A novel distending laryngoscope: implications in transoral surgery.

The objective is to describe an innovative laryngoscope developed to improve visualization, provide greater exposure, and enhance precision and success during transoral procedures. A retrospective review of 170 patients who underwent transoral surgery with a new distending laryngoscope was conducted. We compared and contrasted our exposure within the oropharynx, hypopharynx, and larynx using the laryngoscope with that of currently available instrumentation. Specific mechanical dimensions of the laryngoscope along with the provided working field were calculated. Experience with the new laryngoscope afforded improved exposure over currently available instrumentation. This laryngoscope was manufactured using design elements from the Steiner, Weerda, and Lindholm laryngoscopes, including an anteriorly curved distal tip, distending capability, and lateral wings to protect against tongue herniation. The panoramic view was increased allowing for wider exposure of the supraglottis and pharynx. This design provided enhanced transoral visibility and working room for improved bimanual instrumentation. Direct laryngoscopic technique and instrumentation have continued to evolve. Over the last two decades, there has been a significant movement towards minimally invasive transoral surgical techniques fueling innovative concepts and advancement in laryngoscopic design and application. We present our experience with an innovative laryngoscope allowing for improved visualization, greater exposure, and enhanced proficiency with transoral technique.

Orbital Complications Associated with the Treatment of Chronic Rhinosinusitis.

Orbital injuries from endoscopic sinus surgery are rare but potentially catastrophic. The most feared complications from sinus surgery include blindness and diplopia. Recent publications note that the rate of orbital complications has decreased when compared with the past, reflecting the use of endoscopes, better technology, and improved training. The sinus surgeon must have mastery over the procedure she or he plans to undertake and be aware of the specific potential for orbital injury given the patient's anatomy and disease. The sinus surgeon must also have expert knowledge of the appropriate and immediate medical and surgical management of orbital complications.

The Mayo Clinic Arizona Spasmodic Dysphonia Experience: A Demographic Analysis of 718 Patients.

OBJECTIVE: Analyze demographic data collected over a 25-year experience of 718 patients with spasmodic dysphonia (SD) who have been treated with botulinum toxin-A (BoNT-A) and compare our data with previously published studies. METHODS: Seven hundred eighteen patients with SD were treated with 6621 BoNT-A injections at Mayo Clinic Arizona between 1989 and 2014. All patients were treated by the same physician team. Background demographic data for each patient were recorded. RESULTS: Of 718 patients, 557 patients were female (77.6%). Six hundred sixty of 718 (91.8%) patients had adductor SD (AdSD), and 58 of 718 (8.1%) patients had abductor SD (AbSD). Average age of onset was 51 years. Of 718 patients, 378 (52.6%) had vocal tremor (VT); VT was present in 54.4% of AdSD patients and 32.1% of AbSD patients. Thirty-seven of 718 (5.2%) patients had other dystonias, including cervical dystonia (2.3%), blepharospasm (1.4%), limb dystonia (1.1%), and oromandibular dystonia (0.3%). A positive family history of SD was present in only 6 of 718 patients (0.8%) and of other dystonias in 11 of 718 patients (1.5%). CONCLUSIONS: Spasmodic dysphonia is a chronic and potentially disabling focal laryngeal dystonia. The Mayo Clinic Arizona SD experience compares to prior reports and reveals a female preponderance, onset in middle age, infrequent hereditary pattern, high co-occurrence of VT, and low co-occurrence of other dystonias.

Severe prolonged dysphagia following transoral resection of bilateral synchronous tonsillar carcinoma.

OBJECTIVES: Alert the reader to the complication of severe dysphagia following transoral laser microsurgery (TLM) or transoral robotic surgery (TORS) for bilateral simultaneous or synchronous tonsillar squamous cell carcinoma. METHODS: A case series of four patients treated at an academic tertiary center between 2008 and 2012 is presented; two treated with transoral laser microsurgery and two with transoral robotic surgery for biopsy-proven untreated bilateral primary squamous cell carcinoma. Main outcome measures included functional swallowing determined by the Functional Outcome Swallowing Scale. The incidence of significant postoperative complications was recorded. RESULTS: Two patients had surgery for discontiguous involvement of bilateral palatine tonsils with squamous cell carcinoma, while two patients had surgery for bilateral tonsillar squamous cell carcinoma with unilateral extension into the base of tongue. Complete swallowing failure as characterized by the Functional Outcome Swallowing Scale was seen postoperatively in 3/4 patients who underwent TLM or TORS for bilateral simultaneous tonsillar carcinoma, while one patient was lost to follow-up. CONCLUSIONS: Severe dysphagia in the setting of bilateral oropharyngectomy for simultaneous or synchronous tonsillar squamous cell carcinoma is rarely described but a significant concern. In an era with increased use of transoral surgery as de-escalation therapy, this unusual complication warrants consideration. We report that transoral bilateral pharyngectomy is quite harmful to near-term and intermediate-term swallowing outcomes. This paper serves to provide warning against primary surgical intervention in this setting, while demonstrating that non-surgical treatment may be the best viable option.

Contemporary applications of frontal sinus trephination: A systematic review of the literature.

Our objective was to perform a systematic review of the literature on contemporary indications and outcomes for frontal sinus trephination and present an illustrative case of an endoscopically assisted repair of a subcutaneous frontal sinus fistula by trephination technique. PubMed and Ovid databases were used as data sources. A systematic review of the English literature was completed to review reports of frontal trephination from 1980 to 2014. Articles meeting inclusion criteria for inflammatory and noninflammatory indications were reviewed. Articles were systematically reviewed and graded by evidence-based medicine level. An illustrative case from our institution is then presented. The systematic review identified 2,621 published studies. Thirty-eight studies were identified for inclusion. The indications, techniques, outcomes, safety, and complications were reviewed for noninflammatory and inflammatory conditions. There were 32 retrospective case series, reports, or cohort studies (level 4), four systematic reviews (level 3), one prospective analysis (level 3), and one meta-analysis (level 2). Due to the heterogeneity of study cases and inclusion criteria, a meta-analysis was not feasible. We also present a novel closure of an anterior skull base defect resulting in a subcutaneous fistula with use of a frontal trephination approach. The frontal sinus trephination should not be regarded as a procedure of the past, as it useful in the armamentarium of the modern sinus and skull base surgeon. This approach provides access for instrumentation for hard-to-reach frontal sinus disease either purely through a trephination approach or as a supplementation to the transnasal endoscopic approach. Evidence supporting frontal sinus trephination is of levels 2, 3, and 4. Level of evidence: NA.

Tuberculous retropharyngeal abscess presenting with symptoms of obstructive sleep apnea.

Chronic retropharyngeal abscess (RPA) caused by tuberculosis is an uncommon manifestation of extrapulmonary tuberculosis within the head and neck. Obstructive sleep apnea (OSA) in adults is a common condition with many etiologies that have been well described. Here, we present a case of retropharyngeal abscess caused by chronic tuberculosis with an unusual and interesting presenting symptom in an adult that has not been mentioned in literature, new-onset and worsening stertor or snoring, with signs and symptoms of OSA. The purpose of this manuscript is to present our experience with this case, as well as to emphasize the diagnosis, clinical course, and management of tuberculous retropharyngeal abscess in adults, while also signifying the need to include retropharyngeal abscess in the differential diagnosis for symptoms presenting as new-onset stertor and airway obstruction.

Giant fibrolipoma of the esophagus.

Benign tumors of the esophagus are uncommon, representing <0.5% of esophageal tumors. Fibrolipomas are a subset of benign fibrovascular tumors, which present with dysphagia, odynophagia, and substernal fullness. These intraluminal tumors can become elongated and molded into a long pedunculated polyp by constant peristaltic movements. They can cause esophageal obstruction if large and long enough and can cause asphyxiation if they become lodged into the glottis. A barium swallow is the main diagnostic tool; treatment is surgical via a transoral, transcervical, or transthoracic approach. We report the excision of a large esophageal fibrolipoma through a transoral laser microsurgical approach.

The fourth branchial complex anomaly: a rare clinical entity.

Fourth branchial pouch anomalies are rare congenital disorders of the neck and are a consequence of abnormal development of the branchial apparatus during embryogenesis. Failure to appropriately recognize these anomalies may result in misdiagnosis, insufficient treatment, and continued recurrence. Here, we present an unique presentation of two cases, describe their diagnosis, clinical course, and management, and review the literature regarding these interesting anomalies.

Clonal relationship in multifocal non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue (MALT).

To elucidate the progression of gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, we analyzed a case presenting simultaneously with MALT lymphoma of the stomach and lung, and a gastric high-grade diffuse large lymphoma. The rearranged immunoglobulin heavy chain (IgH) variable regions were analyzed using a polymerase chain reaction (PCR)-based assay. Clonal relationship was shown between the gastric high-grade and the pulmonary low-grade lymphoma. The gastric MALT lymphoma was not related to the other manifestations. Translocation t(11;18) was not detected in the gastric high-grade lymphoma. MALT lymphomas at various locations and with different histologies may derive from a common precursor cell. Lymphomas at identical sites may have different stem cells.

Etiology and therapy of Helicobacter pylori-associated gastric lymphomas.

The WHO separates marginal zone B-cell lymphomas (MZBL) of nodal and extranodal type. Both arise from memory B cells of the marginal zone. Extranodal MZBL of the mucosa-associated lymphatic tissue (MALT) have characteristic features such as homing in epithelial tissue, lymphoepithelial destruction, and a very indolent clinical course. They arise in epithelial tissues normally devoid of lymphatic cells, where the lymphatic tissue was acquired after, for instance, a chronic infection. The best example here is infection of the stomach with Helicobacter pylori ( Hp). Besides the classical association with gastric MALT lymphomas, there have been reports in which an association between Hp and diffuse large B-cell lymphoma (DLBCL) has been observed as well. Consequently, cure of Hp infection resulted in remission induction not only in gastric MALT lymphomas, but also in some patients with very limited stages of DLBCL of the stomach. In addition to the association with Hp, progress has been made with regard to MALT lymphoma biology. Translocation t(1;14) involving the Bcl-10 gene, and translocation t(11;18) involving a novel gene called MLT1, both result in activation of the crucial transcription factor NF-kappaB. These genetic events seem specific in that they have been observed only in MALT lymphomas. Once present, at least the more frequently observed translocation t(11;18) renders cells resistant to cure of Hp infection. Another clinically important question is that in many patients in complete remission after cure of Hp infection, detection of minimal residual disease is positive. Whether these cells are normal memory B cells (with the identical B-cell rearrangement as the original lymphoma clone), or dormant lymphoma cells, is unclear at present. In patients not responding to cure of Hp infection, several treatment options are discussed. MALT lymphomas have opened up a new discussion of lymphoma biology and have thus been called a model disease.

Helicobacter and gastric MALT lymphoma.

Helicobacter pylori infection is a pre-MALT lymphoma condition. H pylori eradication leads to complete remission in 80% of low grade stage E1 lymphomas, with a yearly recurrence rate of approximately 5%. The possibility for complete remission in high grade lymphomas needs to be investigated in prospective studies. In addition, the significance of persistent B cell monoclonality (stable disease? danger of relapse? regression of monoclonality?) needs to be investigated in follow up studies.

Molecular diagnostics in low-grade gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type after Helicobacter pylori eradication therapy.

The primary gastric lymphomas are extranodal non-Hodgkin's lymphomas that likely originate from the mucosa-associated lymphoid tissue (MALT). Data suggest that chronic infection with Helicobacter pylori (H pylori) is significantly associated with the pathogenesis of low-grade gastric MALT lymphomas. This is in keeping with the observation that many patients with early low-grade MALT lymphomas have complete remissions after H pylori eradication therapy. However, the stability of these remissions remains unclear and relapses have been reported. It can be difficult to distinguish between early malignant and benign disorders of the gastric mucosa. A polymerase chain reaction (PCR) assay can detect rearrangements of the variable region of immunoglobulin heavy chains. This assay can be used to distinguish the clonality of B lymphocytes and has been investigated as a test for differential diagnosis of MALT lymphomas. Monoclonality is observed in the majority of MALT-lymphoma samples at diagnosis but has been found in gastritis samples as well. Whether the presence of monoclonal B cells is associated with the risk of lymphoma progression remains unclear. As many as 50% of patients who have complete histologic remissions of MALT lymphoma after H pylori eradication therapy have persisting monoclonal bands in follow-up PCR monitoring. Although it is unclear as to whether monoclonality indicates the presence of minimal residual disease, patients who have persistent monoclonal bands during follow-up should be considered at risk for relapse. The PCR assay for rearrangements of the variable region of the immunoglobulin heavy-chain gene appears to be of low value in the diagnosis of B-cell malignancies but could provide a useful tool in the follow-up of patients who achieve remissions after H pylori eradication.

Long-term follow-up of gastric MALT lymphoma after H. pylori eradication.

For almost 10 years, we have been familiar with the concept of mucosa-associated lymphoid tissue (MALT)-type lymphoma of the stomach caused by chronic Helicobacter pylori infection. Many epidemiologic, biologic, and molecular genetic studies have implicated H. pylori for its role in lymphoma genesis. Since the first reports on complete remission of gastric MALT lymphomas after cure of bacterial infection, many clinical studies have investigated the effect of eradicating H. pylori on the course of MALT lymphoma, and indeed were able to confirm remission of the lymphoma. To date, more than 650 patients worldwide have been treated for gastric MALT lymphoma with antibiotics, and we have gained many new insights concerning the biologic behavior of this disease, especially from the deepened knowledge of cytogenetics. Furthermore, factors relevant for the prediction of treatment outcome have been identified, which has helped to stratify patients into risk groups.

Are lymphocytic monoclonality and immunoglobulin heavy chain (IgH) rearrangement premalignant conditions in chronic gastritis?

Normal gastric mucosa is devoid of lymphoid cells. Any increase of lymphocytes suggests chronic inflammation. Infection with Helicobacter pylori (Hp) is the major cause for nonautoimmune chronic gastritis and induces a mixed cellular response resulting in an acquired lymphoid tissue, or MALT (mucosa-associated lymphoid tissue). Hp has also been implicated in the genesis of gastric MALT-lymphoma. Polymerase chain reaction-based assays to detect the expansion of monoclonal B-cells have also been used to corroborate the diagnosis. In a considerable number of cases monoclonal B-cells remain detectable in follow-up biopsies, with the lymphoma being in complete histological remission. The clinical relevance of this finding is not clear yet. However, there also exist different reports that monoclonal B-cells can be found in gastric biopsies of patients with neither a histological sign nor a present or past history of lymphoma. In the light of these findings we address the question whether B-cell monoclonality can be seen as a premalignant condition in chronic gastritis and conclude that as of now the relevance of the finding of B-cell monoclonality remains unclear. As of now the only and gold standard for the diagnosis of gastric MALT-lymphoma is histopathology.

Long-term persistence of monoclonal B cells after cure of Helicobacter pylori infection and complete histologic remission in gastric mucosa-associated lymphoid tissue B-cell lymphoma.

PURPOSE: Cure of Helicobacter pylori infection is associated with remission induction in the majority of patients with low-grade gastric mucosa associated lymphoid tissue (MALT) lymphoma in localized stages; however, limited data exist as to whether these patients may be cured of their lymphoma. The present study was performed to investigate whether the polymerase chain reaction (PCR) for the rearranged immunoglobulin heavy chain region may be used to define "molecular" remission. PATIENTS AND METHODS: Ninety-seven patients who suffered from low-grade gastric MALT lymphoma stage I(E) were observed with central pathology and molecular biology after cure of H pylori infection. PCR was performed with the use of consensus primers for the framework regions 1, 2, and 3 and monoclonality was corroborated by sequence analysis. In selected cases, microdissection was performed to study the origin of the monoclonal B cells. RESULTS: Of the 97 patients, 77 obtained complete endoscopic and histologic remission (CR). Twenty of 44 patients with PCR monoclonality at diagnosis and with sufficient molecular follow-up displayed monoclonal bands for a median time of 20.5 months after CR (range, 0 to 50.4 months). These B cells were related to the original lymphoma clone by sequence analysis. Microdissection analysis identified basal lymphoid aggregates as the source of these monoclonal B cells. Local relapse occurred in and was observed by PCR in four patients. All four patients displayed monoclonal PCR before relapse, and three of these four showed ongoing PCR monoclonality throughout their course, indicating the persistence of malignant cells. CONCLUSION: Half of all patients with gastric MALT lymphoma show long-term PCR monoclonality up to several years after cure of H pylori infection and CR. Patients with monoclonal PCR should be observed closely, whereas long-term PCR negativity may indicate cure of the disease.

Somatic hypermutation and B-cell lymphoma.

During the B-cell response to T-cell-dependent antigens, the B cells undergo a rapid proliferative phase in the germinal centre. This is accompanied by the introduction of mutations into the immunoglobulin (Ig) variable region (V) genes. The B cells are then selected according to the affinity of the encoded immunoglobulin for antigen, resulting in affinity maturation of the response. Analysis of mutations in IgV genes has given insight into the history of individual B cells and their malignancies. In most cases, analysis of mutations confirms classifications of B-cell lineage designated by studies of cellular morphology and surface antigen expression. However, of particular interest is the subdivision of groups of malignancies by analysis of somatic hypermutation. It is now apparent that there are two subsets of chronic lymphocytic leukaemia (CLL), one with a low load of mutations and poor prognosis. and one with a heavy load of mutations with a much more favourable prognosis. In addition, in Burkitt's lymphoma, sporadic and endemic subtypes are now considered possibly to have a different pathogenesis, reflected in differences in the numbers of mutations. Hodgkin's disease, which was a mystery for many years, has now been shown to be a B-cell tumour. Although in many cases the Ig genes are crippled by somatic hypermutation, it is thought that failure to express Ig is more likely to be associated with problems of transcription. It has been proposed that the distribution of mutations in a B-cell lymphoma can be used to determine whether a lymphoma is selected. We have investigated the load and distribution of mutations in one group of lymphomas--marginal zone B-cell lymphomas of mucosa-associated lymphoid tissues (MALT-type lymphoma), which are dependent on Helicobacter pylori for disease progression, to investigate the limits of information that can be derived from such studies. Comparison of the load of mutations demonstrates that these tumours have approximately the same load of mutations as normal mucosal marginal zone B cells from the Peyer's patches and mucosal plasma cells. This is consistent with the origin of these cells from mucosal marginal zone B cells with plasma cell differentiation. To investigate selection in MALT lymphomas we compared a region of the framework region three in ten MALT lymphomas which use the V(H4) family, with the same codons in groups of V(H4) genes that are out of frame between V and J. The latter accumulate mutations but are not used and are not selected. A group of V(H4) genes are in-frame between V and J were also included for comparison. There were no obvious differences in the distribution of mutations between the groups of genes; the same hot spots and cold spots were apparent in each. In the MALT lymphomas, selection was apparent in the framework regions only and the tendency was to conserve. We therefore feel that there is selection to conserve antibody structure and that this does not reflect selection for antigen. We do not believe that antigen selection can be deduced reliably from sequence information alone. It is possible that somatic hypermutation could be a cause of malignancy since it has been shown that the process may generate DNA strand breaks and is known to be able to generate insertions and deletions. Such events may mediate the translocation of genes--a process that is pivotal in the evolution of many lymphomas.

Development of early gastric cancer 4 and 5 years after complete remission of Helicobacter pylori associated gastric low grade marginal zone B cell lymphoma of MALT type.

AIM: To report 3 of 120 patients on the German MALT lymphoma trial with H. pylori associated gastric MALT lymphoma who developed early gastric cancer 4 and 5 years, after complete lymphoma remission following cure of H. pylori infection. PATIENTS AND RESULTS: Three patients (two men, 74 and 70 years; one women, 77 years) with H. pylori-associated low-grade MALT lymphoma achieved complete lymphoma remission after being cured. Surveillance endoscopies were performed twice a year in accordance to the protocol. Four years after complete lymphoma remission in two patients, and after 5 years in the other, early gastric adenocarcinoma of the mucosa-type, type IIa and type IIc, respectively, was detected, which were completely removed by endoscopic mucosa resection. In one patient, the gastric cancer was diagnosed at the same location as the previous MALT lymphoma, in the other patients it was detected at different sites of the stomach distant from location of the previous MALT lymphoma. The patients were H. pylori negative during the whole follow-up time. CONCLUSION: These findings strengthen the importance of regular Long-term follow-up endoscopies in patients with complete remission of gastric MALT lymphoma after cure of H. pylori infection. Furthermore, gastric adenocarcinoma may develop despite eradication of H. pylori.

Helicobacter pylori eradication therapy in gastric high grade non Hodgkin's lymphoma (NHL).

BACKGROUND: Primary gastric low-grade lymphoma of the mucosa associated lymphoid tissue (MALT) develops on the background of a chronic Helicobacter pylori (H. pylori) infection. Stable remissions can be induced by H. pylori eradication therapy as shown in clinical trials. In 8 cases of high-grade gastric lymphomas remissions after H. pylori eradication were observed retrospectively. AIM: We started a pilot-trial to investigate the value of H. pylori eradication therapy in early gastric high-grade B-cell lymphoma prospectively. PATIENTS AND METHODS: So far, two H. pylori positive patients with high-grade B-cell lymphoma of the stomach stage Ann Arbor I E are included. They received a triple eradication-therapy (Clarithromycin 500 mg/d, Metronidazol 800 mg/d and Omeprazol 40 mg/d) for 7 days. Endoscopic controls are preformed every 4 weeks. RESULTS: Both patients became H. pylori negative after eradication therapy. One patient achieved complete remission (CR) 38 days after eradication. The continuous complete remission lasts now for 170 days. The second patient received only a partial remission (PR) 4 weeks after eradication and showed a slight progress 4 weeks later. He presently receives chemotherapy (CHOP). CONCLUSIONS: Patients with early high-grade gastric B-cell lymphomas should receive H. pylori eradication only within clinical trials. It seems to be possible to induce remissions of early high-grade gastric B-cell lymphomas with exclusive H. pylori eradication therapy. The stability of remission remains to be unclear and should be evaluated by following up the patients closely.

Eradication of Helicobacter pylori and stability of remissions in low-grade gastric B-cell lymphomas of the mucosa-associated lymphoid tissue: results of an ongoing multicenter trial.

The normal human stomach is devoid of any organized lymphatic tissue. Acquisition of mucosa-associated lymphatoid tissue (MALT) in the stomach is considered to be a direct consequence of chronic infection with Helicobacter pylori. Thus, MALT appears to be part of the host defense against the pathogen H. pylori. Consequently, lymphomas arising from gastric MALT may be seen as an end point of a clonal evolution starting from the infection. Cumulative data from several studies show that eradication of H. pylori induces complete histologic remissions in about 70%-80% of the patients. Here we present data of an extended analysis of an ongoing multicenter trial. Eighty-four patients with low-grade gastric MALT lymphoma in stage EI were treated using a dual regimen to eradicate H. pylori. Complete remission was observed in 68 (81%) patients; a partial remission was found in seven (8%) patients. In contrast, nine (11%) patients revealed "no change" and were referred for alternative treatment strategies. The majority of these cases were found to harbor high-grade lymphomas in deeper mucosal areas. Polymerase chain reaction (PCR) performed on the VDJ rearrangements of the immunoglobulin heavy chain yielded monoclonal bands in 50 of 65 analyzed patients (77%) at diagnosis. Interestingly, in patients analyzed during follow up after achieving complete histologic remission, ongoing PCR monoclonality was found in 19 of 39 eligible patients (49%). Several patients who developed local relapse of the lymphoma were found in the group with ongoing PCR monoclonality. Together with data from the literature, these results suggest that the majority of low-grade gastric MALT lymphomas in stage EI respond to eradication of H. pylori. Longer follow-up investigations are necessary to determine whether remissions really indicate a cure from the disease and to elucidate whether PCR monoclonality after complete histological remission is predictive of increased relapse rate.