Patch aortoplasty for supravalvular aortic stenosis in an adult patient: A case report.

INTRODUCTION: Supravalvular aortic stenosis (SVAS) is an uncommon congenital abnormality that presents with intimal thickening of the aortic media at the sinotubular junction. Given the congenital nature of the disease, patients usually become symptomatic in childhood. PRESENTATION OF CASE: A 48-year-old man developed symptomatic SVAS in middle age. A patch aortoplasty with a bovine pericardial patch was performed. His postoperative course was uneventful, and echocardiography revealed a significant decrease in peak velocity and pressure gradient. DISCUSSION: SVAS, a congenital heart disease with an incidence of 1 in 20,000 live births, is often linked to Williams syndrome but can also occur independently. Isolated SVAS is generally less severe and may not show symptoms in childhood. Its narrowing often stabilizes after growth, but in this middle-aged patient, symptoms appeared later in life. SVAS usually presents as discrete thickening above the sinuses of Valsalva or as diffuse narrowing along the ascending aorta. Surgical relief is the common treatment, with flap plasty using various patch techniques. This patient, having discrete stenosis and intact aortic valve function, underwent single-patch expansion. Key to this surgery is avoiding coronary artery stenosis, by considering coronary orifice location and other cardiac anomalies. A bovine pericardial patch was chosen for its bleeding control benefits. CONCLUSION: Although SVAS progression in middle age is quite rare, it can be successfully corrected with detailed and selected surgical procedures.

A real-world study on the safety of the extended dosing schedule for nivolumab and pembrolizumab in patients with solid tumors.

BACKGROUND: In addition to 2-weekly nivolumab 240 mg or 3-weekly pembrolizumab 200 mg, extended dosing intervals of 4-weekly nivolumab 480 mg or 6-weekly pembrolizumab 200 mg were approved. To date, the clinical safety of the extended dosing schedules of immune checkpoint inhibitors (ICIs) has not been adequately investigated in patients with solid tumors. METHODS: This real-world study enrolled patients with solid tumors who received nivolumab 480 mg every 4 weeks or pembrolizumab 400 mg every 6 weeks at the Kyoto Prefectural University of Medicine in Japan, between August 2020 and December 2021. RESULTS: Sixty-nine patients with solid tumors received an extended-interval dosing schedule during this period. Among them, 60 received it during treatment (cohort A), and nine received it for the first time (cohort B). After the extended dosing interval of ICIs in cohort A, 13 (21.7%) patients developed immune-related adverse events (irAEs). Seven of the 13 patients (53.8%) developed irAEs during the first cycle of the extended dosing interval. All patients who developed irAEs during the first cycle of the extended dosing interval had pre-existing antibodies. Multivariate analysis indicated that patients with pre-existing anti-thyroid antibodies had a significantly higher irAE incidence after starting extended dosing intervals (odds ratio: 6.41; 95% confidence interval: 1.46-28.2, p = 0.01). CONCLUSIONS: Most patients were allowed to continue ICI therapy after an extended dosing interval. Patients with pre-existing antibodies, particularly anti-thyroid antibodies, may be prone to developing irAEs after starting extended dosing intervals and should be treated with caution.

Spatially resolved immune microenvironmental profiling for follicular thyroid carcinoma with minimal capsular invasion.

Spatial profiles of the tumor-immune microenvironment are associated with disease progression and clinicopathological factors in various cancers. Follicular thyroid carcinoma (FTC) is the second most common thyroid cancer, where the presence of capsular invasion or angioinvasion determines the pathological diagnosis; however, little is known about the immune microenvironment profiles associated with the acquisition of invasive potential of FTC. In this study, we focused on FTC with minimal capsular invasion, and the spatially resolved immune microenvironment of FTC was studied in the discovery (n = 13) and validation cohorts (n = 40). CD8+ T cells, helper T cells, regulatory T cells, B cells, natural killer cells, tumor-associated macrophages, CD66+ granulocytes, mature dendritic cells, and mast cells were quantitatively evaluated in single tissue sections, via a 12-marker multiplex immunohistochemistry and image cytometry. Cell densities and compositions of immune cells were spatially stratified by six tissue regions including tumor center, subcapsular region, capsular invasion, adjacent stroma of capsular invasion, peritumoral stroma, and adjacent normal. Lymphoid cell lineages in the tumor center and subcapsular regions were significantly lower than those in adjacent normal and peritumoral stroma, potentially related to the lymphoid lineage exclusion from the intratumoral regions of FTC. Interestingly, immune cell composition profiles in the capsular invasive front were distinct from those of intratumoral region. The ratios of T cells to CD66b+ granulocytes with capsular invasion were significantly higher than those without capsular invasion, suggesting the presence of a unique immune microenvironment at the invasive front between tumor foci and stroma. In addition, tumor cells at the capsular invasive front showed significantly higher expression of tumor programmed cell death ligand 1 (PD-L1) than those at the tumor center. This study revealed spatial immune profiles associated with capsular invasion of FTC, providing new insights into the mechanisms underlying its development and initial invasion.

Spatial Profiles of Intratumoral PD-1+ Helper T Cells Predict Prognosis in Head and Neck Squamous Cell Carcinoma.

Background: Functional interactions between immune cells and neoplastic cells in the tumor immune microenvironment have been actively pursued for both biomarker discovery for patient stratification, as well as therapeutic anti-cancer targets to improve clinical outcomes. Although accumulating evidence indicates that intratumoral infiltration of immune cells has prognostic significance, limited information is available on the spatial infiltration patterns of immune cells within intratumoral regions. This study aimed to understand the intratumoral heterogeneity and spatial distribution of immune cell infiltrates associated with cell phenotypes and prognosis in head and neck squamous cell carcinoma (HNSCC). Methods: A total of 88 specimens of oropharyngeal squamous cell carcinoma, categorized into discovery (n = 38) and validation cohorts (n = 51), were analyzed for immune contexture by multiplexed immunohistochemistry (IHC) and image cytometry-based quantification. Tissue segmentation was performed according to a mathematical morphological approach using neoplastic cell IHC images to dissect intratumoral regions into tumor cell nests versus intratumoral stroma. Results: Tissue segmentation revealed heterogeneity in intratumoral T cells, varying from tumor cell nest-polarized to intratumoral stroma-polarized distributions. Leukocyte composition analysis revealed higher ratios of TH1/TH2 in tumor cell nests with higher percentages of helper T cells, B cells, and CD66b+ granulocytes within intratumoral stroma. A discovery and validation approach revealed a high density of programmed death receptor-1 (PD-1)+ helper T cells in tumor cell nests as a negative prognostic factor for short overall survival. CD163+ tumor-associated macrophages (TAM) provided the strongest correlation with PD-1+ helper T cells, and cases with a high density of PD-1+ helper T cells and CD163+ TAM had a significantly shorter overall survival than other cases. Conclusion: This study reveals the significance of analyzing intratumoral cell nests and reports that an immune microenvironment with a high density of PD-1+ helper T cells in tumoral cell nests is a poor prognostic factor for HNSCC.

Docetaxel plus cisplatin in recurrent and/or metastatic non-squamous-cell head and neck cancer: a multicenter phase II trial.

The clinical utility of systemic therapy and genomic profiling in non-squamous-cell head and neck cancer (NSCHNC) has not been fully elucidated. This phase II trial evaluated the efficacy and safety of docetaxel and cisplatin combination in the first-line setting. Eligibility criteria were recurrent and/or metastatic NSCHNC; progressive disease within the last 6 months; no prior systemic therapy; and ECOG performance status of 0-1. Patients received docetaxel (75 mg/m2 on day 1) and cisplatin (75 mg/m2 on day 1), repeated every 21 days for 6 cycles. The primary endpoint was confirmed objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Next-generation sequencing (NGS) was performed using the Ion AmpliSeq Cancer Hotspot Panel v2. Twenty-three patients were enrolled from November 2012 to October 2016, of whom 8 were male. Median age was 57 years. Ninety-six percent of cases were metastatic. Among 22 evaluable patients, confirmed ORR was 45% (95% confidential interval 24-68%). With a median follow-up period of 18.8 months, median PFS and OS were 6.7 and 20.1 months, respectively. Grade 3/4 adverse events included febrile neutropenia (39%) and anemia (22%). No treatment-related deaths were observed. NGS analysis revealed potential treatment targets, including ERBB2, KIT, and ALK. The docetaxel and cisplatin combination regimen can be considered a new treatment option in recurrent and/or metastatic NSCHNC, although primary prophylaxis for febrile neutropenia should be considered. Diverse genomic alterations may lead novel treatment options.This trial was registered with the UMIN Clinical Trials Registry as UMIN000008333 on [September 1st, 2012].

A 14-Marker Multiplexed Imaging Panel for Prognostic Biomarkers and Tumor Heterogeneity in Head and Neck Squamous Cell Carcinoma.

Recent advances made in treatment for head and neck squamous cell carcinoma (HNSCC) highlight the need for new prediction tools to guide therapeutic strategies. In this study, we aimed to develop a HNSCC-targeting multiplex immunohistochemical (IHC) panel that can evaluate prognostic factors and the intratumor heterogeneity of HNSCC. To identify IHC-based tissue biomarkers that constitute new multiplex IHC panel, a systematic review and meta-analysis were performed to analyze reported IHC biomarkers in laryngeal and pharyngeal SCC in the period of 2008-2018. The Cancer Genome Atlas (TCGA) and Reactome pathway databases were used to validate the prognostic and functional significance of the identified biomarkers. A 14-marker chromogenic multiplex IHC panel including identified biomarkers was used to analyze untreated HNSCC tissue. Forty-five high-quality studies and thirty-one candidate tissue biomarkers were identified (N = 7062). Prognostic validation in TCGA laryngeal and pharyngeal SCC cohort (N = 205) showed that ß-catenin, DKK1, PINCH1, ADAM10, and TIMP1 were significantly associated with poor prognosis, which were related to functional categories such as immune system, cellular response, cell cycle, and developmental systems. Selected biomarkers were assembled to build a 14-marker panel, evaluating heterogeneity and polarized expression of tumor biomarkers in the tissue structures, which was particularly related to activation of Wnt/ß-catenin pathway. Integrated IHC analysis based on a systemic review and meta-analysis provides an in situ proteomics tool to assess the aggressiveness and intratumor heterogeneity of HNSCC.

Extracellular acidity in tumor tissue upregulates programmed cell death protein 1 expression on tumor cells via proton-sensing G protein-coupled receptors.

Acidity in the tumor microenvironment has been reported to promote cancer growth and metastasis. In our study, we examined a potential relation between extracellular acidity and expression level of the immune checkpoint molecule programmed cell death protein 1 (PD-L1) in murine squamous cell carcinoma (SCC) and melanoma cell lines. PD-L1 expression in the tumor cells was upregulated by culturing in a low pH culture medium. Tumor-bearing mice were allowed to ingest sodium bicarbonate, resulting in neutralization of acidity in the tumor tissue, a decrease in PD-L1 expression in tumor cells and suppression of tumor growth in vivo. Proton-sensing G protein-coupled receptors, T-cell death-associated gene 8 (TDAG8) and ovarian cancer G-protein-coupled receptor 1 (OGR1), were upregulated by low pH, and essentially involved in the acidity-induced elevation of PD-L1 expression in the tumor cells. Human head and neck SCC RNAseq data from the Cancer Genome Atlas also suggested a statistically significant correlation between expression levels of the proton sensors and PD-L1 mRNA expression. These findings strongly suggest that neutralization of acidity in tumor tissue may result in reduction of PD-L1 expression, potentially leading to inhibition of an immune checkpoint and augmentation of antitumor immunity.

Transoral surgery for superficial head and neck cancer: National Multi-Center Survey in Japan.

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1-75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2-357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1-113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.

Comparison of Three Fractionation Schedules in Radiotherapy for Early Glottic Squamous Cell Carcinoma.

BACKGROUND/AIM: Radiotherapy is widely accepted as the treatment of choice for early glottic squamous cell carcinoma (EGSCC), although it varies greatly with respect to dose, dose per fraction, and treatment techniques. The study aim was to evaluate the use of accelerated fractionation strategy (AFS) for EGSCC in standard clinical practice. PATIENTS AND METHODS: Patients treated with definitive radiotherapy for EGSCC between 2008 and 2019 were retrospectively identified and received either conventional fractionation, hypofractionation, or hyperfractionation. RESULTS: One hundred six patients were analyzed, and 19, 71, and 16 patients underwent conventional fractionation, hypofractionation, and hyperfractionation, respectively. The median follow-up was 56 months. The 5-year local control and overall survival rates were 79% and 83%; 78% and 79%; and 87% and 77%, respectively, and no significant difference was observed between the fractionation schedules. CONCLUSION: Our findings confirmed the utility of AFS in standard clinical practice and support its use for patients with EGSCC.

Safety and tolerability of PD-1/PD-L1 inhibitors in elderly and frail patients with advanced malignancies.

The number of elderly patients with cancer has increased due to aging of the population. However, safety of programmed cell death-1 (PD-1) or programed cell death ligand 1 (PD-L1) inhibitors in elderly patients remains controversial, and limited information exists in frail patients. The present study retrospectively identified 197 patients treated with nivolumab, pembrolizumab or atezolizumab for unresectable advanced cancer between September 2014 and December 2018. Patients were divided into the elderly (age, ≥75 years) and non-elderly (age, <75 years) groups. The detailed immune-related adverse events (irAE) profile and development of critical complications were evaluated. To assess tolerability, the proportion of patients who continued PD-1/PD-L1 inhibitor for >6 months was analyzed. In the two groups, a three-element frailty score, including performance status, Charlson Comorbidity Index and neutrophil-lymphocyte ratio, was estimated, and patients were divided into the low-, intermediate- and high-frailty subgroups. Safety and tolerability were evaluated using the aforementioned items. A total of 58 patients (29.4%) were aged ≥75 years. No significant difference was found in the development of irAEs, hospitalization and treatment discontinuation due to irAEs between the two groups. However, the occurrence of unexpected critical complications was significantly higher in the elderly group (P=0.03). Among the elderly patients with high frailty, more critical complications and fatal irAE (hepatitis) were observed. In this population, 33.3% were able to continue treatment for >6 months without disease progression. The present analysis based on real world data showed similar safety and tolerability of PD-1/PD-L1 inhibitors in elderly patients with advanced malignancies. However, the impact of irAE in elderly patients, especially those with frailty, was occasionally greater compared with that in younger and fit patients.

Does an In-House Computer-Aided Design/Computer-Aided Manufacturing Approach Contribute to Accuracy and Time Shortening in Mandibular Reconstruction?

Mandibular reconstruction using computer-aided design and computer-assisted manufacturing (CAD/CAM) techniques has received recent attention. This technique has theoretical advantages, although this approach can be commercially used in the limited area of the world.The aim is to describe our experience using in-house CAD/CAM guides and the situations in which CAD/CAM may present benefit in the region where commercial guides are unavailable.The authors developed our In-house CAD/CAM approach for mandibular reconstructions with a free fibular flap. Patients were divided into 2 group; CAD/CAM and conventional groups. In the CAD/CAM group, reconstructions were planned virtually using CAD/CAM; these CAD/CAM guides were used in the surgery. In the conventional group, free-hand cutting and fitting of the fibular segments were performed as reconstructions. Later, the bone computed tomographic image was compared with the plan. The averaged deviations and the percentages of the points within 1 mm, 2 mm, and 3 mm deviations were recorded. Total and ischemic time were also recorded.Reconstruction points within 1 mm deviation were 59% of CAD/CAM group (n = 9) and 42% of conventional group (n = 10, P = 0.04), within 2 mm 82% and 69% (P = 0.03). Total time were 1012 and 911 minutes, while flap ischemic time were 147 and 175 minutes (P = 0.03), respectively.In-house CAD/CAM mandibular reconstruction also supported accuracy and shorter flap ischemic time. For a detailed accurate reconstruction, CAD/CAM showed superiority than conventional method. Use of the In-house CAD/CAM guides might be an option where commercial guides are not available.

Clinical features of immune-related thyroid dysfunction and its association with outcomes in patients with advanced malignancies treated by PD-1 blockade.

Programmed cell death protein-1 (PD-1) blockade therapy has improved outcomes in the treatment of advanced cancers. The therapy is well-tolerated, although it occasionally causes immune-related adverse events (irAEs). Thyroid dysfunction is one of the most common irAEs seen. Our aim was to clarify the clinical characteristics of thyroid dysfunction induced by PD-1 blockade and its association with the therapeutic effect of the treatment in advanced cancers. A total of 174 patients who received nivolumab or pembrolizumab for metastatic or unresectable advanced cancers were included in this retrospective study. The patients were divided into two groups: The thyroid dysfunction group and the euthyroid group. In the present study, the clinical characteristics, the association with anti-thyroid antibodies, as well as the progression-free survival (PFS) and overall survival (OS) were estimated. An adjusted Cox proportional hazard regression model was used to evaluate prognostic factors for OS and PFS. This study showed that 25 out of 150 patients (16.7%) developed immune-related thyroid dysfunction. Hypothyroidism occurred in the early stage of the clinical course (median: 12 weeks); subsequently, 9 of the 25 patients underwent a transient period of hyperthyroidism, all with mild symptoms. The presence of positive anti-thyroid antibodies at baseline was significantly higher in the thyroid dysfunction group (13/22) than in the euthyroid group (18/100, P=0.0002). Moreover, PFS (median: 66 vs. 27 weeks, hazard ratio (HR): 0.50, 95% CI: 0.26-0.89, P=0.02) and OS (median 156 vs. 59 weeks, HR: 0.34, 95% CI: 0.13-0.75, P=0.01) were significantly longer in the thyroid dysfunction group than in the euthyroid group. Multivariable analysis also revealed that thyroid dysfunction was an independent prognostic factor for OS (HR: 0.42, 95% CI: 0.16-0.97, P=0.04). These findings may enable the early recognition and appropriate management of thyroid dysfunction, and help in maximizing the therapeutic effect of PD-1 blockade.

Radiation-induced angiosarcoma of the parotid gland after postoperative radiotherapy for hypopharyngeal carcinoma.

Secondary carcinogenesis within the irradiation range is one of the most severe problems in cancer survivors. A 60-year-old woman developed hypopharyngeal carcinoma, and she received radical surgery and postoperative radiotherapy. Eight years later, brown pigmentation and induration were observed in the left subaural region. Fine-needle aspiration biopsy revealed malignancy and the parotid tumor was diagnosed as recurrence of hypopharyngeal carcinoma. Neoadjuvant chemotherapy followed by radical parotidectomy was performed. The pathological diagnosis was angiosarcoma, which was most likely induced by past irradiation. About two months after surgery, lung metastases were detected. Docetaxel did not affect to lung metastases, but paclitaxel therapy was partially effective. The lung tumors increased in size, and brain metastases developed, resulting in death. Both neoadjuvant chemotherapy and radical surgery played important roles in the local disease control. Administration of newer agents as adjuvant chemotherapeutic agent should also be considered for improving the prognosis.

Using an In-House Approach to Computer-Assisted Design and Computer-Aided Manufacturing Reconstruction of the Maxilla.

PURPOSE: Computer-assisted design (CAD) and computer-aided manufacturing (CAM) techniques are in widespread use for maxillofacial reconstruction. However, CAD/CAM surgical guides are commercially available only in limited areas. To use this technology in areas where these commercial guides are not available, the authors developed a CAD/CAM technique in which all processes are performed by the surgeon (in-house approach). The authors describe their experience and the characteristics of their in-house CAD/CAM reconstruction of the maxilla. PATIENTS AND METHODS: This was a retrospective study of maxillary reconstruction with a free osteocutaneous flap. Free CAD software was used for virtual surgery and to design the cutting guides (maxilla and fibula), which were printed by a 3-dimensional printer. After the model surgery and pre-bending of the titanium plates, the actual reconstructions were performed. The authors compared the clinical information, preoperative plan, and postoperative reconstruction data. The reconstruction was judged as accurate if more than 80% of the reconstructed points were within a deviation of 2 mm. RESULTS: Although on-site adjustment was necessary in particular cases, all 4 reconstructions were judged as accurate. In total, 3 days were needed before the surgery for planning, printing, and pre-bending of plates. The average ischemic time was 134 minutes (flap suturing and bone fixation, 70 minutes; vascular anastomoses, 64 minutes). The mean deviation after reconstruction was 0.44 mm (standard deviation, 0.97). The deviations were 67.8% for 1 mm, 93.8% for 2 mm, and 98.6% for 3 mm. The disadvantages of the regular use of CAD/CAM reconstruction are the intraoperative changes in defect size and local tissue scarring. CONCLUSION: Good accuracy was obtained for CAD/CAM-guided reconstructions based on an in-house approach. The theoretical advantage of computer simulation contributes to the accuracy. An in-house approach could be an option for maxillary reconstruction.

Dual Vascular Free Anterolateral Thigh Flap.

BACKGROUND: The optimum number of microvascular anastomoses for safe free tissue transfer is controversial. Although the case for 2 venous anastomoses versus 1 anastomosis has been argued, the use of an additional arterial anastomosis has not been examined in detail. METHODS: Twelve patients who underwent 2 arterial anastomoses for a free flap transfer were identified retrospectively from the medical records of patients undergoing reconstruction for head and neck cancer. The free flaps were limited to anterolateral thigh (ALT) flaps. RESULTS: All flaps survived. Complications included venous thrombosis (n = 1), reexploration (n = 1), and leakage (n = 3). The vascular patterns of dual-arterialized ALT flaps were classified into 3 groups. Types 1 and 2 were ALT flaps that had 2 vascular sources from the descending and lateral branches of the lateral circumflex femoral artery. The number of accompanying veins differed between type 1 (3 veins) and type 2 (2 veins). Type 3 differed from a conventional ALT flap nourished by the descending branch of the lateral circumflex femoral artery (1 vein) by the addition of anastomosis of an artery branching from the descending branch to the vastus medialis muscle. The total operation times for these 3 types of ALT were similar. CONCLUSIONS: An additional arterial anastomosis to the free cutaneous flap did not cause any congestion or disturb the balance between inflow and outflow. If the surgeon considers that the first arterial anastomosis is unreliable, an additional anastomosis might be an option in ALT transfer.

p62/SQSTM1 levels predicts radiotherapy resistance in hypopharyngeal carcinomas.

Hypopharyngeal carcinoma is one of the worst prognostic malignancies among head and neck carcinomas. Therefore, a good biomarker should be identified to predict the best therapeutic option before starting the treatment. In cell models, p62/SQSTM1 levels affected the Nrf2-Keap1 pathway, ROS levels, GSH/GSSG ratios and cell growth, especially under irradiation rather than under CDDP exposure, which was toxic despite p62/SQSTM1 status. In a clinical cohort of hypopharyngeal carcinomas, high levels of p62/SQSTM1 significantly predicted poor prognosis (log-rank test, Chi-square value = 6.750, P = 0.0094) and maximum critical risk (Cox proportional hazard ratio = 4.405, P = 0.0086), especially in the radiotherapy group. Therefore, when p62/SQSTM1 is elevated in the biopsy section, hypopharyngeal carcinoma should be treated with surgical and/or chemotherapeutic options.

Use of systemic low-dose unfractionated heparin in microvascular head and neck reconstruction: Influence in free-flap outcomes.

BACKGROUND: Intravenous heparin administration is used to prevent thrombosis in free-flap transfer. However, it is unknown whether the use of heparin affects free-flap survival. The purpose of this study is to investigate the effect of heparin in free flap transfer. METHODS: Two hundred and six patients who received ablative surgery for head and neck cancer were classified into three groups. Group A received ablative surgery, neck dissection, and free-flap reconstruction, and postoperatively they were administered continuous intravenous unfractionated heparin (5000-10 000 units/day) until postoperative day 7 (POD7); group B received the same procedures as group A but without heparin; group C received only ablative surgery and neck dissection without heparin. As indicators of coagulation time, the prothrombin time-international normalised ratio (PT-INR) and the activated partial thromboplastin time (APTT) were measured, before surgery and on POD1, 3, and 7. Flap failure, bleeding, haematoma formation, re-exploration, and thromboembolic events were recorded. RESULTS: The PT-INR and APTT were 1.3-1.5-times longer in group A (p < 0.01), and 1.3-times longer (p < 0.01) in group B. The PT-INR and APTT were higher in groups A and B than C (p < 0.01). The free-flap success rate was not affected. Only the incidence of haematoma was increased in group A (p = 0.04). CONCLUSION: Heparin increased the haematoma formation, but did not change the incidence of free-flap failure. Thus, the intravenous low-dose heparin use does not affect microvascular flap survival.