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Background The outcome of anti-reflux surgery in patients with suspected gastro-oesophageal reflux-induced cough is frequently uncertain. The aims of this study were to assess the efficacy of laparoscopic fundoplication for controlling cough in patients with chronic cough without asthma, who have pathologic gastro-oesophageal reflux, and to identify predictors of response. Methods From a prospective database of 1598 patients who have undergone laparoscopic fundoplication, 66 (4%) with proven gastro-oesophageal reflux disease (GORD) and chronic cough without asthma were studied. All patients underwent gastroscopy and 24-h pH monitoring before operation. Heartburn and regurgitation were assessed using a modified DeMeester score. Severity of cough before and after surgery was self-assessed by the patient using a visual analog scale at a minimum of 12 months post-operatively (median 43 mo; range: 14–104 mo). Patients were considered to have responded to fundoplication if they had no cough or the cough had improved by 50% or more after operation. Results Cough and heartburn/regurgitation were relieved in 61% (40/66) and 90% (44/49) of the patients, respectively. The presence of typical GORD symptoms or oesophagitis, and pH study variables did not predict the response of the cough to fundoplication. Conclusion Refinement in the aetiological diagnosis of chronic cough due to GORD is necessary for improved outcome. Patients diagnosed with GORD-related chronic cough need to be counseled regarding their expectations from anti-reflux surgery.

Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.

Treatment for metastatic melanoma includes targeted and/or immunotherapy. Although many patients respond, only a subset has complete response. As late-stage patients often have multiple tumors in difficult access sites, non-invasive techniques are necessary for the development of predictive/prognostic biomarkers. PET/CT scans from 52 patients with stage III/IV melanoma were assessed and CT image parameters were evaluated as prognostic biomarkers. Analysis indicated patients with high standard deviation or high mean of positive pixels (MPP) had worse progression-free survival (P = 0.00047 and P = 0.0014, respectively) and worse overall survival (P = 0.0223 and P = 0.0465, respectively). Whole-exome sequencing showed high MPP was associated with BRAF mutation status (P = 0.0389). RNA-sequencing indicated patients with immune “cold” signatures had worse survival, which was associated with CT biomarker, MPP4 (P = 0.0284). Multiplex immunofluorescence confirmed a correlation between CD8 expression and image biomarkers (P = 0.0028).Implications:CT parameters have the potential to be cost-effective biomarkers of survival in melanoma, and reflect the tumor immune-microenvironment.

Kaplan-Meier (log-rank) analysis of MPP4 and SD3 showing the PFS and OS for stage III patients only. a. PFS for MPP4, **p=0.0017, b. OS for MPP4, *p=0.0117, c. PFS for SD3, ***p=0.0003 and d. OS for SD3, **p=0.0094.

Multiplex immunofluorescence staining quantification by Visiopharm Image Analytical System. DAPI nuclei were segmented defining the areas. Then each marker was quantified within this DAPI area. MPP4 low (MelR062) and MPP4 high (MelR166) phenotypes are represented.

Table S1. Patient Characteristics. AJCC: American Joint Committee on Cancer Table S2. Clinical information including histology, stage and survival. Table S3. Univariate analysis of clinico-pathological and CT features. Log-rank (Mantel-Cox) test to determine optimal cut-offs for low/high groups. Table S4. RNAseq immune genes for multiplex analysis.

The association between TMB and SD3/MPP4 is not statistically significant. A. MPP4, not significant, Fisher's exact. B. SD3, not significant, Fisher's exact.

Supplementary Table 1 from Genome-Wide Copy Number Analysis in Esophageal Adenocarcinoma Using High-Density Single-Nucleotide Polymorphism Arrays

Supplementary Figure 2 from Genome-Wide Copy Number Analysis in Esophageal Adenocarcinoma Using High-Density Single-Nucleotide Polymorphism Arrays

Supplementary Figure 1 from Genome-Wide Copy Number Analysis in Esophageal Adenocarcinoma Using High-Density Single-Nucleotide Polymorphism Arrays

We applied whole-genome single-nucleotide polymorphism arrays to define a comprehensive genetic profile of 23 esophageal adenocarcinoma (EAC) primary tumor biopsies based on loss of heterozygosity (LOH) and DNA copy number changes. Alterations were common, averaging 97 (range, 23–208) per tumor. LOH and gains averaged 33 (range, 3–83) and 31 (range, 11–73) per tumor, respectively. Copy neutral LOH events averaged 27 (range, 7–57) per EAC. We noted 126 homozygous deletions (HD) across the EAC panel (range, 0–11 in individual tumors). Frequent HDs within FHIT (17 of 23), WWOX (8 of 23), and DMD (6 of 23) suggest a role for common fragile sites or genomic instability in EAC etiology. HDs were also noted for known tumor suppressor genes (TSG), including CDKN2A, CDKN2B, SMAD4, and GALR1, and identified PDE4D and MGC48628 as potentially novel TSGs. All tumors showed LOH for most of chromosome 17p, suggesting that TSGs other than TP53 may be targeted. Frequent gains were noted around MYC (13 of 23), BCL9 (12 of 23), CTAGE1 (14 of 23), and ZNF217 (12 of 23). Thus, we have confirmed previous reports indicating frequent changes to FHIT, CDKN2A, TP53, and MYC in EAC and identified additional genes of interest. Meta-analysis of previous genome-wide EAC studies together with the data presented here highlighted consistent regions of gain on 8q, 18q, and 20q and multiple LOH regions on 4q, 5q, 17p, and 18q, suggesting that more than one gene may be targeted on each of these chromosome arms. The focal gains and deletions documented here are a step toward identifying the key genes involved in EAC development. [Cancer Res 2008;68(11):4163–72]

IntroductionIn 2017 the Dutch Upper Gastrointestinal Cancer Audit Group proposed a ten-item composite measure for a ‘textbook outcome’ (TBO) following oesophago-gastric resection. Studies have shown associations between TBO and improved conditional and overall survival. The aim of this study was to evaluate the use of TBO to assess the outcomes from a single specialist unit in a country, with low incidence of disease, allowing comparisons with international specialist centres. Materials and Methods Retrospective analysis of prospectively collected oesophageal cancer surgery data at a single centre, in Australia, between 2013 to 2018. Multivariable logistical regression assessed association between baseline factors and TBO. Post-operative complications were analysed in two separate groups as Clavien-Dindo ≥2 (CD≥2) and Clavien-Dindo ≥3 (CD≥3). Cox-proportional hazards regression analysis determined the association between TBO and survival. Results 246 patients were analysed, with 50.8% (n=125) achieving a TBO when complications were defined as CD≥2 and 58.9% (n=145) when using CD≥3. Patients aged ≥75, and those with a pre-operative respiratory co-morbidity were less likely to achieve a TBO. Overall survival was not influenced by TBO when complications were defined as CD≥2, however it was higher when a TBO was achieved, and complications were defined as CD≥3 (HR 0.54, 95% CI, 0.35 to 0.84, P=0.007). Conclusion TBO is a multi-parameter metric that allowed benchmarking of the quality of oesophageal cancer surgery in our unit, providing favourable outcomes compared with other published data. There was an association between TBO and improved overall survival when the definition of severe complications was CD≥3. Key Words: Cancer Surgery, Oesophagectomy, Quality Performance Indicators, Textbook Outcome

Targeted therapy (BRAF inhibitor plus MEK inhibitor) is now among the possible treatment options for patients with BRAF mutation-positive stage III or stage IV melanoma. This makes prompt BRAF mutation testing an important step in the management of patients diagnosed with stage III or IV melanoma; one that can help better ensure that the optimal choice of systemic treatment is initiated with minimal delay. This article offers guidance about when and how BRAF mutation testing should be conducted when patients are diagnosed with melanoma in Australia. Notably, it recommends that pathologists reflexively order BRAF mutation testing whenever a patient is found to have American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage III or IV melanoma (i.e., any metastatic spread beyond the primary tumour) and that patient's BRAF mutation status is hitherto unknown, even if BRAF mutation testing has not been specifically requested by the treating clinician (in Australia, Medicare-subsidised BRAF

BACKGROUND: There is currently a lack of evidence-based guidelines regarding surveillance for recurrence after esophageal and gastric (OG) cancer surgical resection, and which symptoms should prompt endoscopic or radiological investigations for recurrence. The aim of this study was to develop a core symptom set using a modified Delphi consensus process that should guide clinicians to carry out investigations to look for suspected recurrent OG cancer in previously asymptomatic patients. METHODS: A web-based survey of 42 questions was sent to surgeons performing OG cancer resections at high volume centers. The first section evaluated the structure of follow-up and the second, determinants of follow-up. Two rounds of a modified Delphi consensus process and a further consensus workshop were used to determine symptoms warranting further investigations. Symptoms with a 75% consensus agreement as suggestive of recurrent cancer were included in the core symptom set. RESULTS: 27 surgeons completed the questionnaires. A total of 70.3% of centers reported standardized surveillance protocols, whereas 3.7% of surgeons did not undertake any surveillance in asymptomatic patients after OG cancer resection. In asymptomatic patients, 40.1% and 25.9% of centers performed routine imaging and endoscopy, respectively. The core set that reached consensus, consisted of eight symptoms that warranted further investigations included; dysphagia to solid food, dysphagia to liquids, vomiting, abdominal pain, chest pain, regurgitation of foods, unexpected weight loss and progressive hoarseness of voice. CONCLUSION: There is global variation in monitoring patients after OG cancer resection. Eight symptoms were identified by the consensus process as important in prompting radiological or endoscopic investigation for suspected recurrent malignancy. Further randomized controlled trials are necessary to link surveillance strategies to survival outcomes and evaluate prognostic value. ispartof: DISEASES OF THE ESOPHAGUS vol:36 issue:1 ispartof: location:United States status: published

Gastroesophageal reflux disease (GORD) is defined as troublesome symptoms and/or injury to the oesophageal mucosa consistent with acid exposure [1]. GORD is common, with an age-adjusted global prevalence of 9% but significant variation across the world [2]. The diagnosis can often be made on clinical grounds and is more likely if there is at least a partial response to a proton pump inhibitor (PPI) [3]. Indications for oesophageal testing have been recently updated in international consensus guidelines, which include guidelines where diagnosis is not clearly established [4]. Fundoplication is the use of the gastric fundus to create a high-pressure zone on or around the lower oesophagus and is usually performed laparoscopically. It can be considered in terms of the completeness of the wrap (generally from 90 to 360°), and if less than 360°, whether the wrap is brought anterior to the oesophagus, posterior, or both. The efficacy and side effect profiles of many of the approaches have been subjected to randomised trials: anterior 90 vs 360° [5]; anterior 180 vs 360° [6]; and posterior 270 vs 360° [7]. The relative merits of each have been recently reviewed by Morino and colleagues [8]. Fundoplication is at least as safe and effective as PPI in relieving the symptoms of GORD [9]. For PPI-refractory GORD, fundoplication is more effective than escalating medical therapy [10].

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery.Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases.Design, Setting, and Participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022.Interventions: Nodal observation with ultrasonography rather than CLND.Main Outcomes and Measures: In-basin nodal recurrence.Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P Conclusions and Relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients.Trial Registration: ClinicalTrials.gov Identifier: NCT00297895.

The incidence of oesophageal adenocarcinoma (OAC) is rising in Western countries, with a 5-year overall survival (OS) rate of 14%. Curative treatment based on oesophagectomy is only suitable for ~50% of patients due to late-stage diagnosis. While the addition of preoperative chemotherapy or chemoradiotherapy has improved OS in OAC patients, little is known about the molecular basis of treatment response and patient outcomes. We investigated multi-omics data including whole-genome sequencing, RNA sequencing, methylation profiles and immunohistochemistry from 115 OAC patients mostly from DOCTOR phase II clinical trial that utilized neoadjuvant therapy (ANZCTR-ACTRN12609000665235). We identified genomic features associated with poor OS, such as the APOBEC mutational signature. We also showed that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. RNA sequencing and methylation profiles suggested four immune clusters associated with OS and progression-free survival. The immune-suppressed cluster was associated with worse survival and epithelial-mesenchymal transition signature and enriched with myeloid-derived cells. The immune hot cluster was associated with better survival and enriched with T-cells, myeloid-derived cells, interferon-gamma and alpha responses, and immune markers such as CCL5, CD8A, and NKG7. We investigated multi-omic features of OAC tumours from patients who were part of phase II clinical trial. We discovered prognostic features such as mutational signatures and complex genomic events. We identified distinct immune clusters associated with patient outcomes and the potential of immunotherapy for select clusters. We characterized molecular features of OAC patients which has the potential to predict responses to neoadjuvant therapy and develop better-selected therapy, monotherapy, or combination therapy in the future.

The outcome of anti-reflux surgery in patients with cough suspected to be induced by gastro-oesophageal reflux disease is frequently uncertain. The aims of this study were to assess the efficacy of laparoscopic fundoplication (LF) for controlling cough in a patient population suffering chronic cough when alternative aetiologies (e.g. asthma) had been excluded and pathologic gastro-oesophageal reflux had been confirmed on ambulatory pH monitoring, and to identify predictors of response. From a prospective database of 1,598 patients who had undergone laparoscopic fundoplication, 66 (4%) had a principal presenting symptom of chronic cough as well as objective evidence of gastro-oesophageal reflux disease (GORD). Patients completed questionnaires for GORD symptoms (modified DeMeester score) and severity of cough (visual analog scale) both before and after LF, and had pre-operative gastroscopy and 24-hour pH monitoring before operation. Patients were considered to have responded to LF if they had no cough or the cough had improved by 50% or more after operation. Follow-up data was available for 66/66 patients (100%), with a median follow-up time of 43 months (range 14–104 months) after operation. Cough was relieved in 40/66 (61%), while typical GORD symptoms (heartburn, regurgitation) was relieved in 44/49 (90%). The presence of typical GORD symptoms, oesophagitis, or pH study variables did not predict the response of the cough to LF. At 1 year, 67% of patients were satisfied with the results of their surgery, 20% were not and 13% were unsure. For comparison, the 1430/1598 patients in the database with no laryngopharyngeal symptoms had a satisfaction rate of 94%. Based on our study and available literature, it appears there are no reliable pre-operative clinical predictors of a satisfactory response of cough to LF. This probably reflects a current inability to obtain an accurate aetiological diagnosis of chronic cough, even in the presence of known abnormal gastro-oesophageal reflux disease. Regardless, in a well-chosen cohort of patients with chronic cough, LF can yield good patient satisfaction rates, albeit less than for patients with typical GORD symptoms.

Definitive chemoradiotherapy (dCRT) for oesophageal cancer is recommended in selected patients who are unfit for surgery, or where doctor and/or patient prefers to surgery. Salvage oesophagectomy after dCRT is reportedly a morbid procedure compared to oesophagectomy following neoadjuvant chemoradiotherapy (nCRT). If indications for dCRT expand, there will be a larger pool of patients requiring salvage oesophagectomy. We aimed to assess the post-operative clinical outcomes of patients who had dCRT compared with nCRT in our unit. Data were obtained from a prospectively maintained database of patients receiving curative treatment for oesophageal cancer from January 2010 until February 2022. Patients receiving a salvage oesophagectomy after dCRT were compared to those receiving nCRT and planned oesophagectomy. An comparison of differences in group characteristics, post-operative outcomes and survival rates was made. Analysis was completed using t-test, chi-square, log rank and Kaplan–Meier methods. 216 patients had dCRT with 24 undergoing salvage oesophagectomy. 228 had nCRT followed by surgery. The salvage group had more SCC (47% versus 16%; p = 0.002), higher blood loss (434 versus 280 mL; p = 0.033) and more surgeon-rated technical problems (e.g. pleural adhesions or mediastinal fibrosis) (30% versus 11%; p = 0.010). Operative times were not significantly different (357 versus 330 minutes; p = 0.232). There was a trend towards higher complications in the dCRT group (83 versus 63%; p = 0.057). Operative mortality was 0% in both groups. As expected the median survival was worse in the dCRT group (26 versus 66 months; p = 0.040). Patients selected to dCRT who require and are fit for salvage oesophagectomy have worse outcomes compared with those who have nCRT. However, this subgroup still have a modest potential for cancer survival. Our dataset adds to the existing literature and will help to counsel patients being considered for salvage oesophagectomy. The possible future increase in number of patients being offered dCRT makes improving the understanding of peri-operative and cancer-specific outcomes after salvage oesophagectomy a priority.

Metastatic melanoma is a fatal malignancy with a high mortality and morbidity. Since the early 1970s, available medical therapies were limited in improving survival. Surgery represented the best chance for a cure. However, surgery could only be offered to selected patients. The current landscape of treatment has radically evolved since the introduction of targeted and immunotherapies including BRAF and MEK inhibitors, and checkpoint blockers, like PD-1 and CTLA-4 antibodies. These new therapies have seen survival rates matching, and in some cases surpassing, that of surgery. Anti-PD1 and CTLA-4 combination treatments are associated with severe side effects and BRAF and MEK inhibitor combinations may trigger initial tumour responses but prolonged use have resulted in the development of resistant tumour clones and disease relapse. This review examines the role of pulmonary metastasectomy for lung metastasis from malignant melanoma in the current landscape of effective targeted therapy and immunotherapy.

Highlights • Intra-abdominal desmoplastic small round cell tumour is a rare tumour not previously reported in a female over the age of 50. • Disparity between radiological and histological appearances should prompt further review and investigation. • Clear and timely communication between different surgical units in order to provide efficient care. • Due to the rarity of intra-abdominal DSRCT there is little evidence on effective treatment beyond surgical resection., Introduction This case report discusses the rare diagnosis of intra-abdominal desmoplastic small round cell tumour (DSRCT) in a 56-year-old female. Presentation of case An incidental intra-abdominal lesion was found during investigation of joint pain. Ultrasound-guided biopsy suggested desmoid tumour, after undergoing laparotomy and en-bloc excision of the tumour due to concerning radiological progression, the final histology was desmoplastic small round cell tumour. At six-week follow-up imaging, no recurrence or metastatic disease was noted. She declined chemotherapy and specialist follow-up, electing to have routine follow up with her General Practitioner only. Discussion Intra-abdominal DSRCT is rare and mainly seen in young males. To our knowledge, this is the only reported case of DSRCT in a female over the age of 50. Conclusion There should be timely discussion between different surgical units to provide efficient care. Any disparity between radiological and histological appearance should prompt further review and investigation in order to ensure misdiagnosis is avoided and appropriate treatment is provided. Despite cytoreductive surgery, survival is dismal due to the aggressive nature of the tumour, and its low numbers limiting adequate study into post diagnosis care

Background Laparoscopic fundoplication (LF) is the standard surgical procedure for the treatment of gastro-oesophageal reflux disease (GORD). Laparoscopic Roux-en-Y gastric bypass (LRYGB) is commonly performed to achieve weight loss in obese patients, but it also has anti-reflux properties. Hence, in the obese population suffering from GORD, LRYGB could be an alternative to LF. The aim of this trial will be to compare LF and LRYGB in an obese population presenting with GORD and being considered for surgery. Methods This will be an investigator-initiated randomized clinical trial. The research population will be obese patients (BMI 30–34.9 with waist circumference more than 88 cm (women) or more than 102 cm (men), or BMI 35–40 with any waist circumference) referred to a public hospital for consideration of anti-reflux surgery. The primary aim of the study will be to determine the efficacy of LF compared with LRYGB on subjective and objective control of GORD. Secondary aims include determining early and late surgical morbidity and the side-effect profile of LF compared with LRYGB and to quantify any non-reflux benefits of LRYGB (including overall quality of life) compared with LF. Conclusion This trial will determine whether LRYGB is effective and acceptable as an alternative to LF for the surgical treatment of GORD in obese patients Registration number: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000636752p (https://www.anzctr.org.au/).

Based on molecular evidence that melanomas with unknown primary (MUPs) arise from the skin, we hypothesised that sites of MUPs are disproportionately on trunk and lower limbs, sites that are not readily visible to patients and clinicians. We tested this hypothesis by inferring the anatomic site of origin of MUPs from the corresponding known cutaneous sites of melanoma patients with known primary tumours (MKPs). We analysed data from three separate cohorts of patients from Brisbane, Australia (n = 236); Manchester, UK (n = 51) and Padova, Italy (n = 33), respectively, who first presented with stage III melanoma with lymph node metastases. We matched two MKP patients to each MUP patient based on lymph node dissection (LND) site, age and sex, and imputed cutaneous sites of origin of MUPs from their two matched MKPs for study countries, giving two possible sites for each MUP per centre. Overall, results showed that MUP patients were predominantly male, and trunk was the most likely origin, comprising around a third to a half of MUPs across the three cohorts. The remaining MUP inferred sites varied by country. In the Australian cohort, the legs accounted for a third of imputed sites of MUPs, while in the UK and Italian cohorts, the most frequent site was the arms followed by the legs. Our findings suggest the need for regular and thorough skin examination on trunk and limbs, especially in males, to improve early detection of cutaneous melanoma and reduce the risk of metastatic disease at the time of presentation. © 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Dear Editor, Despite overall favourable prognosis, thin (≤ 1·0 mm) cutaneous melanomas account for 23% of melanoma deaths in the high-risk general population of Queensland, Australia (2005–2009), because of the sheer volume of disease. The prospect of adjuvant systemic therapy has increased the focus on identifying patients with thin melanoma who are at high risk of death, such as through gene expression profiling (GEP), sentinel lymph node biopsy (SLNB) or prognostic models.

Background: The impact of hospital characteristics on the quality of surgery and survival following oesophagogastric cancer surgery has not been well established in Australia. We assessed the interaction between hospital volume, service capability and surgical outcomes, with the hypothesis that both the quality of surgery and survival are better following treatment in high-volume, high service capability hospitals. Methods: All patients undergoing oesophagectomy and gastrectomy for cancer in Queensland, between 2001 and 2015, were included. Demographic, pathology and outcome data were collected. Hospitals were categorized into high (HV) (≥5 gastrectomies; ≥6 oesophagectomies) and low volume (LV). Hospital service capability was defined as high (HS) and low (LS), and then linked to hospital volume: HVHS, LVHS and LVLS. Higher quality surgery was defined using six perioperative parameters. Univariable comparisons of quality of surgery between hospital groups used chi-squared tests. The 5-year overall survival was compared using log-rank tests and Cox proportional hazard models. Results: For both gastrectomy and oesophagectomy, higher quality surgery occurred more frequently in HVHS hospitals (gastrectomy: HVHS = 44.2%, LVHS = 23.1%, LVLS = 29.1% (P < 0.01); oesophagectomy: HVHS = 34.5%, LVHS = 24.4%, LVLS = 21.7% (P = 0.01)). Following oesophagectomy, the 3- and 5-year overall survival was better following treatment in HVHS (P < 0.01). There was no difference between the groups following gastrectomy. Conclusion: In Queensland, the quality of surgery was higher in HVHS hospitals performing gastrectomy and oesophagectomy; however, the impact on cancer survival was only seen following oesophagectomy.

To quantify the prevalence of anxiety or depression (overall; melanoma-related) among people with high-risk primary melanoma, their related use of mental health services and medications, and factors associated with persistent new-onset symptoms across 4 years post-diagnosis. A longitudinal study of 675 patients newly diagnosed with tumor-stage 1b–4b melanoma. Participants completed the Hospital Anxiety and Depression Scale and answered questions about fear of cancer recurrence, use of medication, and support, serially over 4 years. We identified anxiety and depression trajectories with group-based trajectories models and factors associated with persistent symptoms with logistic regression. At diagnosis, 93 participants (14%) had melanoma-related anxiety or depression, and 136 (20%) were affected by anxiety and/or depression unrelated to melanoma. After 6 months, no more than 27 (5%) reported melanoma-related anxiety or depression at any time, while the point prevalence of anxiety and depression unrelated to melanoma was unchanged (16–21%) among the disease-free. Of 272 participants reporting clinical symptoms of any cause, 34% were taking medication and/or seeing a psychologist or psychiatrist. Of the participants, 11% (n = 59) had new-onset symptoms that persisted; these participants were more likely aged

Optimal management of regional lymph nodes for thin cutaneous melanoma is uncertain. We evaluated regional lymph node involvement and 5-year melanoma-specific survival (MSS) in patients with thin (≤1 mm) primary melanoma.Patients with a melanoma, American Joint Committee on Cancer Staging 8th Edition pT1a (0.8 mm) or pT1b (ulceration; and/or 0.8-1.0 mm), diagnosed during 2001-2015 were identified from the Queensland Oncology Repository. We extracted demographic, pathology and clinical details, including sentinel lymph node biopsy (SLNB), regional nodal dissection and nodal recurrence. Poisson regression was used to assess recurrence risk in patients who did not undergo SLNB. The 5-year MSS was calculated using the Kaplan-Maier method with Cox regression to compare survival outcomes according to SLNB performance.Of the 27 824 eligible patients, 240 (0.9%) underwent SLNB. One hundred and seventy-eight patients (0.6%) without SLNB had nodal recurrence. Of the 4848 patients with a pT1b lesion, 166 (3.4%) had SLNB with 12 (7.2%) positive; of the remainder, 99 (2.1%) had clinical recurrence. Risk of recurrence was higher in males, nodular subtype and T1b lesions and lower if patients were aged60 years. The 5-year MSS was similar for observed and SLNB cohorts (99.66% versus 98.92%) but worse for T1b lesions (98.90%) and clinical nodal recurrence (66.89%).Overall prognosis for T1 melanoma is excellent with nodal involvement being rare. However, the American Joint Committee on Cancer 8th Edition T1b melanoma correlates with significantly worse 5-year MSS and increased regional nodal recurrence (notably for 0.8-1.0 mm lesions with ulceration). Further characterization of high-risk groups for nodal positivity that impacts patient outcome is needed for the pT1 melanoma cohort.

Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON). ON patients (≥ 80 years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (

There is little long-term follow-up information about how the number of melanoma deaths and case fatality vary over time according to the measured thickness of melanoma at diagnosis. This population-based longitudinal cohort study examines patterns and trends in case fatality among 44,531 people in Queensland (Australia) diagnosed with a single invasive melanoma (International Classification of Diseases for Oncology, third revision [ICD-O-3], C44, Morphology 872-879) between 1987 and 2011, including 11,883 diagnosed between 1987 and 1996, with up to 20 years follow-up (to December 2016). The 20-year case fatality increased by thickness, with the percentage of melanoma deaths within 20 years of diagnosis being up to 4.8% for melanomas with measured thickness

Skin phenotype, host genotype and ultraviolet (UV) damage play a role in the development of melanoma.To ascertain whether the level of UV damage at the site of melanomas was associated with genetic polymorphisms.Deep phenotyping was performed on 1244 individuals; 281 with multiple primary melanomas (MPMs), 304 with single primary melanoma (SPM) and 659 convenience controls. Genotype data was generated using the Illumina CoreExome microarray platform, assaying over 500 000 single-nucleotide polymorphisms. A subset of variants were combined to assess a polygenic risk score (PRS) for melanoma.Most MPM cases were diagnosed in patients aged40 years, in sites with visible chronic UV damage. Women and those diagnosed at age ≤ 40 years were less likely to have perilesional UV damage. Patients with MPM had higher frequencies of MITF E318K, MC1R R-alleles and the ASIP risk haplotype. Individuals who had melanoma in a visibly UV-damaged site were more likely to carry MC1R rs75570604 [odds ratio (OR) 2·5], 9q31.2 rs10816595 (OR 1·4) and MTAP rs869329 (OR 1·4). These same alleles were more common in patients with MPM who were diagnosed at age ≤ 40 years. The mean PRS was significantly higher in MPM than in SPM and controls. Naevus count was comparable in early-onset MPM cases and those diagnosed at age40 years.Our cohort demonstrated higher frequencies of previously reported alleles associated with melanoma. MPM melanomas more commonly occur in UV-damaged areas, and these individuals are more likely to carry MC1R red hair colour alleles. Awareness of the interplay of genetic vulnerability with UV damage can stratify risk and guide recommendations for melanoma screening. What's already known about this topic? Skin phenotype, host genotype and ultraviolet (UV) damage all play a role in melanoma development. One of the main risk factors is a personal history of melanoma; second and subsequent primary melanomas account for over 20% of all melanomas registered in Queensland. Multiple loci are associated with melanoma risk, including many low-penetrance loci, which may have a cumulatively significant risk. Population-wide screening programmes for melanoma are not yet economically viable. What does this study add? Patients diagnosed with melanoma at age ≤ 40 years were more likely than older patients to have melanomas in non-UV-damaged sites. Patients with multiple melanomas had higher frequencies of MITF E318K, MC1R R-alleles, and the ASIP extended risk haplotype than patients with single melanoma. CDKN2A, MC1R and MTAP variants were more frequent in patients who developed melanomas at a younger age, but also in those whose melanomas were all on visibly UV-damaged sites. What is the translational message? Incorporating these genetic findings into the known risk factors of skin phenotype and visible UV damage may allow for a more customized and economically feasible approach to early detection of melanoma, particularly in younger patients. Plain language summary available online.

Marine biofilms are diverse microbial communities and important ecological habitats forming on surfaces submerged in the ocean. Biofilm communities resist environmental disturbance, making them a nuisance to some human activities (“biofouling”). Antifouling solutions rarely address the underlying stability or compositional responses of these biofilms. Using bulk measurements and molecular analyses, we examined temporal and UV-C antifouling-based shifts in marine biofilms in the coastal western North Atlantic Ocean during early fall. Over a 24-day period, bacterial communities shifted from early dominance of Gammaproteobacteria to increased proportions of Alphaproteobacteria, Bacteroidia, and Acidimicrobiia. In a network analysis based on temporal covariance, Rhodobacteraceae (Alphaproteobacteria) nodes were abundant and densely connected with generally positive correlations. In the eukaryotic community, persistent algal, protistan, and invertebrate groups were observed, although consistent temporal succession was not detected. Biofilm UV-C treatment at 13 and 20 days resulted in losses of chlorophyll a and transparent exopolymer particles, indicating biomass disruption. Bacterial community shifts suggested that UV-C treatment decreased the biofilm maturation rate and was associated with proportional shifts among diverse bacterial taxa. UV-C treatment was also associated with increased proportions of protists potentially involved in detritivory and parasitism. Older biofilm communities had increased resistance to UV-C, suggesting that early biofilms are more susceptible to UV-C-based antifouling. The results suggest that UV-C irradiation is potentially an effective antifouling method in marine environments in terms of biomass removal and in slowing maturation. However, as they mature, biofilm communities may accumulate microbial members that are tolerant or resilient under UV treatment. IMPORTANCE Marine biofilms regulate processes ranging from organic matter and pollutant turnover to eukaryotic settlement and growth. Biofilm growth and eukaryotic settlement interfering with human activities via growth on ship hulls, aquaculture operations, or other marine infrastructure are called “biofouling.” There is a need to develop sustainable antifouling techniques by minimizing impacts to surrounding biota. We use the biofouling-antifouling framework to test hypotheses about marine biofilm succession and stability in response to disturbance, using a novel UV-C light-emitting diode (LED) device. We demonstrate strong bacterial biofilm successional patterns and detect taxa potentially contributing to stability under UV-C stress. Despite UV-C-associated biomass losses and varying UV susceptibility of microbial taxa, the overall bacterial community composition remained relatively stable, suggesting decoupling of disruption in biomass and community composition following UV-C irradiation. We also report microbial covariance patterns over 24 days of biofilm growth, pointing to areas for study of microbial interactions and targeted antifouling.

Background: The incidence of oesophageal adenocarcinoma (OAC) is rapidly increasing and despite improvements in treatment, the five-year survival rate remains poor. Prognostic biomarkers that address the genomic heterogeneity in this highly complex disease will aid the development of precision therapeutics and improve patient survival. The aim of this study was to determine whether circulating tumour DNA (ctDNA) has prognostic significance as a biomarker in OAC patients.Methods: We profiled 209 blood and tumour samples from 57 OAC patients. Using a panel of 77 cancer genes, we sequenced ctDNA in plasma samples (n=127) which were taken at multiple time points pre- and post-therapy. In parallel, we sequenced matched tumour samples from 39 patients using the same gene panel. To assess whether the ctDNA profile reflected the tumour heterogeneity, we sequenced additional multi-region primary tumour samples (n=17). In addition, we analysed whole-genome and whole-exome sequencing data from primary tumours for a subset of 18 patients. Results: Using a tumour agnostic approach, we found that detectable ctDNA variants in post-treatment plasma samples were associated with worse disease specific survival. To evaluate whether the ctDNA originated from the primary tumour, we performed a tumour informed analysis which confirmed post-treatment ctDNA variants were associated with worse survival. To determine whether ctDNA could be used as a clinical follow-up test, we assessed blood samples from multiple time points before and after treatment, in a subset of patients. Results showed that the variant allele frequency of ctDNA variants increased with disease recurrence. Conclusion: This study demonstrates that ctDNA variants can be detected in patients with OAC and this has potential clinical utility as a prognostic biomarker for survival.