Management of the neck in T1 and T2 buccal squamous cell carcinoma.

Buccal squamous cell carcinoma (SCC) appears to behave more aggressively than other oral subsites, in particular with regards to regional disease at presentation and regional recurrence. Adequate management of the neck is of the utmost importance but is still the subject of debate. An international multicentre retrospective review of 101 patients treated for T1-T2 buccal SCC was performed. Twenty-four were staged clinical node positive (cN+) and underwent therapeutic neck dissection, while 77 were node negative (cN0), with 32 undergoing elective neck dissection (END), with an occult nodal metastasis rate of 28.1%. Depth of invasion (DOI) < 4 mm was associated with a significantly lower rate of cervical nodal metastasis (87.5% versus 12.5%; P = 0.033). END demonstrated a non-significantly lower regional recurrence rate compared to observation (6.3% versus 8.9%, P = 0.670). Regional recurrence was more common in pN+ (24%) and undissected cases (8.9%) than in pN0 patients (0%) (P = 0.011) and was associated with DOI > 5 mm (P = 0.002). Regional recurrence resulted in a reduction in survival (24 versus 93 months, P < 0.001). In the pT2cN0 group, END improved survival (123 versus 26 months, P = 0.009). It is suggested that END be performed in cT2N0 buccal SCC, particularly for tumours with DOI > 4 mm.

The complementary value of intraoperative fluorescence imaging and Raman spectroscopy for cancer surgery: combining the incompatibles.

A clear margin is an important prognostic factor for most solid tumours treated by surgery. Intraoperative fluorescence imaging using exogenous tumour-specific fluorescent agents has shown particular benefit in improving complete resection of tumour tissue. However, signal processing for fluorescence imaging is complex, and fluorescence signal intensity does not always perfectly correlate with tumour location. Raman spectroscopy has the capacity to accurately differentiate between malignant and healthy tissue based on their molecular composition. In Raman spectroscopy, specificity is uniquely high, but signal intensity is weak and Raman measurements are mainly performed in a point-wise manner on microscopic tissue volumes, making whole-field assessment temporally unfeasible. In this review, we describe the state-of-the-art of both optical techniques, paying special attention to the combined intraoperative application of fluorescence imaging and Raman spectroscopy in current clinical research. We demonstrate how these techniques are complementary and address the technical challenges that have traditionally led them to be considered mutually exclusive for clinical implementation. Finally, we present a novel strategy that exploits the optimal characteristics of both modalities to facilitate resection with clear surgical margins.

Higher healing rate after meniscal repair with concomitant ACL reconstruction for tears located in vascular zone 1 compared to zone 2: a systematic review and meta-analysis.

PURPOSE: The purpose of this study was to determine and compare the percentage of completely healed meniscal tears after arthroscopic repair combined with anterior cruciate ligament reconstruction (ACLR) for the different vascular zones of the meniscus. METHODS: PubMed, Embase, Web of Science, Cochrane library and Emcare were searched on 19 May 2020 for articles reporting healing rates after arthroscopic meniscal repair with concomitant ACLR for the different meniscal vascular zones as assessed by second-look arthroscopy. Data on meniscal tears were extracted as located in zones 1, 2 or 3, according to the Cooper classification. Studies were graded in quality using a modified Newcastle-Ottawa Scale. Pooled analyses were performed utilizing a random-effects model. Meta-analyses were performed using R version 3.6.2 and SPSS statistical software version 25.0. The study was registered with PROSPERO (ID:CRD42020176175). RESULTS: Ten observational cohort studies met the inclusion criteria, accounting for 758 meniscal tear repairs in total. The pooled overall proportion of healing was 78% (95% CI 72-84%). The mean weighted proportion of healing was 83% (95% CI 76-90%) for studies (n = 10) reporting zone 1 tears and 69% (95% CI 59-79%) for studies (n = 9) reporting zone 2 tears. No study reported healing rates for zone 3 tears. The pooled overall odds ratio was 2.5 (95% CI 1.00-6.02), indicating zone 1 tears as 2.5 times more likely to heal than zone 2 tears. CONCLUSION: This study demonstrates that meniscal tears localized in vascular zone 1 were more likely to heal than those in zone 2. LEVEL OF EVIDENCE: IV.

Preclinical uPAR-targeted multimodal imaging of locoregional oral cancer.

OBJECTIVES: Establishing adequate resection margins and lymphatic mapping are crucial for the prognosis of oral cancer patients. Novel targeted imaging modalities are needed, enabling pre- and intraoperative detection of tumour cells, in combination with improved post-surgical examination by the pathologist. The urokinase-receptor (uPAR) is overexpressed in head and neck cancer, where it is associated with tumour progression and metastasis. MATERIAL AND METHODS: To determine suitability of uPAR for molecular imaging of oral cancer surgery, human head and neck tumours were sectioned and stained for uPAR to evaluate the expression pattern compared to normal mucosa. Furthermore, metastatic oral squamous carcinoma cell line OSC-19 was used for targeting uPAR in in vivo mouse models. Using anti-uPAR antibody ATN-658, equipped with a multimodal label, the in vivo specificity was investigated and the optimal dose and time-window were evaluated. RESULTS: All human oral cancer tissues expressed uPAR in epithelial and stromal cells. Hybrid ATN-658 clearly visualized tongue tumours in mice using either NIRF or SPECT imaging. Mean fluorescent TBRs over time were 4.3±0.7 with the specific tracer versus 1.7±0.1 with a control antibody. A significant difference in TBRs could be seen between 1nmol (150µg) and 0.34nmol (50µg) dose groups (n=4, p<0.05). Co-expression between BLI, GFP and the NIR fluorescent signals were seen in the tongue tumour, whereas human cytokeratin staining confirmed presence of malignant cells in the positive cervical lymph nodes. CONCLUSION: This study shows the applicability of an uPAR specific multimodal tracer in an oral cancer model, combining SPECT with intraoperative guidance.

EpCAM as multi-tumour target for near-infrared fluorescence guided surgery.

BACKGROUND: Evaluation of resection margins during cancer surgery can be challenging, often resulting in incomplete tumour removal. Fluorescence-guided surgery (FGS) aims to aid the surgeon to visualize tumours and resection margins during surgery. FGS relies on a clinically applicable imaging system in combination with a specific tumour-targeting contrast agent. In this study EpCAM (epithelial cell adhesion molecule) is evaluated as target for FGS in combination with the novel Artemis imaging system. METHODS: The NIR fluorophore IRDye800CW was conjugated to the well-established EpCAM specific monoclonal antibody 323/A3 and an isotype IgG1 as control. The anti-EpCAM/800CW conjugate was stable in serum and showed preserved binding capacity as evaluated on EpCAM positive and negative cell lines, using flow cytometry and cell-based plate assays. Four clinically relevant orthotopic tumour models, i.e. colorectal cancer, breast cancer, head and neck cancer, and peritonitis carcinomatosa, were used to evaluate the performance of the anti-EpCAM agent with the clinically validated Artemis imaging system. The Pearl Impulse small animal imaging system was used as reference. The specificity of the NIRF signal was confirmed using bioluminescence imaging and green-fluorescent protein. RESULTS: All tumour types could clearly be delineated and resected 72 h after injection of the imaging agent. Using NIRF imaging millimetre sized tumour nodules were detected that were invisible for the naked eye. Fluorescence microscopy demonstrated the distribution and tumour specificity of the anti-EpCAM agent. CONCLUSIONS: This study shows the potential of an EpCAM specific NIR-fluorescent agent in combination with a clinically validated intraoperative imaging system to visualize various tumours during surgery.

Characterization and evaluation of the artemis camera for fluorescence-guided cancer surgery.

PURPOSE: Near-infrared (NIR) fluorescence imaging can provide the surgeon with real-time visualization of, e.g., tumor margins and lymph nodes. We describe and evaluate the Artemis, a novel, handheld NIR fluorescence camera. PROCEDURES: We evaluated minimal detectable cell numbers (FaDu-luc2, 7D12-IRDye 800CW), preclinical intraoperative detection of sentinel lymph nodes (SLN) using indocyanine green (ICG), and of orthotopic tongue tumors using 7D12-800CW. Results were compared with the Pearl imager. Clinically, three patients with liver metastases were imaged using ICG. RESULTS: Minimum detectable cell counts for Artemis and Pearl were 2 × 10(5) and 4 × 10(4) cells, respectively. In vivo, seven SLNs were detected in four mice with both cameras. Orthotopic OSC-19-luc2-cGFP tongue tumors were clearly identifiable, and a minimum FaDu-luc2 tumor size of 1 mm(3) could be identified. Six human malignant lesions were identified during three liver surgery procedures. CONCLUSIONS: Based on this study, the Artemis system has demonstrated its utility in fluorescence-guided cancer surgery.

Intraoperative fluorescence delineation of head and neck cancer with a fluorescent anti-epidermal growth factor receptor nanobody.

Intraoperative near-infrared (NIR) fluorescence imaging is a technology with high potential to provide the surgeon with real-time visualization of tumors during surgery. Our study explores the feasibility for clinical translation of an epidermal growth factor receptor (EGFR)-targeting nanobody for intraoperative imaging and resection of orthotopic tongue tumors and cervical lymph node metastases. The anti-EGFR nanobody 7D12 and the negative control nanobody R2 were conjugated to the NIR fluorophore IRDye800CW (7D12-800CW and R2-800CW). Orthotopic tongue tumors were induced in nude mice using the OSC-19-luc2-cGFP cell line. Tumor-bearing mice were injected with 25 µg 7D12-800CW, R2-800CW or 11 µg 800CW. Subsequently, other mice were injected with 50 or 75 µg of 7D12-800CW. The FLARE imaging system and the IVIS spectrum were used to identify, delineate and resect the primary tumor and cervical lymph node metastases. All tumors could be clearly identified using 7D12-800CW. A significantly higher tumor-to-background ratio (TBR) was observed in mice injected with 7D12-800CW compared to mice injected with R2-800CW and 800CW. The highest average TBR (2.00 ± 0.34 and 2.72 ± 0.17 for FLARE and IVIS spectrum, respectively) was observed 24 hr after administration of the EGFR-specific nanobody. After injection of 75 µg 7D12-800CW cervical lymph node metastases could be clearly detected. Orthotopic tongue tumors and cervical lymph node metastases in a mouse model were clearly identified intraoperatively using a recently developed fluorescent EGFR-targeting nanobody. Translation of this approach to the clinic would potentially improve the rate of radical surgical resections.

Towards a successful clinical implementation of fluorescence-guided surgery.

During the European Molecular Imaging Meeting (EMIM) 2013, the fluorescence-guided surgery study group held its inaugural session to discuss the clinical implementation of fluorescence-guided surgery. The general aim of this study group is to discuss and identify the steps required to successfully and safely bring intraoperative fluorescence imaging to the clinics. The focus group intends to use synergies between interested groups as a tool to address regulatory and implementation hurdles in Europe and operates within the intraoperative focus group of the World Molecular Imaging Society (WMIS) that promotes the same interests at the WMIS level. The major topics on the critical path of implementation identified within the study group were quality controls and standards for ensuring accurate imaging and the ability to compare results from different studies, regulatory affairs, and strategies to increase awareness among physicians, regulators, insurance companies, and a broader audience. These hurdles, and the possible actions discussed to overcome them, are summarized in this report. Furthermore, a number of recommendations for the future shape of the fluorescence-guided study group are discussed. A main driving conclusion remains that intraoperative imaging has great clinical potential and that many of the solutions required are best addressed with the community working together to optimally promote and accelerate the clinical implementation of fluorescence imaging towards improving surgical procedures.

Subglottic stenosis in Shwachman-Diamond syndrome - is there a link?

Clinically relevant cartilaginous subglottic stenosis was found in 2 patients with Shwachman-Diamond syndrome (SDS) for which tracheotomy was required in one case. Considering the pathogenesis of SDS, including deficient chondrogenesis, we hypothesise that subglottic stenosis may be a rare symptom of SDS. Otorhinolaryngologist and paediatricians should be aware of the risk of airway pathology in patients with SDS.

Image-guided surgery in head and neck cancer: current practice and future directions of optical imaging.

A key aspect for the postoperative prognosis of patients with head and neck cancer is complete tumor resection. In current practice, the intraoperative assessment of the tumor-free margin is dependent on visual appearance and palpation of the tumor. Optical imaging has the potential of traversing the gap between radiology and surgery by providing real-time visualization of the tumor, thereby allowing for image-guided surgery. The use of the near-infrared light spectrum offers 2 essential advantages: increased tissue penetration of light and an increased signal-to-background ratio of contrast agents. In this review, the current practice and limitations of image-guided surgery by optical imaging using intrinsic fluorescence or contrast agents are described. Furthermore, we provide an overview of the various molecular contrast agents targeting specific hallmarks of cancer that have been used in other fields of oncologic surgery, and we describe perspectives on its future use in head and neck cancer surgery.

Chronic serous otitis media as a manifestation of temporal meningioma.

Chronic serous otitis media is a common problem in the daily routine of the otorhinolaryngologist. In the majority of cases, the cause is related to dysfunction of the eustachian tube due to viral or bacterial rhinitis and occasionally to nasopharyngeal tumors. We report a case of a patient presenting with chronic serous otitis media that was resistant to conventional therapy. MRI with gadolinium finally revealed that the middle ear fluid was caused by leakage of cerebrospinal fluid (CSF) due to bone destruction by a temporal meningioma. The CSF leakage was closed by surgery. Histopathology confirmed meningioma in the temporal bone.

Dysphagia after an L-shaped reconstruction technique of the free jejunum graft.

BACKGROUND: The free jejunum graft is a well-established reconstruction technique after total laryngopharyngectomy. However, besides necrosis of the jejunum graft, the two most important complications are pharyngocutaneous fistula formation and dysphagia due to stricture formation. OBJECTIVES: This study aims to develop an L-shaped reconstruction technique of the free jejunum graft to decrease pharyngocutaneous fistula formation and long-term stricture formation after total laryngopharyngectomy. METHODS: An L-shaped side-to-end anastomosis was performed at the proximal end of the jejunum graft in six patients treated for piriform sinus carcinoma. Patient and operation characteristics and follow-up were recorded. RESULTS: A successful jejunum transfer was performed in all six patients. No pharyngocutaneous fistula or stricture formation occurred during a median follow-up of 23 months (range: 18-30 months). Swallowing rehabilitation started at the median 12th postoperative day (range: 5-150 days). Four patients developed dysphagia at a median of 2 months (range: 1-6 months) after oral intake was started. X-barium swallow revealed a redundant pouch of the transferred jejunum graft, which resulted in compression on the jejunum interposition during swallowing. In three patients, an operation was required to resolve these problems. After the revision operation, no dysphagia occurred during a median follow-up of 12 months (range: 7-13 months). CONCLUSIONS: Because of dysphagia complaints in the majority of our patients, we cannot recommend the described technique and should find other means to improve direct postoperative results and long-term quality of life in this difficult-to-treat group of patients.

Salvage or what follows the failure of a free jejunum transfer for reconstruction of the hypopharynx?

AIM: To analyse the cases of failure of free jejunum transfer with subsequent secondary reconstruction methods after ablative surgery for malignant tumours of the laryngopharyngeal region and the cervical oesophagus with reconstruction using a jejunum interposition. MATERIALS AND METHODS: Four cases in which failure of the jejunum interposition was managed with a second free or pedicle transfer were identified. The electronic files of patients were studied and analysed for patient characteristics and failure of reconstruction; type of salvage surgery and outcome; swallowing function and rehabilitation; postoperative complications; recurrence of tumour; patient survival and cause of death. RESULTS: Failure of the interposition occurred within 11 days in all patients, with oral bleeding being the most prominent sign. To replace the failed jejunum transfer, two new free jejunum transfers, two gastric pull-ups and one colon interposition after the second failure of a jejunum transfer were used. Three patients started swallowing rehabilitation, of which two achieved complete oral intake, defined as the redundancy of a feeding tube. The median disease-free period and overall survival was 28 and 42 months, respectively. CONCLUSION: Failure of a free jejunum transfer is a rare but inevitable complication when performed in a high-risk patient population, with oral bleeding being the most important sign of necrosis. Salvage of the buried jejunum interposition is hardly ever possible and secondary reconstruction can be performed using a new jejunum interposition or gastric pull-up procedure with considerable early postoperative complications, but relatively good results regarding swallowing rehabilitation and patient survival.

Musculotendinous transfer as a treatment option for irreparable posterosuperior rotator cuff tears: teres major or latissimus dorsi?

Irreparable posterior cuff tears can cause pain and lack of shoulder function. Surgical treatment includes musculotendinous transfers of either latissimus dorsi (LD) or teres major (TM). This study aimed to give a detailed description of the morphology of these two muscles with particular regard to their suitability for use in transfers. Sixty-two shoulders in 31 cadaveric specimens (mean age 50 years) were dissected. The mean length of the TM was 13.7 cm at its superior edge while the distance from the muscle origin to the greater tuberosity (GT) was 19.2 cm. The tendon of the TM had a length of 1.5 cm, a width of 3.4 cm, and a thickness of 1.3 mm. The mean length of the LD was 26.0 cm and the distance from its origin to the GT was 32.9 cm. The mean length of the LD tendon was 5.2 cm, its width 2.9 cm, and its thickness 1.0 mm. The increased length required to achieve transfer was 47% (of the original length) for TM and 33% for LD. Both TM and LD could reach the GT with ease, according to the potential muscle excursions. Tension of the neurovascular bundle is more probable with LD because it enters the muscle relatively closer to the tendon. Problems with regard to reattachment may be more likely to occur in a transfer of the TM because of its short tendon.