Soft Tissue Ulcers Research Articles

Uncommon presentation of diffuse large B-cell lymphoma: oral and pulmonary involvements in a young patient: a case report

BackgroundDiffuse large B-cell lymphoma is the most common subtype of non-Hodgkin lymphomas that remains a major diagnostic challenge due to the variety of its clinical presentations. This case highlights the importance of early biopsy of oral lesions without tendency to heal to attain the diagnosis more quickly. To the best of our knowledge, this study is the first to focus on both oral and pulmonary involvements in a patient with diffuse large B-cell lymphoma.Case presentationThe presented case describes an Iranian 18-year-old girl with chronic cough and dyspnea referred for evaluation of the upper jaw due to bone exposure, bone loss, and soft tissue ulceration. Her medical history revealed mediastinal mass, cavitary lesion, and mediastinal lymphadenopathy. However, cytologic and immunohistochemical analysis did not show any evidence of malignancy. In this case a lymphoproliferative disease was suspected but ultimately the oral biopsy diagnosed diffuse large B-cell lymphoma and chemotherapy could be started.ConclusionsSystemic conditions should be considered as a possible cause of oral lesions and a biopsy should also be performed immediately if there is any doubt concerning the nature of the lesion. Moreover, some conditions necessitate multiple biopsies to attain an accurate diagnosis.

Magnetic Resonance Imaging and 99Tc WBC-SPECT/CT Scanning in Differential Diagnosis between Osteomyelitis and Charcot Neuroarthropathy: A Case Series.

Distinguishing between Charcot Neuroarthropathy (CN), osteomyelitis (OM), and CN complicated with superimposed OM in diabetic patients is crucial for the treatment choice. Given that current diagnostic methods lack specificity, advanced techniques, e.g., magnetic resonance imaging (MRI) and 99mTc-HMPAO-WBC Single Photon Emission Computed Tomography (SPECT/CT), are needed. This study addresses the challenges in distinguishing OM and CN. We included diabetic patients with CN and soft tissue ulceration. MRI and 99mTc-HMPAO-WBC SPECT/CT were used for the diagnosis. The patients were classified into three probability levels for OM (i.e., Definite, Probable, and Unlikely) according to the Consensus Criteria for Diabetic Foot Osteomyelitis (CC-DFO). Eight patients met the eligibility criteria. MRI, supported by SPECT-CT and CC-DFO, showed consistency with the OM diagnosis in three cases. The key diagnostic features included the location of signal abnormalities and secondary features such as skin ulcers, sinus tracts, and abscesses. Notably, cases with inconclusive MRI were clarified by SPECT/CT, emphasizing its efficacy in challenging scenarios. The primary objective of this study was to compare the results of MRI and 99mTc-HMPAO-WBC SPECT/CT with the CC-DFO score in the diabetic foot with CN and suspected OM. Advanced imaging offers a complementary approach to distinguish between CN and OM. This can help delineate the limits of the disease for presurgical planning. While MRI is valuable, 99mTc-HMPAO-WBC SPECT/CT provides additional clarity, especially in challenging cases or when metallic implants affect MRI accuracy.

Toxicity and Dosimetric Analysis of Reirradiation of Head and Neck Cancers with High Dose Rate Brachytherapy

Reirradiation (reRT) of recurrent or second primary head and neck cancers (HNC) after prior curative-intent external beam radiotherapy (EBRT) has historically achieved local control (LC) rates of 40-50% and been associated with high grade toxicity rates estimated at 25-50%. This study evaluated the hypothesis that patients with small reRT target volumes could be selected for high dose rate brachytherapy (HDR-BT) reRT and achieve similar LC without excess toxicity. Included were all patients with HNC squamous cell carcinoma treated with HDR-BT after having previously received curative-intent EBRT for primary HNC from 2000-2021. Patients were selected by a multidisciplinary tumor board to be appropriate candidates for HDR-BT reRT without EBRT generally for definitive or adjuvant treatment of small primary tumors without neck nodal metastases. Univariate analysis was performed using the logistic regression model. Survival outcomes were estimated with the Kaplan Meier method. Twenty-three patients were evaluated. Median follow up time was 19mo. Median age at time of HDR-BT was 64 years. Thirteen patients (57%) were treated for recurrent HNC, of which 7 were in the oral cavity (OC) and 6 were the oropharynx (OPX). Ten patients (43%) were treated for a second primary HNC, of which 5 were in the OC and 5 were in the OPX. Median time from completion of EBRT to HDR-BT was 41 (IQR 14-73) mo. Within their reRT course, 11 patients (48%) were treated with HDR-BT after resection, 9 patients (39%) received concurrent hyperthermia, and 7 patients (30%) received chemotherapy. HDR-BT regimens included 600cGy x5 (N = 11), 600cGy x6 (N = 6), 450cGy x8 (N = 1), 1500cGy x1 (N = 1),1000cGy x1 (N = 1), 500cGy x8 (N = 1), and 700cGy x5 (N = 1). One patient who was treated with two implants received 450cGy x 3 followed by 475cGy x5. A median of 5 brachytherapy catheters were used. Actuarial 2-year LC and overall survival rate was 68% and 62%, respectively. Of the 17 HDR-BT reRT plans available for review, median (IQR) target volume was 15.8 (10.6-34.9) cc. Median (IQR) target V100% was 90.6 (89.4-90.0)%, V150% was 50.5 (49.7-54.4)%, and V200% was 25.4 (23.8-29.0)%. Median (IQR) target D90% was 30.1 (29.8-35.5) Gy, and median D1cc was 116.4 (100.5-171.4) Gy. The mandible dose [median (IQR)] was D2cc:15.1(9.48-18.9) Gy; D1cc:16.9(11.1-21.3) Gy; and D1%:18.8(13.4-22.7) Gy. Nine of the 23 patients (39%) experienced ≥G3 toxicity including fistula, soft tissue necrosis, osteoradionecrosis, ulcer, hemorrhage, and dysphagia requiring a chronic feeding tube. Target D90% was associated with ≥G3 toxicity (p = 0.045). For D90% greater than the median of 30Gy, 45% ≥G3 toxicity was observed. This study suggests that HDR-BT for reRT of small recurrent or second primary HNC can provide similar LC without excess high-grade toxicities as compared to historical outcomes with EBRT reRT. Delivery of equivalent doses higher than 30Gy in 5 fractions should be approached with caution.

Radiation therapy for cT1-2 carcinoma of the palatine tonsil diagnosed via a simple tonsillectomy: Dosimetry and patterns of care in the IMRT era

ObjectiveSmall carcinomas of the palatine tonsil are often diagnosed via simple tonsillectomy, a maneuver with non-therapeutic intent. Herein, practice patterns for this unique situation are evaluated. Patients and methodsA retrospective review was performed across 10 facilities to identify patients with cT1-2 squamous carcinomas of the tonsil diagnosed by simple tonsillectomy between 2010 and 2018. Patients who received curative-intent intensity modulated radiotherapy (IMRT) without additional surgery were included. Target volumes were reviewed, and cumulative incidences of local failure and severe late dysphagia were calculated. ResultsFrom 638 oropharyngeal patients, 91 were diagnosed via simple tonsillectomy. Definitive IMRT with no additional surgery to the primary site was utilized in 57, and three with gross residual disease were excluded, leaving 54 for analysis. Margins were negative in 13%, close (<5 mm) in 13%, microscopically positive in 61%, and not reported in 13%. Doses typically delivered to gross disease (68–70.2 Gy in 33–35 fx or 66 Gy/30 fx) were prescribed to the tonsil bed in 37 (69%). Sixteen patients (29%) received doses from 60 to 66 Gy (≤2 Gy/fx) and one received 50 Gy (2 Gy/fx). No local failures were observed. One late oropharyngeal soft tissue ulcer occurred, treated conservatively (grade 2). At five years, the cumulative incidence of severe late dysphagia was 17.4% (95% CI 6.1–28.8%). ConclusionSmall tonsil carcinomas diagnosed by simple tonsillectomy represent a niche subset with favorable oncologic outcomes. Regardless, radiation oncologists tend to deliver full-dose to the tonsil bed. The necessity of this routine could be questioned in the modern era.

Nivolumab and ipilimumab in combination with radiotherapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck

BackgroundThe combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab...

Study on quantitative analysis of bracket-induced nonlinear response of labio-cheek soft tissue during the orthodontic process

In the orthodontics process, intervention and sliding of an orthodontic bracket during the orthodontic process can arise large response of the labio-cheek soft tissue. Soft tissue damage and ulcers frequently happen at the early stage of orthodontic treatment. In the field of orthodontic medicine, qualitative analysis is always carried out through statistics of clinical cases, while quantitative explanation of bio-mechanical mechanism is lacking. For this purpose, finite element analysis of a three-dimensional labio-cheek-bracket-tooth model is conducted to quantify the bracket-induced mechanical response of the labio-cheek soft tissue, which involves complex coupling of contact nonlinearity, material nonlinearity and geometric nonlinearity. Firstly, based on the biological composition characteristics of labio-cheek, a second-order Ogden model is optimally selected to describe the adipose-like material of the labio-cheek soft tissue. Secondly, according to the characteristics of oral activity, a two-stage simulation model of bracket intervention and orthogonal sliding is established, and the key contact parameters are optimally set. Finally, the two-level analysis method of overall model and submodel is used to achieve efficient solution of high-precision strains in submodels based on the displacement boundary obtained from the overall model calculation. Calculation results with four typical tooth morphologies during orthodontic treatment show that: ① the maximum strain of soft tissue is distributed along the sharp edges of the bracket, consistent with the clinically observed profile of soft tissue deformation; ② the maximum strain of soft tissue is reduced as the teeth align, consistent with the clinical manifestation of common damage and ulcers at the beginning of orthodontic treatment and reduced patient discomfort at the end of treatment. The method in this paper can provide reference for relevant quantitative analysis studies in the field of orthodontic medical treatment at home and abroad, and further benefit to the product development analysis of new orthodontic devices.

In-Field Toxicity Analysis of a Phase 1 Clinical Trial of Nivolumab and Ipilimumab With Definitive Radiation Therapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Combined modality therapy for locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) is associated with increased toxicities. Immunotherapy has a documented benefit in the recurrent/metastatic setting with a favorable toxicity profile. We evaluated in-field toxicities in the context of a single-institution clinical trial with combined nivolumab, a PD-1 inhibitor, and ipilimumab, a CTLA-4 inhibitor, and concurrent radiation therapy (RT) in patients with LA SCCHN. We analyzed in-field toxicity events in 24 cisplatin-eligible patients with newly-diagnosed LA SCCHN (14 HPV-positive oropharyngeal) treated with nivolumab (3 mg/kg every two weeks for 17 doses) and ipilimumab (1 mg/kg every six weeks for 6 doses) starting two weeks prior to intensity-modulated radiation therapy (IMRT; 70 Gy in 2 Gy fractions). All patients completed RT with no treatment delays. 16/24 patients experienced at least one grade 3 in-field toxicity during radiation treatment including radiation dermatitis (5), dysphagia (6), oral mucositis (10), odynophagia (3), oropharyngeal pain (1), and hoarseness (1). There were no grade 4 or 5 AEs during ICI-RT. Five patients (22%) developed soft tissue ulcers (STU) at the primary tumor site during the consolidation phase, one of which led to a fatal carotid rupture. STUs developed at a median of 91 (range 50-107) days post RT and were negative for viable tumor. Three-year locoregional control rate was 94.7% (95% CI, 85.2%-100%). Concurrent radioimmunotherapy with nivolumab and ipilimumab resulted in excellent locoregional control, but may have an increased the risk of STU. Patients treated with such an approach should be closely monitored for in-field toxicity events, including soft tissue ulceration.

Could X-ray Predict Long-term Complications in Patients with Diabetic Foot Osteomyelitis?

To analyze the association between radiologic changes on plain X-rays in patients with diabetic foot osteomyelitis and the development of complications at the 1-year follow-up. A prospective, observational study was conducted involving 115 patients with diabetic foot osteomyelitis. X-ray features that were evaluated during 1-year follow-up visits included affected bone marrow, active periosteal reaction, sequestrum, cortical disruption, and other types of signs. Researchers analyzed the association between the presence of X-ray changes and complication development, such as bone or soft tissue infections, ulcer recurrence, reulceration, amputation, death, and other diabetic foot disease-related events. During follow-up, of 115 patients included in the study, 33 patients (28.7%) showed radiologic changes, and 85 (73.9%) developed complications. The presence of radiologic changes after ulcer healing had a significant association with complication development during the 1-year follow-up in addition to those found at different follow-up visits. Patients who showed radiologic changes had higher percentages of complications during the 1-year follow-up, and patients without radiologic changes had lower percentages of complications. The presence of radiologic changes is related to the development of complications in patients who suffer from diabetic foot osteomyelitis.

A quantitative comparison of plantar soft tissue strainability distribution and homogeneity between ulcerated and non-ulcerated patients using ultrasound strain elastography.

The primary objective of this study was to develop a method that allows accurate quantification of plantar soft tissue stiffness distribution and homogeneity. The secondary aim of this study was to investigate if the differences in soft tissue stiffness distribution and homogeneity can be detected between ulcerated and non-ulcerated foot. Novel measures of individual pixel stiffness, named as quantitative strainability (QS) and relative strainability (RS) were developed. Strain Elastography data obtained from 39 (nine with active diabetic foot ulcers) patients with diabetic neuropathy. The patients with active diabetic foot ulcer had wound in parts of the foot other than the first metatarsal head and the heel where the elastography measures were conducted. RS was used to measure changes and gradients in the stiffness distribution of plantar soft tissues in participants with and without active diabetic foot ulcer. The plantar soft tissue homogeneity in superior-inferior direction in the left forefoot was found to be significantly (p < 0.05) higher in ulcerated group compared to non-ulcerated group. The assessment of homogeneity showed potentials to further explain the nature of the change in tissue that can increase internal stress. This can have implications in assessing the vulnerability to plantar soft tissue damage and ulceration in diabetes.

Platelet Concentrates and Their Clinical Applications in Oral and Maxillofacial Surgery, Periodontal, Dentoalveolar and Reconstructive Surgery and Endodontics. Current Review.

During the last two decades a new technology appeared called platelet rich plasma preparations (PRP) [1], suggesting the main benefit in both hard and soft tissue wound healing for surgical use in regenerative medicine [2], as well as aiding in decreasing: rate of postoperative infections, pain and blood loss [3]. The PRP clinical applications include periodontal surgery, Oral and Maxillofacial surgery, aesthetic plastic surgery, spinal fusion, heart by-pass surgery, treatment of soft tissue ulcers, etc. [3]. However in the recent times there have been described different types of PRP concentrates and different clinical indications for every of them. The aim of this review is to enlist and describe the different types of PRP concentrates and their current clinical use in Dentistry and Oral and Maxillofacial surgery.

Early Clinical, Functional, and Mortality Outcomes for Heel Ulcers Treated With a Vertical Contour Calcanectomy

Heel ulcerations are common complications seen in patients suffering from chronic conditions such as diabetes mellitus, peripheral vascular disease, and in bed ridden patients. When these systemic pathologies lead to heel ulcers, an increased risk of calcaneal osteomyelitis often significantly limits the benefits of conventional therapeutic interventions and increases risk of major lower extremity amputation. The Vertical Contour Calcanectomy (VCC) is a novel surgical procedure specific for the surgical management of these complex and often recalcitrant heel ulcerations. The VCC was described as a reproducible procedure in which wide excision of both the soft tissue ulceration as well as defined bone cuts of the calcaneus allows for decreased bioburden and in many cases, for primary soft tissue closure. The present study describes the outcomes related to the VCC and provides guidance based on the objective findings detailed herein. This study, at the time of publication, represents the largest collection of patients that have undergone the VCC (N=51) and their outcomes at 1 year. Those who remained healed without recurrence, amputation, or mortality at 1-year follow-up were 31.4%. Post-VCC total limb salvage rate is 68.6% at one year, mean follow-up 663.9 ± 464.7 days. One-year all-cause mortality post-VCC was 9.8%. Post-VCC function at 1-year follow-up reflects 79.3% of patients having the same or better function that their perioperative state.

Brachytherapy with 198Au grains for cancer of the floor of the mouth: relationships between radiation dose and complications.

This study aimed to retrospectively evaluate the radiation dose and complications in soft tissue and mandible caused by 198Au grain brachytherapy alone or the combination with other modalities in patients with the cancer of the floor of the mouth. Twelve patients with T1 (n = 5) and T2 (n = 7) squamous cell carcinoma of the floor of the mouth, who were treated with 198Au grain brachytherapy alone (n = 5) or the combination of external beam radiotherapy (EBRT) and/or chemotherapy and 198Au grain brachytherapy (n = 7) from January 2005 to December 2016, were included. The relationships between the radiation dose and the complications of the soft tissue or mandible were investigated. Seven of 12 patients had died. Of these 7 patients, one with T1 and 2 with T2 had died of the causes related to the cancer of the floor of the mouth. Two with T1 and 2 with T2 had died of other diseases. Two patients had grade 2 complications of the soft tissue and mandible. These patients were treated by the combination of EBRT and/or chemotherapy and 198Au grain brachytherapy and irradiated with 123 or 139Gy in total dose, respectively. And one of these patients was treated by the chemotherapy in addition to EBRT. Our study showed that the combination of EBRT and 198Au grains brachytherapy for the floor of the mouth cancer patients might be associated with risks of developing complications of soft tissue ulcer and mandibular bone necrosis.

EFFECT OF PHENTOLAMINE MESYLATE ON THE INCIDENCE OF SELF-INFLICTED SOFT TISSUE INJURY FOLLOWING INFERIOR ALVEOLAR NERVE BLOCK ANESTHESIA IN CHILDREN: (RANDOMIZED CONTROLLED CLINICAL TRIAL)

INTRODUCTION:One of the shortcomings of local anesthesia (LA) is that the soft tissue anesthesia (STA) typically lasts for 3 to 5 hours while most routine dental procedures are completed in less than an hour. Pediatric patients particularly may accidently bite on their lips. OBJECTIVES: The study was conducted to evaluate the effectiveness of phentolamine mesylate (PM) on the reduction of the incidence of self-inflicted soft tissue injury (STI) and its effect on the time of return of normal function, after inferior alveolar nerve block anesthesia. MATERIALS AND METHODS: The study is a blinded randomized controlled parallel group clinical trial with a 1:1 allocation ratio. A total of eighty pediatric patients, with an age range of 5-8 years, selected from the Pediatric Dentistry out-patient clinic, Faculty of Dentistry, Alexandria University, after obtaining necessary consents. Inferior alveolar nerve block anesthesia (2 percent lidocaine with 1:100,000 epinephrine) was administered in the recommended dose. After completion of the operative procedure, participants were randomly allocated into 2 groups: study and control group. The experimental group received a PM injection using the same technique employed for administration of LA, in a cartridge ratio of 1:1. The control group did not receive any reversal agent. The incidence of self-inflicted STA and return to normal function were recorded post-operatively and STI was followed up after 24 hours. RESULTS: There were no significant differences in the incidence of self-inflicted STI between the PM and control group except for the occurrence of ulcers after 24 hours (P=0.04). Phentolamine mesylate accelerated the median time of return to normal function (P =0.001). CONCLUSION: Phentolamine mesylate was efficacious in reducing the incidence of self-inflicted soft-tissue ulceration and accelerated the time of return to normal function after LA.

Comparative analysis of the effect of steroid therapy and blood pressure maintenance on the mid-term outcomes of spinal cord injury

Objective. To analyze the dynamics of neurological symptoms and the structure of complications when using methylprednisolone and the method of maintaining target values of mean arterial pressure during surgical treatment of patients in the acute period of spinal cord injury (SCI). Material and Methods. The study included 110 patients in the acute period of SCI with compression of spinal cord segments who were admitted to the clinic from January 2012 to March 2018 and underwent decompression and stabilization surgery within the first 2–3 hours after admission. In order to improve the blood supply to the damaged segments of the spinal cord and to prevent multiple organ failure, the main direction of intensive care in two groups of patients was to maintain the target blood pressure at the level of 85–90 mm Hg during the first 7–10 days. The MPD group included 43 patients who received methylprednisolone as a neuroprotector at a dose of 30 mg/kg bolus within the first hour after admission, followed by infusion at a dose of 5.4 mg/kg/h for 23 hours; and the MAP group included 67 patients who did not receive methylprednisolone. Non-invasive monitoring of central hemodynamic parameters was carried out on the basis of impedance cardiography data. The objective status of patients and data of X-ray diagnostics at the time of preoperative examination and during instrumental studies, as well as in 3–14 day intervals and in the mid-term (up to 4–6 months) postoperative period were analyzed. Results. In the MPD group, 22 patients had ASIA type A neurological deficit, and an increase in ASIA grade was observed only in 4 (18 %) of them. There were 18 patients with incomplete injury in this group, and 9 of them (50 %) had a positive trend. In the MAP group, 38 patients had ASIA type A, out of them 11 (29 %) improved, and 28 patients had ASIA type B, C or D, out of them 17 (61 %) showed positive dynamics of neurological symptoms. No statistically significant differences were found. In the MPD group, complications such as nosocomial pneumonia and acute endobronchitis were observed three times more often, pulmonary embolism and decubital soft tissue ulcers – four times more often, and sepsis, acute respiratory distress syndrome and surgical site infection – two times more often. There were statistically significant differences in the incidence of nosocomial pneumonia and acute endobronchitis between MPD and MAP groups (p = 0.004 and p = 0.002, respectively.) Conclusion. Maintaining mean arterial pressure at 85–90 mm Hg during the first 7–10 days after admission to the hospital allowed achieving a greater number of cases of improvement in the neurological status of patients, in contrast to the use of methylprednisolone. The use of methylprednisolone in patients with acute SCI increased the risk of nosocomial pneumonia or acute endobronchitis by 2.91 times (p = 0.003).

Multidisciplinary Approach for the Management and Treatment of Diabetic Foot Infections with a Resorbable, Gentamicin-Loaded Bone Graft Substitute.

Diabetic patients are at increased risk of developing foot ulcers which may cause bone infections associated with a high probability of both amputation and mortality. Therefore, prompt diagnosis and adequate treatment are of key importance. In our Diabetic Foot Unit, effective multidisciplinary treatment of osteomyelitis secondary to diabetes involves the application of a gentamicin-eluting calcium sulphate/hydroxyapatite bone graft substitute to fill residual bone voids after debridement. The data of all patients treated with the gentamicin-eluting calcium sulphate/hydroxyapatite bone graft substitute for diabetic foot infections with ulcer formation and osteomyelitis at metatarsals, calcaneus and hindfoot at our institute from July 2013 to September 2016 were retrospectively collected and evaluated. A total of 35 patients were included in this retrospective single-arm case series and were either continuously followed up for at least one year or until healing was confirmed. Nineteen lesions affected the distal row of tarsus/talus, ten the calcaneus and a further six were located at the metatarsals. While all of the metatarsal lesions had healed at 1-year follow-up, the healing rate in the hindfoot region was lower with 62.5% at the calcaneus and 72.2% at the distal tarsus and talus at 12 months, respectively. The overall cure rate for ulcerous bone infection was 81.3%. In two calcaneal lesions (25%) and two lesions of distal tarsus/talus (11.1%) amputation was considered clinically necessary. Promising results were achieved in the treatment of diabetic foot infections with soft tissue ulcers by a multidisciplinary approach involving extensive debridement followed by adequate dead space management with a resorbable gentamicin-eluting bone graft substitute.

Nivolumab and Ipilimumab Combined with Definitive Radiation Therapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: In-field Toxicity Analysis of a Phase I Clinical Trial

Cisplatin added to radiation therapy (RT) for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is associated with a modest improvement in survival at the cost of increased toxicity, highlighting the need for newer agents. Immune checkpoint inhibitors (ICI) have a favorable safety profile and are the standard of care in recurrent/metastatic SCCHN, but their role in the definitive setting with RT remains to be determined. We conducted a single institution clinical trial assessing the safety of combined nivolumab (Nivo), a PD-1 inhibitor, and ipilimumab (Ipi), a CTLA-4 inhibitor, with concurrent RT in patients with high risk LA-SCCHN. Newly diagnosed, chemotherapy eligible patients (pts) with stage IVA-IVB p16(-) SCC of the oral cavity, oropharynx, larynx, and hypopharynx, or T4, N2c, or N3 p16(+) SCC of the oropharynx (AJCC 7th edition) were enrolled. Nivo (3 mg/kg Q2 weeks IV x17 doses) and Ipi (1 mg/kg Q6 weeks IV x6 doses) were administered 2 weeks prior to the start of RT. RT (70 Gy in 2 Gy daily fractions) was delivered to the primary tumor using VMAT and daily cone-beam CT IGRT. The primary objective was safety of combined ICI and RT. Between July 2017 and July 2019, 24 pts were enrolled with a median follow-up of 15 months (range 7-31); median age 60 (range 48-77); 20 male; 16 oropharynx (14 HPV+), 6 larynx, and 2 hypopharynx. All pts completed RT with no treatment delays. Seventeen out of twenty-four pts (71%) experienced grade 3 acute in-field adverse events (AE) consisting of mucositis (9), dysphagia (6), dermatitis (5), odynophagia (4), and dysphonia (1) during concurrent ICI-RT; there were no grade 4/5 AEs during ICI-RT. Five pts (22%) developed soft tissue ulcers (STU) at the primary tumor site during the ICI maintenance phase, one of which was not treated and led to a fatal carotid rupture. All STUs developed at a median of 91 (range 50-107) days post RT and were negative for viable tumor. Four primary site STUs were managed with either hyperbaric oxygen (HBO) (2), lingual artery embolization (1), or surgical debridement (1). One pt treated with HBO healed after 189 days while the pt who underwent debridement healed after 285 days. Two additional pts developed areas of necrosis at adjacent sites not involved by tumor, underwent surgical debridement, and healed after an average of 18.5 days. Two other pts experienced osteoradionecrosis (ORN) at sites of prior teeth extractions and were treated with HBO. Two pts experienced persistent inflammation without ulceration (PI). Six out of eleven pts (55%) with STU, necrosis, ORN, or PI discontinued maintenance ICI. Locoregional PFS is 100%. Combined PD-1 and CTLA-4 blockade with concurrent RT is associated with excellent locoregional control in high risk LA-SCCHN, albeit at the cost of in-field complications. Patients treated with such an approach should be closely monitored for soft tissue ulceration.

SBRT For Head and Neck Skin Cancer: An Initial Experience in 106 Medically Unfit Patients

Stereotactic Body Radiation Therapy (SBRT) is an alternative treatment strategy for patients with head and neck skin cancer (HNSC) unable to undergo a protracted radiotherapy course. We report outcomes of SBRT for HNSC patients treated at a tertiary high-volume institution. A retrospective review of patients who received SBRT from 2012-2019 was conducted. Kaplan-Meier method was used to estimate the one-year local control (LC), locoregional control (LRC) outside of SBRT field, overall survival (OS), progression-free survival (PFS) and late toxicity (LT) rates from time of SBRT completion. Univariate and multivariate Cox proportional hazard models were performed. Acute and late grade 3 and 4 toxicity were reported according to the Common Terminology Criteria for Adverse Events v4.0. A total of 106 patients were identified with 112 lesions treated. The cohort consisted of patients treated for primary (n = 51), nodal (n = 47) and both primary and nodal disease (n = 8). The T and N categories prior to SBRT were Tx-2: n = 78, T3-4: n = 28; N0-1: n = 67, N2-3: n = 39. Median age at diagnosis was 84 years with median ECOG performance status of 2. HNSC histologies included cutaneous squamous cell carcinoma (n = 77), basal cell carcinoma (n = 14), melanoma (n = 8), Merkel cell carcinoma (n = 6), and 1 unconfirmed. Fractionation schemes ranged from 32-50 Gy in 4-6 fractions, with the most common regimens being 45 Gy in 5 fractions [52% (n = 55)] and 40 Gy in 5 fractions [32% (n = 34)]. Median gross tumor volume (GTV) was 31 cm3 (17-56) and mean planning tumor volume (PTV) dose was 44 Gy. Median follow-up was 8 months and actuarial median OS was 14 months. The one-year LC, LRC outside of SBRT field, OS, PFS and LT rates were 78% (69-88), 72% (62-84), 53% (43-65), 52% (40-62), and 25% (16-38), respectively. Larger GTVs were associated with reduced PFS [HR 1.58, p = 0.004], OS [HR 1.37, p = 0.039], and LRC outside of SBRT field [HR 1.83, p = 0.006] but not LC [HR 0.87, p = 0.50]. Multivariable models revealed that larger GTVs [HR 1.47, p = 0.046] and higher biologically effective dose (BED10) [HR 1.05, p = 0.03] were associated with a higher rate of late toxicity. There was no statistical difference between proportions of grade ≥3 acute (p = 0.22) and late toxicities (p = 0.37) in patients treated with doses ≤40 Gy vs. >40 Gy. For acute toxicity, 41 patients had grade 3, and 1 had grade 4. The most common acute toxicity was dermatitis (n = 39). Twenty-eight patients (26%) experienced ≥ late grade 3 toxicity, with the most common being fibrosis (n = 19) and soft tissue ulceration (n = 6). No grade 5 toxicity was observed. SBRT in HNSC provides durable disease control with acceptable toxicity for select medically unfit patients unable to undergo extended radiotherapy courses. Predictive factors of treatment response and toxicity include GTV and BED10. Further prospective studies including quality of life measures and dosimetric correlations with larger cohorts are needed.

Influence of hyperbaric oxygen therapy on thrombus formation ability in humans

Background: Hyperbaric oxygen (HBO2) therapy was introduced nearly 300 years ago. However, its effect on thrombus formation is unclear. This may be because platelet and coagulation functions are unstable, yielding variable results; hence, accurate measurement is difficult. Our study aimed to analyze changes in thrombus formation before and after HBO2 therapy by using a total thrombus formation analysis system (T-TAS). Methods: Six patients were prescribed HBO2 therapy for skin and soft tissue ulcers, and necrotic fasciitis. Blood samples were collected immediately before and after treatment. Then samples were put into a reservoir that connected to AR-chip to assess changes in the thrombus formation ability of both platelets and coagulation factors. We examined the differences in the thrombus formation ability using T-TAS. Time until the onset of white thrombus formation (T10) and complete occlusion of the capillary (T80) were analyzed by a two-way repeated measure analysis of variance (ANOVA). Results: The duration to pressure increase of samples after HBO2 therapy was longer than the duration before HBO2 therapy (p&lt;0.05). This suggests decreased clot adhesiveness to the inner surface of the simulated blood vessel and reduced clot formation ability. Conclusions: The results for T10 and T80 suggest that HBO2 therapy reduced thrombus formation ability in the enrolled patients. We believe that T-TAS is a promising method to predict the efficacy of HBO2 therapy.

Abstract PR09: Postmenopause as a key factor in the composition of the Endometrial Cancer Microbiome (ECbiome): Putative role of Porphyromonas somerae in the disease

Abstract Incidence rates for endometrial cancer (EC) are rising, particularly in postmenopausal and obese women. Our previous work has showed that the uterine and vaginal microbiome distinguishes patients with EC from those without. We now examine the impact of patient factors (such as menopause status, body mass index, and vaginal pH) in the microbiome in the absence of EC and how these might contribute to the microbiome signature in EC. We find that each factor independently alters the microbiome and identified postmenopausal status as the main driver of a polymicrobial network associated with EC (ECbiome). Of the 17 taxa we found enriched in EC patients, 8 were also enriched by postmenopause. Because postmenopausal status is a main risk factor for endometrial cancer, this system can be thought of as an ecological succession towards a disease state. Organisms within the ECbiome have been previously identified as polymicrobial associations in chronic soft tissue infections, ulcers, morbid obesity, and bacterial vaginosis. This suggests that this microbiome network is likely involved in mechanisms of host disease. Within the ECbiome, Porphyromonas somerae stands out because of its very significant and specific association with EC (p = 5.73E-6; Q = 0.009). We had previously identified this species as significantly associated with EC, and hereby validate that finding. Because the association of P. somerae with EC was robust and specific enough to potentially be considered as a biomarker for the disease (AUC 76.7%, CI: 67.9-85.5%), we developed a P. somerae-specific qPCR assay to detect this species in vaginal swabs. This becomes of particular interest because the lower tract and uterine microbiome are significantly correlated in these patients (p = 0.01), indicating that the vaginal microbiome can be used as a proxy for the uterine environment in EC. In agreement with the 16S rRNA gene sequencing data, P. somerae was detected significantly more frequently in vaginal swabs of patients with EC than those without EC (p = 3.02E-7). Overall, the test achieved a sensitivity of 74% and specificity of 63%, with a positive predictive value of 0.86 for obese and postmenopausal patients. In summary, we identify Porphyromas somerae presence as the most predictive microbial marker of EC, and we confirm this using targeted qPCR, which could be of use in detecting EC in high-risk, asymptomatic women. Given the established pathogenic behavior of P.somerae, we have also explored mechanistic routes through which this microbe and associated consortia may be involved in the mechanisms of disease. Citation Format: Marina Walther-Antonio, Dana Walsh, Alexis Hokenstad, Jun Chen, Jayeun Sung, Gregory Jenkins, Nicholas Chia, Heidi Nelson, Andrea Mariani. Postmenopause as a key factor in the composition of the Endometrial Cancer Microbiome (ECbiome): Putative role of Porphyromonas somerae in the disease [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr PR09.

Oral Health Status among Tobacco Users of Selected Rural Population

Introduction: Tobacco smoking is a major risk factor for the development of oral cancer in developing countries. The prevalence of tobacco use is the highest amongst poor people of low educational background. Cancer of oral cavity is the commonest cancer in our country and ranked 5th among male and 4th in female.&#x0D; Objectives: To assess the oral health status among tobacco users in a selected rural population of Dhamrai and Saturia Upazilla in Dhaka district.&#x0D; Materials and Methods: This descriptive cross sectional study was conducted from 1st November 2018 to 15th January 2019. Non-probability purposive sampling was done and data was collected from 445 respondents.&#x0D; Results: Among the respondents, 26% were day laborer and 24% were businessmen with family income were between Tk 5000-Tk 10000. About 78.65% of the respondents have tobacco smoking habit among them 75% had current tobacco chewing habit as jarda. 69.21% of the respondents did not complain of any oral problems. Oral health status among the current tobacco smokers and chewers showed that they had dental stain (90.78%), dental plaque (65.17%), dental calculus (44.49%), dental carries (53.03%), bad breathing smell (75%), soft tissue inflammation (23.82%), loose teeth (26.74%) and ulceration (8.54%) in their oral cavity.&#x0D; Conclusion: Tobacco control protects the rights and health of non-smokers, specially babies, children, youth and pregnant women. The dangers posed to oral health from smoking and chewing tobacco are well documented but the lack of knowledge of the risks is a concern. So oral health should be given great importance from childhood and dental checkup should be done regularly. The general people should be made aware of it through various mass media.&#x0D; Journal of Armed Forces Medical College Bangladesh Vol.14 (2) 2018: 144-147