Cancers

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16 pages, 4058 KiB

Open AccessArticle

Pilot Investigation on p75ICD Expression in Laryngeal Squamous Cell Carcinoma

by Viviana Triaca, Elena Fico, Pamela Rosso, Massimo Ralli, Alessandro Corsi, Cinzia Severini, Alvaro Crevenna, Enzo Agostinelli, Emma Rullo, Mara Riminucci, Andrea Colizza, Antonella Polimeni, Antonio Greco and Paola Tirassa

Cancers 2022, 14(11), 2622; https://doi.org/10.3390/cancers14112622 - 25 May 2022

Cited by 2 | Viewed by 1777

Abstract

We investigated the p75 Neurotrophin Receptor (p75NTR) expression and cleavage product p75NTR Intracellular Domain (p75ICD) as potential oncogenic and metastatic markers in human Laryngeal Squamous Cell Carcinoma (LSCC). p75NTR is highly expressed in Cancer Stem Cells (CSCs) of the laryngeal epithelia and it [...] Read more.

We investigated the p75 Neurotrophin Receptor (p75NTR) expression and cleavage product p75NTR Intracellular Domain (p75ICD) as potential oncogenic and metastatic markers in human Laryngeal Squamous Cell Carcinoma (LSCC). p75NTR is highly expressed in Cancer Stem Cells (CSCs) of the laryngeal epithelia and it has been proposed as a marker for stemness, cell migration, and chemo-resistance in different squamous carcinomas. To investigate the clinical significance of p75NTR cleavage products in solid tumors, full-length and cleaved p75NTR expression was analyzed in laryngeal primary tumors from different-stage LSCC patients, diagnosed at the Policlinico Umberto I Hospital. Molecular and histological techniques were used to detect the expressions of p75NTR and p75ICD, and ATP Binding Cassette Subfamily G Member 2 (ABCG2), a CSC marker. We found regulated p75NTR cleavage during squamous epithelial tumor progression and tissue invasion. Our preliminary investigation suggests p75ICD expression and localization as possible features of tumorigenesis and metastaticity. Its co-localization with ABCG2 in squamous cells in the parenchyma invaded by the tumor formation allows us to hypothesize p75NTR and p75ICD roles in tumor invasion and CSC spreading in LSCC patients. These data might represent a starting point for a comprehensive analysis of p75NTR cleavage and of its clinical relevance as a potential molecular LSCC signature, possibly helping diagnosis, and improving prognosis and personalized therapy. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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11 pages, 357 KiB

Open AccessArticle

From Pathways to Practice: Impact of Implementing Mobilization Recommendations in Head and Neck Cancer Surgery with Free Flap Reconstruction

by Rosie Twomey, T. Wayne Matthews, Steven C. Nakoneshny, Christiaan Schrag, Shamir P. Chandarana, Jennifer Matthews, David McKenzie, Robert D. Hart, Na Li, Joseph C. Dort and Khara M. Sauro

Cancers 2021, 13(12), 2890; https://doi.org/10.3390/cancers13122890 - 9 Jun 2021

Cited by 6 | Viewed by 4060

Abstract

One of the foundational elements of enhanced recovery after surgery (ERAS) guidelines is early postoperative mobilization. For patients undergoing head and neck cancer (HNC) surgery with free flap reconstruction, the ERAS guideline recommends patients be mobilized within 24 h postoperatively. The objective of [...] Read more.

One of the foundational elements of enhanced recovery after surgery (ERAS) guidelines is early postoperative mobilization. For patients undergoing head and neck cancer (HNC) surgery with free flap reconstruction, the ERAS guideline recommends patients be mobilized within 24 h postoperatively. The objective of this study was to evaluate compliance with the ERAS recommendation for early postoperative mobilization in 445 consecutive patients who underwent HNC surgery in the Calgary Head and Neck Enhanced Recovery Program. This retrospective analysis found that recommendation compliance increased by 10% despite a more aggressive target for mobilization (from 48 to 24 h). This resulted in a decrease in postoperative mobilization time and a stark increase in the proportion of patients mobilized within 24 h (from 10% to 64%). There was a significant relationship between compliance with recommended care and time to postoperative mobilization (Spearman’s rho = −0.80; p < 0.001). Hospital length of stay was reduced by a median of 2 days, from 12 (1QR = 9–16) to 10 (1QR = 8–14) days (z = 3.82; p < 0.001) in patients who received guideline-concordant care. Engaging the clinical team and changing the order set to support clinical decision-making resulted in increased adherence to guideline-recommended care for patients undergoing major HNC surgery with free flap reconstruction. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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12 pages, 379 KiB

Open AccessArticle

Impact of Early Mobilization on Recovery after Major Head and Neck Surgery with Free Flap Reconstruction

by Rosie Twomey, T. Wayne Matthews, Steven Nakoneshny, Christiaan Schrag, Shamir P. Chandarana, Jennifer Matthews, David McKenzie, Robert D. Hart, Na Li, Khara M. Sauro and Joseph C. Dort

Cancers 2021, 13(12), 2852; https://doi.org/10.3390/cancers13122852 - 8 Jun 2021

Cited by 20 | Viewed by 3648

Abstract

Surgery with free flap reconstruction is a standard treatment for head and neck cancer (HNC). Because of the complexity of HNC surgery, recovery can be challenging, and complications are common. One of the foundations of enhanced recovery after surgery (ERAS) is early postoperative [...] Read more.

Surgery with free flap reconstruction is a standard treatment for head and neck cancer (HNC). Because of the complexity of HNC surgery, recovery can be challenging, and complications are common. One of the foundations of enhanced recovery after surgery (ERAS) is early postoperative mobilization. The ERAS guidelines for HNC surgery with free flap reconstruction recommend mobilization within 24 h. This is based mainly on evidence from other surgical disciplines, and the extent to which mobilization within 24 h improves recovery after HNC surgery has not been explored. This retrospective analysis included 445 patients from the Calgary Head and Neck Enhanced Recovery Program. Mobilization after 24 h was associated with more complications of any type (OR = 1.73, 95% CI [confidence interval] = 1.16–2.57) and more major complications (OR = 1.76; 95% CI = 1.00–3.16). When accounting for patient and clinical factors, mobilization after 48 h was a significant predictor of major complications (OR = 2.61; 95% CI = 1.10–6.21) and prolonged length of stay (>10 days; OR = 2.85, 95% CI = 1.41–5.76). This comprehensive analysis of the impact of early mobilization on postoperative complications and length of stay in a large HNC cohort provides novel evidence supporting adherence to the ERAS early mobilization recommendations. Early mobilization should be a priority for patients undergoing HNC surgery with free flap reconstruction. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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10 pages, 10665 KiB

Open AccessArticle

Indications and Clinical Outcomes of Transoral Robotic Surgery and Free Flap Reconstruction

by Philippe Gorphe, Stéphane Temam, Antoine Moya-Plana, Nicolas Leymarie, Frédéric Kolb, Apolline Bout-Roumazeilles, Quentin Qassemyar, Nadia Benmoussa and Jean-François Honart

Cancers 2021, 13(11), 2831; https://doi.org/10.3390/cancers13112831 - 6 Jun 2021

Cited by 13 | Viewed by 4109

Abstract

We reviewed the indications, peroperative feasibility, and postoperative clinical outcomes of our first 50 consecutive patients who underwent free flap reconstruction after TORS for complex pharyngeal defects at our institution. We analyzed indications according to previous radiotherapy, the size of the resection, and [...] Read more.

We reviewed the indications, peroperative feasibility, and postoperative clinical outcomes of our first 50 consecutive patients who underwent free flap reconstruction after TORS for complex pharyngeal defects at our institution. We analyzed indications according to previous radiotherapy, the size of the resection, and the transoral exposure of critical structures. We reviewed surgical data, postoperative complications, and functional outcomes comprising tracheostomy and alimentation management. Indications were upfront surgery (34%), a second primary surgery after radiotherapy (28%), or salvage surgery after chemoradiotherapy failure (38%). Localizations were the tongue base (44%), tonsillar fossa (28%), pharyngeal wall (22%), and soft palate (6%). T-classifications were T1 (6%), T2 (52%), T3 (20%), and T4 (22%). The mean length of the surgery was 574 min. Two patients were intraoperatively converted to a conventional approach at the beginning of the learning curve. In conclusion, TORS and free flap reconstruction in complex situations were associated with low rates of postoperative complications and satisfactory functional outcomes. They were, however, associated with a renewed learning curve. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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10 pages, 2676 KiB

Open AccessArticle

Translation of c-Met Targeted Image-Guided Surgery Solutions in Oral Cavity Cancer—Initial Proof of Concept Data

by Tessa Buckle, Maarten van Alphen, Matthias N. van Oosterom, Florian van Beurden, Nina Heimburger, Jaqueline E. van der Wal, Michiel van den Brekel, Fijs W. B. van Leeuwen and Baris Karakullukcu

Cancers 2021, 13(11), 2674; https://doi.org/10.3390/cancers13112674 - 28 May 2021

Cited by 12 | Viewed by 2826

Abstract

Intraoperative tumor identification (extension/margins/metastases) via receptor-specific targeting is one of the ultimate promises of fluorescence-guided surgery. The translation of fluorescent tracers that enable tumor visualization forms a critical component in the realization of this approach. Ex vivo assessment of surgical specimens after topical [...] Read more.

Intraoperative tumor identification (extension/margins/metastases) via receptor-specific targeting is one of the ultimate promises of fluorescence-guided surgery. The translation of fluorescent tracers that enable tumor visualization forms a critical component in the realization of this approach. Ex vivo assessment of surgical specimens after topical tracer application could help provide an intermediate step between preclinical evaluation and first-in-human trials. Here, the suitability of the c-Met receptor as a potential surgical target in oral cavity cancer was explored via topical ex vivo application of the fluorescent tracer EMI-137. Freshly excised tumor specimens obtained from ten patients with squamous cell carcinoma of the tongue were incubated with EMI-137 and imaged with a clinical-grade Cy5 prototype fluorescence camera. In-house developed image processing software allowed video-rate assessment of the tumor-to-background ratio (TBR). Fluorescence imaging results were related to standard pathological evaluation and c-MET immunohistochemistry. After incubation with EMI-137, 9/10 tumors were fluorescently illuminated. Immunohistochemistry revealed c-Met expression in all ten specimens. Non-visualization could be linked to a more deeply situated lesion. Tumor assessment was improved via video representation of the TBR (median TBR: 2.5 (range 1.8–3.1)). Ex vivo evaluation of tumor specimens suggests that c-Met is a possible candidate for fluorescence-guided surgery in oral cavity cancer. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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16 pages, 1279 KiB

Open AccessArticle

Impact of Neck Dissection in Head and Neck Squamous Cell Carcinomas of Unknown Primary

by Yazan Abu-Shama, Julia Salleron, Florent Carsuzaa, Xu-Shan Sun, Carole Pflumio, Idriss Troussier, Claire Petit, Matthieu Caubet, Arnaud Beddok, Valentin Calugaru, Stephanie Servagi-Vernat, Joël Castelli, Jessica Miroir, Marco Krengli, Paul Giraud, Edouard Romano, Jonathan Khalifa, Mélanie Doré, Nicolas Blanchard, Alexandre Coutte, Charles Dupin, Shakeel Sumodhee, Yungan Tao, Vincent Roth, Lionel Geoffrois, Bruno Toussaint, Duc Trung Nguyen, Jean-Christophe Faivre and Juliette Thariat Show full author list Hide full author list

Cancers 2021, 13(10), 2416; https://doi.org/10.3390/cancers13102416 - 17 May 2021

Cited by 2 | Viewed by 2426

Abstract

Purpose: Management of head and neck cancers of unknown primary (HNCUP) combines neck dissection (ND) and radiotherapy, with or without chemotherapy. The prognostic value of ND has hardly been studied in HNCUP. Methods: A retrospective multicentric study assessed the impact of ND extent [...] Read more.

Purpose: Management of head and neck cancers of unknown primary (HNCUP) combines neck dissection (ND) and radiotherapy, with or without chemotherapy. The prognostic value of ND has hardly been studied in HNCUP. Methods: A retrospective multicentric study assessed the impact of ND extent (adenectomy, selective ND, radical/radical-modified ND) on nodal relapse, progression-free survival (PFS) or survival, taking into account nodal stage. Results: 53 patients (16.5%) had no ND, 33 (10.2%) had lymphadenectomy, 116 (36.0%) underwent selective ND and 120 underwent radical/radical-modified ND (37.3%), 15 of which received radical ND (4.7%). With a 34-month median follow-up, the 3-year incidence of nodal relapse was 12.5% and progression-free survival (PFS) 69.1%. In multivariate analysis after adjusting for nodal stage, the risk of nodal relapse or progression was reduced with lymphadenectomy, selective or radical/modified ND, but survival rates were similar. Patients undergoing lymphadenectomy or ND had a better PFS and lowered nodal relapse incidence in the N1 + N2a group, but the improvement was not significant for the N2b or N2 + N3c patients. Severe toxicity rates exceeded 40% with radical ND. Conclusion: In HNCUP, ND improves PFS, regardless of nodal stage. The magnitude of the benefit of ND does not appear to depend on ND extent and decreases with a more advanced nodal stage. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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13 pages, 529 KiB

Open AccessArticle

Lymph Node Yield and Ratio in Selective and Modified Radical Neck Dissection in Head and Neck Cancer—Impact on Oncological Outcome

by Sean C. Sheppard, Lukas Frech, Roland Giger and Lluís Nisa

Cancers 2021, 13(9), 2205; https://doi.org/10.3390/cancers13092205 - 4 May 2021

Cited by 14 | Viewed by 3303

Abstract

Background: Lymph node metastases are associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). Neck dissection (ND) is often performed prior to or after (chemo)radiation (CRT) and is an integral part of HNSCC treatment strategies. The impact of CRT [...] Read more.

Background: Lymph node metastases are associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). Neck dissection (ND) is often performed prior to or after (chemo)radiation (CRT) and is an integral part of HNSCC treatment strategies. The impact of CRT delivered prior to ND on lymph node yield (LNY) and lymph node ratio (LNR) has not been comprehensively investigated. Material and methods: A retrospective cohort study was conducted from January 2014 to 30 June 2019 at the University Hospital of Bern, Switzerland. We included 252 patients with primary HNSCC who underwent NDs either before or after CRT. LNY and LNR were compared in patients undergoing ND prior to or after CRT. A total of 137 and 115 patients underwent modified radical ND (levels I to V) and selective ND, respectively. The impact of several features on survival and disease control was assessed. Results: Of the included patients, 170 were male and 82 were females. There were 141 primaries from the oral cavity, 55 from the oropharynx, and 28 from the larynx. ND specimens showed a pN0 stage in 105 patients and pN+ in 147. LNY, but LNR was not significantly higher in patients undergoing upfront ND than in those after CRT (median: 38 vs. 22, p < 0.0001). Cox hazard ratio regression showed that an LNR ≥ 6.5% correlated with poor overall (HR 2.42, CI 1.12-4.89, p = 0.014) and disease-free survival (HR 3.416, CI 1.54-754, p = 0.003) in MRND. Conclusion: ND after CRT leads to significantly reduced LNY. An LNR ≥6.5% is an independent risk factor for decreased overall, disease-free, and distant metastasis-free survival for MRND. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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12 pages, 6104 KiB

Open AccessArticle

Full-Thickness Tumor Resection of Oral Cancer Involving the Facial Skin—Microsurgical Reconstruction of Extensive Defects after Radical Treatment of Advanced Squamous Cell Carcinoma

by Julius Moratin, Jan Mrosek, Dominik Horn, Karl Metzger, Oliver Ristow, Sven Zittel, Michael Engel, Kolja Freier, Juergen Hoffmann and Christian Freudlsperger

Cancers 2021, 13(9), 2122; https://doi.org/10.3390/cancers13092122 - 28 Apr 2021

Cited by 5 | Viewed by 4208

Abstract

Advanced tumors of the head and neck are challenging for the treatment specialist due to the need to synergize oncological and functional requirements. Free flap reconstruction has been established as the standard of care for defects following tumor resection. However, depending on the [...] Read more.

Advanced tumors of the head and neck are challenging for the treatment specialist due to the need to synergize oncological and functional requirements. Free flap reconstruction has been established as the standard of care for defects following tumor resection. However, depending on the affected anatomic subsite, advanced tumors may impose specific difficulties regarding reconstruction, especially when full-thickness resection is required. This study aimed to evaluate reconstructive strategies and oncological outcomes in patients with full-thickness resection of the oral cavity. A total of 33 patients with extensive defects due to squamous cell carcinoma of the oral cavity were identified. Indications, reconstructive procedures, and clinical outcome were evaluated. Thirty-two patients (97%) presented locally advanced tumors (T3/T4). Complete tumor resection was achieved in 26 patients (78.8%). The anterolateral thigh flap was the most frequently used flap (47.1%), and the primary flap success rate was 84.8%. The cohort demonstrated a good local control rate and moderate overall and progression-free survival rates. Most patients regained full competence regarding oral alimentation and speech. Full-thickness tumor resections of the head and neck area may be necessary due to advanced tumors in critical anatomic areas. In many cases, radical surgical treatment leads to good oncological results. Free flap reconstruction has been shown to be a suitable option for extensive defects in aesthetically challenging regions. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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18 pages, 630 KiB

Open AccessArticle

The Impact of Healthcare-Associated Infections in Patients Undergoing Oncological Microvascular Head and Neck Reconstruction: A Prospective Multicentre Study

by Ana Ramos-Zayas, Francisco López-Medrano, Irene Urquiza-Fornovi, Ignacio Zubillaga, Ramón Gutiérrez, Gregorio Sánchez-Aniceto, Julio Acero, Fernando Almeida, Ana Galdona, María José Morán, Marta Pampin and José Luis Cebrián

Cancers 2021, 13(9), 2109; https://doi.org/10.3390/cancers13092109 - 27 Apr 2021

Cited by 10 | Viewed by 2425

Abstract

(1) Background: Healthcare-associated infections (HAIs) after head and neck free-flap reconstruction are a common postoperative complication. Risk factors for HAIs in this context and their consequences have not been adequately described. (2) Methods: Ongoing prospective multicentre study between 02/2019 and 12/2020. Demographic characteristics [...] Read more.

(1) Background: Healthcare-associated infections (HAIs) after head and neck free-flap reconstruction are a common postoperative complication. Risk factors for HAIs in this context and their consequences have not been adequately described. (2) Methods: Ongoing prospective multicentre study between 02/2019 and 12/2020. Demographic characteristics and outcomes were analysed, focusing on infections. (3) Results: Forty out of 65 patients (61.54%) suffered HAIs (surgical site infection: 52.18%, nosocomial pneumonia: 23.20%, bloodstream infection: 13% and urinary tract infection: 5.80%). Methicillin-resistant Staphylococcus aureus (MRSA) and resistant Pseudomonas aeruginosa, Klebsiella pneumoniae and Enterobacter cloacae were the most frequently implicated. The significant risk factors for infection were: previous radiotherapy (Odds ratio (OR): 5.42; 95% confidence interval (CI), 1.39–21.10), anaemia (OR: 8.00; 95% CI, 0.96–66.95), salvage surgery (eight out of eight patients), tracheostomy (OR: 2.86; 95% CI, 1.01–8.14), surgery duration (OR: 1.01; 95% CI, 1.00–1.02), microvascular reoperation <72 h (eight/eight) and flap loss (eight/eight). The major surgical complications were: a need to reoperate (OR: 6.89; 95% CI, 1.42–33.51), prolonged hospital admission (OR: 1.16; 95% CI, 1.06–1.27) and delay in the initiation of postoperative radiotherapy (OR: 9.07; 95% CI, 1.72–47.67). The sixth month mortality rate in patients with HAIs was 7.69% vs. 0% in patients without HAIs (p = 0.50). (4) Conclusions: HAIs were common after this type of surgery, many of them caused by resistant microorganisms. Some modifiable risk factors were identified. Infections played a role in cancer prognosis by delaying adjuvant therapy. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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15 pages, 7177 KiB

Open AccessArticle

Frequency and Localization of Second Primary Tumors in Patients with Oropharyngeal Carcinoma—The Influence of the Human Papilloma Virus

by Salome L. Bosshart, Grégoire B. Morand and Martina A. Broglie

Cancers 2021, 13(8), 1755; https://doi.org/10.3390/cancers13081755 - 7 Apr 2021

Cited by 7 | Viewed by 2178

Abstract

Purpose: To investigate the frequency, localization, and survival of second primary tumors (SPT) of oropharyngeal squamous cell carcinoma (OPSCC) depending on human papillomavirus (HPV) status. Methods: We performed a retrospective chart analysis of 107 OPSCC patients treated at the Zurich University Hospital from [...] Read more.

Purpose: To investigate the frequency, localization, and survival of second primary tumors (SPT) of oropharyngeal squamous cell carcinoma (OPSCC) depending on human papillomavirus (HPV) status. Methods: We performed a retrospective chart analysis of 107 OPSCC patients treated at the Zurich University Hospital from 2001 to 2010. Rate and localization of SPT after an index OPSCC were stratified according to smoking and HPV infection status. Results: In total, 57/91 (63%) included patients showed an HPV-associated OPSCC. Of these, 37/57 (64.9%) patients with an HPV-positive and 32/34 (94.1%) patients with an HPV-negative OPSCC were smokers. The median age at diagnosis of the SPT was 59.54 years (interquartile range 52.7–65.6). In addition, 8/57 (14%) HPV-positive and 13/34 (38.2%) HPV-negative patients developed SPT. The rate of SPT in patients with HPV-positive index tumors was significantly lower than in patients with HPV-negative OPSCC (p-value 0.01). Smokers showed significantly more SPT in the head and neck area than outside. The development of an SPT led to a significantly lower survival time in HPV-negative patients, while it did not significantly affect the survival time of HPV-positive patients. Conclusions: Patients with HPV-positive index tumors had a significantly lower risk of developing SPT than patients with HPV-negative tumors. If SPT developed, survival was significantly shorter in patients with HPV-negative tumors than with HPV-positive tumors. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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16 pages, 2020 KiB

Open AccessArticle

Matched-Pair Analysis of Survival in the Patients with Advanced Laryngeal and Hypopharyngeal Squamous Cell Carcinoma Treated with Induction Chemotherapy Plus Chemo-Radiation or Total Laryngectomy

by Patricia García-Cabo, Fernando López, Mario Sánchez-Canteli, Laura Fernández-Vañes, César Álvarez-Marcos, José Luis Llorente, Maria Ángeles de la Rúa, Pilar Blay and Juan P. Rodrigo

Cancers 2021, 13(7), 1735; https://doi.org/10.3390/cancers13071735 - 6 Apr 2021

Cited by 11 | Viewed by 2383

Abstract

Background: We performed a comparative analysis between an organ-preservation protocol and surgery followed by radiotherapy in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx; Methods: 60 previously untreated patients who were treated with induction chemotherapy followed by chemoradiotherapy in [...] Read more.

Background: We performed a comparative analysis between an organ-preservation protocol and surgery followed by radiotherapy in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx; Methods: 60 previously untreated patients who were treated with induction chemotherapy followed by chemoradiotherapy in responders were compared with a control group of 60 patients treated with up-front surgery. Both groups were statistically comparable, according to the subsite, TNM (tumor-node-metastasis) stage, age, and sex; Results: Mean age was 58 years and 92% were male. No significant statistical difference was observed for overall survival (OS) (HR 0.75; 95% CI 0.48–1.18; P = 0.22) and disease-specific survival (DSS) (HR 0.98; 95% CI 0.52–1.83, P = 0.96). Also, there was no significant difference for recurrence-free survival (HR 0.931; 95% CI 0.57–1.71; P = 0.81), metastases-free survival (HR 2.23; 95% CI 0.67–7.41; P = 0.19), and the appearance of second primary tumors (HR 1.22; 95% CI 0.51–2.88; P = 0.64); Conclusions: The results of the organ-preservation approach did not appear inferior to those of surgery plus (chemo)radiotherapy for patients with T3/T4a larynx and T2–T4a hypopharynx cancer with respect to OS and DSS, locoregional control and metastases-free survival. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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13 pages, 2661 KiB

Open AccessArticle

Impact of Goal Directed Therapy in Head and Neck Oncological Surgery with Microsurgical Reconstruction: Free Flap Viability and Complications

by Blanca Tapia, Elena Garrido, Jose Luis Cebrian, Jose Luis Del Castillo, Javier Gonzalez, Itsaso Losantos and Fernando Gilsanz

Cancers 2021, 13(7), 1545; https://doi.org/10.3390/cancers13071545 - 27 Mar 2021

Cited by 11 | Viewed by 2560

Abstract

(1) Background: Surgical outcomes in free flap reconstruction of head and neck defects in cancer patients have improved steadily in recent years; however, correct anaesthesia management is also important. The aim of this study has been to show whether goal directed therapy can [...] Read more.

(1) Background: Surgical outcomes in free flap reconstruction of head and neck defects in cancer patients have improved steadily in recent years; however, correct anaesthesia management is also important. The aim of this study has been to show whether goal directed therapy can improve flap viability and morbidity and mortality in surgical patients. (2) Methods: we performed an observational case control study to analyse the impact of introducing a semi invasive device (Flo Trac^®) during anaesthesia management to optimize fluid management. Patients were divided into two groups: one received goal directed therapy (GDT group) and the other conventional fluid management (CFM group). Our objective was to compare surgical outcomes, complications, fluid management, and length of stay between groups. (3) Results: We recruited 140 patients. There were no differences between groups in terms of demographic data. Statistically significant differences were observed in colloid infusion (GDT 53.1% vs. CFM 74.1%, p = 0.023) and also in intraoperative and postoperative infusion of crystalloids (CFM 5.72 (4.2, 6.98) vs. GDT 3.04 (2.29, 4.11), p < 0.001), which reached statistical significance. Vasopressor infusion in the operating room (CFM 25.5% vs. GDT 74.5%, p < 0.001) and during the first postoperative 24h (CFM 40.6% vs. GDT 75%, p > 0.001) also differed. Differences were also found in length of stay in the intensive care unit (hours: CFM 58.5 (40, 110) vs. GDT 40.5 (36, 64.5), p = 0.005) and in the hospital (days: CFM 15.5 (12, 26) vs. GDT 12 (10, 19), p = 0.009). We found differences in free flap necrosis rate (CMF 37.1% vs. GDT 13.6%, p = 0.003). One-year survival did not differ between groups (CFM 95.6% vs. GDT 86.8%, p = 0.08). (4) Conclusions: Goal directed therapy in oncological head and neck surgery improves outcomes in free flap reconstruction and also reduces length of stay in the hospital and intensive care unit, with their corresponding costs. It also appears to reduce morbidity, although these differences were not significant. Our results have shown that optimizing intraoperative fluid therapy improves postoperative morbidity and mortality. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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10 pages, 1635 KiB

Open AccessArticle

Efficacy of Multimodal Analgesia for Postoperative Pain Management in Head and Neck Cancer Patients

by Ashley Hinther, Steven C. Nakoneshny, Shamir P. Chandarana, T. Wayne Matthews, Robert Hart, Christiaan Schrag, Jennifer Matthews, C. David McKenzie, Gordon H. Fick and Joseph C. Dort

Cancers 2021, 13(6), 1266; https://doi.org/10.3390/cancers13061266 - 12 Mar 2021

Cited by 18 | Viewed by 4279

Abstract

Postoperative opioid use has been linked to the subsequent development of opioid dependency. Multimodal analgesia (MMA) can reduce the use of opioids in the postoperative period, but MMA has not been well-studied after major head and neck surgery. Our goal is to explore [...] Read more.

Postoperative opioid use has been linked to the subsequent development of opioid dependency. Multimodal analgesia (MMA) can reduce the use of opioids in the postoperative period, but MMA has not been well-studied after major head and neck surgery. Our goal is to explore the association between MMA and postoperative opioid use and pain control in patients undergoing major head and neck surgery. We performed a retrospective study in adult (age ≥ 18 years) patients undergoing primary head and neck cancer resection with free-flap reconstruction. All patients were treated using an established care pathway. The baseline group was treated between January 2015–December 2015 (n = 41), prior to the implementation of MMA, and were compared to an MMA-treated cohort treated between December 2017–June 2019 (n = 97). The primary outcome was the proportion of opioids prescribed and oral morphine equivalents (OMEs) consumed during the hospitalization. The secondary outcome was pain control. We found that the post-MMA group consumed fewer opioids in the postoperative period compared to the pre-MMA group. Prior to post-operative day (POD) 6, pain control was better in the post-MMA group; however, the pain control lines intersect on POD 6 and the pre-MMA group appeared to have better pain control from PODs 7–10. In conclusion, our data suggest MMA is an effective method of pain control and opioid reduction in patients undergoing surgery for head and neck cancer with free flap reconstruction. MMA use was associated with a significant decrease in the quantity of opioids consumed postoperatively. The MMA protocol was associated with improved pain management early in the postoperative course. Finally, the MMA protocol is a feasible method of pain control and may reduce the adverse side effects associated with opioid use. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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Review

Jump to: Research, Other

28 pages, 2792 KiB

Open AccessReview

Sinonasal Squamous Cell Carcinoma, a Narrative Reappraisal of the Current Evidence

by Marco Ferrari, Stefano Taboni, Andrea Luigi Camillo Carobbio, Enzo Emanuelli, Roberto Maroldi, Paolo Bossi and Piero Nicolai

Cancers 2021, 13(11), 2835; https://doi.org/10.3390/cancers13112835 - 7 Jun 2021

Cited by 37 | Viewed by 8606

Abstract

Sinonasal squamous cell carcinoma is a rare tumor affecting the nasal cavity and paranasal sinuses. Several aspects of this disease, ranging from epidemiology to biology, pathology, diagnosis, staging, treatment, and post-treatment surveillance are controversial, and consensus on how to manage this sinonasal cancer [...] Read more.

Sinonasal squamous cell carcinoma is a rare tumor affecting the nasal cavity and paranasal sinuses. Several aspects of this disease, ranging from epidemiology to biology, pathology, diagnosis, staging, treatment, and post-treatment surveillance are controversial, and consensus on how to manage this sinonasal cancer is lacking. A narrative literature review was performed to summarize the current evidence and provide the reader with available data supporting the decision-making process in patients affected by sinonasal squamous cell carcinoma, alongside the authors’ personal opinion on the unsolved issues of this tumor. The review has highlighted several advances in molecular definition of epithelial cancers of the sinonasal tract. Surgery represents the pivot of treatment and is performed through an endoscopic transnasal approach whenever feasible. Open surgery is required for a large proportion of cases. Reconstruction of the defect follows principles of skull base and cranio-maxillo-facial reconstruction. Chemotherapy is given as neoadjuvant treatment or concomitantly to radiotherapy. Photon-based radiation therapy has a crucial role in the adjuvant setting. Particle therapy is providing promising results. Management of the neck should be planned based on the presence of clinically appreciable metastases, primary tumor extension, and need for recipient vessels. Biotherapy and immunotherapy are still underexplored therapeutical modalities. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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16 pages, 1133 KiB

Open AccessReview

Resection Margins in Head and Neck Cancer Surgery: An Update of Residual Disease and Field Cancerization

by Annouk S. Pierik, C. René Leemans and Ruud H. Brakenhoff

Cancers 2021, 13(11), 2635; https://doi.org/10.3390/cancers13112635 - 27 May 2021

Cited by 29 | Viewed by 5797

Abstract

Surgery is one of the mainstays of head and neck cancer treatment, and aims at radical resection of the tumor with 1 cm tumor-free margins to obtain locoregional control. Surgical margins are evaluated by histopathological examination of the resection specimen. It has been [...] Read more.

Surgery is one of the mainstays of head and neck cancer treatment, and aims at radical resection of the tumor with 1 cm tumor-free margins to obtain locoregional control. Surgical margins are evaluated by histopathological examination of the resection specimen. It has been long an enigma that approximately 10–30% of surgically treated head and neck cancer patients develop locoregional recurrences even though the resection margins were microscopically tumor-free. However, the origins of these recurrences have been elucidated by a variety of molecular studies. Recurrences arise either from minimal residual disease, cancer cells in the surgical margins that escape detection by the pathologist when examining the specimen, or from precancerous mucosal changes that may remain unnoticed. Head and neck tumors develop in mucosal precursor changes that are sometimes visible but mostly not, fueling research into imaging modalities such as autofluorescence, to improve visualization. Mostly unnoticed, these precancerous changes may stay behind when the tumor is resected, and subsequent malignant progression will cause a local relapse. This led to a clinical trial of autofluorescence-guided surgery, of which the results were reported in 2020. This review focuses on the most recent literature of the improved diagnosis of the resection margins of surgically treated head and neck cancer patients, the pathobiological origin of recurrent disease, and relevant biomarkers to predict local relapse. Directions for further research will be discussed, including potential options for improved and personalized treatment, based on the most recently published data. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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12 pages, 3894 KiB

Open AccessSystematic Review

Impact of Previous Irradiation on Wound Healing after Negative Pressure Wound Therapy in Head and Neck Cancer Patients—A Systematic Review

by Muhammad Faisal, Peter D. Berend, Rudolf Seemann, Stefan Janik, Stefan Grasl, Andrea Ritzengruber, Herbert Mendel, Arif Jamshed, Raza Hussain and Boban M. Erovic

Cancers 2021, 13(10), 2482; https://doi.org/10.3390/cancers13102482 - 19 May 2021

Cited by 9 | Viewed by 4967

Abstract

(1) Background: Negative pressure wound therapy (NPWT) has been effectively used for wound management in comparison to traditional dressings. The purpose of this study was to provide an evidence-based review of NPWT in head and neck cancer patients, as well as the impact [...] Read more.

(1) Background: Negative pressure wound therapy (NPWT) has been effectively used for wound management in comparison to traditional dressings. The purpose of this study was to provide an evidence-based review of NPWT in head and neck cancer patients, as well as the impact of previous irradiation and other risk factors on wound healing. (2) Material and Methods: We conducted a comprehensive search in PubMed, Medline, Embase, Web of Science, and Cochrane Library databases for relevant literature. (3) Results: 15 studies fulfilled the inclusion criteria. The most common etiologies requiring NPWT were defects post tumor resection and flap reconstruction and oro/pharyngo-cutaneous fistulas. The neck was found to be the most common site of involvement (47.3%). The overall wound healing response rate was 87.5%. The median negative pressure recorded was 125 mm of Hg, with a median dressing change time of three days. Previous irradiation (p = 0.01; OR = 4.07) and diabetes mellitus (DM) (p = 0.001; OR = 5.62) were found to be significantly associated with delayed wound healing after NPWT. (4) Conclusion: NPWT treats complex wounds in head and neck cancer patients and should represent a significant armamentarium in head and neck cancers. Previous irradiation and DM have detrimental effects on wound healing after NPWT. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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7 pages, 190 KiB

Open AccessCommentary

Opportunities and Limits in Salvage Surgery in Persistent or Recurrent Head and Neck Squamous Cell Carcinoma

by Gerhard Frank Huber

Cancers 2021, 13(10), 2457; https://doi.org/10.3390/cancers13102457 - 18 May 2021

Cited by 2 | Viewed by 1677

Abstract

Except for HPV-induced cancers of the oropharynx, survival rates in patients with squamous cell carcinoma of the head and neck (HNSCC) have not changed substantially over the last decades. Salvage surgery plays an important role where primary treatment was unsuccessful since 50% of [...] Read more.

Except for HPV-induced cancers of the oropharynx, survival rates in patients with squamous cell carcinoma of the head and neck (HNSCC) have not changed substantially over the last decades. Salvage surgery plays an important role where primary treatment was unsuccessful since 50% of advanced-stage patients relapse after nonsurgical primary treatment. Depending on a variety of factors, a considerable number of patients in whom primary treatment was not successful can still be cured by salvage surgery. It is the goal of this review to elucidate these factors with the aim to counsel patients and their relatives realistically about the chances of being cured. Full article

(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))

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