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Seminars in Hematology Apr 2021Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type I (HTLV-1). Between 3% and 5% of HTLV-1-infected...
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type I (HTLV-1). Between 3% and 5% of HTLV-1-infected individuals develop ATL after a long latency. Confirmation of seropositivity of anti-HTLV-1 antibody, and clonal proliferation of CD4 and CD25 positive lymphocytes with nuclear pleomorphism in patients suspicious of malignant lymphoma or chronic lymphocytic leukemia is crucial for the diagnosis of ATL. The clinical course of ATL is very heterogeneous, and divided into acute, lymphoma, chronic, and smoldering types. The chronic type is further subclassified into the favorable and unfavorable subtypes. Acute, lymphoma, and unfavorable chronic type ATL, and favorable chronic and smoldering type ATL are defined as aggressive and indolent ATL, respectively. Recently identified prognostic indices based on clinical parameters and/or genetic predictors of outcomes need to be confirmed and incorporated for more stratified therapeutic interventions. The standard of care for aggressive ATL is multiagent chemotherapy followed by allogeneic hematopoietic stem cell transplantation if possible, while that for indolent ATL is watchful waiting until progression to aggressive ATL. The combination of interferon-α and zidovudine is also standard for leukemic type ATL. In addition, mogamulizumab, lenalidomide, and brentuximab vedotin have been incorporated into clinical practices in Japan. Furthermore, several novel drugs are currently undergoing clinical trials.
Topics: Adult; Hematopoietic Stem Cell Transplantation; Human T-lymphotropic virus 1; Humans; Interferon-alpha; Leukemia-Lymphoma, Adult T-Cell; Prognosis
PubMed: 33906721
DOI: 10.1053/j.seminhematol.2021.02.005 -
BMC Urology Sep 2023Treatment decisions for localized prostate cancer must balance patient preferences, oncologic risk, and preservation of sexual, urinary and bowel function. While Active... (Review)
Review
BACKGROUND
Treatment decisions for localized prostate cancer must balance patient preferences, oncologic risk, and preservation of sexual, urinary and bowel function. While Active Surveillance (AS) is the recommended option for men with Grade Group 1 (Gleason Score 3 + 3 = 6) prostate cancer without other intermediate-risk features, men with Grade Group 2 (Gleason Score 3 + 4 = 7) are typically recommended active treatment. For select patients, AS can be a possible initial management strategy for men with Grade Group 2. Herein, we review current urology guidelines and the urologic literature regarding recommendations and evidence for AS for this patient group.
MAIN BODY
AS benefits men with prostate cancer by maintaining their current quality of life and avoiding treatment side effects. AS protocols with close follow up always allow for an option to change course and pursue curative treatment. All the major guideline organizations now include Grade Group 2 disease with slightly differing definitions of eligibility based on risk using prostate-specific antigen (PSA) level, Gleason score, clinical stage, and other factors. Selected men with Grade Group 2 on AS have similar rates of deferred treatment and metastasis to men with Grade Group 1 on AS. There is a growing body of evidence from randomized controlled trials, large observational (prospective and retrospective) cohorts that confirm the oncologic safety of AS for these men. While some men will inevitably conclude AS at some point due to clinical reclassification with biopsy or imaging, some men may be able to stay on AS until transition to watchful waiting (WW). Magnetic resonance imaging is an important tool to confirm AS eligibility, to monitor progression and guide prostate biopsy.
CONCLUSION
AS is a viable initial management option for well-informed and select men with Grade Group 2 prostate cancer, low volume of pattern 4, and no other adverse clinicopathologic findings following a well-defined monitoring protocol. In the modern era of AS, urologists have tools at their disposal to better stage patients at initial diagnosis, risk stratify patients, and gain information on the biologic potential of a patient's prostate cancer.
Topics: Male; Humans; Watchful Waiting; Neoplasm Grading; Quality of Life; Prospective Studies; Retrospective Studies; Prostatic Neoplasms; Prostate-Specific Antigen
PubMed: 37777716
DOI: 10.1186/s12894-023-01314-6 -
Acta Obstetricia Et Gynecologica... Sep 2023Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment.
MATERIAL AND METHODS
We performed a systematic review and individual participant data meta-analysis (IPD-MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG (<2000 IU/L). A one-stage IPD-MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to <20 IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side-effects and hCG resolution times.
TRIAL REGISTRATION NUMBER
PROSPERO: CRD42021214093.
RESULTS
1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95-1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23-1.14). Mean time to success was 19.7 days (95% CI 17.4-22.3) after MTX and 21.2 days (95% CI 17.8-25.2) after expectant management (P = 0.25). MTX specific side-effects were reported in 33 MTX compared to four in the expectant group.
CONCLUSIONS
Our IPD-MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side-effects.
Topics: Pregnancy; Humans; Female; Methotrexate; Watchful Waiting; Pregnancy, Tubal; Pregnancy, Ectopic; Chorionic Gonadotropin; Abortifacient Agents, Nonsteroidal; Retrospective Studies
PubMed: 37345445
DOI: 10.1111/aogs.14617 -
International Journal of Pediatric... Jul 2020Silent sinus syndrome (SSS) is defined as a progressive enophthalmos and hypoglobus associated with maxillary sinus atelectasis. There is extremely limited literature...
INTRODUCTION
Silent sinus syndrome (SSS) is defined as a progressive enophthalmos and hypoglobus associated with maxillary sinus atelectasis. There is extremely limited literature describing SSS in children. The goals of this study are to characterize SSS in children through an IRB approval retrospective chart review of cases identified through a large health system-wide imaging database and to compare the presentation and outcomes of patients who underwent surgery versus those who were observed.
METHODS
A radiology database of over 26 million reports from 2003 to 2017 was searched to identify children aged 1-18 years diagnosed with maxillary sinus hypoplasia or SSS on CT scan. Chart review was performed on the identified children including clinical presentation, eye symptoms, surgical treatment, and outcome.
RESULTS
Eighty-three children were identified to have maxillary sinus hypoplasia. Eighty-one patients had maxillary sinus opacification and 57 patients had hypoglobus or enophthalmos characteristic of SSS. Thirty-two patients (47%) were seen by a specialist and 19 had surgery. The majority of patients (55%) had headache as their presenting symptom. There were no statistically significant differences in the clinical presentation between those who received surgery and those who were observed clinically.
CONCLUSIONS
Silent sinus syndrome can present at any age. The majority of cases of maxillary sinus hypoplasia will have the orbital floor changes characteristic of SSS. Headaches are a common presenting symptom. Close follow up of pediatric patients is advised and early intervention may be favorable to prevent long term orbital changes and complications.
Topics: Adolescent; Child; Child, Preschool; Enophthalmos; Female; Headache; Humans; Infant; Male; Maxillary Sinus; Paranasal Sinus Diseases; Retrospective Studies; Syndrome; Tomography, X-Ray Computed; Treatment Outcome; Watchful Waiting
PubMed: 32272375
DOI: 10.1016/j.ijporl.2020.110034 -
The Lancet. Oncology Jan 2021Watch and wait is a novel management strategy in patients with rectal cancer who have a clinical complete response after neoadjuvant chemoradiotherapy. Surveillance of...
Conditional recurrence-free survival of clinical complete responders managed by watch and wait after neoadjuvant chemoradiotherapy for rectal cancer in the International Watch & Wait Database: a retrospective, international, multicentre registry study.
BACKGROUND
Watch and wait is a novel management strategy in patients with rectal cancer who have a clinical complete response after neoadjuvant chemoradiotherapy. Surveillance of these patients is generally intensive, because local regrowth (with the potential for salvage) occurs in 25% of patients, and distant metastases occur in 10% of patients. It is unclear for how long these patients should be followed up. To address this issue, we did conditional survival modelling using the International Watch & Wait Database (IWWD), which is a large-scale registry of patients with a clinical complete response after neoadjuvant chemotherapy who have been managed by a watch-and-wait strategy.
METHODS
We did a retrospective, multicentre registry study using a dataset from the IWWD, which includes data from 47 clinics across 15 countries. We selected patients (aged ≥18 years) with rectal cancer who had a clinical complete response after neoadjuvant chemotherapy, and who were subsequently managed by a watch-and-wait strategy between Nov 25, 1991, and Dec 31, 2015. Patients who had not achieved a clinical complete response or who had undergone any surgical procedure were excluded. The criteria used for defining a clinical complete response and the specific surveillance strategies were at the discretion of each participating centre. We used conditional survival modelling to estimate the probability of patients remaining free of local regrowth or distant metastasis for an additional 2 years after sustaining a clinical complete response or being distant metastasis-free for 1, 3, and 5 years from the date of the decision to commence watch and wait. The primary outcomes were conditional local regrowth-free survival at 3 years, and conditional distant metastasis-free survival at 5 years.
FINDINGS
We identified 793 patients in the IWWD with clinical complete response who had been managed by a watch-and-wait strategy. Median follow-up was 55·2 months (IQR 36·0-75·6). The probability of remaining free from local regrowth for an additional 2 years if a patient had a sustained clinical complete response for 1 year was 88·1% (95% CI 85·8-90·9), for 3 years was 97·3% (95·2-98·6), and for 5 years was 98·6% (97·6-100·0). The probably of remaining free from distant metastasis for a further 2 years in patients who had a clinical complete response without distant metastasis for 1 year was 93·8% (92·3-95·9), for 3 years was 97·8% (96·6-99·3), and for 5 years was 96·6% (94·0-98·9).
INTERPRETATION
These results suggest that the intensity of active surveillance in patients with rectal cancer managed by a watch-and-wait approach could be reduced if they achieve and maintain a clinical complete response within the first 3 years of starting this approach.
FUNDING
European Registration of Cancer Care, financed by the European Society of Surgical Oncology, the Champalimaud Foundation Lisbon, the Bas Mulder Award, granted by the Alpe d'HuZes Foundation and the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre.
Topics: Adenocarcinoma; Aged; Chemoradiotherapy, Adjuvant; Databases, Factual; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Rectal Neoplasms; Registries; Remission Induction; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Watchful Waiting
PubMed: 33316218
DOI: 10.1016/S1470-2045(20)30557-X -
Thyroid : Official Journal of the... Nov 2022Active surveillance (AS) is an alternative to thyroidectomy for the management of low-risk papillary thyroid microcarcinoma (PTMC). However, prospective AS data...
Progression of Low-Risk Papillary Thyroid Microcarcinoma During Active Surveillance: Interim Analysis of a Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma in Korea.
Active surveillance (AS) is an alternative to thyroidectomy for the management of low-risk papillary thyroid microcarcinoma (PTMC). However, prospective AS data collected from diverse populations are needed. This multicenter prospective cohort study enrolled patients from three referral hospitals in Korea. The participants were self-assigned into two groups, AS or immediate surgery. All patients underwent neck ultrasound every 6-12 months to monitor for disease progression. Progression under AS was evaluated by a criterion of tumor size increment by 3 mm in one dimension (3 mm), 2 mm in two dimensions (2 × 2 mm), new extrathyroidal extension (ETE), or new lymph node metastasis (LNM), and a composite outcome was defined using all four criteria. A total of 1177 eligible patients with PTMC (919 female, 78.1%) with a median age of 48 years (range 19-87) were enrolled; 755 (64.1%) patients chose AS and 422 (35.9%) underwent surgery. Among 755 patients under AS, 706 (female 537, 76.1%) underwent at least two ultrasound examinations and were analyzed. Over a follow-up period of 41.4 months (standard deviation, 16.0), 163 AS patients (23.1%) underwent surgery. Progression defined by the composite outcome was observed in 9.6% (68/706) of patients, and the 2- and 5-year progression estimates were 5.3% and 14.2%, respectively. The observed progression rates were 5.8% (41/706) and 5.4% (38/706) as defined by tumor size enlargement by 3 mm and 2 × 2 mm, respectively, and 1.3% (9/706) and 0.4% (3/706) for new LNM and ETE, respectively. No distant metastases developed during AS. In multivariate logistic regression analysis examining variables associated with progression under AS, age at diagnosis <30 years (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.10 - 7.45), male sex (OR, 2.48; 95% CI, 1.47 - 4.20), and tumor size ≥6 mm (OR, 1.89; 95% CI, 1.09 - 3.27) were independently significant. The progression of low-risk PTMC during AS in the Korean population was low, but slightly higher than previously reported in other populations. Risk factors for disease progression under AS include younger age, male sex, and larger tumor size. Clinicaltrials.gov NCT02938702.
Topics: Humans; Male; Female; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Prospective Studies; Watchful Waiting; Carcinoma, Papillary; Thyroid Neoplasms; Thyroidectomy; Lymphatic Metastasis; Risk Factors; Disease Progression; Retrospective Studies
PubMed: 36205563
DOI: 10.1089/thy.2021.0614 -
Drugs in Context 2021Obstructive sleep apnoea syndrome (OSAS) is defined as the intermittent reduction or cessation of airflow due to partial or complete obstruction of the upper airway... (Review)
Review
Obstructive sleep apnoea syndrome (OSAS) is defined as the intermittent reduction or cessation of airflow due to partial or complete obstruction of the upper airway during sleep. Paediatric OSAS has specific contributing factors, presenting symptoms and management strategies in various age groups. Untreated OSAS can lead to detrimental effects on neurocognitive development and cardiovascular and metabolic functions of a growing child. In the past decade, practice guidelines have been developed to guide the evaluation and management of OSAS. This article provides a narrative review on the current diagnostic and treatment options for paediatric OSAS. Alternative diagnostic tools other than the standard polysomnography are discussed. Adenotonsillectomy is considered the first-line therapy yet it is not suitable for treatment of all OSAS cases. Nocturnal non-invasive positive airway pressure ventilation is effective and could be the priority treatment for patients with complex comorbidities, residual OSAS post-adenotonsillectomy or obesity. However, intolerance and non-adherence are major challenges of positive airway pressure therapy especially in young children. There is increasing evidence for watchful waiting and other gentler alternative treatment options in mild OSAS. The role of anti-inflammatory drugs as the primary or adjunctive treatment is discussed. Other treatment options, including weight reduction, orthodontic procedures and myofunctional therapy, are indicated for selected patients. Nevertheless, the successful management of paediatric OSAS often requires a multidisciplinary team approach.
PubMed: 33828609
DOI: 10.7573/dic.2020-12-5 -
Current Opinion in Urology Nov 2019Significant morbidity is associated with overtreatment of clinically localized prostate cancer (PCa). Risk stratification tools such as novel biomarkers, MRI and risk... (Review)
Review
PURPOSE OF REVIEW
Significant morbidity is associated with overtreatment of clinically localized prostate cancer (PCa). Risk stratification tools such as novel biomarkers, MRI and risk calculators are useful in predicting which patients would benefit from active surveillance. This review examines current risk stratification tools in localized PCa and the safety of active surveillance in these patients.
RECENT FINDINGS
Very low risk, low-risk and favourable intermediate-risk PCa variants may benefit from treatment with active surveillance. These disease categories have been shown (with up to 10-year follow-up) to have survival and cancer-specific complication rates similar to immediate definitive treatment. Novel biomarkers sensitively predict upstaging, recurrence and metastatic progression while multiparametric MRI reliably detects clinically significant PCa and is valuable in the biopsy naïve patient considering active surveillance. Lastly, risk calculators and nomograms are being developed to combine clinical data and provide optimal individualized treatment while minimizing overtreatment in clinically localized disease.
SUMMARY
Although large randomized trials are needed to validate treatment pathways, current data supports active surveillance in certain clinically localized PCa. Many tools exist to define and support active surveillance in this group.
Topics: Early Detection of Cancer; Humans; Magnetic Resonance Imaging; Male; Medical Overuse; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Assessment; Watchful Waiting
PubMed: 31469662
DOI: 10.1097/MOU.0000000000000672 -
[Rinsho Ketsueki] the Japanese Journal... 2021Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type I. The clinical course of ATL is heterogeneous, and...
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type I. The clinical course of ATL is heterogeneous, and this condition has different types, which are as follows: acute, lymphoma, chronic, and smoldering. The chronic type is further subclassified into favorable and unfavorable subtypes. Acute, lymphoma, and unfavorable chronic type ATL and favorable chronic and smoldering-type ATL are defined as aggressive and indolent ATL, respectively. Newly identified prognostic indices based on clinical parameters and/or genetic predictors should be incorporated in the stratified treatment approach. The standard of care for aggressive ATL is multiagent chemotherapy, followed by allogeneic hematopoietic stem cell transplantation if applicable. Meanwhile, that for indolent ATL is watchful waiting until progression to the aggressive type. The combination of interferon-α and zidovudine is a treatment option for indolent ATL in other countries, and a confirmatory phase 3 trial is ongoing in Japan. In addition to mogamulizumab, lenalidomide, and brentuximab vedotin, which have been recently utilized in clinical practice, the use of a novel histone deacetylase (HDAC) inhibitor has been filed for approval. Moreover, an EZH1/2 inhibitor has completed the enrollment of a phase 2 trial in Japan. The standard of care for elderly patients should be established because the median age of those with newly diagnosed ATL reaches up to 70 years old.
Topics: Adult; Aged; Human T-lymphotropic virus 1; Humans; Interferon-alpha; Japan; Leukemia-Lymphoma, Adult T-Cell; Molecular Targeted Therapy
PubMed: 34349061
DOI: 10.11406/rinketsu.62.766 -
Seminars in Perinatology Mar 2020Elective induction of labor is defined as labor induction in the absence of a clear medical indication. Whether elective labor induction at 39 weeks is a reasonable... (Review)
Review
Elective induction of labor is defined as labor induction in the absence of a clear medical indication. Whether elective labor induction at 39 weeks is a reasonable option for obstetric practice has been a hotly debated topic for decades. Historically, labor induction in low-risk nulliparous women has been discouraged due to the belief that this intervention increases the risk for cesarean delivery without a clear benefit. This review discusses the observational and randomized data that have informed this debate, focusing on recent studies that have reshaped how we think about elective labor induction at 39 weeks of gestation.
Topics: Cesarean Section; Female; Gestational Age; Humans; Labor, Induced; Parity; Pregnancy; Pregnancy Outcome; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Watchful Waiting
PubMed: 31812315
DOI: 10.1016/j.semperi.2019.151214