[Toxicity of targeted therapies and immunotherapy with checkpointinhibitors in Hodgkin lymphoma]. / Toxicité des thérapies ciblées et de l'immunothérapie par inhibiteurs des points de contrôle dans le lymphome de Hodgkin.

TOXICITY OF TARGETED THERAPIES AND IMMUNOTHERAPY WITH CHECKPOINT INHIBITORS IN HODGKIN LYMPHOMA. In patients at increased risk of recurrence or progression after autotransplantation, or in cases of relapse after autotransplantation or after at least two lines of treatment when intensive multidrug therapy is no longer a treatment option, targeted anti-CD30 therapy with brentuximab vedotin may be proposed. Brentuximab vedotin is a monoclonal antibody directed against CD30 and coupled with an anti-microtubule cytotoxic agent, monomethyl auristatin E (MMAE). The main adverse side effect of brentuximab vedotin is peripheral neuropathy. In patients who have relapsed after intensive chemotherapy, including autograft for patients eligible for this treatment, and after failure of brentuximab vedotin, anti-PD1 immunotherapy (nivolumab or pembrolizumab) may be offered. Anti-PD1 (Programmed cell death protein 1) side effects are immune-related, varied and unpredictable (endocrinopathies, rash, colitis, interstitial lung disease). The tolerability profiles of brentuximab vedotin and anti-PD1 and the management of the main undesirable side effects of these treatments are detailed for clinical practice.

TOXICITÉ DES THÉRAPIES CIBLÉES ET DE L'IMMUNOTHÉRAPIE PAR INHIBITEURS DES POINTS DE CONTRÔLE DANS LE LYMPHOME DE HODGKIN. Chez les patients ayant un risque accru de récidive ou de progression après une autogreffe, ou en cas de rechute après autogreffe ou après au moins deux lignes de traitement quand la polychimiothérapie intensive n'est plus une option, un traitement ciblé anti-CD30 par brentuximab vedotin peut être proposé. Le brentuximab vedotin est un anticorps monoclonal dirigé contre le CD30 et couplé à un agent cytotoxique antimicrotubule, la monométhylauristatine E. Le principal effet indésirable du brentuximab vedotin est la neuropathie périphérique. Chez les patients ayant une rechute après chimiothérapie intensive incluant une autogreffe, et après échec de brentuximab vedotin, une immuno­ thérapie anti-PD1 (nivolumab ou pembrolizumab) peut être proposée. Les effets indésirables des anti-PD1 ( programmed cell death protein 1), liés à l'immunité, sont très variés et assez imprévisibles (endocrinopathies, rash, colite, pneumopathies interstitielles). Les profils de tolérance du brentuximab vedotin et des anti-PD1 et la gestion des principaux effets indésirables de ces traitements sont détaillés pour la pratique clinique.

Clinical and epidemiological trends in childhood leprosy: A 20-year retrospective analysis from a tertiary care hospital in Jammu, North India.

Background Slightly more than half the total number of childhood leprosy cases worldwide are from India. Aim To analyze the clinical and epidemiological trends of childhood leprosy over 20 years in a tertiary care hospital. Methods We retrieved the medical records of all children less than 15 years of age registered in the leprosy clinic between April 1998 and March 2018. We tabulated and analyzed data pertaining to demographic details along with clinical findings such as cutaneous lesions, nerves involved, sensory loss, deformities, reactions, smear status, histopathology and treatment. Results Out of total 1548 leprosy cases registered during the study period, 55 (3.55%) cases of childhood leprosy were diagnosed. Thirty five (63.6%) children were in the age group of 11-15 years and 83.7% were migrants from other states. Thirteen (23.6%) children reported contact with a diagnosed case of leprosy, mainly in close contacts. Fifty three (96.4%) children presented with cutaneous lesions while 2 (3.6%) had pure neural involvement. Borderline tuberculoid leprosy was the most common clinical presentation in 27 (49.1%) followed by borderline lepromatous leprosy in 11 (18%). Thickened peripheral nerve trunks were detected in 42 (76.4%), most commonly the ulnar nerve. Reactional episodes occurred in 12 (21.8%) cases (Type 1 reaction, 10 (18.2%); Type 2 reaction, 2 (3.6%)). Grade 2 disability was detected in 4 (7.3%). Multidrug therapy was started in all patients, multibacillary (MB) regimen in 42 (76.3%) patients and paucibacillary (PB) regimen in 13 (23.7%). Twenty five (45.4%) children defaulted from the treatment. On comparing the data of 2008-18 with that of the previous decade (1998-2007), there was a higher proportion of migrant cases as compared to local cases (3:1-11:1) and MB cases as compared to PB cases (2:1-6:1). The proportion of treatment defaulters declined from 60% to 36%. Limitations Relapse rate could not be calculated due to inadequate follow-up period. As it is a hospital-based retrospective study with no active surveys, these findings may not reflect trends in the community. Conclusion Childhood leprosy continues to be a significant problem. There is a clear need to strengthen early detection, treatment and regular follow-up of these cases in both high and low endemic settings.

The 10-year results after national introduction of pelvic lymph node staging in Danish intermediate-risk endometrial cancer patients not given postoperative radiotherapy.

The 10-year results after national introduction of pelvic lymph node staging in Danish intermediate-risk endometrial cancer patients not given postoperative radiotherapy. Gitte Ørtoft; Claus Høgdall; Estrid S Hansen; Margit Dueholm. OBJECTIVE: To prepare for the national introduction of sentinel node staging, we evaluated the consequences of the previous national decision to introduce lymph node staging in intermediate-risk endometrial cancer patients (grade 1/2 with > 50% or grade 3 with < 50% myometrial invasion) by determining the number of patients upstaged by lymphadenectomy and whether upstaging affected the survival and recurrence patterns of non-staged patients and patients with and without lymph node metastases. STUDY DESIGN: In a national cohort study, 2005-12, 1294 stage I-IV patients who should have been offered lymphadenectomy were progressively registered. The number of patients upstaged by lymphadenectomy, 10-year survivals were evaluated by Kaplan-Meier analysis and adjusted Cox regression. RESULTS: This study demonstrates that it takes time to introduce lymphadenectomy at a national level, as indicated by the increasing number of cases staged per year, from 12% in 2005 to 74% in 2012. Pelvic lymphadenectomy was performed in 43.8% (567/1294) and lymph node metastases were found in 13.6% (77/567). As 54 patients had further dissemination outside the uterine body, only 23 patients (6%) were upstaged from stage I to IIIC. Compared to lymph node-negative patients, the 77 patients with lymph node metastasis had significantly lower overall, (55% versus 68%), disease-specific (64% versus 86%), and progression-free survival (51% versus 77%), mainly due to non-local recurrences including a high number of paraaortic recurrences. In 873 final stage I intermediate-risk patients, 10-year survival and recurrence rates were not significantly lower in non-staged as compared to lymph node-negative patients (overall survival 62% versus 70%: disease-specific survival: 90% versus 90%, progression-free survival: 81% vs 83%), probably due to the low number of patients upstaged from stage I to stage IIIC. CONCLUSION: Lymph node metastases were present in 13.6% of patients with intermediate-risk who underwent pelvic lympadenectomy, and these patients had a lower 10-year survival than lymph node-negative patients. Because lymphadenectomy upstaged only 6% from stage I to stage IIIC, survival and recurrence rates were not significantly compromised in non-staged as compared to lymph node-negative intermediate-risk stage I patients. Sentinel node staging has now been implemented in Danish intermediate-risk endometrial cancer patients.

Chronic macrocheilia: a clinico-etiological series of 47 cases.

BACKGROUND: Macrocheilia is an inflammatory disfiguring condition responsible for the swelling of the lips. This multi-etiological entity represents a diagnostic and therapeutic challenge. Published data on macrocheilia is scarce, often limited to granulomatous cheilitis. METHODS: We conducted a retrospective study, including all patients presenting with chronic macrocheilia (CM) for nineteen years. CM was defined as a persistent enlargement of one or both lips for at least eight weeks. Both descriptive and analytical analyses were performed. RESULTS: Of the 47 patients identified, 20 (43%) had cutaneous leishmaniasis, 10 (21%) had Miescher's cheilitis, five (11%) had Melkersson-Rosenthal syndrome, five (11%) had sarcoidosis, one (2%) had lepromatous leprosy, one (2%) had systemic amyloidosis, and one (2%) had Crohn's disease. In four cases, the CM was unlabeled. Ulcerations were significantly associated with leishmaniasis (P < 0.05). Histological study showed a granulomatous infiltrate in 72% of cases. Medical treatment was adapted to the etiology of CM. Surgery was performed in two cases. Improvement of CM secondary to leishmaniasis was seen in all cases. In patients with idiopathic orofacial granulomatosis, partial improvement was noted in four cases and a total improvement in one case. Recurrences were noted in three cases after complete regression. CONCLUSIONS: Macrocheilia is a rare and disfiguring condition that requires an etiological investigation, considering that it can reveal a serious underlying systemic disease. We identified several factors that could help recognize the cause of CM, including age, history of intermittent swelling, the extent of lip enlargement, the existence of ulceration, and systemic symptoms.

Phototherapy as a treatment of early-stage mycosis fungoides and predictive factors for disease recurrence: A 17-year retrospective study.

BACKGROUND: Mycosis fungoides is the most common form of cutaneous T-cell lymphoma. Narrowband ultraviolet B and psoralen and ultraviolet A are effective treatment options, but studies of their treatment efficacy and disease relapse remain limited. OBJECTIVES: This study aimed (1) to determine the efficacy of narrowband ultraviolet B and psoralen and ultraviolet A as a treatment for early-stage mycosis fungoides and explore the predictive factors for complete remission and (2) to determine the relapse rate and analyze their predictive factors, including the utility of maintenance therapy. METHODS: This was a retrospective cohort study consisting of 61 patients with early-stage mycosis fungoides (IA - IB) treated with narrowband ultraviolet B or psoralen and ultraviolet A as the first-line therapy from January 2002 to December 2018 at the Division of Dermatology, Ramathibodi Hospital, Bangkok, Thailand. Cox regression analysis and Kaplan-Meier survival curve were performed for the main outcomes. RESULTS: A complete remission was achieved by 57 (93.5%) patients. The median time to remission was 7.80 ± 0.27 months. Types of phototherapy (narrowband ultraviolet B or psoralen and ultraviolet A), age and gender did not associate with time to remission, while the presence of poikiloderma and higher disease stage led to a longer time to remission. The cumulative incidence of relapse was 50.8%. The median time to relapse was 24.78 ± 5.48 months. In patients receiving phototherapy during the maintenance period, a treatment duration longer than six months was associated with a significantly longer relapse-free interval. CONCLUSION: Narrow-band-ultraviolet B and psoralen and ultraviolet A are effective treatment options for early-stage mycosis fungoides. Maintenance treatment by phototherapy for at least six months seems to prolong remission.

A retrospective comparative study of outcome with surgical excision and repair versus nonsurgical and ablative treatments for basal cell carcinoma.

BACKGROUND: There are few studies on basal cell carcinoma (BCC) from India. Long-term follow-up is available in only one study and the aesthetic outcome of treatment has not been evaluated in Indian patients. AIMS: In this retrospective study on BCC, we compared treatment failure, recurrence rates and aesthetic outcomes on long-term follow-up between surgical excision and repair, and nonsurgical and ablative treatments. METHODS: Records of patients with BCC treated in the dermatologic surgery clinic over the past 10 years were analyzed. Patients with histopathologically confirmed BCC who could be contacted were evaluated for recurrence, treatment failure, overall satisfaction and aesthetic outcomes by global aesthetic improvement scale. RESULTS: Out of 98 patients, 72 were contactable. Four patients received both nonsurgical and ablative treatments and surgical excision and repair sequentially and were excluded. The mean age of patients was 57.9 ± 15.8 years (24-90 years) and the male: female ratio was 1.6:1. The most common site involved was the face (72.1%) followed by trunk and scalp, and the most common type of BCC was the pigmented superficial type (33.8%), followed by the pigmented noduloulcerative type (16.2%). There was no significant difference between the groups in the number of high-risk cases. The mean follow-up period was 37.1 ± 31.4 (range, 4-120) months. Fifty one patients were treated with surgical excision and repair, and 17 with nonsurgical and ablative treatments (9-imiquimod, 5-cryotherapy, 4-radiotherapy). Treatment failure was seen in 5 (7.4%) patients, all in the nonsurgical and ablative treatments group (P = 0.0006). Recurrence was seen in 2 (2.9%) patients, both in the surgical excision and repair group (P > 0.05). Mean patient satisfaction was significantly higher with surgical excision and repair, though there was no significant difference in the Global Aesthetic Improvement Scale between the groups. LIMITATIONS: The sample size was low. Only telephonic and pictorial assessments were done where the patient could not come for follow-up. CONCLUSIONS: Surgical excision and repair was associated with better outcomes than nonsurgical and ablative treatments. Treatment failures and adverse events were high with nonsurgical and ablative treatments. The recurrence rate was low.

First-time versus recurrent penoscrotal extramammary Paget's disease: Clinicopathological characteristics and risk factors in 164 Chinese male patients.

BACKGROUND: Penoscrotal extramammary Paget's disease is a rare, slow-growing neoplasm with high frequency of local recurrence. AIMS: The aim of this study was to investigate the difference in clinicopathological characteristics between first-time and recurrent penoscrotal Paget's disease, and to discover the potential risk factors of recurrence. METHODS: Between January 2007 and February 2014, a total of 164 Chinese patients with biopsy-proven tramammary Paget's diseaseex in penis and scrotum underwent wide local resection in our institution. Among them, 142 patients with first-time disease and other 22 patients with recurrent disease were enrolled in this retrospective analysis. RESULTS: The median duration of symptoms was much shorter in recurrent disease than in first-timers (3 vs. 24 months, P < 0.001). Patients with recurrent disease tended to have lower lesion exudation rates (27.3% vs. 51.8%, P= 0.032). In addition, patients with distant stage were more likely to obtain recurrent disease compared with first-time disease (P = 0.005). Through immunohistochemical detection of extramammary Paget's specimen, we found that HER2/neu protein expression in the recurrent group was significantly higher than first-timers (P = 0.036). LIMITATIONS: In this study, the information on familial history of most patients was insufficient. Moreover, due to the lack of follow-up data of our included cases, we were unable to evaluate the prognosis after diagnosis of extramammary Paget's disease. CONCLUSION: Patients with penoscrotal Paget's disease, especially those with shorter duration of symptoms, exudation of lesions, distant-stage, Paget cells infiltrating into adnexa, and HER2/neu expression, should be followed up more carefully after surgery, as they were more likely to suffer recurrence.

[The clinical observation of NK/T-cell lymphoma of the nasal type]. / Klinicheskoe nabliudenie NK/T-kletochnoi limfomy nazal'nogo tipa.

The objective of the present work was to present the results of the clinical analysis of the patient presenting with natural killer (NK)/T-cell lymphoma of the nasal type. We undertook the analysis of the medical documentation concerning the case of interest. It was shown that the development of progressive perforation of the nasal septum and the pronounced destructive changes in the intranasal and adjacent structures following the endonasal surgical interventions made necessary differential diagnostics between the condition under consideration and certain latent disorders (such as Wegener's granulomatosis, leprosy, syphilis, leishmaniasis, dirofilariasis tuberculosis, etc.). The study has demonstrated that the negative results of the analysis imply the necessity of special attention to the possibility of development of oncological diseases including hematological disorders (e.g. NK/T-cell lymphoma) and the repeat careful follow-up examination of the patients by the experienced experts.

Clear cell odontogenic carcinoma. A review.

INTRODUCTION: Clear cell odontogenic carcinoma (CCOC) is described as an exceptional and hard to diagnose malignant tumor which was first reported by Hansen in 1985. The purpose of this review article is to show that CCOC is a not that rare entity and to discuss its various aspects in order to enhance the diagnosis. MATERIAL AND METHODS: A search in the English language literature was performed using the Scopus, ScienceDirect, PubMed and Medline databases between 1985 and 2016. Data were collected on epidemiologic, clinical, radiographic, histological, immunohistochemistrical, cytogenetic, management, follow-up and prognosis features of CCOC. RESULTS: Sixty-five studies from which a total of 95 case reports were included in the review. CCOC was generally seen in the fifth decade and the most common site was mandibular. The most frequently found symptoms were swelling, tooth mobility and pain. Radiologically, the image was radiolucent and could look like a cyst or a periodontal lesion. In situ hybridization techniques frequently expressed a gene fission of EWSR1. The treatment was mostly a radical surgical excision of the tumor with or without adjuvant radiotherapy or chemotherapy. CCOC showed high rates of recurrence and mortality related with the presence of distance metastasis. DISCUSSION: Fission of EWSR1 gene could be the main element it the diagnosis of CCOC. A multidisciplinary approach, including a radiologist, pathologist and an oral & maxillofacial surgeon may be helpful in the evaluation and management of these lesions. With 95 reports found in English literature, we cannot say that CCOC is extremely rare anymore.

Utility of high-frequency ultrasonography in the diagnosis of benign and malignant skin tumors.

Various benign and malignant tumors may arise from the skin. These may be of epidermal, dermal, subcutaneous or appendageal origin. Skin biopsy is the gold standard for diagnosis of skin tumors. There is paucity of published data on the role of imaging modalities in diagnosis of skin tumors. High-frequency ultrasonography (7-50 MHz) is a potential non-invasive, objective modality which can be utilized in the diagnosis and localization of skin tumors. It provides valuable information about the tumor characteristics such as size, shape, depth, consistency and vascularity before invasive skin biopsy or surgery is planned. Sentinel lymph nodes in malignant melanoma can be well visualized and studied by this technique. It is also a good modality to detect local recurrence of tumors during post-operative follow up, especially those with a high likelihood of local recurrence or lesions excised with inadequate margins. High-frequency ultrasonography is additive to clinical diagnosis and can be considered a useful non-invasive method to plan the management of various skin tumors and is of prognostic value in some cases.