Current clinical practice in the management of phyllodes tumors of the breast: an international cross-sectional study among surgeons and oncologists.

PURPOSE: Phyllodes tumors of the breast are rare fibroepithelial lesions that are classified as benign, borderline or malignant. There is little consensus on best practice for the work-up, management, and follow-up of patients with phyllodes tumors of the breast, and evidence-based guidelines are lacking. METHODS: We conducted a cross-sectional survey of surgeons and oncologists with the aim to describe current clinical practice in the management of phyllodes tumors. The survey was constructed in REDCap and distributed between July 2021 and February 2022 through international collaborators in sixteen countries across four continents. RESULTS: A total of 419 responses were collected and analyzed. The majority of respondents were experienced and worked in a university hospital. Most agreed to recommend a tumor-free excision margin for benign tumors, increasing margins for borderline and malignant tumors. The multidisciplinary team meeting plays a major role in the treatment plan and follow-up. The vast majority did not consider axillary surgery. There were mixed opinions on adjuvant treatment, with a trend towards more liberal regiments in patients with locally advanced tumors. Most respondents preferred a five-year follow-up period for all phyllodes tumor types. CONCLUSIONS: This study shows considerable variation in clinical practice managing phyllodes tumors. This suggests the potential for overtreatment of many patients and the need for education and further research targeting appropriate surgical margins, follow-up time and a multidisciplinary approach. There is a need to develop guidelines that recognize the heterogeneity of phyllodes tumors.

Socioeconomic position is associated with surgical treatment of open fractures of the lower limb: results from a Swedish population-based study.

Background and purpose - High-energy trauma to the lower limbs can result in open fractures, treated by reconstructive surgery or amputation. We examined whether socioeconomic position is associated with choice of primary treatment.Patients and methods - We performed a nationwide population-based study using the Swedish National Patient Register to identify all adult patients who between 1998 and 2013 underwent reconstruction or amputation after an open fracture below the knee. Information on socioeconomic position was collected from Statistics Sweden.Results - Of 275 individuals undergoing surgery after an open fracture below the knee during the study period, the 1st surgery was reconstructive in 58% of the patients and amputation in 42%. The chance of having an initial reconstruction was lower for women than for men (OR 0.5, 95% CI 0.3-0.9), lower with age (OR 0.97, CI 0.96-0.99), and lower for individuals without employment compared with individuals in employment (OR 0.3, CI 0.2-0.5). Primary treatment was in women associated with family composition, whereas in men it was associated with level of education.Interpretation - Choice of primary treatment after open fracture in the lower limb is affected by socioeconomic position including sex, age, employment, family composition, level of education, and income.

History of autoimmune disease is associated with impaired survival in multiple myeloma and monoclonal gammopathy of undetermined significance: a population-based study.

Multiple myeloma (MM) is a plasma cell disorder preceded by monoclonal gammopathy of undetermined significance (MGUS). Incidence of MM and MGUS is higher among patients with autoimmune disease. The aim of this study was to determine whether a history of autoimmunity has an impact on survival in MM and MGUS. Using high-quality national Swedish registries, we identified 8367 patients with MM, 18,768 patients with MGUS, and 110,251 matched control subjects, and obtained information on previous autoimmune disease in patients and controls. Cox regression was used to calculate hazard ratios (HRs) for overall survival with 95 % confidence intervals (CIs). In patients with MM and a prior autoimmune disease, the risk of death was significantly increased, HR = 1.2 (95 % CI 1.2-1.3) compared to MM patients with no history of autoimmunity. In MGUS patients, a prior autoimmune disease was associated with a significantly 1.4-fold elevated risk of death (95 % CI 1.3-1.4). When analyzing different types of autoimmune diseases, a history of ulcerative colitis had a stronger impact on survival in MM than in controls. Our findings that a history of autoimmune disease has a negative impact on survival in MM and MGUS could be due to shared underlying common genetic factors, or that patients with a history of autoimmunity develop more severe cases of MM and MGUS, or cumulative comorbidity in the individual. Our results suggest that more attention should be paid to comorbidity as a prognostic factor in MGUS and MM, and underlines the need for studies aimed at tailoring therapy according to comorbidity.

Personal and family history of immune-related conditions increase the risk of plasma cell disorders: a population-based study.

The associations between immune-related conditions and multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) have previously been investigated with inconsistent results. In a large population-based study, we identified 19 112 patients with MM, 5403 patients with MGUS, 96 617 matched control subjects, and 262 931 first-degree relatives. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MM and MGUS with immune-related conditions by use of logistic regression. A personal history of all infections combined was associated with a significantly increased risk of MM (OR = 1.2; 95% CI, 1.1-1.3), and a personal history of all conditions in the categories infections (OR = 1.6; 95% CI, 1.5-1.7), inflammatory conditions (OR = 1.4; 95% CI, 1.2-1.5), and autoimmune diseases (OR = 2.1; 95% CI, 1.9-2.4) was associated with a significantly increased risk of MGUS. Several specific immune-related conditions elevated the risk of MM and/or MGUS. A family history of autoimmune disease was associated with a significantly increased risk of MGUS (OR = 1.1; 95% CI, 1.00-1.2), but not MM. Our findings suggest that immune-related conditions and/or their treatment are of importance in the etiology of MGUS and possibly MM. The association of both personal and family history of autoimmune disease with MGUS indicates the potential for shared susceptibility for these conditions.

Plastic Surgery Training across Seven Continents: Results from the First Global Trainee Survey.

Little is known about the demographics and ambitions of plastic surgery trainees and if these differ between regions. This study sought opinion from current and recently graduated plastic surgery trainees to map demographics, training structure, and ambitions of plastic surgery trainees worldwide. Methods: A cross-sectional study was designed and administered by the international trainee organization International Confederation of Societies of Plastic Surgery Trainees. A questionnaire of 45 questions was distributed digitally through several international channels using the REDCap platform. Results: A total of 290 junior plastic surgeons, of whom 124 (42.8%) were women, from all seven International Confederation of Societies of Plastic Surgery regions, participated in this study. Of the trainees, 21% have emigrated, and 75% expressed a desire to undertake a part of their training abroad. The most common length of training in plastic surgery is 5 years. There is a difference in working hours between regions, where more than 80-hour work weeks are most common in Asia (24.1%), and work weeks of less than 40 hours are most common in Middle East (30.8%). A majority of trainees (85%) reported a research interest, and we found a negative correlation between the extent of research ambition and reported clinical workload. Conclusions: We present here the first international investigation of trainee experiences of plastic surgery training. We show that training structure and organization vary between institutions, and that plastic surgery trainees report a strong interest in international training as well as in research.

Risk Factors for Complications and Long-Term Outcomes Following Completion Lymph Node Dissection for Cutaneous Melanoma: A Retrospective Cohort Study.

BACKGROUND: Completion lymph node dissection (CLND) for malignant melanoma is performed for regional cancer control and is associated with a high complication rate. It is unknown whether post-operative complications influence cancer recurrence or survival. Our aim was to evaluate the risk factors for short- and long-term complications after CLND, and to determine whether complications affect recurrence or survival. METHOD: We performed a retrospective cohort study including all melanoma patients who underwent CLND in the Stockholm region during 2005-2014. Patient and cancer characteristics were collected from medical records, as were clinical outcomes. Assessment was performed by multivariate logistic regression. RESULTS: Among 144 patients, the risk of any post-operative one year complication was 68.8%. Lymphedema (41.0%), infection (37.5 %), and seroma (31.3 %) were the most common complications. Diabetes and inguinal CLND were associated with nine- and ten-fold increased risks of post-operative complications (p<0.05), respectively. Complications were linked to an increased risk of recurrent cancer (p<0.05), median follow-up time of 49 months, but did not appear to affect five-year survival. CONCLUSION: Post-operative complications are common in melanoma patients undergoing CLND. Strong risk factors for complications are diabetes and inguinal CLND. Post-operative complications appear to be associated with increased risks of recurrent cancer, but the mechanism is unknown.

Complications after pressure ulcer surgery - a study of 118 operations in spinal cord injured patients.

Our aim in this study was to examine which factors are associated with post-operative complications after surgery for pressure ulcers in individuals with spinal cord injury. We performed a retrospective cohort study including all spinal cord injured patients undergoing pressure ulcer surgery in our department between 2002 and 2019. Patient demographics and comorbidity were collected from medical records, as were treatment data and information on post-operative complications within 30 days. Assessment of outcomes was performed through t-tests, χ2-tests and ANOVA. Out of 118 operations, 51 (43%) had a post-operative complication of any kind. The vast majority (44 cases, 86% of all complications) had minor complications (Clavien-Dindo grade I or II). Seven patients (6%) had a complication of Clavien-Dindo grade III or higher, requiring return to theatre or ICU care. We found that a higher age, a low serum albumin (<3.5 g/dl), and over or underweight, were associated with an increased risk of complications (p < 0.05). Out of 143 treated ulcers, 132 were evaluated at a follow-up visit one to two months after surgery, and 99 of these (75%) were healed. Surgery of pressure ulcers in patients with spinal cord injury is not a low-risk venture, however, few patients will suffer serious post-operative complications. A majority of treated ulcers will heal shortly post-operatively. A number of risk factors are associated with post-operative complications, which can be of help to guide patient selection in the future.

Dietary intake is associated with risk of multiple myeloma and its precursor disease.

The etiology of monoclonal gammopathy of undetermined significance (MGUS), the precursor state of multiple myeloma (MM), is mostly unknown and no studies have been conducted on the effect of diet on MGUS or progression from MGUS to MM. We aimed to explore the association between common foods and MGUS and progression to MM. Data from the population-based AGES Study (N = 5,764) were utilized. Food frequency questionnaire was used to assess dietary intake during adolescence, midlife, and late life. Serum protein electrophoresis and serum free light-chain assay was performed to identify MGUS (n = 300) and LC-MGUS cases (n = 275). We cross linked our data with the Icelandic Cancer Registry to find cases of MM in the study group. We found that intake of fruit at least three times per week during adolescence was associated with lower risk of MGUS when compared to lower fruit consumption (OR = 0.62, 95% CI 0.41-0.95). We additionally found that intake of fruit at least three times per week during the late life period was associated with decreased risk of progressing from MGUS to MM (HR = 0.34, 95% CI 0.13-0.89) when compared to lower intake. Adolescent intake of fruit may reduce risk of MGUS, whereas fruit intake after MGUS onset may reduce risk of progressing to MM. Our findings suggest that diet might alter the risk of developing MGUS and progression to MM.

Quality of life improves early after gender reassignment surgery in transgender women.

BACKGROUND: Few studies have examined the long-term quality of life (QoL) of individuals with gender dysphoria, or how it is affected by treatment. Our aim was to examine the QoL of transgender women undergoing gender reassignment surgery (GRS). METHODS: We performed a prospective cohort study on 190 patients undergoing male-to-female GRS at Karolinska University Hospital between 2003 and 2015. We used the Swedish version of the Short Form-36 Health Survey (SF-36), which measures QoL across eight domains. The questionnaire was distributed to patients pre-operatively, as well as 1, 3, and 5 years post-operatively. The results were compared between the different measure points, as well as between the study group and the general population. RESULTS: On most dimensions of the SF-36 questionnaire, transgender women reported a lower QoL than the general population. The scores of SF-36 showed a non-significant trend to be lower 5 years post-GRS compared to pre-operatively, a decline consistent with that of the general population. Self-perceived health compared to 1 year previously rose in the first post-operative year, after which it declined. CONCLUSIONS: To our knowledge, this is the largest prospective study to follow a group of transgender patients with regards to QoL over continuous temporal measure points. Our results show that transgender women generally have a lower QoL compared to the general population. GRS leads to an improvement in general well-being as a trend but over the long-term, QoL decreases slightly in line with that of the comparison group. Level of evidence: Level III, therapeutic study.

Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study.

All multiple myeloma (MM) cases are preceded by the premalignant state monoclonal gammopathy of undetermined significance (MGUS). Results from previous studies show a positive association between obesity and MM; however, the association between obesity and MGUS is controversial. The aims were to determine (1) if obesity is associated with an increased risk of MGUS and light-chain MGUS (LC-MGUS) and (2) whether obesity is associated with a higher risk of progression to MM and other lymphoproliferative (LP) diseases. Data from the population-based Age, Gene/Environment Susceptibility-Reykjavik Study (N = 5764) were used. We performed serum protein electrophoresis and serum free light-chain assay on all subjects to identify MGUS and LC-MGUS cases. We included 11 different measures on current and previous obesity in our analysis. Logistic regression and Cox proportional-hazard regression were used to analyze the associations. A total of 300 (5.2%) MGUS and 275 (4.8%) LC-MGUS cases were identified. During a median follow-up of 8 years, 18 had progressed to MM and 11 to other LP diseases. We found no association between the 11 obesity markers and MGUS or LC-MGUS (odds ratios 0.81 to 1.15 for all 11 variables in both conditions). Interestingly, we found that high midlife body mass index increased risk of progression to MM and other LP diseases (hazard ratio, 2.66; 95% confidence interval, 1.17-6.05). To conclude, obesity was not associated with MGUS. However, we found overweight/obesity to be a risk factor for progression from MGUS to MM and other LP diseases, suggesting that obesity plays a role in the transformation of MGUS to MM.

Bone disease in monoclonal gammopathy of undetermined significance: results from a screened population-based study.

Previous studies have shown that individuals with monoclonal gammopathy of undetermined significance (MGUS) have an increased risk of fractures, although the underlying mechanisms remain unknown. Our aim was to analyze bone mineral density (BMD), bone volume, and risk of fractures among individuals with MGUS. We performed a screening using the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study cohort, consisting of 5764 elderly individuals, identifying 300 individuals with MGUS, and 275 with light-chain MGUS. Quantitative computerized tomography was performed in the lumbar spine and hip to evaluate BMD and bone geometry. Analysis of variance and the Tukey honest significance test were used to compare the groups. Hospital records were used to record fractures, with a mean follow-up of 6.9 years. Cox proportional hazard was used to compare fracture risk. No difference was found in BMD between subjects with MGUS and others in the spine (P = .34) or in total hip (P = .30). Individuals with MGUS had a significant increase in bone volume compared with others in the spine (P < .001) and total hip (P < .001). Overall, the risk of fractures was not significantly increased in individuals with MGUS (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.94-1.50). Men with MGUS had a significantly increased fracture risk, compared with other men (HR, 1.46; 95% CI, 1.03-2.08). Our results show that although individuals with MGUS do not have decreased BMD, bone volume is increased, and MGUS men have a 50% increased fracture risk. These results indicate that bone disease and fractures in MGUS differ from processes known from osteoporosis.

Solely Penile Skin for Neovaginal Construction in Sex Reassignment Surgery.

BACKGROUND: Gender reassignment surgery due to transsexualism (International Classification of Diseases, Tenth Revision: F64.0) is a procedure becoming increasingly common worldwide as a result of a significant increase in diagnostic incidence. Several methods have been described for this complex surgery, but no internationally agreed upon gold standard exists, in particular with regard to which methods allow for creating a sufficient neovaginal depth. METHODS: We use a 2-stage technique using solely penile skin for creating a neovaginal cavity and present the long-term outcome in terms of measured neovaginal depth. Eighty patients were included. Patients' neovaginal depth was measured in a standardized fashion 6 months or more after initial surgery. Results were compared with published data on female anatomy. RESULTS: The average neovaginal depth achieved was 10.2 cm. Having had a postoperative complication and noncompliance to neovaginal dilatation were both negatively correlated with neovaginal depth, whereas higher body mass index was not. Most patients received a neovaginal depth sufficient for penetrative intercourse and within the range for biological women. CONCLUSIONS: Using solely penile skin for the vaginal lining is a satisfactory surgical method to achieve adequate vaginal depth, provided that the postoperative dilatation regimen is followed. This holds true regardless of age or body mass index.

Incidence and risk factors for suicide and attempted suicide following a diagnosis of hematological malignancy.

Solid tumors are associated with an increased risk of suicide, however, there is limited detailed information on the risk of suicide in patients with hematological malignancies. Therefore, we conducted a population-based study including 47,220 patients with hematological malignancies (diagnosed 1992-2006) and their 235,868 matched controls to define the incidence and risk factors for suicide and suicide attempt. Information on suicides, suicide attempts, and preexisting psychiatric disorders was obtained from Swedish registers and individual medical records. There was a twofold increased (hazard ratio [HR] = 1.9, 95% confidence interval 1.5-2.3, P < 0.0001) risk of suicide/suicide attempt during the first 3 years after diagnosis in patients with hematological malignancies compared to matched controls. Of all hematological malignancies, multiple myeloma was associated with the highest risk (HR = 3.4; 2.3-5.0, P < 0.0001). Patients with a preexisting psychiatric disorder were at a very high risk of suicide and suicide attempt (HR = 23.3; 16.6-32.6, P < 0.0001), regardless of type of hematological malignancy. Among patients who committed suicide, 19% were in a palliative phase and 44% were in remission with no active treatment. In conclusion, the risk of suicide and suicide attempt is elevated in patients with hematological malignancies. Certain high-risk patients may benefit from early detection and preventive measures.

The Role of Diagnosis and Clinical Follow-up of Monoclonal Gammopathy of Undetermined Significance on Survival in Multiple Myeloma.

IMPORTANCE: Multiple myeloma (MM) is consistently preceded by the precursor state, monoclonal gammopathy of undetermined significance (MGUS). The average annual risk of progression from MGUS to multiple myeloma is 0.5% to 1.0%. Current guidelines suggest life-long clinical follow-up of individuals diagnosed as having MGUS depending on risk stratification. The impact of diagnosing and conducting clinical follow-up of MGUS on MM survival is unclear. OBJECTIVE: To estimate the impact of prior knowledge of MGUS diagnosis and comorbidities on MM survival. DESIGN, SETTING, AND PARTICIPANTS: We conducted a population-based study including all patients with MM (MM patients) diagnosed in Sweden (n = 14,798) from 1976 to 2005 (with follow-up until 2007); 394 (2.7%) had previously been diagnosed as having MGUS. Information on comorbidities was gathered for all patients. We calculated survival rates from the time of MM diagnosis, comparing patients with vs those without prior knowledge of MGUS. Using Cox proportional hazards models, we calculated hazard ratios (HRs) and 95% CIs for risk factors for death. χ2 Tests were used to evaluate differences in comorbidities. EXPOSURES: Prior knowledge of MGUS among MM patients. In a subanalysis, monoclonal (M)-protein concentration and type were used as exposure. MAIN OUTCOMES AND MEASURES: Risk of death and comorbidities. RESULTS: Patients with MM with prior knowledge of MGUS had significantly (HR, 0.86; 95% CI, 0.77-0.96; P < .01) better overall survival (median survival, 2.8 years) than MM patients without prior knowledge of MGUS (median survival, 2.1 years), although MM patients with (vs without) prior knowledge of MGUS had more comorbidities (P < .001). Among MM patients with prior knowledge of MGUS, low M-protein concentration (<0.5 g/dL) at MGUS diagnosis was associated with poorer MM survival (HR, 1.86; 95% CI, 1.13-3.04; P = .01). CONCLUSIONS AND RELEVANCE: Patients with MM with prior knowledge of MGUS had better MM survival, suggesting that earlier treatment of MM leads to better survival. The observation that a low M-protein concentration at MGUS diagnosis was associated with poorer MM survival may reflect less frequent clinical follow-up. Our observations stress the importance of clinical follow-up in patients with MGUS, regardless of risk stratification.