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Graphical abstract, Highlights • Skin cancer is a fatal public health concern rising continuously all over the world. • Several environmental and genetic risk factors are associated with cutaneous carcinogenesis. • Use of nanocarriers for targeted delivery of anticancer agents is the most advanced approach. • Polymeric structures are suitable for tumor selective delivery of drugs, genes and imaging agents. • Polymeric micro/nanostructures have successfully used for combination anticancer therapies., Background Skin cancer has been the leading type of cancer worldwide. Melanoma and non-melanoma skin cancers are now the most common types of skin cancer that have been reached to epidemic proportion. Based on the rapid prevalence of skin cancers, and lack of efficient drug delivery systems, it is essential to surge the possible ways to prevent or cure the disease. Aim of review Although surgical modalities and therapies have been made great progress in recent years, however, there is still an urgent need to alleviate its increased burden. Hence, understanding the precise pathophysiological signaling mechanisms and all other factors of such skin insults will be beneficial for the development of more efficient therapies. Key scientific concepts of review In this review, we explained new understandings about onset and development of skin cancer and described its management via polymeric micro/nano carriers-based therapies, highlighting the current key bottlenecks and future prospective in this field. In therapeutic drug/gene delivery approaches, polymeric carriers-based system is the most promising strategy. This review discusses that how polymers have successfully been exploited for development of micro/nanosized systems for efficient delivery of anticancer genes and drugs overcoming all the barriers and limitations associated with available conventional therapies. In addition to drug/gene delivery, intelligent polymeric nanocarriers platforms have also been established for combination anticancer therapies including photodynamic and photothermal, and for theranostic applications. This portfolio of latest approaches could promote the blooming growth of research and their clinical availability.

Background Achilles tendon rupture is one of the most common serious injuries in athletes. Various studies to accelerate the healing process of the Achilles tendon have been performed as it takes a longer time to repair the tissue compared to other tendons. Here, we report a case of an acute Achilles tendon rupture in a male basketball player treated by a combination of an intra-tissue injection of freeze-dried platelet-derived factor concentrate, which included a platelet-derived growth factor with an early rehabilitation protocol after the operative treatment to facilitate the biological healing of the injured tendon tissue. To the best of our knowledge, this case is the first instance that enabled the athlete to return to original sport activity at only 3-months after the injury. Case report A 23-year-old male basketball player who belonged to a university basketball team sustained an Achilles tendon rupture during running in a training match. The remaining time period until the final tournament of the university league as a senior player was only 3 months. The patient received a combination of an intra-tissue injection of freeze-dried platelet-derived factor concentrate and early rehabilitation protocol after operative treatment. Surgery was performed 4 days after the injury and the early rehabilitation protocols were applied postoperatively. A freeze-dried platelet-derived factor concentrate was injected into the ruptured site of the Achilles tendon under ultrasound guide at 4 weeks postoperatively. The patient could return to play at the pre-injury level without any symptoms and disfunctions at 3 months after surgery. At two years postoperatively, the patient could play basketball without symptoms or rerupture. Conclusions We reported a case of an Achilles tendon rupture which was treated by a combination of intra-tissue injection of freeze-dried platelet-derived factor concentrate and an early rehabilitation protocol after the operative treatment. The patient could return to play basketball at the pre-injury activity level at only 3-months after the injury, suggesting that the role of applying excessively early rehabilitation of mechanical loading could facilitate tendon tissue healing when combined with an intra-tissue injection of freeze-dried platelet-derived factor concentrate., Highlights • FD-PFC has rich growth factors such as PDGF-BB, which is a part of the PDGF growth family. • An achilles tendon rupture was treated by a combination of injection of FD-PFC and excessively postoperative rehabilitation. • The patient could return to play basketball at the pre-injury activity level at only 3-months after the injury.

Introduction Low anterior resection syndrome (LARS) is the most common complication after total mesorectal excision (TME) in patients with low rectal cancer and has been a challenge in colorectal surgery that severely impacts the quality of life of patients. This study aimed to introduce a revised surgical procedure which could effectively maintain rectal compliance and significantly improve LARS after the operation. Methods We performed mesorectal reconstruction after routine Dixon TME using greater omental pedicle flap transplantation in 11 patients with low rectal cancer (5 cases of preoperative neoadjuvant chemoradiotherapy, 5 cases of preoperative neoadjuvant chemotherapy, and 1 case of postoperative adjuvant chemotherapy), thereby simulating the initial anatomical structure of the mesorectum and significantly reducing the postoperative anterior resection syndrome. The lars precision syndrome assessment scale (LARSS) was used to access the LARS. Results At 12 weeks after the 11 patients recovered from the anal defecation function, the average score on the LARS questionnaire was 25.5 ± 1.5 (minor). The average time at which anal function began to recover was 6.2 ± 2.6 weeks after surgery. The recovery was rapid, as the rectal and anal function of all patients generally returned to normal levels within 12 weeks, and the quality of life was close to that before surgery. Conclusion Greater omental flap transplantation can significantly improve LARS after Dixon TME in patients with low rectal cancer., Highlights • Omental pedicle flap transplantation is a revised and promising surgical procedure. • The procedure reconstructing the mesorectum could maintain rectal compliance. • The procedure can significantly improve low anterior resection syndrome.

Objective: Diabetes insipidus (DI) can be classified into 2 types: central/neurogenic DI and nephrogenic DI. Most cases of central DI occur after brain surgery, trauma, tumor, or infection. Here we report a rare case of familial central DI due to a heterozygous AVP gene mutation. Methods: A case of familial neurogenic DI has been described with thorough clinical, laboratory, and genetic workup. PubMed and Google scholar databases were used for literature discussion. Results: A 22-year-old man presented with polyuria and polydipsia. He drank about 4 gallons of water everyday and urinated large volumes very frequently. His physical examination was unremarkable. After 2 hours of water-deprivation, his serum sodium level was 147 mmol/L, serum osmolality was 302 mOsm/kg with concurrent urine osmolality of 78 mOsm/kg, vasopressin level was

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

Artificial intelligence (AI) is a general term that refers to the use of a machine to imitate intelligent behavior for performing complex tasks with minimal human intervention, such as machine learning; this technology is revolutionizing and reshaping medicine. AI has considerable potential to perfect health-care systems in areas such as diagnostics, risk analysis, health information administration, lifestyle supervision, and virtual health assistance. In terms of immunotherapy, AI has been applied to the prediction of immunotherapy responses based on immune signatures, medical imaging and histological analysis. These features could also be highly useful in the management of cancer immunotherapy given their ever-increasing performance in improving diagnostic accuracy, optimizing treatment planning, predicting outcomes of care and reducing human resource costs. In this review, we present the details of AI and the current progression and state of the art in employing AI for cancer immunotherapy. Furthermore, we discuss the challenges, opportunities and corresponding strategies in applying the technology for widespread clinical deployment. Finally, we summarize the impact of AI on cancer immunotherapy and provide our perspectives about underlying applications of AI in the future., Graphical abstract With the increasing of clinical data and advanced AI methodologies, AI-based technologies have the potential to increase the functional roles in cancer immunotherapy response.Image 1

Foix-Alajouanine syndrome is a rare progressive form of spinal AVM predominantly affecting the lower thoracic and/or lumbosacral regions. This study aims to describe the imaging findings of spinal AVM causing Foix-Alajouanine syndrome and to review the literature. We present a 48-year-old man with progressive back pain, leg weakness, and gait imbalance without urinary retention. We discuss the clinical and imaging findings and the significance of MRI in establishing the diagnosis. A definitive diagnosis of spinal AVM requires radiographic demonstration of the vascular anomaly. Despite the high sensitivity of angiography for the diagnosis of spinal AVM, the result of the study may be inconclusive and/or negative. The key MRI findings are the presence of abnormally dilated perimedullary vessels with signal voids from a high-velocity flow on T1 and T2 weighted images.

Blood–brain barrier (BBB) strictly controls matter exchange between blood and brain, and severely limits brain penetration of systemically administered drugs, resulting in ineffective drug therapy of brain diseases. However, during the onset and progression of brain diseases, BBB alterations evolve inevitably. In this review, we focus on nanoscale brain-targeting drug delivery strategies designed based on BBB evolutions and related applications in various brain diseases including Alzheimer's disease, Parkinson's disease, epilepsy, stroke, traumatic brain injury and brain tumor. The advances on optimization of small molecules for BBB crossing and non-systemic administration routes (e.g., intranasal treatment) for BBB bypassing are not included in this review., Graphical abstract Blood–brain barrier (BBB) is evolving during the onset and progression of brain diseases. BBB evolution-based nanoscale brain-targeting drug delivery strategies are summarized in this review for various brain diseases.Image 1

Herlyn–Werner–Wunderlich syndrome (HWWS) is a rare congenital malformation characterized by uterus didelphys, unilateral blind hemivagina, and ipsilateral renal agenesis. The obstructed vagina affects menstrual flow, leading to related clinical symptoms after menarche. However, the age of onset, initial symptoms, and clinical complications differ among patients owing to the different types of vaginal septum. Herein, we report 2 cases. The first case is of a 20-year-old woman who presented with fever; she was diagnosed with vaginitis and pelvic inflammation due to the vaginal septum with ostiole. The second case is of a 12-year-old girl who complained of abdominal pain; she was diagnosed as having pelvic inflammation, omentitis, and suppurative appendicitis due to the atretic vaginal septum.

Uterine rupture and postterm pregnancy pose a number of life-threatening complications to both mother and child, including severe intra-abdominal bleeding and peritonitis, birth injury, hypoxia, and fetal loss. This report presents a rare case of a 20-year-old female experiencing fetal demise at 60 weeks of pregnancy, with uterine rupture and bone tissue discharge from her vagina without severe intra-abdominal bleeding and peritonitis. The mild clinical course despite complete uterine rupture was due to the firm adhesion of the amniotic sac to the uterus caused by inflammation. The adhesion of the intestines to the rupture site prevented dehiscence of the ruptured wound. Suppuration and bone tissue discharge relieved the pressure on the patient's abdominal cavity and prevented subsequent occurrence of severe peritonitis. Radiologists mistakenly regarded the thick amniotic sac wall on the right side of the uterine wall as a right cornual pregnancy with uterine rupture caused by chronic inflammation. This report aims to bring awareness of this rare condition to medical students and radiologists.

Objective Pycnodysostosis is commonly associated with growth hormone (GH) deficiency and responds well to GH therapy with achievement of normal or near-normal height and restoration of body proportions. Case Report A 22-month-old extremely short (−4.05 height standard deviation score) disproportionate boy with skeletal dysplasia presented to clinic. Skeletal survey, genetic panel, magnetic resonance imaging, and an insulin-like growth factor generation tests were performed. Results Skeletal survey showed increased bone density with classic features of pycnodysostosis, subsequently confirmed to be due to a deleterious homozygous frameshift mutation in CTSK. Uniquely among skeletal dysplasias, GH deficiency is a common association, secondary to pituitary hypoplasia. Magnetic resonance imaging confirmed pituitary hypoplasia and he subsequently underwent an insulin-like growth factor generation test that demonstrated biochemical responsiveness to GH therapy. This was thought to be safer than a classic GH stimulation test, in view of his very small size. Subsequently, his height has markedly improved on GH therapy. His height is now −2.25 SD, with an annualized growth velocity of 9.65 cm/y over a period of 18 months . Conclusion It is important to consider GH therapy in children with pycnodysostosis, with the greatest benefit seen in children started at a young age.

While germ cell testicular cancer is rare and only accounts for 1% of cancers in males, it is the most common solid malignancy among men between 14 and 44 years of age. Testicular cancer can be surgically excised by orchiectomy and is highly responsive to both chemotherapy and radiation therapy. Therefore, testicular tumors generally have the best cancer prognoses, especially since the majority are localized in the initial stage. However, long-term outcome depends on the potential for germ cell testicular cancer to metastasize, both proximal to the testicles and distally throughout the body. Germ cell testicular cancer metastasis to soft tissue, including the trunk, and extremities, appears to be exceedingly rare, as reflected in the extremely limited number of published cases (total of seven patients reported in literature). Vague symptomatology, delayed medical attention, and inconsistent treatment compliance may contribute to testicular soft tissue metastasis and underreporting of these tumors. Here, we report a case of metastatic non–seminomatous germ cell testicular cancer with a large necrotizing, ulcerative mass in the left Iliopsoas muscle and posterior abdominal wall.

Magnetic resonance imaging (MRI) has become the gold standard for the diagnosis of many pathologies. Using MRI in patients with auditory implants can however raise concerns due to mutual interactions between the implant and imaging device, resulting in potential patient risks. Several implant manufacturers have been working towards more MRI safe devices. Older devices are however often labelled for more stringent conditions, possibly creating confusion with patients and professionals. With this myriad of different devices that are implanted in patients for lifetimes of at least 20 years, it is crucial that both patients and professionals have a clear understanding of the safety of their devices. This work aims at providing an exhaustive overview on the MRI safety of active auditory implants. The available industry standards that are followed by manufacturers are outlined and an overview of the latest scientific developments focusing on the last five years is provided. In addition, based on the analysis of the adverse events reported to the Food and Drug Administration (FDA) and in literature within the past ten years, a systematic review of the most commonly occurring issues for patients with auditory implants in the MRI environment is provided. Results indicate that despite the release of more MRI conditional active hearing implants on the market, adverse events still occur. An extensive overview is provided on the MRI safety of active auditory implants, aiming to increase the understanding of the topic for healthcare professionals and contribute to safer scanning conditions for patients. ispartof: Journal of Otology vol:16 issue:3 pages:185-198 ispartof: location:China status: Published online

A 7-year-old boy was admitted to the Pediatric Cardiology Department with blood pressure of 160/120 mmHg accompanied by burning pain in his hands and feet and tachycardia, followed by a seizure attack for the first time in his life, which presented shortly after admission. The child underwent a widespread diagnostic process – including laboratory tests and imaging – showing inconclusive results. Acute autonomic neuropathy was eventually diagnosed and successfully treated with intravenous immunoglobulin. The described case illustrates the need for a careful and open-minded approach to patients with hypertension.

Objective: Tumor-induced osteomalacia (TIO) is a rare osteomalacia characterized by paraneoplastic secretion of fibroblast growth factor 23. Concomitant occurrence of TIO during pregnancy is rarer still. Our objective was to report a young patient with debilitating fractures diagnosed with TIO who became pregnant and subsequently had her tumor localized by gallium-68 (Ga-68) DOTATATE positron emission tomography/magnetic resonance imaging (PET/MRI). Case Report: A 28 year-old woman with a 2-year history of stress fractures was found to have the following: (1) alkaline phosphatase level, 220 (reference range, 30-95) U/L; (2) phosphorus level, 2.1 (2.5-5.0) mg/dL; (3) 1,25-dihydroxyvitamin D3 level

The blood-brain barrier (BBB) is a major anatomical and physiological barrier limiting the passage of drugs into brain. Central nervous system tumors can impair the BBB by changing the tumor microenvironment leading to the formation of a leaky barrier, known as the blood-tumor barrier (BTB). Despite the change in integrity, the BTB remains effective in preventing delivery of chemotherapy into brain tumors. Focused ultrasound is a unique noninvasive technique that can transiently disrupt the BBB and increase accumulation of drugs within targeted areas of the brain. Herein, we summarize the current understanding of different types of targeted ultrasound mediated BBB/BTB disruption techniques. We also discuss influence of the tumor microenvironment on BBB opening, as well as the role of immunological response following disruption. Lastly, we highlight the gaps between evaluation of the parameters governing opening of the BBB/BTB. A deeper understanding of physical opening of the BBB/BTB and the biological effects following disruption can potentially enhance treatment strategies for patients with brain tumors.

Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography-related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4-SC from cholangiocarcinoma and/or primary SC.

The transcatheter approach is nowadays considered a cost-effective alternative to surgery in adults with “complex” aortic coarctation. The printed 3D model was crucial in planning transcatheter treatment of a complex case of postsurgical aortic re-coarctation, due to coexistence of transverse aortic arch stenosis and pseudoaneurysm as well as aneurysm of the descending aorta. (Level of Difficulty: Advanced.), Central Illustration

Graphical abstract, Highlights • Quantitative ultrasound (QUS) delta-radiomics to predict recurrence. • Machine learning model can predict recurrence with accuracy >80%. • Classification performances improve when features are taken from weeks 1 and 4., Purpose This study investigated the use of quantitative ultrasound (QUS) obtained during radical radiotherapy (RT) as a radiomics biomarker for predicting recurrence in patients with node-positive head-neck squamous cell carcinoma (HNSCC). Methods Fifty-one patients with HNSCC were treated with RT (70 Gy/33 fractions) (±concurrent chemotherapy) were included. QUS Data acquisition involved scanning an index neck node with a clinical ultrasound device. Radiofrequency data were collected before starting RT, and after weeks 1, and 4. From this data, 31 spectral and related-texture features were determined for each time and delta (difference) features were computed. Patients were categorized into two groups based on clinical outcomes (recurrence or non-recurrence). Three machine learning classifiers were used for the development of a radiomics model. Features were selected using a forward sequential selection method and validated using leave-one-out cross-validation. Results The median follow up for the entire group was 38 months (range 7–64 months). The disease sites involved neck masses in patients with oropharynx (39), larynx (5), carcinoma unknown primary (5), and hypopharynx carcinoma (2). Concurrent chemotherapy and cetuximab were used in 41 and 1 patient(s), respectively. Recurrence was seen in 17 patients. At week 1 of RT, the support vector machine classifier resulted in the best performance, with accuracy and area under the curve (AUC) of 80% and 0.75, respectively. The accuracy and AUC improved to 82% and 0.81, respectively, at week 4 of treatment. Conclusion QUS Delta-radiomics can predict higher risk of recurrence with reasonable accuracy in HNSCC. Clinical trial registration: clinicaltrials.gov.in identifier NCT03908684.

Inverted Meckel's diverticulum is an entity often discovered incidentally or through a clinical evaluation for gastrointestinal bleeding. While rare, inverted Meckel's diverticulum should be considered in the evaluation of a patient presenting with gastrointestinal bleeding, intestinal obstruction, or intussusception. In this case, a 67-year-old female with a remote history of surgically treated breast cancer presents to an urgent care facility with weakness and fatigue. She was found to be anemic with hemoglobin of 4. Imaging revealed a blind-ending pouch in the mid to distal ileum consistent with an inverted Meckel's diverticulum. Inverted Meckel's diverticulum is identified on computerized tomography as an intraluminal, blind-ending structure in the mid to distal ileum. The possibility of a lead point should be investigated and surgical resection is indicated to prevent intestinal obstruction.

An immune response for a nasal ovalbumin (OVA) powder formulation with an applied nasal delivery platform technology, consisting of a powdery nasal carrier and a device, was evaluated in monkeys with similar upper respiratory tracts and immune systems to those of humans, in order to assess the applicability to a vaccine antigen. Nasal distribution and retention studies using a 3D nasal cavity model and manganese-enhanced MRI were conducted by administering nasal dye and manganese powder formulations with the applied technology. Systemic and mucosal immune responses for the nasal OVA powder formulation were evaluated by determining serum IgG and nasal wash IgA antibody titers. The nasal dye and manganese powder formulations showed wider distribution and longer retention time than did a nasal liquid formulation. The nasal OVA powder formulation also showed comparable and higher antigen-specific IgG antibody titer to an injection and nasal liquid formulation, respectively. Furthermore, antigen-specific IgA antibody response was detected only for the nasal OVA powder formulation. The present study suggests that the technology, originally designed for drug absorption, is promising for nasal vaccines, enabling both a mucosal immunity response as the first line of defense and systemic immunity response as a second line of defense against infection.

Objective Primary hypophysitis refers to the isolated inflammation of the pituitary gland not associated with other secondary causes. Among its histopathologic subtypes, xanthomatous is the rarest. Methods We describe a 22-year-old woman with xanthomatous hypophysitis (XH), its clinical progression over 8 years as well as the treatment effects of prednisolone and azathioprine. Our patient was first referred for severe short stature and delayed puberty at the age of 14 years. Results Investigations revealed multiple pituitary deficiencies. Magnetic resonance imaging showed a pituitary mass whereby a partial resection was performed. A full resection was not feasible due to the location of the mass. The histopathologic analysis of the tissue was consistent with XH. The results of secondary workout for neoplasm, infection, autoimmune, and inflammatory disorders were negative. After surgery, a progressive enlargement of the mass was observed. Two courses of prednisolone were administered with a significant reduction in the mass size. Azathioprine was added due to the unsustained effects of prednisolone when tapered off and the concern of steroid toxicity with continued use. No further increase in the mass size was noted after 6 months on azathioprine. Conclusion Glucocorticoid and immunotherapy are treatment options for XH; however, more cases are needed to better understand its pathogenesis and clinical progression.

A 23-year-old man with sickle cell disease treated with splenectomy and allogenic stem cell transplantation presented with recurrent chest pain, elevated cardiac enzymes, and unremarkable electrocardiography. His work-up revealed eosinophilia, raising concern for eosinophilic myocarditis. Cardiac magnetic resonance imaging showed patchy late gadolinium enhancement of the left ventricular free wall, suggestive of myocarditis. He was treated with high-dose intravenous steroids followed by oral prednisone, with improvement in his symptoms and eosinophilia and a decrease in cardiac enhancement on follow-up imaging. (Level of Difficulty: Intermediate.), Central Illustration

Objective We report a case of pituitary apoplexy (PA) with negative radiographic findings for PA and cerebrospinal fluid (CSF) analysis consistent with neutrophilic meningitis. PA is a rare endocrinopathy requiring prompt diagnosis and treatment. Presentation with acute neutrophilic meningitis is uncommon. Methods The diagnostic modalities included pituitary function tests (adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, prolactin), brain computed tomography and magnetic resonance imaging (MRI), and CSF analysis. Results A 67-year-old man presented with worsening headache, nausea, and retching. He was somnolent with an overall normal neurologic examination other than a peripheral vision defect in the left eye. MRI showed a pituitary mass bulging into the suprasellar cistern with optic chiasm elevation, consistent with pituitary macroadenoma. Laboratory evaluation revealed decreased levels of adrenocorticotropic hormone, random cortisol, thyroid-stimulating hormone, thyroxine, luteinizing hormone, and testosterone. He had worsening encephalopathy with left eye ptosis and decreased vision, prompting a repeat computed tomography and MRI, showing no interval change in the pituitary adenoma or evidence of bleeding. CSF analysis revealed a leukocyte count of 1106/mm3 (89% neutrophils), a total protein level of 138 mg/dL, red blood cell count of 2040/mm3 without xanthochromia, and glucose level of 130 mg/dL. The CSF culture result was negative. Transsphenoidal resection revealed a necrotic pituitary adenoma with apoplexy. Conclusions Including PA in the differential diagnosis of acute headache is important, particularly in patients with visual disturbances. PA can present with sterile meningitis, mimicking acute bacterial meningitis. While neuroimaging can help detect PA, the diagnosis of PA remains largely clinical.

Objective: Our objective is to present a case of Cushing’s disease (CD) with 2 adrenocorticotropic hormone (ACTH)-secreting pituitary tumors. Multiple monohormonal pituitary tumors are rare. This case supports a consideration of repeat transsphenoidal surgery (TSS) in patients with initial surgical failure. Methods: Salivary, 24-h urine, serum cortisol testing, and magnetic resonance imaging (MRI) were used to diagnose CD. Treatment included TSS and postoperative hydrocortisone. Results: A 36-year-old woman followed for hypothyroidism presented with a new left supraclavicular fossa swelling and underwent Cushing’s syndrome screening. The levels of late-night salivary cortisol were 0.636 and 0.316 μg/dL, 24-h urine cortisol was 162 μg/24 h, cortisol after 1-mg dexamethasone suppression was 14.0 μg/dL, and serum morning cortisol was 26.4 μg/dL with ACTH of 66.7 pg/mL. A 7-mm hypoenhancing anterior pituitary lesion was noted on pituitary MRI. The cortisol level was 2.7 μg/dL after an 8-mg dexamethasone suppression. She underwent TSS, and her histopathology read as pituitary adenoma staining positive for ACTH. No residual tumor was seen intraoperatively. Postoperative morning serum cortisol was 17.9 μg/dL, and ACTH level was 79 pg/mL. Repeat TSS revealed a second adenoma previously unseen on MRI, which also stained positive for ACTH. Postoperative morning cortisol was 0.7 μg/dL, and ACTH was

Surgery is recommended for endocarditis complicated by annular abscess or destruction of the native valve. Guidelines also recommend valvular repair over replacement for endocarditis when feasible. Guidance on management of early repair failure is not well described. (Level of Difficulty: Intermediate.), Central Illustration

In the midst of the national opioid crisis, it is necessary for emergency physicians and radiologists to be familiar with presentations of opioid-related complications. We describe a case report of a 51-year-old female who developed bilateral cerebellar hemorrhages following opioid and benzodiazepine overdose. Malignant cerebellar edema is a rare but recognized complication following opiate overdose in children or chronic heroin toxicity. However, acute cerebellar involvement is rarely reported in adults. We feel that clinicians and radiologists should keep in mind the possibility of opioid toxic encephalopathy in their differential for adults with acute bilateral cerebellar infarcts and/or hemorrhages.

Objective Hyperglycemia may cause acute central nervous system dysfunction manifesting as agonizing involuntary movements due to insult to the basal ganglia. We report a case of hemichorea-hemiballism (HCHB) in a patient with diabetes. Method Clinical assessment of the patient was performed, along with laboratory tests and brain imaging. Results The patient was a 50-year-old man with newly detected diabetes with persistent involuntary movement of the right upper and lower limbs for few weeks. The involuntary movement was nonrhythmic, nonpatterned, purposeless, and often jerky with variable amplitude and frequency, sometimes wild and flailing in the form of hemichorea with a ballistic component (HCHB). He had a history of poor compliance to prescribed oral antidiabetic drugs. At presentation, although he was hemodynamically stable, random capillary blood glucose level was 18 mmol/L and glycated hemoglobin A1 level was 15.1% (141.5 mmol/mol). Clinical examination did not reveal any focal deficit or positive Babinski sign. There was a hyperintensity in the left basal ganglia region in T1-weighted magnetic resonance imaging (MRI) of the brain, which was iso-to-hyperintense in T2-weighted image and fluid-attenuated inversion recovery sequence. There was no restriction of diffusion on the diffusion-weighted image or blooming on gradient echo sequences, indicating absence of infarction or hemorrhage. Control of hyperglycemia resulted in disappearance of the involuntary movement within 1 month. Conclusion While there are many differential diagnoses for HCHB, the clinical scenario suggests hyperglycemia as the underlying cause in this patient. This case reiterates that multiple central nervous system manifestations may be attributable to diabetes.

The undifferentiated embryonal sarcoma of the liver is a rare tumor with a poor prognosis, with improved outcomes being reported with more recently multimodality treatments. We report a case of a 6-year-old girl with an incidentally diagnosed and histologically proven localized undifferentiated embryonal sarcoma of the liver. The divergence between solid appearance at US and cystic-like appearance on CT/MRI, which has been attributed to the presence of myxoid component frequently described with this tumor, was crucial for the diagnosis and subsequent treatment.

Objective Nelson syndrome (NS) is a rare clinical disorder that can occur after total bilateral adrenalectomy (TBA), performed as a treatment for Cushing disease. NS is defined as the accelerated growth of an adrenocorticotropic hormone-producing pituitary adenoma. Our objective is to describe a case of NS and discuss it based on existing knowledge of this syndrome. Methods We describe the case of a woman diagnosed with NS at our facility in the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran and review published cases of NS. Results The patient, a 35-year-old woman with Cushing disease, had been diagnosed in 2006 at the endocrinology department in the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. In 2007, a laparoscopic TBA was performed, and 2 years later, she presented with hyperpigmentation and adrenocorticotropic hormone levels of up to 11 846 pg/mL. NS was suspected, and as magnetic resonance imaging showed macroadenoma, transsphenoidal surgery was performed. The patient remained asymptomatic until 2012, when she presented with a right hemicranial headache, photophobia, and phonophobia. A fresh magnetic resonance imaging was performed, which documented tumor growth. She was referred to the Instituto Nacional de Neurologia y Neurocirugia, where she underwent surgery. Conclusion NS develops as a complication of TBA, which is used as a treatment of Cushing disease. The main treatment is surgery and radiotherapy.

A 21-year-old man presented with new-onset seizures and brain abscess. Echocardiography and cardiac magnetic resonance imaging revealed underlying Ebstein anomaly, secundum atrial septal defect, and cor triatriatum dexter. The elevated right heart pressures shunting through the septal defect and transient bacteremia were the likely mechanisms for his presentation. (Level of Difficulty: Intermediate.), Graphical abstract

Bileaflet mitral valve prolapse (Bi-MVP) is associated with increased risk for cardiac arrest. We describe a patient who presented after a cardiac arrest with Bi-MVP and variants in Lamin A/C (LMNA) and the sodium channel alpha-subunit 5a (SCN5A). Genetic variants may be the culprit for arrhythmogenesis in Bi-MVP patients. (Level of Difficulty: Intermediate.), Central Illustration

Highlights • Distribution of recurrent HNSCC in relation to radiotherapy volume was evaluated. • Both p16 positive and negative HNSCC recur in high-risk treatment volume. • This indicates potential failure of multimodality imaging to disclose significant disease. • A need for biomarkers other than p16 to predict radiosensitivity continues to exist., Background Locoregional recurrence remains a major cause of failure in head and neck squamous cell carcinoma (HNSCC). Human papilloma virus (HPV)-associated HNSCCs generally have a good prognosis but may recur even after standard photon radiotherapy (RT). Another incentive in observing patterns of recurrence is increased use of highly conformal techniques such as proton therapy. We therefore studied geographic distribution of recurrent tumors in relation to the high-risk treatment volume in a cohort of patients with HNSCC receiving combined modality therapy. Methods Medical records of 508 patients diagnosed with HNSCC in 2010–2015 were reviewed. We identified a subgroup that had local and/or regional recurrence at hybrid positron emission tomography (PET)/computed tomography (CT) and/or magnetic resonance imaging (MRI). We adapted p16 as a surrogate marker for HPV-positivity and only patients with known p16 status were eligible for a detailed analysis where recurrent tumor was copied on the planning CT and the dose received by the recurrent tumor volume was determined using dose-volume histograms. Results Twenty-five patients who had received either cisplatin (n = 23) or cetuximab-enhanced (n = 2) RT were identified. 31 locoregional recurrent tumors were detected among 18 p16 negative and 7 p16 positive patients. Of recurrent tumors 14 (45%) were classified as in-field, 5 (16%) as marginal miss, and 12 (39%) as true miss. p16 positive patients had 4 in-field, 2 marginal, and 1 true miss. By contrast, p16 negative patients had 10 in-field, 3 marginal, and 11 true miss recurrences. Conclusions Both p16 positive and negative HNSCC recur in high-risk treatment volume despite the common view of high radiosensitivity of the former. Biomarkers predicting radioresistance should be characterized in p16 positive tumors before widely embarking on de-escalated CRT protocols. Another concern is how to decrease the number of true or marginal misses in p16 negative cases despite multimodality imaging-based target delineation.

Robert's uterus is a rare Müllerian malformation first characterized by a French gynecologist Héléne Robert in 1969. It represents an asymmetric division of the uterine cavity. A 45-year-old female patient presented with vaginal bleeding and vague abdominal pain for the course of 20 days, with a blood human chorionic gonadotropin level of 10331.00 mIU/mL, and a gestational sac in the right uterine horn without a fetal heart beat revealed by the ultrasound. Ectopic pregnancy in the right uterine horn seemed to be the most likely diagnosis. Laparoscopic and hysteroscopic attempts to terminate the pregnancy failed. A pelvic magnetic resonance imaging (MRI) performed after the surgery demonstrated Robert's uterus with pregnancy in the blind hemicavity. When a pregnancy sac has been revealed by an ultrasound but nothing has been found by a hysteroscopy, a possibility of uterine malformation should be considered. Radiologists and gynecologists should consider the application of MRI for diagnosis of congenital Müllerian uterine anomalies.

Highlights • Blunt thoracic aortic injuries are life threatening and require urgent intervention. • Rare presentation of a blunt thoracic aortic injury in a patient with an aberrant right subclavian artery off the aortic arch distal to the takeoff of the left subclavian artery. • An aberrant right subclavian artery originating from the aortic arch, distal to the left subclavian artery is an anatomic variant that adds significant complexity to TEVAR., Introduction Blunt thoracic aortic injuries (BTAIs) are an uncommon traumatic injury that if not treated promptly, can result in death. We present the case of a BTAI with aberrant aortic anatomy. Presentation of case A 60-year-old female was involved in a motor vehicle crash where she suffered significant polytrauma including a BTAI. She was also found to have an aberrant right subclavian artery originating from the aortic arch. Thoracic Endovascular Aortic Repair (TEVAR) with a right common carotid artery to right subclavian artery bypass was accomplished. She required three more vascular surgical interventions, two for persistent type II endoleak and the third for left upper extremity acute limb ischemia. She had a 2-month hospital course for her devastating injuries and was eventually discharged home. A follow-up CT angiogram showed a stable thoracic aortic arch stent. Discussion BTAIs are uncommon in the trauma population. In our patient who had an aberrant right subclavian artery, further procedures were required in the form of a right common carotid artery to right subclavian artery bypass and embolizations to resolve endoleaks. Conclusion Blunt thoracic aortic injuries are life threatening and require urgent intervention. TEVAR is associated with better outcomes. An aberrant right subclavian artery originating from the aortic arch, distal to the left subclavian artery is an anatomic variant that adds significant complexity to TEVAR. TEVAR is still an option for repair of blunt thoracic aortic injuries despite anatomic variations as open repair still carries an increased risk of morbidity and mortality.

We describe an extracardiac mass in a 72-year-old man with a history of pericardiectomy for constrictive pericarditis. Imaging studies revealed that progressive shrinkage of the residual pericardium compressed mitral valve anteriority, and fat replacement of the secondarily enlarged posterior space of the atrioventricular groove appeared as a space-occupying lesion. (Level of Difficulty: Intermediate.), Graphical abstract

Two middle-aged women had evidence suggesting right ventricular hypertrophy on routine electrocardiograms. Their echocardiograms showed right ventricular thickening and cardiac magnetic resonance imaging revealed right ventricular fatty infiltration. Neither patient fulfilled the criteria for arrhythmogenic right ventricular cardiomyopathy, and both had a benign clinical course. (Level of Difficulty: Intermediate.), Graphical abstract

Chiari 1 Malformation in children is defined as 6 mm or more caudal extension of cerebellar tonsils below the foramen magnum. It is one of the deformities in the spectrum of craniovertebral junction anomalies. We report an unusual case of newborn girl with hypoplasia of bassiocciput of the clivus and extension of brainstem into the oropharynx, in addition to extension of cerebellar tonsils below the foramen magnum. Right anterior arch and right posterior arch of C1 vertebra are absent. Dens of C2 vertebra is asymmetric. Laryngoscope showed a membrane covering the brainstem in the oropharynx. Endotracheal and orogastric tubes were placed. A ventriculo-peritoneal shunt was placed for hydrocephalus. The patient was discharged home at 4.5 months of age with home Hospice care. To the best of our knowledge, this has not been described in the literature. The case illustrates a rare defect in the clivus and unusual protrusion of brainstem into oropharynx.

Objective: To assess the health care costs and utilization in patients with hereditary hemorrhagic telangiectasia (HHT) in the United States. Patients and Methods: Retrospective analysis of patients with HHT diagnosed between 2007 and 2017 was performed using deidentified administrative claims data from the OptumLabs Data Warehouse. Adult patients with new (incident) diagnosis of HHT between January 1, 2007, and December 31, 2017, were included. Comparisons were made using the Wilcoxon rank sum test. Results: Three thousand nine hundred seventy-seven patients with a first diagnosis of HHT between 2007 and 2017 were identified, of which 3590 were matched 1:1 to non-HHT patients with similar baseline characteristics and comorbidities. These 3590 patients with HHT were 63.1% female and 83.9% white with a mean age of 51.1 ± 18.5 years, and a mean follow-up period of 3.2 ± 2.2 years (range, 1.0-11.7 years). Compared with the control group, the cumulative 5-year median total health care cost for patients with HHT was 41.4% higher ($21,118 vs $14,929; P < .001) in those with private commercial insurance and 31.7% higher ($35,462 vs $26,925; P < .001) in those with Medicare Advantage coverage. The median annual health care costs were significantly higher in patients with HHT with commercial insurance and Medicare Advantage in the first year after diagnosis ($4,333 vs $1,804; P < .001), and ($7,322 vs $5,245; P < .001), respectively, and remained higher throughout the duration of follow-up. Further analysis showed that outpatient clinic visits, hospital admission, imaging rates, invasive procedures, iron infusions, and blood transfusions were all significantly higher in the HHT group. Conclusion: Patients with HHT have significantly higher health care costs compared with a matched control group. A better understanding of the reasons underlying these cost differences will provide opportunities for patients, providers, and other stakeholders to better manage this rare condition.

Highlights • The patient presented with an atypical complex elbow dislocation with fracture. • The patient underwent lateral collateral ligament repair. • The patient also underwent medial collateral ligament reconstruction. • Elbow stability improved and the patient experienced improved functionality. • Care is needed to identify and manage the underlying injury in this type of case., Introduction and importance Elbow dislocation is common in adults, and complex elbow dislocations are generally associated with bone fractures. Anteromedial coronoid fracture, in association with lateral collateral ligament (LCL) disruption, often results from varus posteromedial forces. “Terrible triad” injuries are more likely to result from valgus posterolateral forces. However, our case presentation has combined medial and lateral elbow instability in addition to “terrible triad” injury of the elbow with no radial head injury. Case presentation The patient was a 38-year-old man with an atypical complex elbow dislocation. He was successfully treated by stabilizing the medial epicondyle and coronoid anterolateral facet fractures, in addition to LCL repair and medial collateral ligament (MCL) reconstruction. A radial head fracture was unnoted. The procedure yielded satisfactory functional outcome, with a stable and painless full elbow range of motion. Clinical discussion Multi-ligament injuries with coronoid fractures result in highly unstable elbow joints, forming a variant of the “terrible triad” injury. Surgical options vary according to the surgeon’s experience and equipment availability. In this case, direct LCL repair and MCL reconstruction were performed and were well tolerated. Elbow stability improved and the patient experienced improved functionality with minimal pain. However, it may be premature to report a definite outcome in this case because of short follow-up time postoperatively. Conclusion The injury described in this case has a unique presentation as a multi-ligamentous injury will make the elbow very unstable. Thus, careful clinical judgment, knowledge, and experience are needed to identify the underlying injury and for optimal management.

Highlights • Brain and thyroid metastasis of rectal cancer are uncommon, and prognosis are poor. • Lung, brain and thyroid metastasis of rectal cancer was resected metachronous. • This case survived 19 years after the initial rectal surgery. • Patients whose metastases were resected completely may get a prolonged survival., Introduction and importance Brain and thyroid metastasis from rectal cancer are uncommon, and the prognosis is poor. We report a patient with rectal cancer who developed metachronous lung, brain and thyroid metastases. Each metastatic lesion was curatively resected resulting in prolonged survival. Case presentation A 60-year-old male underwent rectal cancer resection, and the pathological diagnosis was tubular adenocarcinoma, pT2,pN1a,M0, pStageⅢa. Ten years after rectal resection, a solitary tumor in the left lung was detected. The tumor was resected thoracoscopically and the pathological diagnosis was metastatic tumor. Three years after the pulmonary resection, a solitary brain tumor was detected. The tumor was removed surgically, and the pathology was metastatic tumor. Two years after brain resection, a thyroid mass was detected. A partial thyroidectomy was performed and the pathology with immunohistochemical staining confirmed the thyroid lesion as a metastasis from the previous rectal cancer. Four years after thyroid resection (19 years after the initial rectal resection), he died from multiple lung and bone metastases. Clinical discussion Colorectal metastases to the brain and thyroid gland are uncommon and are usually found with other distant metastases. Overall survival has been reported to be extremely poor. In this patient, lung, brain, and thyroid metastases were solitary and metachronous, and each lesion was curatively resected. Surgical treatment might contribute to prolonged survival. Conclusion The treatment strategy of each patient should be individualized and depends on the timing of metastasis development. Selected patients with complete resection of metachronous metastases may have prolonged survival.

Background Breast cancer disease is the most common cancer in US women and the second cause of cancer death among women. Objectives To compare and evaluate the performance and accuracy of the key supervised and semi-supervised machine learning algorithms for breast cancer prediction. Materials and methods We have used nine machine learning classification algorithms for supervised (SL) and semi-supervised learning (SSL): 1) Logistic regression; 2) Gaussian Naive Bayes; 3) Linear Support vector machine; 4) RBF Support vector machine; 5) Decision Tree; 6) Random Forest; 7) Xgboost; 8) Gradient Boosting; 9) KNN. The Wisconsin Diagnosis Cancer dataset was used to train and test these models. To ensure the robustness of the model, we have applied K-fold cross-validation and optimized hyperparameters. We have evaluated and compared the models using accuracy, precision, recall, F1-score, and ROC curves. Results The results of all models are inspiring using both SL and SSL. The SSL has high accuracy (90%–98%) with just half of the training data. The KNN model for the SL and logistic regression for the SSL achieved the highest accuracy of 98% Conclusion The accuracies of SSL algorithms are very close to the SL algorithms. The accuracies of all models are in the range of 91–98%. SSL is a promising and competitive approach to solve the problem. Using a small sample of labeled and low computational power, the SSL is fully capable of replacing SL algorithms in diagnosing tumor type., Highlights • Semi-supervised algorithms in integration with hyperparameters optimization yielded accurate prediction of breast cancer. • Semi-supervised models take full advantage of the available information in the data and obtain the most accurate prediction. • Semi-supervised algorithms can give very high accuracy (90%–98%) with just half of the training data. • The KNN model for supervised and Logistic Regression for the semi-supervised learning have the most accurate prediction.

A 62-year-old man presented with a history of atypical meningioma (World Health Organization grade II) and recurrent as anaplastic meningioma (World Health Organization grade III). His previous treatments included multiple surgical resections, fractionated radiation therapy, stereotactic radiosurgery, everolimus/octreotide long-acting release, bevacizumab, and hydroxyurea. Magnetic resonance imaging revealed rapid volumetric progression over the prior 9 months, with a near tripling in size from 29.9 cm3 to 80.4 cm3. Indium In 111 octreotide scanning confirmed the presence of somatostatin receptors within the tumor. Lutetium Lu 177 dotatate was administered intravenously at a dose of 200 mCi per dose every 8 weeks for 4 cycles. Treatment was tolerated very well, with no notable adverse events. Tumor volume initially increased to 98.3 cm3 after cycle 1 of treatment and subsequently decreased to 91.2 cm3 after cycle 2. Eight months after treatment onset, the tumor volume remained stable (93.4 cm3).

Imaging tools are potentially able to provide valuable data regarding the development of an efficient vaccine against viral diseases. Tracking immune cells in vivo by imaging modalities can help us understand the intrinsic behaviors of immune cells in response to vaccine components. Imaging patterns at the vaccination site and draining lymph nodes might provide useful information about the vaccine potency. Besides, serial lung CT imaging has been purposed to evaluate vaccine efficiency regarding its protection against typical lung lesions of viral pneumonias. On the other hand, vaccination causes various confusing radiologic patterns that pose diagnostic challenges for clinicians and pitfalls for reading radiologists. This manuscript reviews potential applications of imaging modalities in the process of vaccine development and also goes over some of the imaging findings/pitfalls following vaccination., Highlights • Imaging tools could track the immune cell dynamics in vivo, which holds valuable research attention in the vaccination field. • Serial CT imaging might be a great indicator of vaccine efficiency in research setting. • Vaccination causes various confusing radiologic patterns that pose diagnostic challenges for clinicians and radiologists.

Highlights • Subcortical grey matter is susceptible to dose-dependent volume loss after RT. • Hippocampal age increases 1 year after radiotherapy, by a median of 11 years. • We may need to reconsider current sparing strategies in RT for brain tumours. • Future studies should examine the impact of deep GM volume loss on cognition., Background and purpose The relation between radiotherapy (RT) dose to the brain and morphological changes in healthy tissue has seen recent increased interest. There already is evidence for changes in the cerebral cortex and white matter, as well as selected subcortical grey matter (GM) structures. We studied this relation in all deep GM structures, to help understand the aetiology of post-RT neurocognitive symptoms. Materials and methods We selected 31 patients treated with RT for grade II-IV glioma. Pre-RT and 1 year post-RT 3D T1-weighted MRIs were automatically segmented, and the changes in volume of the following structures were assessed: amygdala, nucleus accumbens, caudate nucleus, hippocampus, globus pallidus, putamen, and thalamus. The volumetric changes were related to the mean RT dose received by each structure. Hippocampal volumes were entered into a population-based nomogram to estimate hippocampal age. Results A significant relation between RT dose and volume loss was seen in all examined structures, except the caudate nucleus. The volume loss rates ranged from 0.16 to 1.37%/Gy, corresponding to 4.9–41.2% per 30 Gy. Hippocampal age, as derived from the nomogram, was seen to increase by a median of 11 years. Conclusion Almost all subcortical GM structures are susceptible to radiation-induced volume loss, with higher volume loss being observed with increasing dose. Volume loss of these structures is associated with neurological deterioration, including cognitive decline, in neurodegenerative diseases. To support a causal relationship between radiation-induced deep GM loss and neurocognitive functioning in glioma patients, future studies are needed that directly correlate volumetrics to clinical outcomes.

Highlights • Vaginal agenesis is a complex pediatric condition that lead to long-term urinary, gastrointestinal, and sexual dysfunction. • A meticulous physical examination and in-depth diagnostic investigations are necessary to determine the appropriate surgical management. • Reconstruction of neovagina can be retrieved from the ileum., Vaginal agenesis with anorectal malformations is a complex pediatric condition that adversely affects various physiological processes in the body. It may cause disturbances in defecation and urination, abnormalities in the urinary and gastrointestinal tract, dysfunction of the genital and reproductive organs, and sexual function disorders. The complexity in the surgical management of vaginal agenesis includes the selection of a functional reconstruction technique for anal and vaginal formation, timing of the reconstruction, and management of complications in the associated organ system. Herein, we describe a patient with Mayer–Rokitansky–Küster–Hauser syndrome accompanied by a rectovesical fistula. Other abnormalities, such as microcephaly, polydactyly, long urethral abnormalities resembling the male urethra, and complications in the kidney and urinary tract, were observed in the patient. The associated complications included recurrent urinary tract infections, urinary overflow incontinence, vesicoureteric reflux, hydroureter, and left renal hydronephrosis. The patient underwent posterior sagittal anorectoplasty surgery and vaginal reconstruction. The long-term vaginal physiological development of patients with this condition remains unknown.

Background & Aims Hepatocellular carcinoma (HCC) arises in a cirrhotic, pro-angiogenic microenvironment. Inhibiting angiogenesis is a key mode of action of multikinase inhibitors and current non-cirrhotic models are unable to predict treatment response. We present a novel mouse cirrhotic model of xenotransplant that predicts the natural biology of HCC and allows personalized therapy. Methods Cirrhosis was induced in NOD Scid gamma mice with 4 months of thioacetamide administration. Patient derived xenografts (PDXs) were created by transplant of human HCC subcutaneously into non-cirrhotic mice and intra-hepatically into both cirrhotic and non-cirrhotic mice. The applicability of cirrhotic PDXs for drug testing was tested with 16 days of either sorafenib or lenvatinib. Treatment response was evaluated by MRI. Results 8 out of 19 (42%) human HCC engrafted in the cirrhotic model compared with only 3 out of 19 (16%) that engrafted in the subcutaneous non-cirrhotic model. Tumor vasculature was preserved in the cirrhotic model but was diminished in the non-cirrhotic models. Metastasis developed in 3 cirrhotic PDX lines and was associated with early HCC recurrence in all 3 corresponding patients (100%), compared with only 5 out of 16 (31%) of the other PDX lines, P = .027. The cirrhotic model was able to predict response and non-response to lenvatinib and sorafenib respectively in the corresponding patients. Response to lenvatinib in the cirrhotic PDX was associated with reduction in CD34, VEGFR2 and CLEC4G immunofluorescence area and intensity (all P ≤ .03). Conclusions A clinically relevant cirrhotic PDX model preserves tumor angiogenesis and allows prediction of response to multikinase inhibitors for personalized therapy., Graphical abstract

Highlights • Implantation of solid gold markers safe. • Inter-fractional motion for markers in distal oesophagus largest cranio-caudally. • Reduced radiotherapy treatment margins with soft-tissue vs. bony-anatomy matching. • Impact of intra-fractional baseline shifts on margin calculation rather small., Purpose To prospectively evaluate the feasibility of solid gold marker placement in oesophageal cancer patients and to quantify inter-fractional and intra-fractional (baseline shift) marker motion during radiation treatment. Radiotherapy target margins and matching strategies were investigated. Materials/methods Thirty-four markers were implanted by echo-endoscopy in 10 patients. Patients received a planning 4D CT, daily pre-treatment cone-beam CT (CBCT) and a post-treatment CBCT for at least five fractions. For fractions with both pre- and post-treatment CBCT, marker displacement between planning CT and pre-treatment CBCT (inter-fractional) and between pre-treatment and post-treatment CBCT (intra-fractional; only for fractions without rotational treatment couch correction) were calculated in left–right (LR), cranio-caudal (CC) and anterior-posterior (AP) direction after bony-anatomy and soft-tissue matching. Systematic/random setup errors were estimated; treatment margins were calculated. Results No serious adverse events occurred. Twenty-three (67.6%) markers were visible during radiotherapy (n = 3 middle oesophagus, n = 16 distal oesophagus, n = 4 proximal stomach). Margins for inter-fractional displacement after bony-anatomy match depended on the localisation of the primary tumour and were 11.2 mm (LR), 16.4 mm (CC) and 8.2 mm (AP) for distal markers. Soft-tissue matching reduced the CC margin for these markers (16.4 mm to 10.5 mm). The mean intra-fractional shift of 12 distal markers was 0.4 mm (LR), 2.3 mm (CC) and 0.7 mm (AP). Inclusion of this shift resulted in treatment margins for distal markers of 12.8 mm (LR), 17.3 mm (CC) and 10.4 mm (AP) after bony-anatomy matching and 12.4 mm (LR), 11.4 mm (CC) and 9.7 mm (AP) after soft-tissue matching. Conclusion This study demonstrated that the implantation of gold markers was safe, albeit less stable compared to other marker types. Inter-fractional motion was largest cranio-caudally for markers in the distal oesophagus, which was reduced after soft-tissue compared to bony-anatomy matching. The impact of intra-fractional baseline shifts on margin calculation was rather small.

Highlights • Carbon-ion re-irradiation for pancreatic cancer; feasibility and efficacy. • Adjuvant chemotherapy improve local control of re-irradiation using carbon ions. • Carbon-ion radiotherapy for recurrent pancreatic cancer; reasonable option., Background and purpose Patients who receive carbon-ion radiotherapy (C-ion RT) for primary pancreatic cancer may experience locoregional recurrence; however, the treatment options for such patients are limited. We aimed to investigate the feasibility and efficacy of carbon-ion re-irradiation for patients with pancreatic cancer who experienced recurrence after initial C-ion RT. Materials and methods Twenty-one patients with recurrent pancreatic cancer who underwent repeat C-ion RT between December 2010 and November 2016 at our institute were retrospectively evaluated. The sites of post-initial C-ion RT failure were in-field central in 16 patients (76.2%) and marginal in 5 (23.8%). The median doses of initial and repeat C-ion RT were both 52.8 Gy (relative biological effectiveness [RBE]). Thirteen patients (61.9%) received concurrent chemotherapy with re-irradiation, while 11 (52.4%) received adjuvant chemotherapy. Results The median follow-up period after re-irradiation was 11 months. The 1-year local control, progression-free survival, and overall survival rates were 53.5%, 24.5%, and 48.7%, respectively. Toxicity data was obtained from the patients’ charts. Only 1 patient (4.8%) developed grade 3 acute toxicities and none developed grade ≥3 late toxicities. Univariate analysis indicated that patients who received adjuvant chemotherapy had significantly improved local control rates compared with those who did not; the 1-year local control rates were 80.0% and 0.0%, respectively (P = 0.0469). Conclusion Repeating C-ion RT may be a reasonable option with tolerable toxicity for patients with recurrent pancreatic cancers. Adjuvant chemotherapy appears to improve the local control rate. This is the first study to examine re-irradiation using C-ion for recurrent pancreatic cancer after initial C-ion RT.

Highlights • Postoperative pseudoaneurysms occur after upper gastrointestinal operations. • Almost half (52%) of the pseudoaneurysms are diagnosed when a rupture occurs. • Rupture of the pseudoaneurysm can be treated by embolism of the artery. • The formation of the pseudoaneurysm, occured in less than 48h as in earlier CTA the gastroduodenal artery appeared normal., Introduction Post operative pseudoaneurysm of the gastroduodenal artery is a very rare entity. Rupture of the pseudoaneurysm can be treated by embolism of the artery. Presentation of case A 71 years old male with a perforated pyloric ulcer was treated with controlled external duodenal fistula. Due to postoperative bleeding a subtotal gastrectomy was performed. A second episode of bleeding occurred and rupture of a pseudoaneurysm of the gastroduodenal artery was diagnosed by computed angiography and treated by embolism of the artery. Three days later the duodenal stump was ruptured and a new controlled external duodenal fistula was surgically created. The patient died 6 weeks later due to multiple organ failure. Discussion Pseudoaneurysm is the result of self-contained ruptures of one or more layers of the vascular wall. Computed angiography is the golden standard to identify pseudoaneurysms (100% sensitivity). Early suspicion for the presence of a pseudoaneurysm is crucial, as when the rupture actually occurs, the mortality rate is remarkably high. Endovascular approach is a minimally invasive procedure with high success rates (70–100%) and significantly lower morbidity and mortality rates. Surgical is reserved in case of bleeding recurrence. The fact that is particularly interesting in this patient is the timing of the formation of the pseudoaneurysm, considering the fact that 48 h earlier the gastroduodenal artery appeared normal. Conclusion There are no guidelines regarding the treatment of the pseudoaneurysm of the gastroduodenal artery. It seems reasonable to treat them immediately after diagnosis because a possible rupture of the aneurysm has an extremely high mortality.