using immunohistochemistry. CONCLUSIONS: Established melanoma cell lines exhibit, to variable extents, the typical features of CSCs. The tumorigenic cell line D10, expressing CD133 and growing in spheroids and might qualify as a potential model of melanoma CSCs.

Orbital lymphoma: diagnostic approach and treatment outcome.

BACKGROUND: Lymphomas of the orbit and orbital adnexae are rare tumors, comprising only 1% of all non-Hodgkin's lymphoma. The majority of non-Hodgkin's lymphomas of the orbit are extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue type. Because of nonspecific clinical signs and symptoms, some diagnostic delay may occur. The purpose of the study was to evaluate the diagnostic approach in orbital lymphomas and to analyze their treatment outcome. METHODS: In the period from 2005 to 2012, from a group of 135 patients with tumors of the orbit, we identified 11 patients diagnosed with orbital lymphoma. This patient cohort was reviewed retrospectively. RESULTS: The patient group consisted of 11 patients (seven females, male males) with a median age of 57.7 years (range 42 to 88 years). Orbital swelling, pain and motility impairment were the leading clinical symptoms. Diagnosis was confirmed by surgical biopsy. Depending on the anatomic location of the tumor, a surgical biopsy was taken using a blepharoplasty incision, a lateral orbitotomy or a navigation-guided biopsy. The predominant histology was extranodal non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue type (82%). All patients underwent complete clinical staging. These were clinical stage IEA in seven patients, and stages IIEA (n = 2) and IIIEA (n = 2) in four patients . Patients in stage IEA were treated with radiation therapy alone, with radiation doses between 25 and 40 Gy, and patients with stage IIEA received systemic chemotherapy with bendamustin/rituximab. Those two patients diagnosed with diffuse large B-cell lymphoma and mantle cell lymphoma received systemic chemotherapy according to the R-CHOP protocol. CONCLUSIONS: Owing to unspecific clinical symptoms, some diagnostic delay may occur in orbital lymphoma. If unspecific orbital symptoms are present, adequate imaging studies followed by early surgical biopsy will contribute to early diagnosis. Once diagnosis is established and staging is complete, radiation therapy is the recommended treatment for stage IEA patients. Systemic chemotherapy is indicated in selected stage IIEA patients and in patients with stage IIIEA disease.

Adenoid cystic carcinoma of the nasal cavity and paranasal sinuses: a meta-analysis.

Objectives To identify independent predictors of outcome in patients with adenoid cystic carcinoma (ACC) of the paranasal sinuses and skull base. Design Meta-analysis of the literature and data from the International ACC Study Group. Setting University-affiliated medical center. Participants The study group consisted of 520 patients, 99 of them from the international cohort. The median follow-up period was 60 months (range, 32 to 100 months). Main Outcome Measures Overall survival (OS) and disease-specific survival (DSS). Results The 5-year OS and DSS of the entire cohort were 62% and 67%, respectively. The local recurrence rate was 36.6%, and the regional recurrence rate was 7%. Distant metastasis, most commonly present in the lung, was recorded in 106 patients (29.1%). In the international cohort, positive margins and ACC of the sphenoid or ethmoidal sinuses were significant predictors of outcome (p < 0.001). Perineural invasion and adjuvant treatment (radiotherapy or chemoradiation) were not associated with prognosis. Conclusion Tumor margin status and tumor site are associated with prognosis in ACC of the paranasal sinuses, whereas perineural invasion is not. Adjuvant treatment apparently has no impact on outcome.

Platysma myocutaneous flap - its current role in reconstructive surgery of oral soft tissue defects.

Reconstruction of oral soft-tissue defects following resection of oral carcinomas can be achieved using various techniques including microsurgical tissue transfer. However, there seems to be a role for regional or local flaps. Small to medium-size defects can be functionally reconstructed with the platysma myocutaneous flap as an excellent choice particularly in medically compromised patients not being eligible for free tissue transfer. The present paper reviews the indication, surgical technique, and complications following reconstruction of defects of the oral cavity with the platysma myocutaneous flap.

Squamous cell carcinoma of the oral cavity and the oropharynx in patients less than 40 years of age: a 20-year analysis.

BACKGROUND: Squamous cell carcinoma mainly afflicts patients older than 40 years of age however, few cases are seen in younger patients. The aim of this study therefore was to determine the incidence of squamous cell carcinoma of the oral cavity and oropharynx in patients less than 40 years of age with a view to assessing the prognosis over a period of time. METHODS: This was a 20 years retrospective review of patients who were histologically diagnosed with squamous cell carcinoma of the oral cavity and the oropharynx at the Department of Cranio-Maxillo-Facial Surgery of the Hannover Medical School, Germany and had not received treatment anywhere else. Records of these patients were analysed for age and sex distribution, tumour staging and differentiation, location, treatment given, recurrences and metastasis, time between diagnosis and death or last contact with patient, and possible cause of death. Comparisons were also made with patients older than 40 years of age. RESULTS AND DISCUSSION: A total of 977 patients treated for squamous cell carcinoma of the oral cavity and the oropharynx in the 20-year period of this study were included. Thirty eight (3.9 %) of the overall patient population were under 40 years of age. Among these, 30 (78.9%) were males and 8 (21.1%) were females. The incidence was highest in the 30-39 year age group accounting for 31 (81.6%) of the 38 patients. The moderately differentiated carcinoma was commonest (24; 63.2%). The floor of the mouth had the highest number of tumours (15; 39.5%), but none was seen in the oropharynx. Surgery alone was the main stay of treatment given to 26 (68.4%) patients. At the end of the study period, 13 (34.2%) patients had died of the tumour and the 5-year survival rate was 66.2%. In the older patient group (>40 years), 42.7% died from the tumour and the 5-year survival rate was 57.6%. CONCLUSION: The results from the present study showed that young adults may have a better prognosis especially in terms of long term overall survival from oral and oropharyngeal carcinoma.

Surgical treatment of zygomatic bone fracture using two points fixation versus three point fixation--a randomised prospective clinical trial.

BACKGROUND: The zygoma plays an important role in the facial contour for both cosmetic and functional reasons; therefore zygomatic bone injuries should be properly diagnosed and adequately treated. Comparison of various surgical approaches and their complications can only be done objectively using outcome measurements which in turn require protocol management and long-term follow up. The preference for open reduction and internal fixation of zygomatic fractures at three points has continued to grow in response to observations of inadequate results from two point and one point fixation techniques.The objectives of this study were to compare the efficacy of zygomatic bone after treatment with ORIF using 2 point fixation and ORIF using 3 point fixation and compare the outcome of two procedures. METHODS: 100 patients were randomly divided equally into two groups. In group A, 50 patients were treated by ORIF using two point fixation by miniplates and in group B, 50 patients were treated by ORIF using three point fixation by miniplates. They were evaluated for their complications during and after surgery with their advantages and disadvantages and the difference between the two groups was observed. RESULTS: A total of 100 fractures were sustained. We found that postoperative complication like decreased malar height and vertical dystopia was more common in those patients who were treated by two point fixation than those who were treated with three point fixation. CONCLUSIONS: Based on this study open reduction and internal fixation using three point fixation by miniplates is the best available method for the treatment zygomatic bone fractures.

Advances and innovations in computer-assisted head and neck oncologic surgery.

Over the past years, computer-assisted surgery has gained more importance in craniomaxillofacial surgery, especially in primary and secondary treatment of head and neck malignancies. The basis for oncologic treatment of the head and neck region requires detailed planning using computed tomography, cone-beam computed tomography, or magnetic resonance imaging in combination with computer-assisted, infrared-based navigation system. These techniques allow a preplanned image-guided path to the tumor region for taking biopsies, resection, or reconstruction. The aim of this work was to show the advances and technical benefits for tumor surgery in a daily clinical routine from the view of the craniomaxillofacial surgeon. The target of our working group was to develop and clinically evaluate a novel three-dimensional planning and navigation software solution for treatment of craniofacial tumors. This work was carried out on 5 categories for oncologic surgical procedures in which computer-assisted surgery was applied from 2005 to 2011: preplanned trajectorial-guided tumor biopsy, intraoperative image-controlled tumor resection, tumor mapping, reconstruction after tumor surgery (true to original), and oral rehabilitation (backward planning). Successful preoperative planning, import of image data suitable for navigation, and intraoperative precise infrared-based navigation were obtained for all 5 categories without any complications. Image-guided navigation technique for head and neck oncologic surgery provides a precise, safe surgical method with real-time excellent anatomic orientation. Regarding the advantages of computer-assisted surgery, this technique will play a major part in craniofacial reconstructive surgery and will address widespread general methodologic solutions that are of great interest in multidisciplinary oncologic treatment.

Clinical evaluation of an autofluorescence diagnostic device for oral cancer detection: a prospective randomized diagnostic study.

The prognosis for patients with oral squamous cell carcinoma remains poor despite advances in multimodal treatment concepts. Early diagnosis and treatment is the key to improved patient survival. A device (VELscope) that uses autofluorescence technology, allowing direct fluorescence visualization of the oral cavity, might be a useful tool for oral cancer detection or as an adjunct to standard clinical examination. A total of 289 patients with oral premalignant lesions were randomly divided into two groups for clinical examination of precancerous oral lesions. In group 1, 166 patients were examined conventionally with white light, and in group 2, 123 patients were examined with the autofluorescence visualization device (VELscope) in addition to the white light examination. Biopsies were obtained from all suspicious areas identified in both examination groups (n=52). In the first step, baseline characteristics of the two groups (only white light vs. white light and VELscope) were compared to exclude selection bias. In the second step, for the group examined with white light and VELscope (123 patients), the diagnostic strategies were compared with regard to sensitivity and specificity using biopsy as the gold standard. The results showed that using the VELscope leads to higher sensitivity (100% instead of 17%), but to lower specificity (74% instead of 97%). Thus, we can conclude that the VELscope is a useful new diagnostic device for detection of oral cancer diseases.

Reconstruction of defects of maxillary sinus wall after removal of a huge odontogenic lesion using prebended 3D titanium-mesh and CAD/CAM technique.

A 63 year-old male with a huge odontogenic lesion of sinus maxillaris was treated with computer-assisted surgery. After resection of the odontogenic lesion, the sinus wall was reconstructed with a prebended 3D titanium-mesh using CAD/CAM technique. This work provides a new treatment device for maxillary reconstruction via rapid prototyping procedures.

Piezoelectric-assisted removal of a benign fibrous histiocytoma of the mandible: an innovative technique for prevention of dentoalveolar nerve injury.

In this article, we present our experience with a piezoelectric-assisted surgical device by resection of a benign fibrous histiocytoma of the mandible.A 41 year-old male was admitted to our hospital because of slowly progressive right buccal swelling. After further radiographic diagnosis surgical removal of the yellowish-white mass was performed. Histologic analysis showed proliferating histiocytic cells with foamy, granular cytoplasm and no signs of malignancy. The tumor was positive for CD68 and vimentin in immunohistochemical staining. Therefore the tumor was diagnosed as primary benign fibrous histiocytoma. This work provides a new treatment device for benign mandibular tumour disease. By using a novel piezoelectric-assisted cutting device, protection of the dentoalveolar nerve could be achieved.

Virtual 3D tumor marking-exact intraoperative coordinate mapping improve post-operative radiotherapy.

The quality of the interdisciplinary interface in oncological treatment between surgery, pathology and radiotherapy is mainly dependent on reliable anatomical three-dimensional (3D) allocation of specimen and their context sensitive interpretation which defines further treatment protocols. Computer-assisted preoperative planning (CAPP) allows for outlining macroscopical tumor size and margins. A new technique facilitates the 3D virtual marking and mapping of frozen sections and resection margins or important surgical intraoperative information. These data could be stored in DICOM format (Digital Imaging and Communication in Medicine) in terms of augmented reality and transferred to communicate patient's specific tumor information (invasion to vessels and nerves, non-resectable tumor) to oncologists, radiotherapists and pathologists.