Surgical site complications of isolated salvage neck dissection post-radiotherapy and post-chemoradiotherapy - A cohort analysis (1997-2017).

INTRODUCTION: This study aims to quantify surgical site complications (SSC) after isolated salvage neck dissection (ND) compared with primary ND. PATIENTS AND METHODS: Between 1997 and 2017 in the Netherlands Cancer Institute - Antoni van Leeuwenhoek, a total of 323 isolated NDs were performed in 308 patients: primary ND (n = 144), post-radiotherapy (RT) ND (n = 53) and post-chemoradiotherapy (CRT) ND (n = 126). Patient, tumor and therapy characteristics were recorded. SSCs were scored according to the Clavien-Dindo Classification (CDC). RESULTS: 101 NDs (31%) were complicated by at least one SSC. In total, 189 different SSCs occurred. Translated to CDC, 45 complications were grade 2, 25 grade 3a and 31 grade 3b. No significant difference in occurrence of SSC (CDC >1) was found between all groups. However, post-CRT, selective (SND) and modified radical ND and radical ND (MRND/RND) (p = 0.005), resection of sternocleidomastoid muscle (SCM) (p = 0.039) and duration of super selective ND surgery (p = 0.048) were significantly associated with more SSC. SCM muscle removal was associated with more surgical site infection (p = 0.045) and necrosis (p = 0.036). From week 10 post-RT/CRT, no difference in complication frequency with primary ND was seen. CONCLUSION: Post-CRT SND, MRND/RND and SCM muscle resection were associated with an increased incidence of SSCs. If oncologically possible, limit the extent of ND and when an MRND is inevitable, preserve the SCM muscle for optimal prevention of SSC. Concerning SSC, optimal timing of salvage ND is minimal 10 weeks after RT/CRT.

c-MET Receptor-Targeted Fluorescence on the Road to Image-Guided Surgery in Penile Squamous Cell Carcinoma Patients.

In penile squamous cell carcinoma (pSCC), primary surgery aims to obtain oncologically safe margins while minimizing mutilation. Surgical guidance provided by receptor-specific tracers could potentially improve margin detection and reduce unnecessary excision of healthy tissue. Here, we present the first results of a prospective feasibility study for real-time intraoperative visualization of pSCC using a fluorescent mesenchymal-epithelial transition factor (c-MET) receptor targeting tracer (EMI-137). Methods: EMI-137 tracer performance was initially assessed ex vivo (n = 10) via incubation of freshly excised pSCC in a solution containing EMI-137 (500 nM). The in vivo potential of c-MET targeting and intraoperative tumor visualization was assessed after intravenous administration of EMI-137 to 5 pSCC patients scheduled for surgical resection using a cyanine-5 fluorescence camera. Fluorescence imaging results were related to standard pathologic tumor evaluation and c-MET immunohistochemistry. Three of the 5 in vivo patients also underwent a sentinel node resection after local administration of the hybrid tracer indocyanine green- 99mTc-nanocolloid, which could be imaged using a near-infrared fluorescence camera. Results: No tracer-related adverse events were encountered. Both ex vivo and in vivo, EMI-137 enabled c-MET-based tumor visualization in all patients. Histopathologic analyses showed that all pSCCs expressed c-MET, with expression levels of at least 70% in 14 of 15 patients. Moreover, the highest c-MET expression levels were seen on the outside rim of the tumors, and a visual correlation was found between c-MET expression and fluorescence signal intensity. No complications were encountered when combining primary tumor targeting with lymphatic mapping. As such, simultaneous use of cyanine-5 and indocyanine green in the same patient proved to be feasible. Conclusion: Fluorescence imaging of c-MET receptor- expressing pSCC tumors after intravenous injection of EMI-137 was shown to be feasible and can be combined with fluorescence-based lymphatic mapping. This combination is unique and paves the way toward further development of this surgical guidance approach.

Surgical site complications of post-chemoradiotherapy neck dissection: Urgent need for standard registration.

Nowadays, a substantial number of head and neck cancer patients are treated by organ-preserving chemoradiation (CRT), with a possible increased risk of complications after planned or salvage neck dissections. We try to determine the risk pattern of surgical site complications (SSC) post-CRT.

On the Development of a Light Dosimetry Planning Tool for Photodynamic Therapy in Arbitrary Shaped Cavities: Initial Results.

Previous dosimetric studies during photodynamic therapy (PDT) of superficial lesions within a cavity such as the nasopharynx, demonstrated significant intra- and interpatient variations in fluence rate build-up as a result of tissue surface re-emitted and reflected photons, which depends on the optical properties. This scattering effect affects the response to PDT. Recently, a meta-tetra(hydroxyphenyl)chlorin-mediated PDT study of malignancies in the paranasal sinuses after salvage surgery was initiated. These geometries are complex in shape, with spatially varying optical properties. Therefore, preplanning and in vivo dosimetry is required to ensure an effective fluence delivered to the tumor. For this purpose, two 3D light distribution models were developed: first, a simple empirical model that directly calculates the fluence rate at the cavity surface using a simple linear function that includes the scatter contribution as function of the light source to surface distance. And second, an analytical model based on Lambert's cosine law assuming a global diffuse reflectance constant. The models were evaluated by means of three 3D printed optical phantoms and one porcine tissue phantom. Predictive fluence rate distributions of both models are within ± 20% accurate and have the potential to determine the optimal source location and light source output power settings.

Toward assessment of resection margins using hyperspectral diffuse reflection imaging (400-1,700 nm) during tongue cancer surgery.

BACKGROUND AND OBJECTIVES: There is a clinical need to assess the resection margins of tongue cancer specimens, intraoperatively. In the current ex vivo study, we evaluated the feasibility of hyperspectral diffuse reflectance imaging (HSI) for distinguishing tumor from the healthy tongue tissue. STUDY DESIGN/MATERIALS AND METHODS: Fresh surgical specimens (n = 14) of squamous cell carcinoma of the tongue were scanned with two hyperspectral cameras that cover the visible and near-infrared spectrum (400-1,700 nm). Each pixel of the hyperspectral image represents a measure of the diffuse optical reflectance. A neural network was used for tissue-type prediction of the hyperspectral images of the visual and near-infrared data sets separately as well as both data sets combined. RESULTS: HSI was able to distinguish tumor from muscle with a good accuracy. The diagnostic performance of both wavelength ranges (sensitivity/specificity of visual and near-infrared were 84%/80% and 77%/77%, respectively) appears to be comparable and there is no additional benefit of combining the two wavelength ranges (sensitivity and specificity were 83%/76%). CONCLUSIONS: HSI has a strong potential for intra-operative assessment of tumor resection margins of squamous cell carcinoma of the tongue. This may optimize surgery, as the entire resection surface can be scanned in a single run and the results can be readily available. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Surgical site complications after parotid gland surgery for benign tumors in a centralized setting: A Clavien-Dindo class cohort analysis.

BACKGROUND: Surgical resection is the standard of care for parotid gland tumors. Comprehensive reports on the surgical complications of parotidectomy are lacking. This study focuses on surgical wound complications of parotid gland surgery. PATIENTS AND METHODS: In the period 2002-2012, 390 consecutive patients (395 procedures) who underwent parotid gland surgery were selected for retrospective analysis. Based on subsequent management, the impact of surgical site complications was graded by the Clavien-Dindo Classification (CDC). RESULTS: In 83 (21.0%) of the procedures, at least one complication was registered. In total, 118 complications were described. Rated to CDC, 61 patients (15.4%) were graded as class 2 or higher. This implies therapy was dictated. Fortyfive (11.4%) of the complications were surgical site infections (SSI). In 9 patients (2.3%) surgical complications required a surgical intervention under general anesthesia (CDC class 3b), and in 19 patients (4.8%) other invasive treatment (CDC class 3a) was needed. CONCLUSIONS: The Clavien-Dindo Classification proved to be very useful for retrospective registration of surgical complications. Of the 61 patients, 33 were managed by conservative therapy. No risk profile was found for patients at risk for direct surgical complications.

Toward complete oral cavity cancer resection using a handheld diffuse reflectance spectroscopy probe.

This ex-vivo study evaluates the feasibility of diffuse reflectance spectroscopy (DRS) for discriminating tumor from healthy tissue, with the aim to develop a technology that can assess resection margins for the presence of tumor cells during oral cavity cancer surgery. Diffuse reflectance spectra were acquired on fresh surgical specimens from 28 patients with oral cavity squamous cell carcinoma. The spectra (400 to 1600 nm) were detected after illuminating tissue with a source fiber at 0.3-, 0.7-, 1.0-, and 2.0-mm distances from a detection fiber, obtaining spectral information from different sampling depths. The spectra were correlated with histopathology. A total of 76 spectra were obtained from tumor tissue and 110 spectra from healthy muscle tissue. The first- and second-order derivatives of the spectra were calculated and a classification algorithm was developed using fivefold cross validation with a linear support vector machine. The best results were obtained by the reflectance measured with a 1-mm source-detector distance (sensitivity, specificity, and accuracy are 89%, 82%, and 86%, respectively). DRS can accurately discriminate tumor from healthy tissue in an ex-vivo setting using a 1-mm source-detector distance. Accurate validation methods are warranted for larger sampling depths to allow for guidance during oral cavity cancer excision.

Bloom syndrome does not always present with sun-sensitive facial erythema.

Bloom syndrome is an autosomal recessive condition characterized by severe pre- and postnatal growth deficiency, immunodeficiency, an increased risk for malignancies, craniofacial dysmorphisms, and "typical" erythematous sun-sensitive skin lesions of the face. This facial rash has a butterfly-shaped distribution around the nose and is usually observed for the first time during the early years of life. Though reported as being a main feature of Bloom syndrome, there seems to be phenotypic variability regarding this facial skin rash among patients. It has been previously reported that in some individuals with Bloom syndrome these sun-sensitive lesions are less prominent or even absent. In this report we describe a 36 year old woman with short stature, microcephaly, several dysmorphisms, congenital hypothyroidism and premature ovarian failure. She was diagnosed with nasopharyngeal carcinoma at 36 years of age, only a few months after her consultation at the department of Clinical Genetics. Whole Exome Sequencing demonstrated that she had Bloom syndrome caused by a compound heterozygous mutation in BLM (c.2207_2212delinsTAGATTC; p.(Tyr736Leufs*5) and c.3681del; p.(Lys1227Asnfs*52)). She did not have facial sun-sensitive erythematous rash during childhood nor adulthood. We conclude that Bloom syndrome does not always present with erythematous sun-sensitive skin lesions of the face. We would like to underline that phenotypic variation regarding this "hallmark" feature of Bloom syndrome exists. Being aware of this might prevent a delay in diagnosing this rare short-stature syndrome and, subsequently, its potential clinical implications.

Adjuvant photodynamic therapy in head and neck cancer after tumor-positive resection margins.

OBJECTIVE: In case of close or positive resection margins after oncological resection in head and neck surgery, additional treatment is necessary. When conventional options are exhausted, photodynamic therapy (PDT) can play a role in achieving clear margins. The purpose of the current study was to evaluate the clinical benefit of PDT as adjuvant therapy next to surgery with positive resection margins. The role of the time interval between surgery and PDT on survival outcomes also was investigated. STUDY DESIGN: Retrospective cohort analysis. METHODS: Adjuvant PDT was performed in patients with a malignancy in the head and neck region with close or positive resection margins who were not eligible for conventional treatment options. The primary endpoint was progression-free survival. Secondary endpoints were disease-free survival, overall survival, and optimal time interval between surgery and PDT. RESULTS: Fifty-four patients were treated with surgery followed by meta-tetrahydroxyphenylchlorin-mediated PDT. There was a large diversity in tumor location and histopathology, as well as in time interval between surgery and PDT. The 2-year progression-free survival rate was 30%; 2-year disease-free survival rate was 28%; and 2-year overall survival was 51%. Disease-free survival was significantly better when the time interval between surgery and PDT was ≥ 6 weeks (P = 0.02). CONCLUSION: PDT can be applied as adjuvant therapy after surgery in cases of a malignancy with close or positive tumor resection margins. However, the clinical benefits are yet to be determined. There is a significantly better disease-free survival with a time interval between surgery and PDT of minimal 6 weeks. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:657-663, 2018.

Skin adnexal carcinoma of the head and neck: a retrospective study in a tertiary referral center.

The objective of this study is to give more insight in the diagnosis, clinical course and therapy of skin adnexal carcinoma of the head and neck. Forty cases of skin adnexal carcinoma of the head and neck treated from 1977 to 2011 were identified by searching the hospitals cancer registration database. After pathology review by a pathologist specialized in skin cancer, 17 cases were excluded. A retrospective chart review of the remaining 23 patients was performed. Clinical course was recorded by endpoints including survival, loco-regional control and recurrence free survival. Prognostic factors considered for analysis were differentiation of the tumor and location of the tumor. Five-year overall survival (OS) was 78 % (95 % CI 61-100 %). Five-year recurrence free survival (RFS) was 58 % (95 % CI 40-84 %). Poor differentiation of the tumor significantly reduced OS (p = 0.002) and RFS (p = 0.01). Tumor location 'face' demonstrated a significantly better survival than other tumor locations (p < 0.001). Local recurrence occurred in five cases, regional metastasis was seen in seven patients, distant metastasis in three patients. Three cases with distant metastases died of disease. Based on the findings of this small group of patients in a tertiary referral center, we conclude that skin adnexal carcinoma is a very rare skin carcinoma that can behave locally aggressive but also has the potential for regional and distant metastasis. The recognition of skin adnexal carcinoma and subsequent wide excision in an early stage of the disease is of major importance for loco-regional control and survival.

Sealing of small postlaryngectomy pharyngocutaneous fistulas with voice prosthesis.

Pharyngocutaneous fistulas (PCFs) following total laryngectomy is a common complication. The standard therapy is conservative management, and if this is not successful, surgical closure. There is a group of patients with limited survival chance who have small PCFs. In these patients who are not candidates for surgery, sealing of the PCF with a voice prosthesis can significantly improve the functionality of these patients allowing them to swallow and phonate.