Automatic Patient Modeling for Hyperthermia Treatment Planning of Head and Neck Cancer

Head and neck (H&N) cancer is the term used to describe a wide range of malig- nant tumors originating in the upper airways and swallowing tracts. In 2012, this disease accounted for approximately 5% of all cancers worldwide, with 680,000 new cases diagnosed and 370,000 recorded deaths, resulting as the seventh most common cancer worldwide. The H&N region is often divided in subregions containing dfferent tumor sites, as depicted in Figure 1.1: the oral cavity, paranasal sinus and nasal cavity, salivary glands, nasopharynx, oropharynx, hypopharynx (bot- tom part of the throat) and larynx. Tumors in the eyes, brain and skin are generally not considered H&N cancer

Advanced chondrosarcoma of the pelvis: a rare case of urinary obstruction

Chondrosarcoma is the second most common malignant tumor of the bone with an incidence of 1 in 200.000 per year. Axial skeleton is frequently involved showing poorer oncological outcomes than appendicular one: human pelvis is a site predilection. It is rarely associated to urinary obstruction but according to its localization, it can be frequently linked to compression of pelvic organs as bladder, prostate or bowel. We describe the case of a 52 years old caucasian male with history of advanced pelvic chondrosarcoma and severe hydronephrosis due to total bladder dislocation

In vitro and in vivo gene transfer to pulmonary cells mediated by cationic liposomes

Cationic liposomes have been proposed as alternative to adenovirus in the treatment of cystic fibrosis lung disease. Therefore, we have investigated the efficiency of two lipid mixtures in mediating gene transfer in in vitro and in vivo models. The cationic lipid DOTMA (N-(1-(2,3(dioleyloxy)propyl)-n,n,n-trimethylammoniumchloride) and DOGS (dioctadecylamidoglycylspermine) were used in combination with the neutral lipid DOPE (dioleoylphosphatidylethanolamine). The relative transfection efficiencies of the two cationic liposomes were tested using the bacterial β-galactosidase (lacZ) and the firefly luciferase genes. Gene expression was detected in both cell lines and primary culture of rhesus monkey airway epithelium after transfection with plasmid DNA complexed with DOGS/DOPE or DOTMA/DOPE. Transfection efficiency of both types of lipids was higher in the mouse fibroblast 3T3 cell line as compared to human carcinoma A549 cells and primary epithelial cultures. Administration of DNA-liposome complexes via intratracheal instillation resulted in expression of the lacZ and luciferase marker gene in the mouse airways. In vivo transfection mediated by both types of liposomes were proven to be far less efficient than adenovirus treatment

Feasibility and relevance of discrete vasculature modeling in routine hyperthermia treatment planning

Purpose: To investigate the effect of patient specific vessel cooling on head and neck hyperthermia treatment planning (HTP). Methods and materials: Twelve patients undergoing radiotherapy were scanned using computed tomography (CT), magnetic resonance imaging (MRI) and contrast enhanced MR angiography (CEMRA). 3D patient models were constructed using the CT and MRI data. The arterial vessel tree was constructed from the MRA images using the ‘graph-cut’ method, combining information from Frangi vesselness filtering and region growing, and the results were validated against manually placed markers in/outside the vessels. Patient specific HTP was performed and the change in thermal distribution prediction caused by arterial cooling was evaluated by adding discrete vasculature (DIVA) modeling to the Pennes bioheat equation (PBHE). Results: Inclusion of arterial cooling showed a relevant impact, i.e., DIVA modeling predicts a decreased treatment quality by on average 0.19 °C (T90), 0.32 °C (T50) and 0.35 °C (T20) that is robust against variations in the inflow blood rate (|ΔT| 0.5 °C) were observed. Conclusion: Addition of patient-specific DIVA into the thermal modeling can significantly change predicted treatment quality. In cases where clinically detectable vessels pass the heated region, we advise to perform DIVA modeling

Epidermoid cyst of the adult testis. Case report and literature review

BACKGROUND: Testicular epidermoid cysts (TEC) are rare lesions often incidentally discovered and radically treated. They present as testicular firm palpable mass. Ultrasound and MR may be useful in characterizing the lesion. Diagnosis depends on histology. The real understanding of biological behaviour and clinical management is unresolved. We report the case of a young male who underwent to surgical keratocyst enucleation. CASE REPORT: A 16 y.o. male presented for a firm mass in the testis. The right testis presented with a palpable painless mass in the middle portion. Inguinal and supraclavicular lymph nodes were negative. Serum markers (AFP, bHCG, PLAP and LDH) were normal. Scrotal sonography (US) reported a well circumscribed 2 centimetres mass with intervening septa and coexisting solid areas: intralesional calcifications were not described. Magnetic Resonance (MR) ruled out secundarisms and intralesional contrast enhancement. Biopsy with was offered. RESULTS: Frozen section was suggestive for mature keratocyst and surgical enucleation of the mass was offered. DISCUSSION: TEC are benign tumors which arise from ectoderm, endoderm or mesoderm tissues. They account for around 1-2% of all testicular masses and tipically present in mid-adulthood. The etiology is still debated and whether these should be classed as a variant of mature teratoma is still under discussion. Simple TEC correspond to the prepubertal-type teratoma of the 2018 WHO classification and are unrelated to germ cell neoplasm in situ (GCNIS). Post-pubertal variant may be more frequently associated with invasive GCT and should be radically treated especially when bad prognostic features coexist: due to this reason the are identifyed as complex TEC. Clinically keratocysts are highly indistinguishable to all testicular neoplasms. Serum markers are negative too. Sonographic study (US) may guide diagnosis: they present as non-vascular, well marginated intratesticular masses with a lamellar ‘onion skin’ or ‘bull-eye’ image and avascular centre. Contrast enhanced ultrasound (CEUS) and Magnetic Resonance (MR) also provide with more informations since the absence of contrast enhancement highly suggest the benign nature of the lesions. Diagnosis only depends on histology: differentiation from coexisting enthities such as teratomas, germ cell tumors (GCT) and granulomatous disease is mandatory also in pre-pubertal forms. Microscopically, cellular atypia, mitotic activity, necrosis, hemorrhage and epythelial hyperplasia are usually missing in pre-pubertal ones totally suggesting a benign behaviour. Moreover, no case of recurrence or metastases have been to date reported in literature: partial orchiectomy or testis-sparing excision with frozen section is becoming day by day the standard treatment. CONCLUSION: Testicular keratocysts are rare lesions commonly presenting in young male and indistinguishable from other testicular lesions. Pre- and post-pubertal form represent the main variants. Biologic behaviour and clinical management is still unresolved. Pre-pubertal form are not related to IGCNIS and no cases of spreading have been reported to date: differently from post-pubertal ones they are considered benign tumors to date. Serum markers, sonographic features and MR may be helpful in making diagnosis and surgical planning. Only histology confirms the nature of the lesion and ruling out coexisting histotype. The importance of accurate diagnosis is crucial for preventing unncessary orchiectomy since testicular sparing surgery shoudl be offered

Post-pubertal testicular epidermoid cyst: surgical options and literature review

POST-PUBERTAL TESTICULAR EPIDERMOID CYST: SURGICAL OPTIONS AND LITERATURE REVIEW Olivieri Valerio1, Fortunati Valentina2, Corongiu Emanuele3, Forte Flavio3, De Luca Francesco4, Ruggiero Gabriele1 and Griffa Daniele1 1 Division of Urology, Ivrea Hospital – ASL TO4, Ivrea (Turin), Italy 2 Division of Pathology, Hospital “Policlinico of Tor Vergata”, Rome, Italy 3 Division of Urology, Hospital “Madre Giuseppina Vannini”, Rome, Italy 4 Department of Gynecological, Obstetrics and Urological Sciences, Hospital, Policlinico Umberto I, Rome, Italy INTRODUCTION AND OBJECTIVES: Epidermoid cysts (TEC) are uncommon benign tumors accounting for around 1-2% of all testicular lesions. Incidence is higher in people between the ages of 10 and 40 years. Caucasian males are frequently involved and righ testis more than left one. Etiology is not completely understood. Clinically they present with a firm, painless palpable mass highly indistinguishable to all testicular neoplasms. Preoperative serum markers are always negative. Radiology and biopsy are important criteria for surgical planning. Scrotal sonography (US) confirm its typical “onion-ring” appearance. Magnetic resonance (MR) add more informations on vascularity and borders. Diagnosis depends on histology: frozen section may be useful in preventing unnecessary orchiectomy. Two forms of TEC have been described. Prepubertal ones are considered as a benign tumors since they’re not associated with germ cell tumor (GCT) and no cases of metastatic spread have been reported: unfavorable prognostic features are usually missing. Post-pubertal TEC or “complex” may act differently. Association with GCT has been rarely described totally representing an unfavorable prognostic features: cellular atypia, high mitotic activity, necrosis are rare but may be present. MATERIALS AND METHODS: We present the case of an adult male affected by TEC.and reviewed the literature. A 40 y.o. caucasian male presented for a mass in the left testis discovered on self-examination. No familiarity for testicular cancer was reported. Inguinal lymph nodes were negative. Serum markers (AFP, bHCG and LDH) were normal too. The testis presented with a painless firm lesion at the upper pole. US revealed a 15 mm heterogeneous well-circumscribed mass being chraracterized by an echogenic rim: MR ruled out intralesional vascularity. Testicular biopsy was offered. RESULTS: Frozen section was suggestive for mature TEC and a testing sparing surgery was offered. Macroscopically the lesion presented as indishinguable from any malignant neoplasm. On microscopic evaluation, the cyst was lined by a fibrous membrane (Fig. 1) filled with layers of cornifying squamous epithelium composing the wall. Coexisting teratomatous element were ruled out. Association with GCT and atypical features were also excluded. It was classed as post-pubertal mature TEC. Surgical enucleation was offered. CONCLUSIONS: TEC are rare benign tumors incidentally discovered during self examination or scrotal ultrasound frequently affecting young males. Sonography and testicular MR helps in characterizing the lesion. Diagnosis depends on histology. The biological behaviour of these neoplasms in the adult testis still remains unknown leading to different surgical approaches. Testis sparing surgery represent the gold standard. Radical orchiectomy is mandatory as unfavorable features coexist. BIBLIOGRAPHY: 1. Anheuser P, Kranz J, Stolle E, Höflmayer D, Büscheck F, Mühlstädt S, Lock G, Dieckmann KP. Testicular epidermoid cysts: a reevaluation. BMC Urol. 2019 Jun 11;19(1):52 2. Çakıroğlu B, Sönmez NC, Sinanoğlu O, Ateş L, Aksoy SH, Özcan F. Testicular epidermoid cyst. Afr J Paediatr Surg. 2015 Jan-Mar;12(1):89-90. 3. Cook FE Jr, Kimbrough JC. Epidermoid cysts of the testicle. J Urol. 1954 Aug;72(2):236-8. 4. Dieckmann KP, Loy V. Epidermoid cyst of the testis: A review of clinical and histogenetic considerations. Br J Urol. 1994;73:436–41. 5. Dockerty M, Priestly JY. Dermoid cysts of the testis. J Urol. 1942;48:392–7 6. Ewen SW. Epidermoid cyst of the testis. Scott Med J. 1969;14:57–8 7. Heidenreich A, Zumbe J, Vorreuther R, Klotz T, Vietsch H, Engelmann UH. Testikuläre Epidermiszyste: Orchiektomie oder Enukleationsresektion? Urologe A. 1996;35:1):1–5. 8. Huyghe E, Mazerolles C, Moran C, Khedis M, Khoury E, Nohra J, Soulie M, Plante P. Synchronous epidermoid cyst and mature teratoma of the testis: an unusual association. Urol Int. 2007;78:364–6. 9. Kenan B. Ashouri, Joshua M. Heiman, Emily F. Kelly. Testicular epidermoid cyst:: a rare case. Urol Ann. 2017 Jul-Sep; 9(3): 296–298. 10. Maizlin ZV, Belenky A, Baniel J, Gottlieb P, Sandbank J, Strauss S. Epidermoid cyst and teratoma of the testis: sonographic and histologic similarities. J Ultrasound Med. 2005;24:1403–9 11. Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO classification of Tumours of the urinary system and male genital organs-part a: renal, penile, and testicular Tumours. Eur Urol. 2016;70:93–105. 12. Muoka OE, Dahar N. Testicular epidermoid cysts. BMJ Case Rep 2013. 2013:pii: Bcr2013009103. 13. Shah KH, Maxted WC, Chun B. Epidermoid cysts of the testis: A report of three cases and an analysis of 141 cases from the world literature. Cancer. 1981;47:577–82. 14. Ulbright TM, Srigley JR (2001) Dermoid cyst of the testis: a study of five postpubertal cases, including a pilomatrixoma-like variant, with evidence supporting its separate classification from mature testicular teratoma. Am J Surg Pathol 25: 788-793. 15. Umar SA, MacLennan GT. Epidermoid cyst of the testis. J Urol. 2008;180:33

Temperature simulations in hyperthermia treatment planning of the head and neck region Rigorous optimization of tissue properties

Hyperthermia treatment planning (HTP) is used in the head and neck region (H&N) for pretreatment optimization, decision making, and real-time HTP-guided adaptive application of hyperthermia. In current clinical practice, HTP is based on power-absorption predictions, but thermal dose-effect relationships advocate its extension to temperature predictions. Exploitation of temperature simulations requires region- and temperature-specific thermal tissue properties due to the strong thermoregulatory response of H&N tissues. The purpose of our work was to develop a technique for patient group-specific optimization of thermal tissue properties based on invasively measured temperatures, and to evaluate the accuracy achievable. Data from 17 treated patients were used to optimize the perfusion and thermal conductivity values for the Pennes bioheat equation-based thermal model. A leave-one-out approach was applied to accurately assess the difference between measured and simulated temperature (a dagger T). The improvement in a dagger T for optimized thermal property values was assessed by comparison with the a dagger T for values from the literature, i.e., baseline and under thermal stress. The optimized perfusion and conductivity values of tumor, muscle, and fat led to an improvement in simulation accuracy (a dagger T: 2.1 +/- 1.2 A degrees C) compared with the accuracy for baseline (a dagger T: 12.7 A +/- 11.1 A degrees C) or thermal stress (a dagger T: 4.4 A +/- 3.5 A degrees C) property values. The presented technique leads to patient group-specific temperature property values that effectively improve simulation accuracy for the challenging H&N region, thereby making simulations an elegant addition to invasive measurements. The rigorous leave-one-out assessment indicates that improvements in accuracy are required to rely only on temperature-based HTP in the clinic

Accurate 3D temperature dosimetry during hyperthermia therapy by combining invasive measurements and patient-specific simulations

Purpose: Dosimetry during deep local hyperthermia treatments in the head and neck currently relies on a limited number of invasively placed temperature sensors. The purpose of this study was to assess the feasibility of 3D dosimetry based on patient-specific temperature simulations and sensory feedback. Materials and methods: The study includes 10 patients with invasive thermometry applied in at least two treatments. Based on their invasive thermometry, we optimised patient-group thermal conductivity and perfusion values for muscle, fat and tumour using a 'leave-one-out' approach. Next, we compared the accuracy of the predicted temperature (Delta T) and the hyperthermia treatment quality (Delta T50) of the optimisations based on the patient-group properties to those based on patient-specific properties, which were optimised using previous treatment measurements. As a robustness check, and to enable comparisons with previous studies, we optimised the parameters not only for an applicator efficiency factor of 40%, but also for 100% efficiency. Results: The accuracy of the predicted temperature (Delta T) improved significantly using patient-specific tissue properties, i.e. 1.0 degrees C (inter-quartile range (IQR) 0.8 degrees C) compared to 1.3 degrees C (IQR 0.7 degrees C) for patient-group averaged tissue properties for 100% applicator efficiency. A similar accuracy was found for optimisations using an applicator efficiency factor of 40%, indicating the robustness of the optimisation method. Moreover, in eight patients with repeated measurements in the target region, Delta T50 significantly improved, i.e. Delta T50 reduced from 0.9 degrees C (IQR 0.8 degrees C) to 0.4 degrees C (IQR 0.5 degrees C) using an applicator efficiency factor of 40%. Conclusion: This study shows that patient-specific temperature simulations combined with tissue property reconstruction from sensory data provides accurate minimally invasive 3D dosimetry during hyperthermia treatments: T50 in sessions without invasive measurements can be predicted with a median accuracy of 0.4 degrees C