Prognosis after neoadjuvant chemoradiation or chemotherapy for locally advanced gastro-oesophageal junctional adenocarcinoma.

BACKGROUND: Trials typically group cancers of the gastro-oesophageal junction (GOJ) with oesophageal or gastric cancer when studying neoadjuvant chemoradiation and perioperative chemotherapy, so the results may not be fully applicable to GOJ cancer. Because optimal neoadjuvant treatment for GOJ cancer remains controversial, outcomes with neoadjuvant chemoradiation versus chemotherapy for locally advanced GOJ adenocarcinoma were compared retrospectively. METHODS: Data were collected from all patients who underwent neoadjuvant treatment followed by surgery for adenocarcinoma located at the GOJ at a single high-volume institution between 2002 and 2017. Postoperative major complications and mortality were compared between groups using Fisher's exact test. Overall survival (OS) and disease-free survival (DFS) were assessed by log rank test and multivariable Cox regression analyses. Cumulative incidence functions were used to estimate recurrence, and groups were compared using Gray's test. RESULTS: Of 775 patients, 650 had neoadjuvant chemoradiation and 125 had chemotherapy. These groups were comparable in terms of clinical tumour and lymph node categories, although the chemoradiation group had greater proportions of white men, complete pathological response to chemotherapy, and smaller proportions of diffuse cancer, poor differentiation, and neurovascular invasion. Postoperative major complications (20.0 versus 17.6 per cent) and 30-day mortality (1.7 versus 1.6 per cent) were not significantly different between the chemoradiation and chemotherapy groups. After adjustment, type of therapy (chemoradiation versus chemotherapy) was not significantly associated with OS (hazard ratio (HR) 1.26, 95 per cent c.i. 0.96 to 1.67) or DFS (HR 1.27, 0.98 to 1.64). Type of recurrence (local, regional, or distant) did not differ after neoadjuvant chemoradiation versus chemotherapy. CONCLUSION: In patients undergoing surgical resection for locally advanced adenocarcinoma of the GOJ, OS and DFS did not differ significantly between patients who had neoadjuvant chemoradiation compared with chemotherapy.

Treating advanced cancer of the gastro-oesophageal junction (GOJ) poses a challenge given its location in the distal oesophagus and proximal stomach, and whether it should be treated as oesophageal or gastric cancer. Given the indistinct location, it is unclear whether GOJ cancer should be treated with neoadjuvant chemoradiation, which is the treatment of choice for advanced oesophageal cancers, or perioperative chemotherapy, which is the treatment of choice for advanced gastric cancers. Few studies have addressed treatment options specifically for GOJ cancers. This study investigated whether there was a difference in survival between patients with GOJ cancer who were treated with chemoradiation versus chemotherapy.

Identification of microRNAs that promote erlotinib resistance in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related deaths, demanding improvement in current treatment modalities to reduce the mortality rates. Lung cancer is divided into two major classes with non-small cell lung cancer representing ~84% of lung cancer cases. One strategy widely used to treat non-small cell lung cancer patients includes targeting the epidermal growth factor receptor (EGFR) using EGFR-inhibitors, such as erlotinib, gefitinib, and afatinib. However, most patients develop resistance to EGFR-inhibitors within a year post-treatment. Although some mechanisms that drive resistance to EGFR-inhibitors have been identified, there are many cases in which the mechanisms are unknown. Thus, in this study, we examined the role of microRNAs in driving EGFR-inhibitor resistance. As mediators of critical pro-growth pathways, microRNAs are severely dysregulated in multiple diseases, including non-small cell lung cancer where microRNA dysregulation also contributes to drug resistance. In this work, through screening of 2019 mature microRNAs, multiple microRNAs were identified that drive EGFR-inhibitor resistance in non-small cell lung cancer cell lines, including miR-432-5p.

A qualitative study exploring factors influencing clinical decision-making for influenza-like illness in Solapur city, Maharashtra, India.

The co-existence of different types of medical systems (medical pluralism) is a typical feature of India's healthcare system. For conditions such as influenza-like illness (ILI), where non-specific disease signs/symptoms exist, clinical reasoning in the context of medical pluralism becomes crucial. Recognising this need, we undertook a qualitative study, which explored factors underpinning clinical decisions on diagnosis and management of ILI. The study involved semi-structured interviews including clinical vignettes with 20 healthcare practitioners (working within allopathy, homeopathy and Ayurveda) working in the private healthcare sector in Solapur city, India. An inquiry was conducted into criteria influencing the diagnosis, treatment, referral to specialist care and role of treatment guidelines for ILI. Thematic analysis was used to identify aspects relating to ILI diagnosis, treatment and referral. The diagnosis of influenza was based largely on clinical symptoms suggestive of influenza in the absence of other diagnoses. Referral for laboratory tests was only initiated if illness did not resolve, generally after 2-3 consultations. Antibiotics were often prescribed for persistent illness, with antivirals rarely considered. Some differences between practitioners from different medical systems were observed in relation to treatment and referral in case of persistent illness. A combination of analytical and intuitive clinical reasoning was used by the participants and clinical decisions were based on both social and clinical factors. Clinical decision-making was rarely a linear process and respondents felt that broad guidelines on influenza that allowed doctors to account for the sociocultural context within which they practised medicine would be helpful.

Microwave Ablation in the Management of Colorectal Cancer Pulmonary Metastases.

PURPOSE: To review outcomes following microwave ablation (MWA) of colorectal cancer pulmonary metastases and assess predictors of oncologic outcomes. METHODS: Technical success, primary and secondary technique efficacy rates were evaluated for 50 patients with 90 colorectal cancer pulmonary metastases at immediate, 4-8 weeks post-MWA and subsequent follow-up CT and/or 18F-FDG PET/CT. Local tumor progression (LTP) rate, LTP-free survival (LTPFS), cancer-specific and overall survivals were assessed. Complications were recorded according to SIR classification. RESULTS: Median follow-up was 25.6 months. Median tumor size was 1 cm (0.3-3.2 cm). Technical success, primary and secondary technique efficacy rates were 99, 90 and 92%, respectively. LTP rate was 10%. One-, 2- and 3-year LTPFS were: 93, 86 and 86%, respectively, with median LTPFS not reached. Median overall survival was 58.6 months, and median cancer-specific survival (CSS) was not reached. One-, 2- and 3-year overall and CSS were 94% and 98, 82 and 90%, 61 and 70%, respectively. On univariate analysis, minimal ablation margin (p < 0.001) and tumor size (p = 0.001) predicted LTPFS, with no LTP for minimal margin ≥ 5 mm and/or tumor size < 1 cm. Pleural-based metastases were associated with increased LTP risk (p = 0.002, SHR = 7.7). Pre-MWA CEA level > 10 ng/ml (p = 0.046) and ≥ 3 prior chemotherapy lines predicted decreased CSS (p = 0.02). There was no 90-day death. Major complications rate was 13%. CONCLUSIONS: MWA with minimal ablation margin ≥ 5 mm is essential for local control of colorectal cancer pulmonary metastases. Pleural-based metastases and larger tumor size were associated with higher risk of LTP. CEA level and pre-MWA chemotherapy impacted CSS.

Nature of events and alcohol-related content in marketing materials at a university freshers' fair: a summative content analysis.

Introduction: The transition to university is a potentially influential time upon students' drinking behaviour. This study explored the nature of activities and alcohol-related content in marketing materials from student-led societies and local businesses provided to students, at a university freshers' fair in the UK. Methods: All marketing materials handed out at the fair were collected across the 5-day event in September 2015. Written and visual content was analysed using a summative qualitative content analysis. Results: Most student-led societies promoted social events they were hosting (n = 530), most of which took place in a drinking venue or referred to drinking (n = 335). Only four explicitly alcohol-free events were promoted. Student-led societies also promoted activities relating to their interest, e.g. sports training (n = 519), a small proportion of which had references to drinking and drinking venues (n = 54). Three societies provided promotional handouts from local bars or nightclubs. Local bars, pubs and nightclubs promoted events they hosted (n = 81) as well as alcoholic drink promotions (n = 79) and alcohol branded advertising (n = 22), albeit infrequently for the latter. Conclusions: In the first week of university, students are exposed to alcohol-related events, promotions and advertising, which may act as an incentive to participate in drinking.

Patients' attitudes to risk in lung cancer surgery: A qualitative study.

OBJECTIVES: Lung cancer surgery leads to long term survival for some patients but little is known about how patients decide whether to accept the associated surgical risks. The objective of this qualitative study was to explore patients' attitudes to the risks associated with lung cancer surgery. METHODS: Fifteen patients with resectable lung cancer, recruited via multi-disciplinary team meetings at an English tertiary referral centre, participated in semi-structured interviews to explore their attitudes to the morbidity and mortality risks associated with lung cancer surgery. Transcripts were analysed using the framework method. RESULTS: Participants reported being 'pleased' to hear that they were suitable for surgery and felt that surgery was not a treatment to be turned down because they did not see any alternatives. Participants had some knowledge of perioperative risks, including mortality estimates; however, many voiced a preference not to know these risks and to let the medical team decide their treatment plan. Some found it difficult to relate the potential risks and complications of surgery to their own situation and appeared willing to accept high perioperative mortality risks. Generally, participants were willing to accept quite severe long-term postoperative breathlessness; however, it was apparent that many actually found this possibility difficult to imagine. CONCLUSION: Patients do not necessarily wish to know details of risks associated with lung cancer surgery and may wish to defer decisions about treatment to their medical team. Investment in the doctor-patient relationship, particularly for the surgeon, is therefore important in the management of patients with lung cancer.

Clinical tools do not predict pathological complete response in patients with esophageal squamous cell cancer treated with definitive chemoradiotherapy.

Chemoradiotherapy for locally advanced esophageal squamous cell carcinoma is associated with high rates of pathological complete response. A pathological complete response is recognized to be an important predictor of improved survival, to the extent that observation rather than surgery is advocated by some in patients with presumed pathological complete response based on their clinical response. The goal of this study was to look at the ability of clinical variables to predict pathological complete response after chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. We reviewed retrospectively patients with locally advanced esophageal squamous cell carcinoma who underwent chemoradiotherapy followed by surgery and compared those with pathological complete response to patients with residual disease. Between January 1996 and December 2010, 116 patients met inclusion criteria. Fifty-six percent of patients had a pathological complete response and a median survival of 128.1 months versus 28.4 months in patients with residual disease. When compared with patients with residual disease, patients with a pathological complete response had a lower post-neoadjuvant positron emission tomography (PET) maximum standardized uptake value (SUVmax), a larger decrease in PET SUVmax, a less thick tumor on post-chemoradiotherapy computed tomography and a higher rate of normal appearing post-chemoradiotherapy endoscopy with benign biopsy of the tumor bed. However, none of these characteristics alone was able to correctly identify patients with a pathological complete response, and none has significant specificity. Although the rate of pathological complete response after chemoradiotherapy is high in patients with esophageal squamous cell carcinoma, the ability of identifying patients with pathological complete response is limited. A reduction of the PET SUVmax by >70%, a normal appearing endoscopic examination, and no residual disease on biopsy all were seen in >65% of the patients with a pathological complete response. Even if these findings were unable to confirm the absence of residual disease in the primary tumor, they can help guide expectant management in high-risk patients.

Outcomes of induction chemotherapy followed by chemoradiation using intensity-modulated radiation therapy for esophageal adenocarcinoma.

This study looks at toxicity and survival data when chemoradiation (CRT) is delivered using intensity-modulated radiation therapy (IMRT) after induction chemotherapy. Forty-one patients with esophageal adenocarcinoma treated with IMRT from March 2007 to May 2009 at Memorial Sloan-Kettering Cancer Center were analyzed. All patients received induction chemotherapy prior to CRT. Thirty-nine percent (n = 16) of patients underwent surgical resection less than 4 months after completing CRT. Patients were predominantly male (78%), with a median age of 68 years (range 32-85 years). The majority of acute treatment-related toxicity was hematologic or gastrointestinal, with 17% of patients having grade 3+ hematologic toxicity and 12% of patients having grade 3+ gastrointestinal toxicity. Only two patients developed grade 2-3 pneumonitis (5%) and 5 patients experienced post-operative pulmonary complications (29%). Eight patients (20%) required a treatment break. With a median follow up of 41 months for surviving patients, 2-year overall survival was 61%, and the cumulative incidences of local failure (LF) and distant metastases were 40% and 51%, respectively. This rate of LF was reduced to 13% in patients who underwent surgical resection. Surgery and younger age were significant predictors of decreased time to LF on univariate analysis. Induction chemotherapy followed by CRT using IMRT in the treatment of esophageal cancer is well tolerated and is not associated with an elevated risk of postoperative pulmonary complications. The use of IMRT may allow for integration of more intensified systemic therapy or radiation dose escalation for esophageal adenocarcinoma, ultimately improving outcomes for patients with this aggressive disease.

The impact of colorectal cancer and self-efficacy beliefs on work ability and employment status: a longitudinal study.

We examined how colorectal cancer patients' treatment and symptom management impacted perceptions of work ability and subsequent work decisions. Fifty patients completed questionnaires at baseline (post-surgery/pretreatment), 3 months and 6 months. Questionnaires assessed fatigue, depression, quality-of-life (QoL), cancer self-efficacy, job self-efficacy (JSE) and work ability. Factors related to perceived work ability were occupation (ß= 0.31, P= 0.0005) and QoL (ß= 0.42, P= 0.01) at baseline, treatment type (ß=-0.19, P= 0.05) at 3 months, and JSE at 3 months (ß= 0.57, P= 0.0005) and 6 months (ß= 0.50, P= 0.006). Factors related to being on sick leave were lower levels of JSE (OR = 2.20, 95% CI: 1.17-4.13) at baseline and being employed in a manual occupation (OR = 0.03, 95% CI: 0.00-0.86), and perceived work ability (OR = 3.05, 95% CI: 1.00-12.80) at 6 months. Along with self-assessed work ability at baseline (ß= 0.67, P= 0.0005), receiving chemotherapy or a combination of treatments (ß=-0.24, P= 0.05) were the strongest predictors of poorer perceptions of follow-up work ability. Self-efficacy beliefs may add to understanding and should be considered in future research.

Effectiveness and acceptability of face-to-face, blended and e-learning: a randomised trial of orthodontic undergraduates.

AIM: This study compared e-learning (EL), face-to-face learning (F2FL) and blended learning (BL) with respect to their effectiveness and student attitudes towards them. It also evaluated the effect of the order in which the components (EL and F2FL) of blended learning are delivered. DESIGN: This was a prospective cluster randomised trial comparing four parallel groups. METHOD: Eight groups of fourth year dental undergraduate students were randomly allocated to one of four intervention groups: EL, F2FL, BL1 or BL2. These four groups were assessed for their baseline comparability of knowledge and skills. Each then received the same cephalometric tutorial but delivered by the allocated mode of learning. Effectiveness was immediately assessed with a MCQ which measured short-term recall of knowledge. Student attitudes were evaluated with a questionnaire followed by a focus group discussion. RESULTS: Ninety (57%) students completed the study. Pearson's chi-square test found no statistically significant difference between F2FL and BL; EL alone was less effective (P<0.05) for four MCQ questions but with no difference for the remaining six questions. Overall students were positive towards each learning modality, but a one-way analysis of variance found BL was the most and F2FL was the least accepted (P=0.002). EL was significantly (P=0.028) less preferred. The order of the components in BL had no significant effects. CONCLUSION: These results suggest that BL is more likely than either F2FL or EL alone, to be both effective and accepted when delivering cephalometric education to undergraduates.

The role of communication and support in return to work following cancer-related absence.

OBJECTIVE: Many cancer survivors experience difficulties returning to work. However, there have been relatively few attempts to understand why problems with employer support and work adjustment occur. This paper aims to extend previous work in two ways: first, through exploring the way in which communication and support at work effect cancer survivors on their return to work and during the post-return period; and second, by drawing on a research sample working in the United Kingdom. METHODS: In all, 26 cancer survivors took part in a semi-structured telephone interview. Interviews were transcribed and analysed using thematic analysis. RESULTS: The analysis revealed three key findings. First, the central role of communication and support from (and between) occupational health, line managers, and colleagues was highlighted. Second, two discrete processes or periods of return to work were identified: the experience of return to work during the initial period of return and the experiences of post-return to work. Third, during the post-return period, the importance of the delayed impact of cancer on the ability to work, the lack of follow-up and monitoring, and the wear-off effect of empathy and support were highlighted as contributing to return-to-work difficulties. CONCLUSIONS: This qualitative study highlights the importance of communication within the workplace with regard to the return-to-work process and the need to provide better support and guidance to cancer survivors, line managers and colleagues. Research is required in delineating how employers without occupational health or human resources support manage the return-to-work process.

Predictors of return to work following carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is an important part of secondary prevention in selected patients following a transient ischaemic attack or stroke. A key marker of success, return to work following surgery, was assessed in a retrospective cohort study. METHODS: Patients from the UK aged less than 65 years at operation were sent a questionnaire concerning return to work after CEA. Data were analysed using univariable tests and logistic regression. RESULTS: Some 174 (64.4 per cent) of 270 patients responded; their median age was 60 (range 35-64) years and 124 were men. Seventy-five per cent of respondents employed preoperatively returned to work following CEA. Newly retiring patients were older (62 versus 58 years; P < 0.001). Univariable analysis confirmed that age and preoperative stroke influenced return to work. The adjusted odds ratio for patients with versus without a preoperative stroke was 0.46 (95 per cent confidence interval 0.22 to 0.97) (P = 0.040). Median convalescence was 4 weeks, but was shorter in the self-employed (P = 0.039) and prolonged in patients with symptomatic cardiovascular disease (P = 0.023) and those who required postoperative critical care (P = 0.039). CONCLUSION: Return to work following CEA was influenced by age and preoperative stroke.

Small-cell carcinoma of the esophagus and gastroesophageal junction: review of the Memorial Sloan-Kettering experience.

BACKGROUND: Esophageal small-cell carcinoma (SCC) is rare, highly malignant and the optimal treatment approach has not been defined. PATIENTS AND METHODS: We report the largest single-institution retrospective review of patients with esophageal and gastroesophageal (GE) junction SCC. RESULTS: Twenty-five patients were identified, with complete records available for 22. Eighty-two percent were male, 82% had pure SCC histology and 86% of tumors were in the lower esophagus or GE junction. On the basis of the Veterans' Administration Lung Study Group criteria, 14 patients (64%) presented with limited disease (LD). Median survival was 19.8 months (range, 1.5 months to 11.2+ years); for LD patients, 22.3 months (range, 6 months to 11.2+ years); for extensive disease (ED) patients, 8.5 months (range, 1.5 months to 2.2 years, P = 0.02). With a median follow-up of 38 months, six patients (27%) are alive, one with ED and five with LD. Two LD patients are alive and free of disease for >5 years. Four of the five LD patients who are long-term survivors received induction chemotherapy followed by chemoradiotherapy without surgery. CONCLUSIONS: Our data indicate that patients with LD esophageal SCC treated with induction chemotherapy followed by consolidative chemoradiation can achieve long-term survival. The contribution of surgery remains unclear.

Combined modality chemoradiation in elderly oesophageal cancer patients.

We present a single institution experience with 5-FU, mitomycin-C based chemoradiation for the primary treatment of elderly patients with oesophageal cancer. Twenty-five patients with a median age of 77 years (range 66-88) with a diagnosis of stage II-III squamous cell or adenocarcinoma of the oesophagus were treated at Memorial Sloan Kettering from 1996 to 2001 with two cycles of concurrent 5-FU, mitomycin-C and 50.4 Gy. Owing to age and comorbidity, these patients were not considered surgical candidates. The Charlson comorbidity score was used to evaluate patient comorbidity. Nine patients (36%) experienced grade 3-4 haematologic toxicity. Of the 23 patients evaluable for response, 17 patients (68%) had a negative post-treatment endoscopy and CT scan without evidence of progressive disease. Eleven patients (44%) are alive and 10 (40%) remain without evidence of recurrent or progressive oesophageal cancer at a median follow-up of 35 months. The median overall survival was 35 months and 2-year survival 64%. There was no significant difference in overall survival between Charlson score /=2 (P=0.10). Similar survival was observed for patients with adenocarcinoma or squamous carcinoma. Primary chemoradiation with two cycles of 5-FU, mitomycin-C, and 50.4 Gy in elderly patients is an active regimen with moderate toxicity, despite the advanced age and heavy comorbidity burden of this cohort. Patients with local/regional oesophageal cancer with adequate functional status should not be excluded from potentially curative treatment based on age alone.

Palatal perforations: past and present. Two case reports and a literature review.

Syphilis and cocaine abuse are posing a growing public health problem on a global and national scale. Clinicians are increasingly likely to come across associated oral manifestations. We present two cases of palatal perforations caused by tertiary syphilis and cocaine abuse respectively. The literature review discusses issues specific to palatal perforations and those general to both conditions. The purpose of the report is to focus attention on syphilis and cocaine abuse as rising problems for the dental profession.

The role of thoracotomy in managing postchemotherapy residual thoracic masses in patients with nonseminomatous germ cell tumours.

OBJECTIVE: To evaluate the clinical outcome and identify prognostic variables in patients with nonseminomatous germ cell tumours undergoing postchemotherapy thoracotomy for residual masses, as the role of this procedure is controversial. PATIENTS AND METHODS: Of 385 patients who underwent postchemotherapy retroperitoneal lymph node dissections between 1988 and 1998, 105 also had 130 thoracotomies. The clinical presentation, chemotherapy regimens, marker status, primary tumour histology, pathology of all resected masses, and clinical outcome of these 105 patients were analysed. RESULTS: The overall discordance rate for synchronous thoracic and retroperitoneal masses was 28%; that for asynchronous thoracic and retroperitoneal masses was 57%. Independent prognostic factors for residual thoracic teratoma or cancer were teratoma (mature or immature) in the primary tumour or retroperitoneal teratoma or cancer. Although three of 12 patients with residual thoracic cancer remained with no evidence of disease, residual thoracic cancer is an independent prognostic factor (P < 0.001) against disease-free survival. CONCLUSION: Postchemotherapy thoracotomy yields important prognostic information, and is therapeutic for most patients with teratoma and a subset with residual viable cancer. The prognostic criteria predictive of fibrosis are not sufficiently accurate to omit resection of residual thoracic masses.

A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma.

BACKGROUND: Surgical resection of malignant pleural mesothelioma is reported to have up to an 80% rate of local recurrence. We performed a phase II trial of high-dose hemithoracic radiation after complete resection to determine feasibility and to estimate rates of local recurrence and survival. METHODS: Patients were eligible if they had a resectable tumor, as determined by computed tomographic scanning, and adequate cardiopulmonary function for extrapleural pneumonectomy or pleurectomy/decortication. After complete resection, patients received hemithoracic radiation (54 Gy) and then were followed up with serial computed tomographic scanning. RESULTS: From 1995 to 1998, 88 patients (73 men and 15 women; median age, 62.5 years) were entered into the study. The operations performed included 62 extrapleural pneumonectomies (70%) and 5 pleurectomies/decortications; procedures for exploration only were performed in 21 patients. Seven (7.9%) patients died postoperatively. Adjuvant radiation administered to 57 patients (54 undergoing extrapleural pneumonectomy and 3 undergoing pleurectomy/decortication) at a median dose of 54 Gy was well tolerated (grade 0-2 fatigue, esophagitis), except for one late esophageal fistula. The median survival was 33.8 months for stage I and II tumors but only 10 months for stage III and IV tumors (P =.04). For the patients undergoing extrapleural pneumonectomy, the sites of recurrence were locoregional in 2, locoregional and distant in 5, and distant only in 30. CONCLUSION: Hemithoracic radiation after complete surgical resection at a dose not previously reported is feasible. This approach dramatically reduces local recurrence and is associated with prolonged survival for early-stage tumors. Stage III disease has a high risk of early distant relapse and should be considered for trials of systemic therapy added to this regimen of resection and radiation.