Preliminary Biopsy Research Articles

Clinical features, diagnostics and treatment of FGF23 secreting tumors: series of 40 clinical cases

Tumor-induced osteomalacia is an acquired rare disease manifested by hypophosphatemic osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23). FGF 23 is a non-classical hormone secreted by bone tissue (osteocytes) and regulates phosphorus metabolism.The aim of this work is to present clinical experience in the diagnosis, treatment and rehabilitation of patients with tumor-induced osteomalacia. 40 patients with clinically-confirmed tumor-induced osteomalacia were included in the study, 34 of whom had the tumor localized, 27 underwent surgical treatment and 21 achieved stable remission. The median age was 48 [41; 63] years, 43% were men, the time left from the the onset of the disease was 8 [4; 10] years. Biochemical findings were hypophosphatemia 0.47 [0.4; 0.53] mmol/l, a decrease in the tubular reabsorption phosphate 62 [52; 67]%, and an increase in alkaline phosphatase of 183 [112; 294] units/l. At the time of diagnosis, 100% had multiple pathological fractures, only 10% could move independently, and 77.5% classified the pain as unbearable (8-10 points according to the 10-point pain syndrome scale ). Among the methods used to detect tumors, the most sensitive were scintigraphy with tectrotide with SPECT/CT 71.4% (20/28) and MRI 90% (18/20). In 35% of cases, the tumor was localized in soft tissues and in 65% in bone tissue; The tumor was most often detected in the lower extremities, followed by the head in frequency of localization. 18 patients currently have no remission and they receive conservative treatment (phosphorus and alfacalcidol n=15 and burosumab n=3). In case of achieving remission (n=21), regression of clinical symptoms and restoration of bone and muscle mass was observed. Extensive excision of the tumor without prior biopsy resulted in the best percentage of remission - 87%. Tumor-induced osteomalacia is characterized by severe damage to bone and muscle tissue with the development of multiple fractures, muscle weakness and severe pain syndrome. In laboratory diagnostics, attention should be paid to hypophosphatemia, a decrease in the tubular reabsorption phosphate index and increased alkaline phosphatase. The use of functional diagnostic methods with a labeled somatostatin analogue to the subtype 2 receptor and MRI with contrast enhancement are the most accurate methods of topical diagnostics. In case of localization of the tumor, a wide excision without a preliminary biopsy is recommended.

Study of the role of various diagnostic methods in patients with benign and neoplastic cervical diseases

Introduction. Cervical intraepithelial neoplasias that have been recognized as a precursor of squamous cell carcinoma are subject to active detection for the purpose of eradication. Human papillomavirus (HPV) exposure of women is the major risk factor for carcinogenesis, which is a necessary part for the formation of a pre-tumour and malignant phenotype. Cervical intraepithelial neoplasias that precede the development of squamous cell carcinoma should be actively detected and treated early. The identification of patients with HPV is an important part of subsequent therapies. Inosine pranobex is used as one of the components of the treatment of HPV-associated diseases.Aim. To study the role of various diagnostic methods in patients with benign and neoplastic cervical processes.Materials and methods. The study included 311 women who were 21–64 years old. Colposcopy, cytological examination, HPV testing, preliminary biopsy, cervical excise with histological evaluation of tissue sampling were carried out.Results. HPV 16 was more often detected in a malignant tumour and CIN 3; HPV type 31 and 33 were more often detected in CIN 2 and CIN 3; HPV type 18 was detected in almost all patient with CIN, and malignant and benign neoplastic disorders in preliminary biopsy, that was not typical of results of the excision. In excision CIN 1 were confirmed in 17.07%, CIN 2 in 31.88%, CIN 3 in 66.67%. Preliminary results of benign process in 6.67% turned out to be CIN 1, and in 6.67% – CIN 2, that confirms the need for a comprehensive evaluation. Studies of prevalence of various types of HPV showed that the established sequence of recommended tests, which consists of extended colposcopy, cytology and identification of HPV types, if necessary, does not always correspond to the biopsy results and histological findings on cervical excision specimens. According to our sources, the final result can be determined after excision procedure of cervical tissue and histological examination of the tissue obtained.Conclusion. No strong correlations between examination methods and cervical pathology have been revealed. The final diagnosis is made after cervical biopsy. High prevalence of different types of HPV raises the question of need for complex therapy with inclusion the inosine pranobex.

THU462 Clinical Features & Management Of FGF23 Secreting Tumors: Series Of 40 Clinical Cases

Abstract Disclosure: S. Gronskaia: None. Z. Belaya: None. L. Rozhinskaya: None. T. Dubovitskaya: None. E. Mamedova: None. E.A. Pigarova: None. M. Degtyarev: None. S. Rodionova: None. Y. Buklemishev: None. D. Babaeva: None. V. Vladimirova: None. N. Tarbaeva: None. S. Serzhenko: None. A. Grigoriev: None. L. Dzeranova: None. V. Karpenko: None. A. Karasev: None. R. Fedotov: None. I. Ulyanova: None. D. Trukhina: None. N. Toroptsova: None. O. Lesnyak: None. N.G. Mokrysheva: None. G.A. Melnichenko: None. I. Dedov: None. Introduction: Tumor-induced osteomalacia is an acquired rare disease manifested by hypophosphatemic osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23). FGF 23 is a non-classical hormone secreted by bone tissue (osteocytes) and regulates phosphorus metabolism.The aim of this work is to present clinical experience in the diagnosis, treatment and rehabilitation of patients with tumor-induced osteomalacia. Materials and methods: 40 patients with clinically-confirmed tumor-induced osteomalacia were included in the study, 34 of whom had the tumor localized, 27 underwent surgical treatment and 21 achieved stable remission. Results: The average age was 48 +/- 14 years, 43% were men, the time left from the the onset of the disease was 8 +/- 6 years. Biochemical fundings were hypophosphatemia 0.47 [0.4 ; 0.53] mmol/l, a decrease in the tubular reabsorption phosphate 62 [52 ; 67]%, and an increase in alkaline phosphatase of 183 [112 ; 294] units/l. At the time of diagnosis, 100% had multiple pathological fractures, only 10% could move independently, and 76.3% classified the pain as unbearable (8-10 points according to the 10-point pain syndrome scale ). Among the methods used to detect tumors, the most sensitive were scintigraphy with tectrotide with SPECT/CT 71.4% (20/28) and MRI 90% (18/20). In 55% of cases, the tumor was localized in soft tissues and in 45% in bone tissue; The tumor was most often detected in the lower extremities, followed by the head in frequency of localization. 18 patients currently have no remission and they receive conservative treatment (phosphorus and alfacalcidol n=15 and burozumab n=3). In case of achieving remission (n=21), regression of clinical symptoms and restoration of bone and muscle mass was observed. Extensive excision of the tumor without prior biopsy resulted in the best percentage of remission - 87%. Conclusion: Tumor-induced osteomalacia is most common in the middle age people. It is characterized by severe damage to bone and muscle tissue with the development of multiple fractures, muscle weakness and severe pain syndrome. In laboratory diagnostics, attention should be paid to hypophosphatemia, a decrease in the tubutar reabsorption phosphate index and increased alkaline phosphatase. The use of functional diagnostic methods with a labeled somatostatin analogue to the subtype 2 receptor and MRI with contrast enhancement are the most accurate methods of topical diagnostics. In case of localization of the tumor, a wide excision without a preliminary biopsy is recommended. Presentation: Thursday, June 15, 2023

Pathomorphism of buccal grafts used in surgery of extensive bulbar urethral strictures: immunohistochemical analysis

Introduction. The adverse effects of urine on unadapted tissues are known. This is also entirely relevant for buccal grafts used in augmentation urethroplasty, where these effects have not been thoroughly studied so far.Objective. To assess the ongoing pathomorphosis in buccal grafts used for urethral augmentation of extensive strictures in the bulbous region and to evaluate how much urine influences their histological transformation following surgery.Materials & methods. The study included 15 patients with extensive strictures of the bulbous urethra, who underwent a two-stage augmentation urethroplasty with buccal grafts. The grafts pathomorphosis was studied 6 months after the first surgery stage where urethrotomy had been performed with graft augmentation of the dorsal semicircle and the formation of distal and proximal neomeatuses. Natural urination through the latter was restored on days 14 – 20 following the surgery. During the second stage, six months later, urethral tubularisation was performed with two preliminary biopsies of the proximal and distal segments of the grafts implanted in the areas of the neomeatuses formed earlier. The distal area of the graft had no contact with urine, while this contact has occurred in the proximal segment since restoration of natural urination. In biopsy specimens, pathomorphosis of the grafts was studied using immunohistochemical markers: vimentin, clone SRL33; CD34, clone QBEnd/10; MSA HHF-35; СD3, clone LN10; Bcl-2, clone bcl-2\100\D5; CK-HMW 34BE-12.Results. It was found that inflammation was minimal in areas of grafts implanted that had no contact with urine, while in areas where such contact occurred it was verified to be pronounced even 6 months after the operation. On the submucosal level, this was manifested by an uneven arrangement of collagen fibers, a dysplastically developed vascular network, uneven proliferation of the endothelium with swelling and loss of cellular connectivity, in contrast to areas where there was no contact with urine. In such areas, the graft submucosa had a dense collagen framework with organized microvasculature and uniform epithelial surface.Conclusion. The impact of urine on buccal grafts used in augmentation urethroplasty is characterised by the disorganisation of its collagen framework, with a pronounced inflammatory component and the “reactivity” of the epithelial lining to the “toxic agent” that persists even 6 months after surgery. This may underlie the risk of a stenosis relapse in the proximal anastomosis area.

Management of melanoma of the foot in our subregion: Is preliminary biopsy always required?

Background: Majority of patients with melanoma of the foot in our subregion present late. After preliminary excision biopsy for these patients, many of them do not come back for further excision when there is an indication to do so following biopsy result. A better result could be achieved by using wider margins for excision biopsy in patients with low socio-economic status. Objectives: We assessed the role of excision of melanoma of the foot without preliminary biopsy as an option in the management of melanoma of the foot in our subregion. Materials and Methods: This was a 5-year retrospective review of patients with melanoma of the foot that presented to a tertiary health institution in Nigeria from December 1, 2014 to November 30, 2019. Results: Half of the patients with lesions that have not advanced locally (35.3%) had wide local excision with 2–3 cm margin without preliminary biopsy, relying on clinical diagnosis of melanoma. Another 35.3% of same number as those mentioned above were managed by doing a preliminary biopsy. Incision biopsy was employed for those with distant metastasis or lesions where amputation of any form was indicated (29.4%). Conclusion: Melanoma of the foot can be diagnosed clinically with a high degree of accuracy in majority of patients. Preliminary biopsy is essential for lesions requiring amputation or very large lesions. For small lesions, excision biopsy with wider margins than is used for preliminary biopsy is beneficial especially for poor patients who tend to delay having a second surgery that is definitive due to financial constraint, ignorance, or other reasons.

Aggressive Pilomatrixoma of the Scalp in a Geriatric Patient: A Rare Occurrence

Pilomatrixoma is a benign cutaneous adnexal neoplasm that arises from the hair matrix. This lesion is typically observed in the first two decades of life, with most cases occurring before the age of 20. However, it is rare in the elderly. While aggressive and malignant variants of pilomatrixoma exist, they are rarely reported compared to their benign counterparts. In this case, we present an instance of aggressive pilomatrixoma in a 90-year-old female. The patient exhibited a large ulceroproliferative growth on the scalp. A preliminary biopsy was performed, followed by wide local excision. Both the biopsy and excision specimens exhibited characteristics of pilomatrixoma, with a focal infiltrative growth pattern and moderate nuclear atypia. Features indicative of malignancy, such as geographic necrosis, brisk mitosis, atypical mitosis, vascular invasion, and perineural invasion, were not observed. Therefore, the diagnosis of aggressive pilomatrixoma was made. Wide local excision and subsequent skin grafting were conducted, with no involvement of deeper subcutaneous tissue and intact pericranium. The patient is currently faring well during follow-up. This case underscores the importance of meticulous histopathological examination for distinguishing aggressive variants, as they carry a higher risk of recurrence and aid in distinguishing aggressive pilomatrixoma from carcinoma. Failure to recognise the aggressive variant may result in inadequate management.

Updates in the Diagnosis and Management of Linear IgA Disease: A Systematic Review.

Background and Objectives: Linear IgA disease (LAD) is a rare autoimmune blistering disease with linear IgA deposits along the basement membrane zone. Direct immunofluorescence remains the gold standard for diagnosis, but other diagnostic measures reported in recent literature have proven useful in the setting of inconclusive preliminary results. Dapsone is a commonly used treatment, but many therapeutic agents have emerged in recent years. The objective of this study is to provide a comprehensive overview of updates on the diagnosis and management of LAD. Materials and Methods: A literature search was conducted from May to June of 2021 for articles published in the last 5 years that were related to the diagnosis and management of LAD. Results: False-negative results in cases of drug-induced LAD and the presence of IgG and IgM antibodies on immunofluorescence studies were reported. Serration pattern analysis has been reported to be useful in distinguishing LAD from sublamina densa-type LAD. Rituximab, omalizumab, etanercept, IVIg, sulfonamides, topical corticosteroids, and others have been used successfully in adult and pediatric patients with varying disease severity. Topical corticosteroids were preferred for pediatric patients while rituximab and IVIg were used in adults with recalcitrant LAD. Sulfonamides were utilized in places without access to dapsone. Conclusion: In cases where preliminary biopsy results are negative and clinical suspicion is high, repeat biopsy and additional diagnostic studies should be used. Patient factors such as age, medical comorbidities, and disease severity play a role in therapeutic selection.

Heavy Metals Assessment in the Medjerda River Basin (Northeastern Algeria): A Preliminary Water Analysis and Toad Skin Biopsy

Our study attempted to monitor the quality of water in Medjarda basin (Northeastern Algeria) and to provide baseline information of heavy metals in the water as well as in a potential amphibian biosentinel, the spiny toad, Bufo spinosus. We measured pH, temperature, dissolved oxygen and biological oxygen demand of water and levels of heavy metals in toad skin using an atomic absorption flame spectrophotometer. Lead (Pb) concentration in water and in toad skin at all sites exceeded respectively 60 and 96 times the standard reference values. The heavy metal concentrations, in descending order, in water and in male toad skin were as follows: Pb > Fe > Cu > Zn and Fe > Pb > Zn > Cu respectively. This study highlights the ecological status of the surrounding areas upstream of the Medjarda basin as being a point source of heavy metal pollution. It is further stated that a non-invasive skin removal is an ethically sound technique to evaluate heavy metal accumulation in aquatic animals like toad, without euthanizing the specimens and making any loss to biodiversity of the species.

Individualized robotic organ‐sparing surgery in a paediatric case of renal perivascular epithelioid cell tumour

Perivascular epithelioid cell tumours (PEComas) represent a rare group of mesenchymal tumours with an unpredictable outcome. They are usually observed in middle-aged women whilst they are very rare in children, with limited cases described. Due to the rare anatomical location in kidneys, a correct diagnosis and treatment is really challenging. We observed and treated a case of kidney's PEComa in a 14-year-old boy. An individualized approach based on anatomical (3D CT-reconstructions) and histopathological (US-guided preliminary biopsy) features lead us to perform a successful robotic-sparing surgery enabling the preservation of two-thirds of the kidney involved. A meticulous preoperative planning in selected patients can lead to a minimally invasive approach even in some paediatric kidney's neoplasms.

Soft tissue sarcomas: Evaluation by immunohistochemistry

Soft tissue sarcomas represent a histologically heterogenous group of malignant tumors arising from the soft tissue compartments, i.e smooth muscles, skeletal muscles, adipose tissue, blood vessels, connective tissue mesenchyme, neural tissue and other tumors of uncertain histogenesis(1). Soft tissue sarcomas are relatively rare tumors, represent less than 1% of adult malignancies based on data report from American Cancer Society (2). The crude incidence rate in Iraq for soft tissue sarcomas was 219/ 100,000 population during 2014 with male: female ratio of 1.3:1, and highest peak age between 30-34 years (3). The histological subtype and microscopic criteria are two parameters that influence the tumor grade which is the best predictor for aggressiveness. ( 2)
 Objectives:
 A retrospective evaluation of soft tissue sarcomas, using immunohistochemical study of Myosin, Desmin, Smooth muscle Actin (SMA) and Vimentin, aiming to re-evaluate the primary diagnosis and whether IHC assessment in soft tissue sarcoma is mandatory to reach a final interpretation.
 Material and Patients: 
 A total of 50 cases soft tissue sarcomas were reviewed retrospectively from case archives of histopathology department/ Central Public Health Laboratory, for the period (2011-2018). The data for these cases were collected including the age, gender, site of the tumor and the preliminary biopsy report findings. Hematoxylin& Eosin (H&E) stain and IHC staining of unstained sections from formalin-fixed, paraffin-embedded tissue were performed using SMA, Vimentin, Desmin and Myosin.
 Methods: Age and gender distribution of the 50 cases was correlated. The IHC staining performed on 5 microns paraffin sections, applying peroxidase-Antiperoxidase technique and both positive and negative control slides were included for Smooth muscle actin (SMA), clone 1A4, Desmin (clone D33), Myosin (clone 2F12.A9) and Vimentin (Clone V9). The monoclonal antibodies used were from DAKO manufacturer as ready to use monoclonal antibodies while freeze-dried antibodies used for myosin with 1:20 dilution. Negative and positive control slides were used simultaneously. The staining intensity was assessed based on the percentage of positive cells expression of the four IHC monoclonal antibodies. Negative staining reported when no stain seen. Positive (+) means up to 30% of tumor cells with antigen expression. Positive (++) interpretation given when 31-60% of tumor cells show staining reaction, while Positive (+++) interpretation reported when over 60% of tumor cells showing staining reaction.
 Results:
 The staining interpretation of the four monoclonal antibodies were confirmatory for the original diagnosis in 40% of cases, while 60% of the final diagnoses were against the original interpretation. SMA was positive in 38/50 cases (76%). Desmin was positive in 8/50 cases (20%) Vimentin was positive in 42/50 of cases (84%), Myosin was positive in 30/50 of cases (71.4%).
 The current study focus on histological re-evaluation of different types of soft tissue sarcomas (including RMS-with its subtypes), MFH-storiform, pleomorphic and myxoid subtypes), fibrosarcoma, leiomyosarcoma, alveolar soft part sarcoma and synovial sarcoma depending on immunohistochemical study. The original diagnosis have been changed after the immunohistochemistry stain from fibrosarcoma to rhabdomyosarcoma and leiomyosarcoma , Malignant fibrous histiocytoma to rhabdomyosarcoma, alveolar rhabdomyosarcoma to Malignant fibrous histiocytoma, soft tissue sarcoma to rhabdomyosarcoma , pleomorphic MFH to pleomorphic rhabdomyosarcoma. Embryonal and alveolar rhabdomyosarcoma were confirmed by IHC as so. Leiomyosarcoma was confirmed as the same in one case. Embryonal Rhabdomyosarcoma changed to leiomyosarcoma by IHC positivity for desmin. Six cases of MFH were confirmed as malignant fibrous histiocytoma after IHC. Two cases of synovial sarcoma were re-evaluated as rhabdomyosarcoma. Vimentin revealed 100% positivity in 10 cases and regarded as a sensitive marker for mesenchymal tissue but it is not specific for certain types of sarcomas. The presence of desmin diffusely throughout a tumor is an indication of myoid differentiation and the presence of either SMA or desmin focally should not necessarily be equated with myoid lineage but rather with myofibroblastic lineage, which go in the same direction with Hirofumi N. et al. (1998).(4)
 Conclusions: The co-expression of SMA and Desmin helped in the diagnosis of leiomyosarcoma (LMS). Myosin expression was helpful in the diagnosis of rhabdomyosarcoma (RMS) and alveolar soft part sarcoma (ASPS). Smooth muscle actin (SMA) and vimentin were not specific for the diagnosis of malignant fibrous histiocytoma (MFH). High grade spindle cell sarcoma express SMA only without myosin or desmin can be categorized as pleomorphic myogenic sarcoma. By applying immunohistochemical markers, 60% of soft tissue sarcomas were different from the preliminary diagnosis while 40% of cases were supportive of the original H&E diagnosis.

Endometriosis in a case with Fraser Syndrome

Introduction: Fraser Syndrome is a rare genetic disorder characterized by urogenital defects, cutaneous syndactyly and cryptophthalmos commonly diagnosed during foetal autopsy. Vaginal atresia is one of the major diagnostic criteria of Fraser Syndrome and could be a contributing factor of endometriosis following the development of hematocolpos. Imperforate hymen, often misdiagnosed as vaginal atresia, is a rare diagnosis in patients with Müllerian anomalies. Here, we report a case of Fraser Syndrome with chronic pelvic pain as a result of delayed hymenotomy and the extensive management of endometriosis. Case Report: A 15-year-old girl with Fraser Syndrome presented with pelvic pain. Examination revealed a large hematocolpos caused by an imperforate hymen. Due to the lack of paediatric intensive care locally, she had a delayed hymenotomy. She continued to suffer from chronic pelvic non-cyclical pain post-hymenotomy. Preliminary laparoscopy and biopsy showed endometriosis. Despite excision and clearance of endometriosis, she experienced persistent pain while taking morphine and was trialled with several hormonal therapies such as leuprorelin acetate, progestogen and combined hormonal therapy. She received medical therapy for 10 years until she re-presented with erratic bleeding and pain. Laparoscopy again identified endometriosis. Conclusion: Early recognition and treatment minimize risk of endometriosis especially in premenarcheal adolescent girls with obstructive Müllerian anomalies presenting with pelvic pain. Adequate pain control and medical management permit a delay in surgical intervention facilitating further investigations and thorough counselling with the patient and family about the implications of endometriosis on fertility and quality of life.

The diagnostic value of routine preliminary biopsy in diagnosing late prosthetic joint infection after hip and knee arthroplasty.

Biopsy of the periprosthetic tissue is an important diagnostic tool for prosthetic joint infection (PJI) as it enables the detection of the responsible microorganism with its sensitivity to antibiotics. We aimed to investigate how often the bacteria identified in the tissue analysis differed between samples obtained from preoperative biopsy and intraoperative revision surgery in cases of late PJI; and whether there was a therapeutic consequence. A total of 508 patients who required revision surgery of total hip arthroplasty (THA) (n = 231) or total knee arthroplasty (TKA) (n = 277) because of component loosening underwent biopsy before revision surgery. The tissue samples collected at biopsy and during revision surgery were analyzed according to the criteria of the Musculoskeletal Infection Society (MSIS). In total, 178 (113 THA, 65 TKA) were classified as infected. The biopsy procedure had a sensitivity of 93.8%, a specificity of 97.3%, a positive predictive value (PPV) of 94.9%, a negative predictive value (NPV) of 96.7%, and an accuracy of 96.1%. Of the 178 infected patients, 26 showed a difference in the detected bacteria from the biopsy and the revision surgery (14.6%). This difference required a change to antibiotic therapy in only two cases (1.1%). Biopsy is a useful tool to diagnose PJI, but there may be a difference in the detected bacteria between the biopsy and revision surgery. However, this did not affect the choice of antibiotic therapy in most cases, rendering the clinical relevance of this phenomenon as low. Cite this article: Bone Joint J 2020;102-B(3):329-335.

2056 CMV Colitis Superimposed on Ischemic Colitis in an Immunocompetent Individual

INTRODUCTION: Cytomegalovirus (CMV) infections are more commonly seen in individuals with immunosuppressive diseases. We present a unique case of CMV colitis superimposed as ischemic colitis in an immunocompetent individual. CASE DESCRIPTION/METHODS: A 68-year-old man with history of PE (on Xarelto), pneumothorax & COPD presented with 10 weeks of diarrhea, associated with chills, lower abdominal discomfort, poor appetite, and weight loss of 15 pounds. Rectal exam showed dark stool and FOBT was positive Lab data showed elevated ESR and CRP. All stool studies were negative. CT Abdomen reported colonic findings suggestive of colitis with areas of active inflammation. Colonoscopy showed inflammation characterized by congestion (edema), erosions, granularity & ulcerations in a continuous and circumferential pattern from the sigmoid colon to the terminal ileum with sparing of mid & distal sigmoid colon and the rectum (Figures 1 and 2). Preliminary biopsies were suspicious for Crohns Disease. Patient was started on PO Prednisone 60 mgs daily & Pentasa TID and discharged for close follow up with GI. He kept on failing outpatient treatment, and was re-admitted twice with worsening of symptoms. Repeat CT scans showed worsening diffuse colitis. C Diff was checked, which was –ve. He was re-started on IV Abx, IV Steroids and supportive care. His symptoms continued to worsen, so Colorectal Surgery was consulted and, he underwent open subtotal colectomy. Pathology Slides from the Surgical Specimen were diagnostic for Ischemic looking bowel, and showed no features of IBD. So, decision was made to send the slides for second opinion. Meanwhile, he continued to deteriorate, so he was taken for emergent exploratory laparotomy and was found to have diffusely ischemic and distended bowel. Confirmation of pathology was not consistent with IBD. It showed Ischemic ileocolitis with possible superimposed CMV colitis with CMV inclusion bodies (Figure 3). IV Ganciclovir was initiated, steroids were discontinued. He began to improve, diet was advanced and was discharged with GI follow up. DISCUSSION: Suspicion of CMV colitis should be investigated by endoscopic evidence. The typical findings such as owl’s eye inclusion bodies on histology is specific for CMV. This is an unusual case of CMV associated ischemic colitis in an immunocompetent individual. This case report also should sound an alarm to GI physicians on thinking about CMV colitis infections even in immunocompetent individuals.

2085 Suspected Crohn’s in Acute Salmonella Enterocolitis: A Journey of Differentiating Two Common Terminal Ileitis Etiologies

INTRODUCTION: Terminal ileitis signifies a generalized inflammatory process in the most distal portion of the small bowel, with an expansive range of underlying etiologies including Crohn’s disease and salmonella. Although stool cultures may reveal a salmonella infection, the diagnosis becomes more difficult if stool cultures are positive but patients do not respond to antibiotics. Treating such pathology with two potential underlying etiologies may lead to further complications, specifically, when administering corticosteroids and immunotherapy for an autoimmune disorder may conflict with active treatment against an acute infection. Our case presents a patient who had known salmonella positive stool cultures but inconsistent colonoscopy and pathology results. He ultimately improved with steroid and anti-TNF therapy. CASE DESCRIPTION/METHODS: A 29-year-old male with history of small bowel obstruction of unclear etiology five months prior, presented with acute on chronic diarrhea and abdominal pain. He denied any recent sick contacts, ingestion of raw or undercooked food, or personal or family history of inflammatory bowel disease (IBD). A CT scan identified terminal ileitis. Stool cultures returned positive for salmonella. Despite treatment with ciprofloxacin, patient’s symptoms persisted. Colonoscopy revealed diffuse inflammation and ulceration of the terminal ileum without stricture, with extension into the ascending and transverse colon. Preliminary biopsy revealed reduction in goblet cells. The patient was treated with solumedrol and subsequent infliximab due to the high suspicion of underlying IBD pathology after receiving a course of antibiotics. Though his hospital course was complicated by partial small bowel obstruction, his symptoms ultimately resolved. DISCUSSION: Terminal ileitis secondary to Crohn’s disease and salmonella may overlap in presentation which can complicate therapy. In this case, it is probable that there was a component of IBD superimposed with a bacterial infection, given the acute on chronic nature of his symptoms. In the case of superimposed infection, antibiotics should be initiated prior to prescribing immunosuppressive therapy that could allow further invasion. However, waiting to initiate immunosuppressants must be balanced with a patient’s worsening clinical picture and complications such as small bowel obstruction.

Cryopreservation of incomplete compacted morulae and preliminary biopsy of excluded fragments.

The complexity of predicting embryo development potential at the cleavage stages and the emergence of epigenetic risks during prolonged in vitro culture of pre-implantation embryos made it more advantageous to transfer embryos at the morula stage to the uterine cavity. The criteria for estimating embryos at this stage that allow prediction of cryopreservation outcomes have been poorly described. All day 4 embryos (n = 224) were graded 1, 2, 3, 4 or 5 according to blastomere compaction degree (BCD = 100, 75, 50, 25 or 0%, respectively) and the survival and blastocyst formation rate of these morulae were studied after cryopreservation. An inverse dependence was found between survival rate and BCD. Excluded fragments were characterized by low osmotic reaction during exposure to cryoprotective medium and, after freeze-thawing, they were destroyed. As damaged necrotic areas of the embryo can affect their further development rate we proposed blastomeres and biopsy fragments of incomplete compacted morula be removed before embryo cryopreservation. This step led to significant increase in the post-thawing survival rate up to 93.1 ± 4.1%, 75 ± 8.8% and blastocyst formation rate up to 85.2 ± 10.4%, 59.4 ± 5.2% in grade 2 and grade 3 embryos, respectively. There was no significant difference in grade 4 embryos. Therefore the removal of blastomeres and biopsy fragments in incomplete compacted morulae can improve cryopreservation outcomes of grade 2 and grade 3 embryos with BCD.

Interim analysis of ibrutinib plus paclitaxel for patients with advanced urothelial carcinoma previously treated with platinum-based chemotherapy.

4522 Background: Patients (pts) with advanced urothelial carcinoma (aUC) who progressed after platinum-based chemotherapy (PBCT) have a median overall survival (OS) of ~6 mo on CT and 8-10 mo on novel immune checkpoint inhibitors (ICIs). Treatment (tx) with ibrutinib (ibr), a first-in-class, once-daily inhibitor of Bruton’s tyrosine kinase (BTK) with immunomodulatory properties, plus paclitaxel (pac) may improve outcomes for pts with aUC. Methods: Pts with aUC who had 1-2 prior tx (≥1 PBCT and/or ICIs) formed one cohort of this phase 1b/2 study. Recommended phase 2 dose per phase 1b was ibr 840 mg/d + weekly pac 80 mg/m2 in 21-d cycles; starting ibr dose of 560 mg/d. nanoString gene expression assay (NanoString Technologies) was used for preliminary assessment of ibr-targeted kinases in baseline tumor biopsies. Results: This interim analysis included the first 29 pts treated (ibr 840/560 mg/d, n = 25/4; median age 67 y). 52% had 2 prior regimens (prior PD-L1 inhibitors, 100%). Median time on study/tx was 7.2/2.3 mo (max tx: 11.5 mo). Unconfirmed overall response rate (ORR) was 41% (complete/partial response: 10%/31%). Disease control rate was 62%. ORR was 71% for 7 pts with only lymph node metastases; ORR was 36% for 14 pts with 1 prior tx and 47% for 15 pts with 2 prior tx. Median duration of response was 4.2 mo (90% CI: 1.9-7.1). Median progression-free survival was 3.6 mo (90% CI: 1.6-5.4). Median OS was 14.7 mo (90% CI: 7.7-15.9). Follow-up is ongoing for durability/survival with 6 pts alive without progression, including 4 still on ibr. 76% of pts had grade ≥3 adverse events (AEs); 4 discontinued ibr + pac due to AEs and 1 had major hemorrhage. Pac exposure was not impacted by ibr; pac geometric mean Cmax (2066 ng/mL) and AUC0-∞ (3813 ng·h/mL) were consistent with historical data. Preliminary tumor biopsy data showed a nonsignificant trend of higher BTK/ITK/BMX expression in tx responders; analyses are ongoing. Conclusions: Ibr + pac shows promising results for ORR/OS in pts with aUC previously treated with PBCT and ICIs. No unexpected safety signals were seen; ibr + pac seemed tolerable. Follow-up of these and additional pts will support the activity and safety of ibr + pac in this study. Clinical trial information: NCT02599324.

Interim analysis of ibrutinib plus paclitaxel for patients with metastatic urothelial carcinoma previously treated with platinum-based chemotherapy.

365 Background: In patients (pts) with advanced urothelial carcinoma (aUC) who progressed after platinum-based chemotherapy (CT), median overall survival (OS) is ~6 mo with CT and 8-10 mo with novel immune checkpoint inhibitors (ICIs). Ibrutinib (ibr), a first-in-class, once-daily, inhibitor of Bruton’s tyrosine kinase (BTK) with immunomodulatory properties, plus paclitaxel (pac) may be an effective treatment (tx) for pts with UC. Methods: One cohort in this phase 1b/2 study assessed ibr + pac in pts who had 1-2 prior tx (≥1 platinum-based and/or ICIs) with aUC. Recommended phase 2 dose per Phase 1b was ibr 840 mg/d + weekly pac 80 mg/m2 in 21-d cycles; starting ibr dose: 560 mg/d. Preliminary BTK/other kinase assessment in baseline tumor biopsies was done by NanoString gene expression assay. Results: Based on interim analysis of the first 29 pts treated (ibr 840/560 mg/d, n = 25/4), median time on study/ tx was 7.2/2.3 mo (max tx: 11.5 mo). Median age was 67 y; 52% had 2 prior regimens (prior PDL-1 inhibitors, 100%). Unconfirmed ORR was 41% (complete/partial response: 10%/31%) and disease control rate was 62%. ORR was 71% for subset of 7 pts with only lymph node metastases, and 36% for 14 pts with 1 prior tx and 47% for 15 with 2 prior tx. Median duration of response was 4.2 mo (90% CI: 1.9, 7.1). Median PFS was 3.6 mo (90% CI: 1.6, 5.4) and median OS was 14.7 mo (90% CI: 7.7, 15.9). Follow-up for durability/survival is ongoing with 6 pts alive without progression, with 4 still on ibr tx. 76% of pts had grade ≥3 adverse events (AEs); 4 discontinued ibr + pac due to AEs and 1 had major hemorrhage. Pac exposure was not impacted by ibr; pac geometric mean Cmax (2066 ng/mL) and AUC0-∞ (3813 ng.h/mL) were consistent with historical data. Preliminary tumor biopsy data showed a non-significant trend of higher BTK/ITK/BMX expression in responders; analyses are ongoing for ibr-targeted kinases. Conclusions: These results indicate that ibr + pac shows promising results for ORR and OS in pts with aUC previously treated with platinum-based CT and ICIs. There were no unexpected safety signals; ibr + pac seemed tolerable. Follow up of these and additional pts will support the efficacy and safety of ibr + pac in this study. Clinical trial information: NCT02599324.

Thulium Laser Treatment of Upper Urinary Tract Carcinoma: A Multi-Institutional Analysis of Surgical and Oncological Outcomes.

To evaluate the efficacy and safety of ureteroscopic thulium laser (TL) treatment of upper urinary tract carcinoma (UTUC). Forty-two consecutive patients underwent conservative TL treatment for UTUC at two referral institutions. All patients underwent preliminary biopsy and then laser vaporization. A 272 μm and 365 μm laser fibers were used with a flexible and semirigid scope, respectively. Ablation was carried out with a 10 to 20 W power. Mean age at surgery was 68 years (SD 10.7). Mean tumor size was 14.3 mm (range 2-30 mm). Preliminary biopsy revealed the presence of low-grade disease in 29 (69.1%) patients, high-grade disease in 4 (9.5%) and 1 carcinoma in situ 1 (2.4%), whereas it was not conclusive in 8 (19%) cases. Final stage was pTa and pTis in 41 (97.6%) and 1 (2.4%) patients, respectively. Thirty eight percent (16) experienced Clavien-Dindo grade I complication, 47.6% (20) grade II, and 2.4% (1) grade III. Five (12%) patients underwent a second-look procedure due to residual disease. Eight (19%) patients experienced clinical recurrence. The median estimated recurrence-free survival was 44 months (SE 3.68). Four patients (9.5%) underwent a nephroureterectomy. Final pathological stage was pTis, pT3 high grade, pTa low grade, and pT0. Median follow-up was 26.3 months (range 2-54 months), and no progression or upstaging of disease occurred. TL management of UTUC is a safe and efficacious conservative treatment. Our experience shows optimal vaporization and hemostatic control in the absence of major complications.

A study on the role of receptor (ER,PR,HER-2/neu) in patients of carcinoma breast

Objective: To evaluate the expression of HER-2/neu, estrogen receptor (ER) and progesterone receptor (PR) in breast carcinomas. Methods: This was a prospective hospital based study conducted on patients of carcinoma breast. The study population comprised of patients who were diagnosed to have carcinoma breast on the basis of preliminary Trucut biopsy/ open biopsies, and subsequently underwent surgery for the disease. All patients who had undergone previous chemo or radiotherapy were excluded from the study. A total of 72 patients were included in the study. Results: About one third of patients were between 41-50 years of age (30.6%). TNM stage IIIB was among in 30.6% patients and IIIA was in 25%. Tumor grade III was among more than half of patients (61.1%). Infiltrating ductal carcinoma was among 88.9% patients. ER and PR was positive in 41.7% and 25% patients respectively. ER-/PR- was among 54.2% patients. HER2neu was positive in 22.2% of the patients. Luminal A and B was in 36.1% and 13.9% patients respectively. Conclusion: Breast cancer in Indian patients has been found to be histologically aggressive, presents at a younger age, and is less likely to be susceptible to conventional hormonal and targeted antibody treatment. Detecting and treating this increasingly important cause of mortality is an enormous challenge.

Dermoscopy and Pigmented Lesions of Oral Cavity

Dear editor, Pigmented lesions are relatively rare in the oral cavity. They represent a variety of entities ranging from racial pigmentation to manifestation of systemic illness (Addison’s disease), to benign (hemangioma, lymphangioma, melanotic nevi) and malignant neoplasms (Kaposi’s sarcoma, malignant melanoma, pigmented basal cell carcinoma). 1 Biopsy is usually avoided in vascular lesions like hemangioma, Kaposi’s sarcoma etc. by general dentists owing to the risk of excessive bleeding due to the possibility of their association with a feeder vessel. A color Doppler ultrasonography is sometime required in order to rule out this association; otherwise sclerosing agents are used for diagnostic and therapeutic purposes. 2 Melanotic lesions like malignant melanoma or melanotic nevi are sometimes seen in the oral cavity; some clinicians believe that incisional biopsy of a melanoma might disseminate the disease. 3 A guideline of biopsy taking for melanoma has been issued. It includes a full thickness excisional biopsy allowing assessment of the Breslow thickness, but preliminary biopsies are only advisable in case of acral melanoma; however, shave and punch biopsy are no more recommended, but hesitation of clinicians for taking biopsy from pigmented lesions cannot be ignored. 4 Dermoscopy is a non – invasive technique that allows a visualization of morphological features of the lesion that are not visible to a naked eye. This is useful in dermatology for making an early differential diagnosis of different pigmented lesions. 5 Despite their popularity in dermatology, they are not very popular in investigation of the mucosal lesions of lip and oral cavity. 6 Dermoscopy can be extremely helpful in making demarcation between melanotic nevi and malignant melanoma (Figure 1). There is a need to intensify the research pertaining to the use of dermoscopy in oral mucosal lesions, also a criterion has to be introduced for the diagnosis of oral pigmented lesions on dermoscopy. It minimizes the risk of the exposure of the patient to excisional biopsy that may be resulting in facial disfigurement. This procedure can be easily adopted by dentists working in private sectors and corporate sectors. Dental curriculum has to be enhanced with the use of dermoscopes in diagnosing pigmented oral lesions on graduate and post-graduate level.