Current Management of T1 Colon Cancer in Denmark: A Nationwide Cohort Study.

OBJECTIVE: To describe the management of T1 colon cancer in a retrospective study of a national cancer registry. BACKGROUND: There is increasing interest in the potential of local excision (LE) as an organ-preserving treatment for early colon cancer. However, accurate identification of patients who may have lymph node metastases (LNM) and require further surgery is a major challenge. METHODS: Patients diagnosed with T1 colon cancer in Denmark from 2016 to 2020 were included and divided according to treatment: polypectomy (referred to as LE), upfront colectomy and completion colectomy. Primary outcome was the proportion of patients diagnosed by LE. Secondary outcomes included the rate of LNM, the association of histopathological risk factors with LNM, and overall survival. RESULTS: 1,749 patients were included, and 1,022 patients (58.4%) underwent initial LE. The rate of R1 margins after initial LE was 31.0%. Colectomy was performed in 1,160 patients (upfront in 727, completion in 433), of whom 58.3% had pT1 cancer. The rate of LNM was 11.5%. Rates of LNM were similar in patients undergoing upfront or completion colectomy (10.2% vs 12.4%, P=0.392), and in patients with any single histopathological risk factor compared to those with none (8.9% vs 10.6%, P=0.565). Although overall survival was significantly shorter in patients undergoing LE alone, no association between survival and treatment strategy was found on multivariable analysis. CONCLUSIONS: LE is the most common mode of diagnosis in patients with T1 colon cancer and does not negatively impact survival and postoperative outcomes. Current strategies to stratify patients to completion surgery appear insufficient, and more robust predictors are needed.

The Association of Mismatch Repair Status with Microscopically Positive (R1) Margins in Stage III Colorectal Cancer: A Retrospective Cohort Study.

BACKGROUND: There is mounting evidence that microscopically positive (R1) margins in patients with colorectal cancer (CRC) may represent a surrogate for aggressive cancer biology rather than technical failure during surgery. However, whether detectable biological differences exist between CRC with R0 and R1 margins is unknown. We sought to investigate whether mismatch repair (MMR) status differs between Stage III CRC with R0 or R1 margins. METHODS: Patients treated for Stage III CRC from January 1, 2016 to December 31, 2019 were identified by using the Danish Colorectal Cancer Group database. Patients were stratified according to MMR status (proficient [pMMR] vs. deficient [dMMR]) and margin status. Outcomes of interest included the R1 rate according to MMR and overall survival. RESULTS: A total of 3636 patients were included, of whom 473 (13.0%) had dMMR colorectal cancers. Patients with dMMR cancers were more likely to be elderly, female, and have right-sided cancers. R1 margins were significantly more common in patients with dMMR cancers (20.5% vs. 15.2%, p < 0.001), with the greatest difference seen in the rate of R1 margins related to the primary tumour (8.9% vs. 4.7%) rather than to lymph node metastases (11.6% vs. 10.5%). This association was seen in both right- and left-sided cancers. On multivariable analyses, R1 margins, but not MMR status, were associated with poorer survival, alongside age, pN stage, perineural invasion, and extramural venous invasion. CONCLUSIONS: In patients with Stage III CRC, dMMR status is associated with increased risks of R1 margins following potentially curative surgery, supporting the use of neoadjuvant immunotherapy in this patient group.

A network model of legal relations.

From at least the early twentieth century, legal scholars have recognized that rights and other legal relations inhere between individual legal actors, forming a vast and complex social network. Yet, no legal scholar has used the mathematical machinery of network theory to formalize these relationships. Here, we propose the first such approach by modelling a rudimentary, static set of real property relations using network theory. Then, we apply our toy model to measure the level of modularity-essentially, the community structure-among aggregations of these real property relations and associated actors. In so doing, we show that even for a very basic set of relations and actors, law may employ modular structures to manage complexity. Property, torts, contracts, intellectual property, and other areas of the law arguably reduce information costs in similar, quantifiable ways by chopping up the world of interactions between parties into manageable modules that are semi-autonomous. We also posit that our network science approach to jurisprudential issues can be adapted to quantify many other important aspects of legal systems. This article is part of the theme issue 'A complexity science approach to law and governance'.

Current treatment of pT1 rectal cancers in Denmark: A retrospective national cohort study.

AIM: Organ preservation strategies for patients with rectal cancer are increasingly common. In appropriately selected patients, local excision (LE) of pT1 cancers can reduce morbidity without compromising cancer-related outcomes. However, determining the need for completion surgery after LE can be challenging, and it is unknown if prior LE compromises subsequent total mesorectal excision (TME). The aim of this study is to describe the current management of patients with pT1 rectal cancers. METHOD: This is a retrospective national cohort study of the Danish Colorectal Cancer Group database, including patients with newly diagnosed pT1 cancers between 2016 and 2020. Patients were stratified according to treatment into LE alone, completion TME after LE or upfront TME. The treatment and outcomes of these groups were compared. RESULTS: A total of 1056 patients were included. Initial LE was performed in 715 patients (67.7%), of whom 194 underwent completion TME (27.1%). The remaining 341 patients underwent upfront TME (32.3%). Patients undergoing LE alone were more likely to be male with low rectal cancers and greater comorbidity. No differences in specimen quality or perioperative outcomes were noted between patients undergoing completion or upfront TME. Eighty-five patients (15.9%) had lymph node metastases (LNM). Pathological risk factors poorly discriminated between patients with and without LNM, with similar rates seen in patients with zero (14.1%), one (12.0%) or two (14.4%) risk factors. CONCLUSION: LE is a key component of the treatment of pT1 rectal cancer and does not appear to affect the outcomes of completion TME. Patient selection for completion TME remains a major challenge, with current stratification methods appearing to be inadequate.

Leaf Spot Disease Development and Its Effect on Yield of Essential Oil-Producing Hemp Cultivars in Kentucky.

Leaf spot diseases are common on field hemp, causing defoliation, and blighting. The most prevalent leaf spot diseases of hemp in Kentucky are Bipolaris leaf spot (Bipolaris gigantea), Cercospora leaf spot (Cercospora flagellaris), and Septoria leaf spot (Septoria cannabis). In this study, disease progression, cultivar susceptibility, and yield loss were examined using cultivars from four relatedness groups at two locations and in two growing seasons. Septoria leaf spot was the first leaf spot disease to be observed in the field, followed by Bipolaris leaf spot. Both diseases reduced canopy density. Cercospora leaf spot developed in the late reproductive stages as harvest approached. A wide range of susceptibility was documented, suggesting genetic variability across cultivars. Trump group cultivars were the most susceptible, while Otto II group cultivars were the least susceptible. Most importantly, leaf spot diseases had minimal influence on floral biomass and no effect on CBD yield, suggesting that, regardless of disease severity, leaf spot diseases may seldom warrant management. While the importance of foliar disease and corresponding yield loss can shift over time, variation in disease progress among leaf spot diseases and susceptibility of hemp cultivars documented in this study suggest potential disease management through cultural practices such as cultivar and planting date selections.

Prognostic Factors for Lymph Node Metastases in pT1 Colorectal Cancer Differ According to Tumor Morphology: A Nationwide Cohort Study.

OBJECTIVE: To investigate whether there is a differential impact of histopathological risk factors for lymph node metastases (LNM) in pedunculated and nonpedunculated pT1 colorectal cancers (CRC). BACKGROUND: Tumor budding, lymphovascular invasion (LVI), and venous invasion (VI) are recognized risk factors for LNM in pT1 CRC. Whether the importance of these factors varies according to tumor morphology is unknown. METHODS: Patients undergoing resection with lymphadenectomy for pT1 CRC in Denmark from January 2016 to January 2019 were identified in the Danish Colorectal Cancer Database and clinicopathological data was reviewed. Prognostic factors for LNM were investigated using multivariable analyses on the cohort as a whole as well as when stratifying according to tumor morphology (pedunculated vs. nonpedunculated). RESULTS: A total of 1167 eligible patients were identified, of whom 170 had LNM (14.6%). Independent prognostic factors for LNM included LVI [odds ratio (OR)=4.26, P <0.001], VI (OR=3.42, P <0.001), tumor budding (OR=2.12, P =0.002), high tumor grade (OR=2.76, P =0.020), and age per additional year (OR=0.96, P <0.001). On subgroup analyses, LVI and VI remained independently prognostic for LNM regardless of tumor morphology. However, tumor budding was only prognostic for LNM in pedunculated tumors (OR=4.19, P <0.001), whereas age was only prognostic in nonpedunculated tumors (OR=0.61, P =0.003). CONCLUSIONS: While LVI and LI were found to be prognostic of LNM in all pT1 CRC, the prognostic value of tumor budding differs between pedunculated and nonpedunculated tumors. Thus, tumor morphology should be taken into account when considering completion surgery in patients undergoing local excision.

Impact of adjuvant chemotherapy on long-term overall survival in patients with high-risk stage II colon cancer: a nationwide cohort study.

BACKGROUND: This study aimed to investigate the impact of adjuvant chemotherapy on long-term survival in unselected patients with high-risk stage II colon cancer including an analysis of each high-risk feature. MATERIALS AND METHODS: Data from the Danish Colorectal Cancer Group, the National Patient Registry and the Danish Pathology Registry from 2014 to 2018 were merged. Patients surviving > 90 days were included. High-risk features were defined as emergency presentation, including self-expanding metal stents (SEMS)/loop-ostomy as a bridge to resection, grade B or C anastomotic leakage, pT4 tumors, lymph node yield < 12 or signet cell carcinoma. Eligibility criteria for chemotherapy were age < 75 years, proficient MMR gene expression, and performance status ≤ 2. The primary outcome was 5-year overall survival. Secondary outcomes included the proportion of eligible patients allocated for adjuvant chemotherapy and the time to first administration. RESULTS: In total 939 of 3937 patients with stage II colon cancer had high-risk features, of whom 408 were eligible for chemotherapy. 201 (49.3%) patients received adjuvant chemotherapy, with a median time to first administration of 35 days after surgery. The crude 5-year overall survival was 84.9% in patients receiving adjuvant chemotherapy compared with 66.3% in patients not receiving chemotherapy, p < 0.001. This association corresponded to an absolute risk difference of 14%. CONCLUSION: 5-year overall survival was significantly higher in patients with high-risk stage II colon cancer treated with adjuvant chemotherapy compared with no chemotherapy. Adjuvant treatment was given to less than half of the patients who were eligible for it.

Do differences in surgical quality account for the higher rate of R1 margins to lymph node metastases in right- versus left-sided Stage III colon cancer: A retrospective cohort study.

AIM: Microscopically positive (R1) margins to lymph node metastases (R1LNM) are associated with poorer oncological outcomes in patients with Stage III colon cancer. R1LNM margins are more common in right-sided cancer, although the cause of this phenomenon is unknown. We sought to investigate whether differences in surgical quality account for the higher rate of R1LNM in right-sided cancers. METHOD: Patients treated for Stage III colon cancer from 1 January 2016 to 31 December 2018 were identified using the Danish national cancer registry. Indicators of surgical quality (mesocolic resection grade, median lymph node yield, and length to the distal colonic margin) were compared according to tumour site and margin status. RESULTS: In all, 1765 patients were included, 981 (55.6%) with right-sided cancers. R1LNM margins were more common in right-sided cancers (14.4% vs. 6.1%, P < 0.001). All three surgical quality indicators were higher in patients with right-sided cancers (mesocolic resection planes 81.7% vs. 69.5%, P < 0.001; median lymph node yield 28 vs. 25, P < 0.001; ≥5 cm to the distal colon margin 81.2% vs. 53.6%, P < 0.001). When stratified according to margin status, no differences in mesocolic resection planes or resectate length were noted, whilst median lymph node yield was higher in patients with R1LNM margins (29 vs. 27, P = 0.009). CONCLUSION: Surgical quality does not appear to be poorer in patients undergoing surgery for right-sided versus left-sided colon cancers in Denmark. Suboptimal surgery does not appear to be responsible for R1LNM margins, implying that these margins may be a surrogate for more aggressive biology.

HPV vaccine narratives on Twitter during the COVID-19 pandemic: a social network, thematic, and sentiment analysis.

INTRODUCTION: The COVID-19 pandemic has increased online interactions and the spread of misinformation. Some researchers anticipate benefits stemming from improved public awareness of the value of vaccines while others worry concerns around vaccine development and public health mandates may have damaged public trust. There is a need to understand whether the COVID-19 pandemic, vaccine development, and vaccine mandates have influenced HPV vaccine attitudes and sentiments to inform health communication strategies. METHODS: We collected 596,987 global English-language tweets from January 2019-May 2021 using Twitter's Academic Research Product track. We determined vaccine confident and hesitant networks discussing HPV immunization using social network analysis. Then, we used a neural network approach to natural language processing to measure narratives and sentiment pertaining to HPV immunization. RESULTS: Most of the tweets in the vaccine hesitant network were negative in tone (54.9%) and focused on safety concerns surrounding the HPV vaccine while most of the tweets in the vaccine confident network were neutral (51.6%) and emphasized the health benefits of vaccination. Growth in negative sentiment among the vaccine hesitant network corresponded with legislative efforts in the State of New York to mandate HPV vaccination for public school students in 2019 and the WHO declaration of COVID-19 as a Global Health Emergency in 2020. In the vaccine confident network, the number of tweets concerning the HPV vaccine decreased during the COVID-19 pandemic but in both vaccine hesitant and confident networks, the sentiments, and themes of tweets about HPV vaccine were unchanged. CONCLUSIONS: Although we did not observe a difference in narratives or sentiments surrounding the HPV vaccine during the COVID-19 pandemic, we observed a decreased focus on the HPV vaccine among vaccine confident groups. As routine vaccine catch-up programs restart, there is a need to invest in health communication online to raise awareness about the benefits and safety of the HPV vaccine.

How Psychiatrists' Beliefs on Free Will Influence Their Clinical Practice.

BACKROUND: Literature suggests that most people believe in free will and that this belief is associated with more prosocial behavior. However, with the advent of neuroscience, free will seems to have been progressively excluded from psychiatry. This paper is a narrative literature review of the ways in which mental health professionals' premises and beliefs in free will influence their clinical practice. METHODS: The Scopus database was searched for papers concerning free will and psychiatric practice, 24 papers were included. This review looks at explicit links made by authors between free will and clinical practice as well as logical threads linking a premise of free will to clinical implications. RESULTS: The results suggest that belief in free will leads to trying to strengthen free will in patients. It also appears to be associated with using meaning in psychotherapy, with self-blame in patients, and with ethical questions such as involuntary psychiatric care and assisted suicide requests. Some authors believe the concept of free will should be discarded to make place for concepts such as autonomy, agency, decision-making capacity and self-control. CONCLUSION: While definitional ambiguity and paucity of data are limiting, the results indicate that mental health professionals' beliefs concerning free will can influence their clinical practice. Concepts such as autonomy and agency can sometimes hide psychiatrists' underlying beliefs. Increasing mental health professionals' awareness of their beliefs could be beneficial for psychiatric care.

How to Improve Collaboration Between General Practitioners and Clinical Psychologists for Their Patients' Common Mental Health Problems in Primary Care Context?

BACKGROUND: Mental health problems have become a major topic of public health these last years, particularly since the pandemic of COVID-19. Primary care givers are confronted with high rates of common mental health problems (CMHPs) in population. This questions healthcare organization and specifically collaboration between general practitioners (GPs) and clinical psychologists (CPs). In this paper we aim to review recent literature to identify factors that facilitate or hinder collaboration between GPs and CPs when caring for their patients' CMHPs. METHODS: A non-systematic qualitative literature review was performed, using the PRISMA method. We restricted the review to papers published between 2010 and 2023. RESULTS: We identified 52 papers and after filtering, only 6 were included in the synthesis. Six main themes were identified: barriers to interprofessional collaboration, lack of mutual trust, mutual dissatisfaction with information exchanged, the paradox of professional secrecy, the necessity of a paradigm shift, and conceptual frameworks of collaboration. These themes were discussed to improve collaboration between GPs and CPs. CONCLUSION: This work provides some recommendations to support the development of interprofessional collaboration between GPs and CPs in primary care.

The impact of subdivisions of microscopically positive (R1) margins on patterns of relapse in stage III colorectal cancer - A retrospective cohort study.

AIM: Microscopically positive (R1) margins are associated with poorer outcomes in patients with colorectal cancer. However, the impact of subdivisions of R1 margins, be they to the primary tumour (R1 tumour) or to lymph node metastases (R1LNM), on patterns of relapse is unknown. METHODS: Patients treated for stage III colorectal cancer from 01 January 2016 to 31 December 2019 in four specialist centres were identified from the Danish national cancer registry. Patients were stratified into three groups according to margin status (R0 vs. R1 tumour vs. R1LNM). The primary outcomes were local recurrence-free survival (LRFS), distant metastases-free survival (DMFS) and disease-specific survival (DSS). RESULTS: A total of 1,164 patients were included, with R1 margins found in 237 (20.4%). Irrespective of tumour location, R1 tumour and R1LNM margins were independent prognostic factors for systemic relapse (R1 tumour HR 1.84, CI: 1.17-2.88, p = 0.008; R1LNM HR 1.59, CI: 1.12-2.27, p = 0.009) and disease-related death (R1 tumour HR 2.08, CI: 1.12-3.85, p = 0.020; R1LNM HR 1.84, CI: 1.12-3.02, p = 0.016). Whereas R1 tumour margins were associated with poorer 3-year LRFS in both colon and rectum cancer, R1LNM margins only reduced LRFS in patients with rectal cancer. Patterns of relapse differed between R1 subdivisions, with R1 tumour margins more likely to affect multiple anatomical sites, with a predilection for extra-hepatic/pulmonary metastases. CONCLUSION: Subdivisions of R1 margins have a distinct impact on the oncological outcomes and patterns of disease relapse in patients with stage III colorectal cancer.

The significance of subdivisions of microscopically positive (R1) margins in colorectal cancer: A retrospective study of a national cancer registry.

AIM: Microscopically positive (R1) margins are associated with poorer outcomes in patients with colorectal cancer. However, little is known of the differential impact of subdivisions of R1 margins, be they to the primary tumour (R1tumour) or to lymph node metastases/tumour deposits (R1LNM). METHODS: Patients treated for Stage III colorectal cancer from 1 January 2016 to 31 December 2019 were identified from the Danish national cancer registry. Patients were stratified into three groups according to margin status (R0 vs. R1tumour vs. R1LNM). The primary outcome was overall survival. RESULTS: In all, 4186 patients were included, comprising 3012 patients with colon cancer and 1174 patients with rectal cancer. The R1 resection rates were 16.5% and 18.2% in patients with colon and rectum cancer, respectively. In colon cancers, 3-year overall survival was reduced in patients with R1LNM (65.7%, 95% CI 62.8-68.6) or R1tumour margins (51.8%, 95% CI 47.3-56.3) compared with R0 resections (80.8%, 95% CI 79.9-81.6, P < 0.001). A similar impact on survival was seen in rectal cancers (R0, 84.2%, 95% CI 82.9-85.5; R1LNM, 72.2%, 95% CI 67.8-76.6; R1tumour, 56.6%, 95% CI 50.0-63.2, P < 0.001). Margin status was independently prognostic of survival in both colon (R1tumour, hazard ratio 2.08, 95% CI 1.50-2.89, P < 0.001; R1LNM, hazard ratio 1.48, 95% CI 1.11-1.97, P = 0.008) and rectal cancers (R1tumour, hazard ratio 2.35, 95% CI 1.42-3.90, P < 0.001; R1LNM, hazard ratio 1.54, 95% CI 0.95-2.48, P = 0.077). CONCLUSION: R1 subdivisions have distinct impacts on survival in Stage III colorectal cancer. Further focused research in these patient subgroups is warranted.

First Report of Fusarium graminearum Causing Flower Blight On Hemp (Cannabis sativa) in Kentucky.

In October of 2020, a grower in Boyle County, KY, reported mold and blight symptoms on flowers of field-grown hemp. Plants were approaching harvest, and the mold was affecting 100% of the cultivar 'White CBG' being grown for cannabinoid (CBD) extraction. Mycelium colonized the flower heads and any seeds within bracts. Affected flower bracts were necrotic, and mycelium and necrosis in the most severe cases also encompassed adjacent (sugar) leaves. Necrotic symptomatic tissue was collected, disinfested in 10% bleach for one minute, and cultured on acidified potato dextrose agar (APDA). Each isolate was single-spored, transferred to PDA, stored in 15% glycerol at -80°C and maintained at room temperature under blacklight blue and fluorescent bulbs on a 12-hour light-dark cycle. Colonies produced white-pink mycelia with a dark red pigment on the undersides. Conidia collected after 7-9 days were falcate and septate (5 to 6). No microconidia were produced. Macroconidia measured 35.4-49.7 µm x 3.4-5.8 µm (n=50). The strains produced blue-black fertile perithecia on carrot agar when induced according to the method of (Bowden and Leslie, 1999). To confirm pathogenicity, flowers of hemp cultivars 'Lifter', 'Trump Towers', 'Wife' and 'White CBG' were inoculated in the greenhouse with a representative fungal strain (20Hemp010). Plants were inoculated at two different stages: when the styles were still green or after they had become senescent. Macroconidia were collected from 7- to 9-day-old cultures grown under a 12-hour light-dark cycle. Plants were spray-inoculated with a 5 x 105 per ml conidial suspension in 0.05% Tween 20 until runoff. Flower heads were individually covered with clear plastic bags and incubated for 72 h at 95-100% humidity under greenhouse benches to avoid direct light. Bags were removed after 72 h and returned to the bench. Greenhouse conditions were 23-25°C with a 14-hour photoperiod and 50% RH. Symptoms developed 7 dai in 1% of the flowers inoculated when styles were green, and 36% of the flowers that had senescent styles. Symptoms were similar to those initially noticed in Boyle County, including necrotic flower bracts and sugar leaves, and visible fungal growth. Symptoms were more severe on plants inoculated when styles were necrotic. Recovered fungi were morphologically similar to 20Hemp010. Genomic DNA was extracted from the mycelium with the Zymo Research Quick-DNA Fungal/Bacterial Miniprep Kit. A fragment of the translation elongation factor 1-alpha 1 gene was amplified with primers EF1 and EF2 as described by (O'Donnell et al. 1998). Amplicons were sequenced and the consensus (MZ407909) was compared with the NCBI GenBank Refseq database by BLASTn. The top hit was Fusarium graminearum with 100% identity (JF270185.1). Pairwise alignments via MycoBank Fusarium MLST and Fusarium-ID also revealed a top hit of F. graminearum with 100% identity (AY452957.1). Conidial and colony morphology were also consistent with F. graminearum (Leslie and Summerell, 2006), thus we conclude that this species was the causal agent of the flower blight and mold. The same disease was subsequently confirmed on hemp in Breathitt and Franklin Counties in KY in 2020. This is the first report of this disease in KY, although F. graminearum has been reported previously causing a similar flower blight on hemp in NY and NC (Bergstrom et al., 2019, Thiessen et al. 2020). Fusarium graminearum is common in KY as a cause of Fusarium head blight on wheat and Gibberella ear rot on corn. In cereals, fungal infection is facilitated by the production of the mycotoxin deoxynivalenol (DON), which is harmful to humans and livestock (Desjardins and Hohn, 1997). As hemp production in Kentucky continues to rise for production of CBD products and edible grains, accumulation and concentration of DON in these products could become a concern.

The effect of a diverting stoma on morbidity and risk of permanent stoma following anastomotic leakage after low anterior resection for rectal cancer: a nationwide cohort study.

BACKGROUND: Diverting stomata (DS) have been shown to mitigate the clinical impact of anastomotic leakage (AL) but not without complications, and their routine use remains a matter of international debate. The objective of this study was to examine the association between stomata and the clinical consequences of AL. METHODS: This was a nationwide retrospective cohort study including all patients suffering from AL after low anterior resection from 2001 to 2010. RESULTS: Four thousand sixty-three patients were treated in the period of whom 581 (11.9%) developed AL. In case of AL, patients without a diverting stoma had a slightly higher 90-day mortality rate (13.5% versus 8.7%, p = 0.089). Patients suffered more complications due to AL, both surgical (52% versus 28%, p < 0.001) and non-surgical (48% versus 35%, p = 0.004) with a higher Clavien-Dindo score. Twenty percent of patients developed stoma-related complications prior to stoma reversal. Mortality related to stoma reversal was 2.4%. Factors associated with a risk of a permanent stoma were age (HR 1.04, 95% CI 1.01-1.08), blood transfusion during primary surgery (HR 2.35, 95% CI 1.16-4-78), conserved anastomosis after AL (HR 0.019, 95% CI 0.009-0.04), and a diverting stoma fashioned at the index operation (HR 0.50, 95% CI 0.26-0.97). CONCLUSION: The use of diverting stomata during low anterior resection mitigates the clinical impact of AL. However, this benefit needs to be balanced against the risk of stoma-related complications, seen in 20%, and mortality with stoma reversal (2.4%). Where practical, the decision to divert should be made pre-operatively in a multidisciplinary setting.

Major Amputations for Extremity Soft-Tissue Sarcoma.

INTRODUCTION: With modern techniques facilitating limb conservation, amputation for extremity soft-tissue sarcoma (ESTS) is now rare. We sought to determine the indications and outcomes following major amputation for ESTS and whether amputation is prognostic of oncological outcomes in primary disease. PATIENTS AND METHODS: Patients undergoing major amputations for ESTS from 2004 to 2014 were identified from electronic patient records. RESULTS: The amputation rate in primary localized disease was 4.1%. Overall, 69 patients were identified, including 23 (33.3%) amputations for primary localized disease, 36 (52.2%) amputations for recurrent disease, and 10 (14.5%) amputations for metastatic disease. The local recurrence rate for localized disease at 3 years was 10.4%. Three-year overall survival (OS) was 50.3% following curative amputation, with a median survival of 41 months, and median OS following palliative amputation was 6 months. In the context of primary, localized disease, patients undergoing amputation had a greater proportion of high-grade tumors (69.6% vs. 41.1%; p = 0.009) of greater size (median 16.0 vs. 9.0 cm; p = 0.003) when compared with patients undergoing limb-conserving surgery. The rates of systemic relapse and disease-specific survival were poorer following amputation compared with limb-conserving surgery, however mode of surgery (amputation vs. limb conservation) was only prognostic for OS. CONCLUSIONS: Amputation maintains an important role in ESTS and achieves durable local control in those unsuitable for limb-conserving surgery. Survival following amputation in the presence of metastatic disease is poor and should be reserved for patients with significant symptoms.

Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: a retrospective analysis.

BACKGROUND: The current American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system does not have sufficient details to encompass the variety of soft-tissue sarcomas, and available prognostic methods need refinement. We aimed to develop and externally validate two prediction nomograms for overall survival and distant metastases in patients with soft-tissue sarcoma in their extremities. METHODS: Consecutive patients who had had an operation at the Istituto Nazionale Tumori (Milan, Italy), from Jan 1, 1994, to Dec 31, 2013, formed the development cohort. Three cohorts of patient data from the Institut Gustave Roussy (Villejuif, France; from Jan 1, 1996, to May 15, 2012), Mount Sinai Hospital (Toronto, ON, Canada; from Jan 1, 1994, to Dec 31, 2013), and the Royal Marsden Hospital (London, UK; from Jan 1, 2006, to Dec 31, 2013) formed the external validation cohorts. We developed the nomogram for overall survival using a Cox multivariable model, and a Fine and Gray multivariable model for the distant metastases nomogram. We applied a backward procedure for variables selection for both nomograms. We assessed nomogram model performance by examining overall accuracy (Brier score), calibration (calibration plots and Hosmer-Lemeshow calibration test), and discrimination (Harrell C index). We plotted decision curves to evaluate the clinical usefulness of the two nomograms. FINDINGS: 1452 patients were included in the development cohort, with 420 patients included in the French validation cohort, 1436 patients in the Canadian validation cohort, and 444 patients in the UK validation cohort. In the development cohort, 10-year overall survival was 72·9% (95% CI 70·2-75·7) and 10-year crude cumulative incidence of distant metastases was 25·0% (95% CI 22·7-27·5). For the overall survival nomogram, the variables selected applying a backward procedure in the multivariable Cox model (patient's age, tumour size, Fédération Française des Centres de Lutte Contre le Cancer [FNCLCC] grade, and histological subtype) had a significant effect on overall survival. The same variables, except for patient age, were selected for the distant metastases nomogram. In the development cohort, the Harrell C index for overall survival was 0·767 (95% CI 0·743-0·789) and for distant metastases was 0·759 (0·736-0·781). In the validation cohorts, the Harrell C index for overall survival and distant metastases were 0·698 (0·638-0·754) and 0·652 (0·605-0·699; French), 0·775 (0·754-0·796) and 0·744 (0·720-0·768; Canadian), and 0·762 (0·720-0·806) and 0·749 (0·707-0·791; UK). The two nomograms both performed well in terms of discrimination (ability to distinguish between patients who have had an event from those who have not) and calibration (accuracy of nomogram prediction) when applied to the validation cohorts. INTERPRETATION: Our nomograms are reliable prognostic methods that can be used to predict overall survival and distant metastases in patients after surgical resection of soft-tissue sarcoma of the extremities. These nomograms can be offered to clinicians to improve their abilities to assess patient prognosis, strengthen the prognosis-based decision making, enhance patient stratification, and inform patients in the clinic. FUNDING: None.

The impact of additional malignancies in patients diagnosed with gastrointestinal stromal tumors.

A higher incidence of additional malignancies has been described in patients diagnosed with gastrointestinal stromal tumors (GIST). This study aimed to identify risk factors for developing additional malignancies in patients diagnosed with GIST and evaluate the impact on survival. Individuals diagnosed with GIST from 2001 to2009 were identified from the SEER database. Logistic regression was used to identify predictors of additional malignancies and Cox-proportional hazards regression used to identify predictors of survival. In the study period, 1705 cases of GIST were identified, with 181 (10.6%) patients developing additional malignancies. Colorectal cancer was the most common cancer developing within 6 months of GIST diagnosis (30%). The median time to diagnosis of a malignancy after 6 months of GIST diagnosis was 21.9 months. Older age (p < 0.0001) and extraoesophagogastric GIST (p = 0.0027) were significant prognostic factors associated with additional malignancies. The overall 5-year survival was 65%, with the presence of additional malignancies within 6 months of GIST diagnosis associated with poor overall survival (54%, HR 1.55 1.05-2.3 95% CI, p = 0.04). Predictive factors of additional malignancies in patients diagnosed with GIST are increasing age and the primary disease site. Developing additional malignancies within 6 months of GIST diagnosis is associated with poorer overall survival. Targeted surveillance may be warranted in patients diagnosed with GIST that are at high risk of developing additional malignancies.