Efficacy and Safety of Biological Drugs in Still's Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Still's disease is a rare autoinflammatory disorder characterized by systemic inflammation, fever, rash, and arthritis. The term "Still's disease" covers the pediatric subtype systemic Juvenile Idiopathic Arthritis (sJIA) and adult-onset Still's disease (AOSD), which affects adults. Biological drugs, including anti-interleukin-1 agents anakinra, canakinumab, rilonacept, and the interleukin-6 antagonist tocilizumab, are used in the management of Still's disease. METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials, and the study protocol was registered in PROSPERO (CRD42023450442). MEDLINE, EMBASE, and CENTRAL were screened from inception until September 17, 2023. We included patients with Still's disease who received placebo or biological drugs: anakinra, canakinumab, rilonacept, or tocilizumab. The primary efficacy and safety outcomes were achievement of ACR50 response and occurrence of serious adverse events, respectively. The interventions were ranked using rankograms and SUCRA values. RESULTS: Nine trials with 430 patients were included. All biological drugs were associated with greater odds of ACR50 response compared with placebo. There was no statistically significant association between biological drugs and serious adverse events. The multivariate meta-analysis found no difference between biological drugs. As per SUCRA rankings, anakinra was the most effective and safe option with respect to ACR50 response and occurrence of serious adverse events. CONCLUSION: This is the first systematic review and meta-analysis to assess the efficacy and safety of biological drugs in pediatric and adult patients with Still's disease. Biological drugs were effective in achieving ACR response and demonstrated a low adverse event profile in the management of Still's disease.

Efficacy and safety of anti-interleukin-1 treatment in familial Mediterranean fever patients: a systematic review and meta-analysis.

OBJECTIVES: FMF is the most common hereditary monogenic fever syndrome marked by recurrent attacks of fever and polyserositis. Colchicine is the current recommended first-line treatment for FMF. However, a small portion of FMF patients are unresponsive or intolerant to colchicine. Anti-IL-1 agents are alternative treatment options for colchicine-resistant or -intolerant FMF patients. This systematic review and meta-analysis aimed to provide qualitative and quantitative evidence for the efficacy and safety of anti-IL-1 agents in adult and paediatric FMF patients. METHODS: MEDLINE, EMBASE, CENTRAL and Web of Science were screened from inception to May 2023. We included adult and paediatric FMF patients who received continuous treatment with at least one of the anti-IL-1 drugs: anakinra, canakinumab and rilonacept. The primary efficacy outcome was the proportion of patients who achieved complete remission of attacks and the primary safety outcome was the proportion of patients who experienced at least one adverse event during treatment. A random-effects meta-analysis was performed for the quantitative synthesis. RESULTS: Fourty-four reports consisting of 1399 FMF patients were included. Sixty percent (95% CI 49%, 72%) of the adult patients and 81% (95% CI 72%, 89%) of the paediatric patients achieved complete remission. Anti-IL-1 agents significantly decreased levels of inflammatory markers. At least one adverse event was observed in 25% (95% CI 13%, 37%) of the adult patients and 12% (95% CI 3%, 21%) of the paediatric patients. CONCLUSION: Anti-IL-1 agents were effective and demonstrated a low adverse event profile in paediatric and adult FMF patients.

Cancer incidence in Familial Mediterranean Fever: A retrospective analysis.

OBJECTIVES: Familial Mediterranean Fever (FMF) is the most common hereditary monogenic fever syndrome that is characterized by recurrent attacks of fever and polyserositis. Anti-inflammatory drugs, with colchicine being the first-line therapy, have been used in the management of FMF. This study aims to evaluate the risk of cancer in Turkish FMF patients. METHODS: We retrospectively screened the cancer-related outcomes of our study group which consisted of Turkish FMF patients registered at our division. Cancer estimates of the Turkish population were published by the Turkish Ministry of Health in the Turkey Cancer Statistics Report 2018. Standardized incidence rates (SIR) were calculated to compare the cancer incidence observed in our study group with the expected cancer incidence of the Turkish population. Subgroup analyses were conducted on the subgroups, based on gender and usage of biological agents. RESULTS: Our study included 1734 FMF patients, 1054 (60.8 %) of whom were females. The total follow-up was 68,784 person-years. Cancer was observed in 35 (2 %) of these patients. Turkish FMF patients had a significantly lower incidence of cancer, compared with the overall Turkish population [SIR 0.64 (95 % CI 0.46-0.89), p < 0.01]. No significant association was found between cancer and biological agent therapies in FMF patients. CONCLUSIONS: Findings from our study indicate that the risk of cancer was decreased by 36 % in Turkish patients with FMF, compared with the outcomes of the overall Turkish population. Life-long exposure to anti-inflammatory drugs, primarily colchicine, may be the underlying reason for this outcome. Further studies are needed for the confirmation and explanation of this association.

Pushing the Limits of Breast-Conserving Surgery with Extreme Oncoplasty.

Introduction: We aimed to report the long-term surgical outcomes of extreme oncoplasty techniques in selected patients with unifocal (UF)/cT3 or multifocal-multicentric tumors (MFMC). Material and Methods: Patients who were initially recommended to have mastectomy underwent extreme oncoplastic breast-conserving surgery (eOBCS) including therapeutic reduction mammoplasty, racquet, and round-block mammoplasty, Grisotti flap, or combined technique were included. Preoperative tumor parameters, clinical outcomes, rate of local recurrence, survival, and patients' satisfaction were assessed. Results: Eighty-six patients with a median age of 51 years were followed for a median follow-up of 75 (8-154) months; 31 (36%) had cT3 and 55 (64%) had MFMC tumors. The majority of patients (83.6%) had invasive cancer. The median UF tumor size was 58 mm (range 51-100) on imaging and 51 mm (range 50-60) on final pathology. The median tumor span for MFMC was 65 mm (range 53-95) on imaging, whereas the median of the largest tumor size was 30 mm (range 22-60) on final pathology. Seventy-one patients (82.5%) were ER-positive, 17 (19.7%) were HER2 positive, and 8 (9.3%) were triple-negative breast cancer. Four patients (4.7%) required further intervention for having positive margins (3 re-excisions, 1 completion mastectomy). Three local recurrences (3.4%) and 10 (11.6%) distant metastasis occurred. The cosmetic outcome was excellent in 37 (43%) patients. No major complications were observed. Conclusions: eOBCS can be a good option for patients who initially require mastectomy. Appropriate patient selection, a multidisciplinary approach, and patient consent are essential steps of the procedure.

Novel Janus-kinase (JAK) Inhibitors in Myelofibrosis.

INTRODUCTION: JAK inhibitors (JAKis), used in the treatment of myelofibrosis, have entered standard treatment, providing significant improvements in spleen size and symptom burden. Although splenomegaly provides a reduction and some improvement in cytopenia, there is still a way to go. Novel JAKis are being investigated to overcome barriers to treatment access, such as therapeutic challenges, intolerance, and unresponsiveness. AREAS COVERED: This review includes the current status of JAKi treatment for myelofibrosis, mainly focusing on investigational JAKis; jaktinib, lestaurtinib, itacitinib, gandotinib, BMS-911543, ilginatinib, TQ05105, and flonoltinib maleate. MEDLINE and clinicaltrials.gov were screened to identify all completed or active studies on this topic. The outcomes of the preclinical studies and clinical trials are presented and discussed for each drug. EXPERT OPINION: In patients with myelofibrosis, momelotinib was effective in treating anemia, whereas jaktinib was effective in both anemia and Total Symptom Score (TSS). More phase 3 studies are needed to provide more precise evidence. The increasing variety of JAKis will allow for more personalized treatment options for myelofibrosis in the future. The potential impact on disease progression, molecular responses, and the duration of this response will become important parameters for future evaluations of these drugs.

The impact of intraoperative cavity shaving on re-excision rates in breast-conserving surgery.

BACKGROUND AND OBJECTIVES: This trial aimed to investigate the effects of circumferential shaving on reducing the reoperation rates during breast-conserving surgery (BCS). METHODS: In the study, before 2014, 404 (39.9%) breast cancers (BCs) out of a total of 1012 BCs underwent BCS without intraoperative cavity shaving (ICS) and constituted the no-ICS group. After this date, ICS was added to 608 (60.1%) BCSs (ICS group) and intraoperative margin analysis was not requested from pathologists during these second BCS procedures. RESULTS: The patient and BC characteristics in the no-ICS and ICS groups were similar. Carcinoma detection at the margin and reoperation rates were 13.9% in the no-ICS group and 7.6% in the ICS group (p = 0.001). No significant difference was detected between patients who underwent BCS with intraoperative frozen section analysis (FSA) and patients who underwent BCS with additional ICS (5.6% vs. 7.6%, p = 0.383). CONCLUSIONS: ICS decreased the rates of positive margins and reoperations among patients with BCS to an acceptable level compared with intraoperative FSA. It may be concluded that ICS is feasible to achieve BC margin control.

Breast-Conserving Surgery Under Local Anesthesia in Elderly Patients with Severe Cardiorespiratory Comorbidities: A Hospital-Based Case-Control Study.

INTRODUCTION: We report the feasibility and safety of local anesthesia (LA) in patients having breast-conserving surgery (BCS). METHODS: 37 patients with American Society of Anesthesiologists (ASA) score of 4 having BCS under LA and 54 age-matched subjects with ASA score of 3-4 having BCS under general anesthesia (GA) were included. Patients were retrospectively evaluated for the follow-up duration, duration of surgery, postoperative satisfaction scores (1-10), complication and survival time for locoregional recurrence and overall survival rates. RESULTS: The mean follow-up duration was 55.09 ± 13.49 months (range 38-104) in GA group, and 58.7 ± 15.5 months (range 20-99) in LA group. There was a significant difference in the duration of surgery (p < 0.001). In the LA group, 5 patients (13.5%) had minor complications including seroma, wound infection or hematoma, whereas 6 patients (11.1%) had minor complications in the GA group (p > 0.05). The re-excision rate due to positive tumor margins was 5.4% (2 patients) in the LA group and 5.5% in the GA group, respectively. The locoregional recurrence-free survival and overall survival rate was not different between 2 groups (p = 0.192, p = 0.93). CONCLUSION: BCS under LA seemed to be effective and safe in selected high-risk elderly patients.

Correlation of 18F-FDG PET/CT with pathological features and survival in primary breast cancer.

OBJECTIVE: The aim of this study was to determine the correlation between the primary tumor (PT) maximum standardized uptake value (SUVmax) and breast cancer prognostic factors, overall survival, and relapse-free survival on the basis of histopathological and molecular characteristics. PATIENTS AND METHODS: In this retrospective study, 436 female patients with breast cancer were evaluated following a pretreatment F-FDG PET/CT scan. The PT SUVmax and histopathological/molecular characteristics were determined from primary tumor tissues and analyzed using the Mann-Whitney U and Kruskal-Wallis tests. RESULTS: The median SUVmax of 436 PT was 10.1 (1.7-72). The PT SUVmax values were higher in ER- versus ER+ (P=0.001), PR- versus PR+ (P=0.001), Her2+ versus Her2- (P=0.01), Ki-67% of at least 20 versus Ki-67% of less than 20 (P<0.001), histological grade 3 versus grade 1-2 (P<0.001), nuclear pleomorphism score 3 versus score 1-2 (P<0.001), and mitotic score 3 versus score 1-2 patients (P<0.001). The lowest SUVmax levels were observed in the LumA group and the highest SUVmax levels were observed in the Her2 group (P<0.001). LumA patients with PR values greater than 20% had lower PT SUVmax values than the patients with PR values of 20% or less (P=0.023). The PT SUVmax was higher in patients with recurrence (P=0.03) and died related to disease (P<0.001) independent of time. CONCLUSION: The PT SUVmax showed a significant correlation with most of the prognostic factors and histopathological subtypes as a noninvasive tool. It is also usable in the prediction of tumor-related deaths or relapse independent of time. Our results could guide future studies to provide new histopathologic subtype definitions on the basis of new PR criteria.

Sentinel lymph node biopsy and aberrant lymphatic drainage in recurrent breast cancer: Findings likely to change treatment decisions.

BACKGROUND AND OBJECTIVES: It is not clear whether sentinel lymph node biopsy (SLNB) can be applied to patients with a second breast cancer or recurrence occurring at previously treated breast. The purpose of this study was to assess the feasibility of SLNB procedure in patients with recurrent breast cancer. METHODS: Patients with non-metastatic recurrent N0 breast cancer at ipsilateral breast were included. Patients were grouped according to their initial breast, axilla, and overall surgery. Presence of drainage and its pattern as well as SLNB success rate and overall axillary involvement rates were assessed. Findings were compared. RESULTS: Out of 75 patients, mean age was 52.5 years and disease-free interval was 82 (9-312) months. Lymphatic drainage was successful in 42 (56%) patients. Drainage positivity was more frequent in patients who were previously treated with SLNB (82.6%) than in patients who underwent axillary lymph node dissection (ALND) (44.2%; P = 0,002). Aberrant lymphatic drainage was detected in 64.3% of drainage positive patients. Success rate of reoperative SLNB was 92.9%. Adjuvant treatment plan was altered in 12 (16%) patients. In 15 patients, negative SLNB prevented axillary dissection. CONCLUSIONS: Reoperative SLNB seems to be technically feasible in N0 recurrent breast cancer patients. It may further avoid unnecessary ALND and lead changes in adjuvant treatment plans. J. Surg. Oncol. 2016;114:796-802. © 2016 2016 Wiley Periodicals, Inc.

Safety and feasibility of laparoscopic adrenalectomy: What is the role of tumour size? A single institution experience.

BACKGROUND: Although, there are studies in the literature having shown the feasibility and safety of laparoscopic adrenalectomy, there are still debates for tumour size and the requirement of the minimal invasive approach. Our hypothesis was that the use of laparoscopy facilitates minimally invasive resection of large adrenal tumours regardless of tumour size. MATERIALS AND METHODS: Within 7 years, 149 patients underwent laparoscopic adrenalectomy at one institution. The patients were divided into two study groups according to tumour size. Group 1 included patients with adrenal tumours smaller than 5 cm and group 2 included larger than 5 cm. Patient demographics and clinical parameters, operative time, complications, hospital stay and final pathology were analysed. Statistical analyses of clinical and perioperative parameters were performed using Student's t-test and Chi-square tests. RESULTS: There were 88 patients in group 1 and 70 in group 2. There were no significant differences between study groups regarding patient demographics, operative time, hospital stay, and complications. Estimated blood loss was significantly higher in group 2 (P = 0.002). The conversion to open rate was similar between study groups with 5.6% versus 4.2%, respectively. Pathology was similar between groups. CONCLUSION: Our study shows that the use laparoscopy for adrenal tumours larger than 5 cm is a safe and feasible technique. Laparoscopic adrenalectomy is our preferred minimally invasive surgical approach for removing large adrenal tumours.

Comparison of single port and three port laparoscopic splenectomy in patients with immune thrombocytopenic purpura: Clinical comparative study.

AIM: Single-port laparoscopic surgery (SILS) has become increasingly popular during the last decades. This prospective study was undertaken to evaluate the feasibility of single-port laparoscopic splenectomy compared with conventional multiport laparoscopic splenectomy. MATERIALS AND METHODS: Between February 2, 2009 and August 29, 2011, a total of 40 patients with the diagnosis of immune thrombocytopenic purpura were included to study. Patients were alienated into two groups according to the procedure type including SILS and conventional multiport splenectomy. RESULTS: There were 19 patients in group 1, and 21 in group 2. Operative time was significantly shorter in group 1 versus group 2 (112.4 ± 13.56 vs 71.2 ±18.1 minutes, respectively, P < 0.05). One patient in group 1 had converted to laparatomy due to preoperative bleeding. Postoperative pain analyses (VAS Score) revealed superiority of SILS in the early post-operative days (P < 0.05). CONCLUSIONS: SILS splenectomy is a safe and effective alternative to standard laparoscopic splenectomy.

Is there any effect of first-day usage of a totally implantable venous access device on complications?

BACKGROUND: Our aim was to evaluate whether it is safe to use a totally implantable venous access device (TIVAD) on the day of implantation. METHODS: We investigated data from 1315 cancer patients divided into two groups according to the time interval between TIVAD placement and the first use of the TIVAD to adminster chemotherapy: patients whose devices were used during the first 24 h after placement were enrolled into group 1 and patients whose devices were first used more than 24 h after device placement were enrolled into group 2. RESULTS: Early complications were all related to device insertion and occurred before chemotherapy administration. Infection and venous thrombosis were the most frequent complications during the first 6 months after TIVAD insertion in both groups. However, the frequency of late complications was statistically the same for the two groups. CONCLUSIONS: The early use of TIVADs appears safe. Usage of the catheter for chemotherapy administration during the first 24 h after insertion has no effect on the rate of complications.

Factors that affect the false-negative outcomes of fine-needle aspiration biopsy in thyroid nodules.

Background. The purpose of this study was to assess the factors that affect the false-negative outcomes of fine-needle aspiration biopsies (FNABs) in thyroid nodules. Methods. Thyroid nodules that underwent FNAB and surgery between August 2005 and January 2012 were analyzed. FNABs were taken from the suspicious nodules regardless of nodule size. Results. Nodules were analyzed in 2 different groups: Group 1 was the false-negatives (n = 81) and Group 2 was the remaining true-positives, true-negatives, and false-positives (n = 649). A cytopathologist attended in 559 (77%) of FNAB procedures. There was a positive correlation between the nodule size and false-negative rates, and the absence of an interpreting cytopathologist for the examination of the FNAB procedure was the most significant parameter with a 76-fold increased risk of false-negative results. Conclusion. The contribution of cytopathologists extends the time of the procedure, and this could be a difficult practice in centres with high patient turnovers. We currently request the contribution of a cytopathologist for selected patients whom should be followed up without surgery.

Laparoscopic surgery of the splenic artery and vein aneurysm with spontaneous arteriovenous fistula.

Visceral artery aneurysms are rare and important vascular entities due to the quarter of all cases presented as surgical emergency. Nevertheless, splenic artery aneurysm (SAA) is the most common visceral and third most common intra-abdominal artery aneurysm after aorta and iliac artery. SAA accompany splenic vein aneurysm because arteriovenous fistula communication between them is a very rare entity. Location and size of the SAA determine the likelihood of rupture. Women of child-bearing age who have SAAs are at particularly high risk of death as a result of aneurysm rupture and should be treated with elective repair. Herein, we report a case of a splenic artery and vein aneurysm with arteriovenous fistula in a 25-year-old young female patient who presented with left upper quadrant pain. Diagnosis was established by computerized tomography angiogram. The patient underwent laparoscopic resection of splenic artery and vein, as well as with splenectomy. Laparoscopic therapy for SAA should be considered for the patient with a low periprocedural morbidity at experienced surgical clinics.

A New Era in Minimally Invasive Liver Resection (MILR) Single-Incision Laparoscopic Liver Resection (SIL-LR): The First Two Cases.

Laparoscopy has gained a place in everyday surgical routine as an alternative surgical approach that decreases morbidity and postoperative hospitalization. Single port laparoscopic surgery has been introduced as a further development of laparoscopy. The feasibility and safety of single port laparoscopy is under extensive evaluation in specialized laparoscopic centers. Nevertheless, wide acceptance of the technique requires adequate documentation of the advantages of the approach over conventional laparoscopy and further refinement of surgical instrumentation to overcome intraoperative ergonomic problems.