Head and neck cancer surgery is often a complex multi-step procedure that includes major resections, vascularised tissue reconstruction, and extensive neck dissection. The upper aerodigestive tract ...mucosal lining is often disrupted during surgery, which requires the management of a clean-contaminated field and the need to reconstruct the mucosal lining. With bacterial contamination, surgical site infections (SSI) are a serious complication that can result in delayed wound healing, wound breakdown, fistula formation, and compromised tissue reconstruction. Methods to reduce SSI in patients with head and neck cancer have been intensely researched, yielding evolving and varied practice patterns. In this Review, we outline the data supporting perioperative antibiotic prophylaxis for clean-contaminated surgeries, which suggest that clindamycin is an inadequate prophylactic antibiotic therapy in the reduction of SSI, and that prolonged antibiotic courses have no established benefit. For salvage laryngectomy after radiotherapy with or without chemotherapy, reconstruction with vascularised tissue reduces the frequency and severity of pharyngocutaneous fistula formation. These evidence-based recommendations have been shown to reduce the chance of SSI after head and neck surgery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Loss of the maxilla and midfacial structures after tumour removal has substantial functional and aesthetic consequences. The variable loss of soft tissue, bone, or both, leading to collapse of the ...lip, cheek, periorbital soft tissues, and palatal competence present a challenging dilemma for reconstructive surgeons. Efforts have been made to classify these midfacial defects and provide appropriate algorithms for optimum reconstruction. Not only does the cavity need to be obliterated and midfacial contours recreated, but swallowing function, phonation, and mastication need to be restored for an ideal result. Traditionally, these defects would have been repaired by a maxillofacial prosthesis but advances in tissue transfers, particularly of microvascular free flaps, have greatly increased reconstructive options. The wide variety of free flaps that contain both soft tissue and bone offer unique properties that could be applicable depending on the defect. Combinations of free tissue transfer, local flaps, and maxillofacial prostheses might achieve a more ideal result than one technique alone. Advances in osseointegration have also enhanced the ability to achieve the best function and form. No one flap or technique is sufficient to reconstruct midface defects in all patients. The choices should be tailored to the bony and soft-tissue needs of each specific defect, denture-bearing potential of the original tissues, and available prosthodontic support. Use of a multidisciplinary approach to reconstruct these defects can yield excellent results. The complexity of the techniques should match the desired goals and needs of each individual patient.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Oral squamous cell carcinoma (OSCC) is associated with substantial mortality and morbidity. To identify potential biomarkers
for the early detection of invasive OSCC, we compared the gene expressions ...of incident primary OSCC, oral dysplasia, and clinically
normal oral tissue from surgical patients without head and neck cancer or preneoplastic oral lesions (controls), using Affymetrix
U133 2.0 Plus arrays. We identified 131 differentially expressed probe sets using a training set of 119 OSCC patients and
35 controls. Forward and stepwise logistic regression analyses identified 10 successive combinations of genes which expression
differentiated OSCC from controls. The best model included LAMC2 , encoding laminin-γ2 chain, and COL4A1 , encoding collagen, type IV α1 chain. Subsequent modeling without these two markers showed that COL1A1 , encoding collagen, type I α1 chain, and PADI1 , encoding peptidyl arginine deiminase, type 1, could also distinguish OSCC from controls. We validated these two models using
an internal independent testing set of 48 invasive OSCC and 10 controls and an external testing set of 42 head and neck squamous
cell carcinoma cases and 14 controls (GEO GSE6791), with sensitivity and specificity above 95%. These two models were also
able to distinguish dysplasia ( n = 17) from control ( n = 35) tissue. Differential expression of these four genes was confirmed by quantitative reverse transcription-PCR. If confirmed
in larger studies, the proposed models may hold promise for monitoring local recurrence at surgical margins and the development
of second primary oral cancer in patients with OSCC. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2152–62)
Evidence supports short courses of perioperative antibiotics for patients receiving minor head and neck procedures. Few studies have addressed antibiotic prophylaxis for patients undergoing free flap ...reconstruction of head and neck defects.
To determine ideal antibiotic prophylaxis in patients undergoing head and neck free flap reconstruction.
Retrospective cohort study of 427 adults receiving free flap reconstruction of head and neck defects at 2 affiliated tertiary care academic hospitals between January 1, 2006, and January 28, 2013.
Prophylactic antibiotic type and duration were recorded from patient records.
Outcome data were abstracted from patients' medical records including infection at the surgical sites and distant nonsurgical sites and flap site complications including flap compromise, dehiscence, or fistula. Multivariate logistic regression was used to determine the association of risk factors with the primary outcome of any infection within 30 days of surgery.
Ninety-six patients (22.5%) received prophylactic antibiotics for 24 hours or less, and 331 patients received prolonged courses of prophylactic antibiotics. The majority of patients received ampicillin-sulbactam alone for prophylaxis (53.2%), while 36.5% received clindamycin alone and 10.3% received an alternative regimen. Postoperative infections occurred in 46% of patients, and 22% of patients had an infection at the flap inset site or neck incision. The use of clindamycin (odds ratio OR, 2.54; 95% CI, 1.25-5.14 P = .01) was associated with an increased risk of postoperative infection; extended duration of antibiotics (OR, 0.63; 95% CI, 0.34-1.19 P = .18) was not associated with increased risk of postoperative infection. By multivariate analysis, use of clindamycin (OR, 6.71; 95% CI, 1.83-24.60 P = .004) and oral tobacco use (OR, 1.20; 95% CI, 1.04-1.39 P = .02), but not extended course of prophylactic antibiotics (OR, 0.75; 95% CI, 0.30-1.86 P = .53), were associated with a higher risk of postoperative flap or neck infections.
The choice of antibiotic appears to affect the rate of all postoperative infections and flap site infections more than the duration of antibiotics following head and neck free flap reconstruction. At our institutions, ampicillin-sulbactam is the preferred prophylactic antibiotic for major clean-contaminated head and neck procedures when possible.
The WEE1 tyrosine kinase regulates G
-M transition and maintains genomic stability, particularly in p53-deficient tumors which require DNA repair after genotoxic therapy. Thus, a need arises to ...exploit the role of WEE1 inhibition in head and neck squamous cell carcinoma (HNSCC) mostly driven by tumor-suppressor loss. This completed phase I clinical trial represents the first published clinical experience using the WEE1 inhibitor, AZD1775, with cisplatin and docetaxel.
We implemented an open-label phase I clinical trial using a 3+3 dose-escalation design for patients with stage III/IVB HNSCC with borderline-resectable or -unresectable disease, but who were candidates for definitive chemoradiation. Escalating AZD1775 was administered orally twice a day over 2.5 days on the first week, then in combination with fixed cisplatin (25 mg/m
) and docetaxel (35 mg/m
) for 3 additional weeks. The primary outcome measure was adverse events to establish MTD. Secondary measures included response rates, pharmacokinetics (PK), pharmacodynamics, and genomic data.
The MTD for AZD1775 was established at 150 mg orally twice per day for 2.5 days. RECISTv1.1 responses were seen in 5 of 10 patients; histologic adjustment revealed three additional responders. The only drug-limiting toxicity was grade 3 diarrhea. The PK C8hr target of 240 nmol/L was achieved on day 4 at all three doses tested. Pharmacodynamic analysis revealed a reduction in pY15-Cdk, and increases in γH2AX, CC3, and RPA32/RPA2 were noted in responders versus nonresponders.
The triplet combination of AZD1775, cisplatin, and docetaxel is safe and tolerable. Preliminary results show promising antitumor efficacy in advanced HNSCC, meriting further investigation at the recommended phase II dose.
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Purpose The surgical margin is the main prognostic factor over which the surgeon has control during resection of oral squamous cell carcinoma (OSCC). This study examined the association between ...surgical excision margins of patients with OSCC and outcomes of disease-free and overall survival. Materials and Methods The authors implemented a retrospective cohort study. The sample was composed of patients with OSCC having resection as their initial treatment. The predictor variable was the pathologic surgical margin, defined as clear (>5 mm), close (1 to 5 mm), or involved (<1 mm). The outcome variables were disease-free (absence of locoregional recurrence) and overall survival. Data were analyzed using Kaplan-Meier survival curves and Cox regression hazard model. Results The sample was composed of 54 patients with a mean age of 60.5 years (range, 19 to 85 yr) and 26% were women. The 2- and 5-year overall survival rates were 59 and 50%, respectively. The clear surgical margin group showed higher disease-free survival rates than patients with close and involved margins (5-yr probability, 0.78 vs 0.43 and 0.29; P = .014) and a trend toward increased overall survival at 2 and 5 years ( P = .093). Conclusion The results suggest that the presence of a close surgical margin (1 to 5 mm) is an adverse risk feature comparable to an involved margin and therefore is associated with decreased disease-free and overall survival. Future studies are needed to replicate these findings before they can be used as a basis for clinical recommendations.
•Survival and recurrence outcomes are excellent after transoral robotic surgery.•Cervical node positivity was 93%, 84% in level IIa.•Neck dissection of levels II–IV is sufficient to accurately stage ...the neck and prevent regional recurrences.•Single-staged operations did not result in any postoperative pharyngocutaneous fistula.
(1) Report the patterns of cervical node positivity for HPV + oropharyngeal squamous cell carcinoma (OPSCC) treated with transoral robotic surgery (TORS) and a unilateral level II–IV node dissection. (2) Investigate the regional failure rate following this operation. (3) Report the rate of pharyngocutaneous fistula (PCF) formation intraoperatively and postoperatively following TORS/neck dissection.
Retrospective case series of 88 patients with HPV+ OPSCC treated with TORS and simultaneous neck dissection levels II–IV at the University of Washington from 2010 to 2016. Primary endpoints were PCF, regional recurrence, disease-free survival (DFS), and overall survival (OS).
The overall frequency of cervical node positivity was 93%, with 84% in level IIa, 7% in IIb, 23% in III, and 13% in IV. Two patients developed PCF intraoperatively, repaired with a local digastric flap, and no postoperative PCF occurred. Sixteen patients (18%) received surgery alone, 49 patients (56%) received adjuvant radiation, and 23 patients (26%) underwent adjuvant chemoradiation. DFS at 2 years was 95% and OS at 2 years was 100%. No concerning level Ib nodes were identified preoperatively or during surgery, and no regional failures occurred in this location.
Our data suggests, in TORS for HPV+ OPSCC, neck dissection of levels II–IV accurately stages the neck pathologically and prevents regional recurrences, with adjuvant therapy when indicated, and survival outcomes are excellent. Single-staged operations did not result in any postoperative PCF. Avoiding dissection of level Ib with TORS oropharyngectomy limits morbidity to the marginal mandibular nerve and salivary function, and resulted in no postoperative fistulas with minimal reconstruction interventions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background
Survival outcomes in recurrent head and neck squamous cell carcinoma (HNSCC) are poor. This study aimed to compare survival outcomes between salvage surgery and immunotherapy in patients ...with recurrent advanced HNSCC.
Methods
Patients with advanced stage (stage III or IV) recurrent HNSCC following treatment with platinum‐based chemotherapy were included. Survival was estimated using the Kaplan–Meier method, and Cox regression was used for multivariate logistic regression.
Results
Two‐year overall survival after salvage surgery was 68.6% and after immunotherapy patients was 24.6%. Multivariate logistic regression showed that salvage surgery was associated with improved survival without statistical significance (hazard ratio HR 0.12, p = 0.25). Subgroup analysis of patients with oral cavity/oropharyngeal cancer noted improved survival with salvage surgery over immunotherapy (HR 0.006, p = 0.01) and decreased survival with neutrophil‐to‐lymphocyte ratio (NLR) > 5 (HR 6.4, p = 0.02).
Conclusion
Our retrospective single‐institutional data suggest that resectable advanced stage recurrent HNSCC may have improved survival with salvage surgery in appropriately selected patients, but larger prospective studies are required.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objectives/Hypothesis:
To describe the clinical entity and therapeutic challenges of bisphosphonate‐related osteonecrosis of the jaws (BRONJ). The use of vascularized bone grafts for reconstruction ...of the mandible in extensive BRONJ is proposed.
Study Design:
Multi‐institutional retrospective review.
Methods:
Patients undergoing mandible reconstruction with vascularized bone grafts after segmental mandible resection for BRONJ were evaluated. Mandible reconstruction was only performed on patients with intractable pain, fistulae, or pathologic fracture and after failure of comprehensive conservative therapy. No patients had a history of primary or metastatic head and neck malignancy or radiation therapy. Bone union was established with follow‐up radiography.
Results:
Eleven patients met inclusion criteria. Mean patient age was 61.3 years. Median follow‐up was 13.9 months. All patients had undergone therapy with bisphosphonates and had no other identifiable cause of mandible osteonecrosis. Preoperatively, pathologic mandible fractures were present in 73% of patients, and 36% had orocutaneous fistulae. Fibula osteocutaneous flaps were used in all cases with no failures. In all patients, bony union was demonstrated clinically and radiographically. Postoperative wound complications occurred in 36% of patients but were all treated successfully with conservative therapy. There was no BRONJ recurrence within the study follow‐up period.
Conclusions:
Osteonecrosis is a significant complication of bisphosphonate therapy, and current literature does not support vascularized reconstruction. We demonstrate that vascularized bone graft reconstruction with the fibula free flap offers a high success rate of bony union and fistula closure and should be offered to selected patients with advanced cases of BRONJ. Laryngoscope, 2010
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The matrix metalloproteinases (MMP) cause degradation of the extracellular matrix and basement membranes, and thus may play a key role in cancer development.
In our search for biomarkers for oral ...squamous cell carcinomas (OSCC), we compared primary OSCC, oral dysplasia and control subjects with respect to: (i) expression of MMP1, MMP3, MMP10, and MMP12 in oral epithelial tissue using Affymetrix U133 2.0 Plus GeneChip arrays, followed by quantitative reverse transcription-PCR (qRT-PCR) for MMP1, and (ii) determination of MMP1 and MMP3 concentrations in saliva.
MMP1 expression in primary OSCC (n = 119) was >200-fold higher (P = 7.16 × 10(-40)) compared with expression levels in nonneoplastic oral epithelium from controls (n = 35). qRT-PCR results on 30 cases and 22 controls confirmed this substantial differential expression. The exceptional discriminatory power to separate OSCC from controls was validated in two independent testing sets (AUC% = 100; 95% CI: 100-100 and AUC% = 98.4; 95% CI: 95.6-100). Salivary concentrations of MMP1 and MMP3 in OSCC patients (33 stage I/II, 26 stage III/IV) were 6.2 times (95% CI: 3.32-11.73) and 14.8 times (95% CI: 6.75-32.56) higher, respectively, than in controls, and displayed an increasing trend with higher stage disease.
Tumor and salivary MMPs are robust diagnostic biomarkers of OSCC.
The capacity of MMP gene expression to identify OSCC provides support for further investigation into MMPs as potential markers for OSCC development. Detection of MMP proteins in saliva in particular may provide a promising means to detect and monitor OSCC noninvasively.
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