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1. Obesity and Cancer Treatment Outcomes: Interpreting the Complex Evidence

Author

Corinna Slawinski, Andrew G Renehan, Jorge Barriuso, and Hui Guo

Subjects
Oncology, medicine.medical_specialty, Context (language use), Overweight, Body Mass Index, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Obesity, Prospective cohort study, Randomized Controlled Trials as Topic, business.industry, Patient Selection, Confounding, Prognosis, Combined Modality Therapy, Causality, Survival Rate, Clinical trial, 030220 oncology & carcinogenesis, medicine.symptom, business, Body mass index, Obesity paradox
Abstract

A wealth of epidemiological evidence, combined with plausible biological mechanisms, present a convincing argument for a causal relationship between excess adiposity, commonly approximated as body mass index (BMI, kg/m2), and incident cancer risk. Beyond this relationship, there are a number of challenges posed in the context of interpreting whether being overweight (BMI 25.0–29.9 kg/m2) or obese (BMI ≥ 30.0 kg/m2) adversely influences disease progression, cancer mortality and survival. Elevated BMI (≥ 25.0 kg/m2) may influence treatment selection of, for example, the approach to surgery; the choice of chemotherapy dosing; the inclusion of patients into randomised clinical trials. Furthermore, the technical challenges posed by an elevated BMI may adversely affect surgical outcomes, for example, morbidity (increasing the risk of surgical site infections), reduced lymph node harvest (and subsequent risk of under-staging and under-treatment) and increased risk of margin positivity. Suboptimal chemotherapy dosing, associated with capping chemotherapy in obese patients as an attempt to avoid excess toxicity, might be a driver of poor prognostic outcomes. By contrast, the efficacy of immune checkpoint inhibition may be enhanced in patients who are obese, although in turn, this observation might be due to reverse causality. So, a central research question is whether being overweight or obese adversely affects outcomes either directly through effects of cancer biology or whether adverse outcomes are mediated through indirect pathways. A further dimension to this complex relationship is the obesity paradox, a phenomenon where being overweight or obese is associated with improved survival where the reverse is expected. In this overview, we describe a framework for evaluating methodological problems such as selection bias, confounding and reverse causality, which may contribute to spurious interpretations. Future studies will need to focus on prospective studies with well-considered methodology in order to improve the interpretation of causality.

Published
2020

2. Preoperative risk factors for conversion from laparoscopic to open cholecystectomy: a validated risk score derived from a prospective U.K. database of 8820 patients

Author

Robert P. Sutcliffe, Marianne Hollyman, James Hodson, Glenn Bonney, Ravi S. Vohra, Ewen A. Griffiths, Stephen Fenwick, Mohamed Elmasry, Quentin Nunes, David Kennedy, Raja B. Khan, Muhammad A.S. Khan, Conor J. Magee, Steven M. Jones, Denise Mason, Ciny P. Parappally, Pawan Mathur, Michael Saunders, Sara Jamel, Samer U.l. Haque, Sara Zafar, Muhammad H. Shiwani, Nehemiah Samuel, Farooq Dar, Andrew Jackson, Bryony Lovett, Shiva Dindyal, Hannah Winter, Saquib Rahman, Kevin Wheatley, Tom Nieto, Soofiyah Ayaani, Haney Youssef, Rajwinder S. Nijjar, Helen Watkin, David Naumann, Sophie Emeshi, Piyush B. Sarmah, Kathryn Lee, Nikita Joji, Jonathan Heath, Rebecca L. Teasdale, Chamindri Weerasinghe, Paul J. Needham, Hannah Welbourn, Luke Forster, David Finch, Jane M. Blazeby, William Robb, Angus G.K. McNair, Alex Hrycaiczuk, Alexandros Charalabopoulos, Sritharan Kadirkamanathan, Cheuk-Bong Tang, Naga V.G. Jayanthi, Nigel Noor, Brian Dobbins, Andrew J. Cockbain, April Nilsen-Nunn, Jonathan de Siqueira, Mike Pellen, Jonathan B. Cowley, Wei-Min Ho, Victor Miu, Timothy J. White, Kathryn A. Hodgkins, Alison Kinghorn, Matthew G. Tutton, Yahya A. Al-Abed, Donald Menzies, Anwar Ahmad, Joanna Reed, Shabuddin Khan, David Monk, Louis J. Vitone, Ghulam Murtaza, Abraham Joel, Stephen Brennan, David Shier, Catherine Zhang, Thusidaran Yoganathan, Steven J. Robinson, Iain J.D. McCallum, Michael J. Jones, Mohammed Elsayed, Liz Tuck, John Wayman, Kate Carney, Somaiah Aroori, Kenneth B. Hosie, Adam Kimble, David M. Bunting, Adeshina S. Fawole, Mohammed Basheer, Rajiv V. Dave, Janahan Sarveswaran, Elinor Jones, Chris Kendal, Michael P. Tilston, Martin Gough, Tom Wallace, Shailendra Singh, Justine Downing, Katherine A. Mockford, Eyad Issa, Nayab Shah, Neal Chauhan, Timothy R. Wilson, Amir Forouzanfar, Jonathan R.L. Wild, Emma Nofal, Catherine Bunnell, Khaliel Madbak, Sudhindra T.V. Rao, Laurence Devoto, Najaf Siddiqi, Zechan Khawaja, James C. Hewes, Laura Gould, Alice Chambers, Daniel U. Rodriguez, Gourab Sen, Stuart Robinson, Francis Bartlett, David M. Rae, Thomas E.J. Stevenson, Kas Sarvananthan, Simon J. Dwerryhouse, Simon M. Higgs, Oliver J. Old, Thomas J. Hardy, Reena Shah, Steve T. Hornby, Ken Keogh, Lucinda Frank, Musallam Al-Akash, Emma A. Upchurch, Richard J. Frame, Michael Hughes, Clare Jelley, Simon Weaver, Sudipta Roy, Toritseju O. Sillo, Giorgios Galanopoulos, Tamzin Cuming, Pedro Cunha, Salim Tayeh, Sarantos Kaptanis, Mohamed Heshaishi, Abdalla Eisawi, Michael Abayomi, Wee S. Ngu, Katie Fleming, Dalvir S. Bajwa, Vivek Chitre, Kamal Aryal, Paul Ferris, Michael Silva, Simon Lammy, Sarah Mohamed, Amir Khawaja, Adnan Hussain, Mudassar A. Ghazanfar, Maria I. Bellini, Hamdi Ebdewi, Mohamed Elshaer, Gianpiero Gravante, Benjamin Drake, Arikoge Ogedegbe, Dipankar Mukherjee, Chanpreet Arhi, Lola Giwa, Nusrat Iqbal, Nicholas F. Watson, Smeer K. Aggarwal, Philippa Orchard, Eduardo Villatoro, Peter D. Willson, Kam W.J. Mok, Thomas Woodman, Jean Deguara, Giuseppe Garcea, Benoy I. Babu, Alistair R. Dennison, Deep Malde, David Lloyd, John P. Slavin, Robert P. Jones, Laura Ballance, Stratos Gerakopoulos, Periyathambi Jambulingam, Sami Mansour, Naomi Sakai, Vikas Acharya, Mohammed M. Sadat, Lawen Karim, David Larkin, Khalid Amin, Amarah Khan, Jennifer Law, Saurabh Jamdar, Stella R. Smith, Keerthika Sampat, Kathryn M. O'shea, Mangta Manu, Fotini M. Asprou, Nabeela S. Malik, Jessica Chang, Marianne Johnstone, Michael Lewis, Geoffrey P. Roberts, Babu Karavadra, Evangelos Photi, James Hewes, Dan Rodriguez, Derek A. O'Reilly, Anthony J. Rate, Hema Sekhar, Lucy T. Henderson, Benjamin Z. Starmer, Peter O. Coe, Sotonye Tolofari, Jenifer Barrie, Gareth Bashir, Jake Sloane, Suroosh Madanipour, Constantine Halkias, Alexander E.J. Trevatt, David W. Borowski, Jane Hornsby, Michael J. Courtney, Suvi Virupaksha, Keith Seymour, Sarah Robinson, Helen Hawkins, Sadiq Bawa, Paul V. Gallagher, Alistair Reid, Peter Wood, Jonathan G. Finch, J.Guy Finch, Jitesh Parmar, Euan Stirland, James Gardner-Thorpe, Ahmed Al-Muhktar, Mark Peterson, Ali Majeed, Farrukh M. Bajwa, Jack Martin, Alfred Choy, Andrew Tsang, Naresh Pore, David R. Andrew, Waleed Al-Khyatt, Christopher Taylor Santosh Bhandari, Adam Chambers, Dhivya Subramanium, Simon K.C. Toh, Nicholas C. Carter, Stuart J. Mercer, Benjamin Knight, Vardhini Vijay, Swethan Alagaratnam, Sidhartha Sinha, Shahab Khan, Shamsi S. El-Hasani, Abdulzahra A. Hussain, Vish Bhattacharya, Nisheeth Kansal, Tani Fasih, Claire Jackson, Midhat N. Siddiqui, Imran A. Chishti, Imogen J. Fordham, Zohaib Siddiqui, Harald Bausbacher, Ileana Geogloma, Kabita Gurung, George Tsavellas, Pradeep Basynat, Ashish K. Shrestha, Sanjoy Basu, Alok Chhabra, Mohan Harilingam, Mohamed Rabie, Mansoor Akhtar, Pradeep Kumar, Sadaf F. Jafferbhoy, Najam Hussain, Soulat Raza, Manzarul Haque, Imran Alam, Rabiya Aseem, Shakira Patel, Mehek Asad, Michael I. Booth, William R. Ball, Christopher P.J. Wood, Ana C. Pinho-Gomes, Ambareen Kausar, Mohammed Obeidallah, Joseph Varghase, Joshil Lodhia, Donal Bradley, Carla Rengifo, David Lindsay, Sivakumar Gopalswamy, Ian Finlay, Stacy Wardle, Naomi Bullen, Syed Y. Iftikhar, Altaf Awan, Javed Ahmed, Paul Leeder, Guiseppe Fusai, Giles Bond-Smith, Alicja Psica, Yogesh Puri, David Hou, Fergus Noble, Karoly Szentpali, Jack Broadhurst, Ravindra Date, Martin R. Hossack, Yan L. Goh, Paul Turner, Vinutha Shetty, Manel Riera, Christina A.W. Macano, Anisha Sukha, Shaun R. Preston, Jennifer R. Hoban, Daniel J. Puntis, Sophie V. Williams, Richard Krysztopik, James Kynaston, Jeremy Batt, Matthew Doe, Andrzej Goscimski, Gareth H. Jones, Claire Hall, Nick Carty, Jamil Ahmed, Sofoklis Panteleimonitis, Rohan T. Gunasekera, Andrea R.G. Sheel, Hannah Lennon, Caroline Hindley, Marcus Reddy, Ross Kenny, Natalie Elkheir, Emma R. McGlone, Rajasundaram Rajaganeshan, Kate Hancorn, Anita Hargreaves, Raj Prasad, David A. Longbotham, Dhakshinamoorthy Vijayanand, Imeshi Wijetunga, Paul Ziprin, Christopher R. Nicolay, Geoffrey Yeldham, Edward Read, James A. Gossage, Rachel C. Rolph, Husam Ebied, Manraj Phull, Mohammad A. Khan, Matthew Popplewell, Dimitrios Kyriakidis, Anwar Hussain, Natasha Henley, Jessica R. Packer, Laura Derbyshire, Jonathan Porter, Shaun Appleton, Marwan Farouk, Melvinder Basra, Neil A. Jennings, Shahda Ali, Venkatesh Kanakala, Haythem Ali, Risha Lane, Richard Dickson-Lowe, Prizzi Zarsadias, Darius Mirza, Sonia Puig, Khalid Al Amari, Deepak Vijayan, Robert Sutcliffe, Ravi Marudanayagam, Zayed Hamady, Abheesh R. Prasad, Abhilasha Patel, Damien Durkin, Parminder Kaur, Laura Bowen, James P. Byrne, Katherine L. Pearson, Theo G. Delisle, James Davies, Mark A. Tomlinson, Michelle A. Johnpulle, Corinna Slawinski, Andrew Macdonald, James Nicholson, Katy Newton, James Mbuvi, Ansar Farooq, Bhavani S. Mothe, Zakhi Zafrani, Daniel Brett, James Francombe, Philip Spreadborough, James Barnes, Melanie Cheung, Ahmed Z. Al-Bahrani, Giuseppe Preziosi, Tomas Urbonas, Justin Alberts, Mekhlola Mallik, Krashna Patel, Ashvina Segaran, Triantafyllos Doulias, Pratik A. Sufi, Caroline Yao, Sarah Pollock, Antonio Manzelli, Saj Wajed, Michail Kourkulos, Roberto Pezzuto, Martin Wadley, Emma Hamilton, Shameen Jaunoo, Robert Padwick, Mazin Sayegh, Richard C. Newton, Madhusoodhana Hebbar, Sameh F. Farag, Madhu Hebbar, John Spearman, Mohammed F. Hamdan, Conrad D'Costa, Christine Blane, Mathew Giles, Mark B. Peter, Natalie A. Hirst, Tanvir Hossain, Arslan Pannu, Yesar El-Dhuwaib, Tamsin E.M. Morrison, Greg W. Taylor, Ronald L.E. Thompson, Ken McCune, Paula Loughlin, Roger Lawther, Colman K. Byrnes, Duncan J. Simpson, Abi Mawhinney, Conor Warren, Damian McKay, Colin McIlmunn, Serena Martin, Matthew MacArtney, Tom Diamond, Phil Davey, Claire Jones, Joshua M. Clements, Ruairi Digney, Wei M. Chan, Stephen McCain, Sadaf Gull, Adam Janeczko, Emmet Dorrian, Andrew Harris, Suzanne Dawson, Dorothy Johnston, Barry McAree, Essam Ghareeb, George Thomas, Martin Connelly, Stephen McKenzie, Krzysztos Cieplucha, Gary Spence, William Campbell, Gareth Hooks, Neil Bradley, Arnold D.K. Hill, John T. Cassidy, Michael Boland, Paul Burke, Deirdre M. Nally, Elmoataz Khogali, Wael Shabo, Edrin Iskandar, Gerry P. McEntee, Maeve A. O'Neill, Colin Peirce, Emma M. Lyons, Adrian W. O'Sullivan, Rohan Thakkar, Paul Carroll, Ivan Ivanovski, Paul Balfe, Matthew Lee, Des C. Winter, Michael E. Kelly, Emir Hoti, Donal Maguire, Priyadarssini Karunakaran, Justin G. Geoghegan, Sean T. Martin, Keith S. Cross, Fiachra Cooke, Saquib Zeeshan, James O. Murphy, Ken Mealy, Helen M. Mohan, Yuwaraja Nedujchelyn, Muhammad F. Ullah, Irfan Ahmed, Francesco Giovinazzo, James Milburn, Sarah Prince, Eleanor Brooke, Joanna Buchan, Ahmed M. Khalil, Elizabeth M. Vaughan, Michael I. Ramage, Roland C. Aldridge, Simon Gibson, Gary A. Nicholson, David G. Vass, Alan J. Grant, David J. Holroyd, Angharad Jones, Cherith M.L.R. Sutton, Patrick O'Dwyer, Frida Nilsson, Beatrix Weber, Tracey K. Williamson, Kushik Lalla, Alice Bryant, Ross Carter, Craig R. Forrest, David I. Hunter, Ahmad H. Nassar, Mavis N. Orizu, Katrina Knight, Haitham Qandeel, Stuart Suttie, Rowena Belding, Andrew McClarey, Alan T. Boyd, Graeme J.K. Guthrie, Pei J. Lim, Andreas Luhmann, Angus J.M. Watson, Colin H. Richards, Laura Nicol, Marta Madurska, Ewen Harrison, Kathryn M. Boyce, Amanda Roebuck, Graeme Ferguson, Pradeep Pati, Michael S.J. Wilson, Faith Dalgaty, Laura Fothergill, Peter J. Driscoll, Kirsty L. Mozolowski, Victoria Banwell, Stephen P. Bennett, Paul N. Rogers, Brendan L. Skelly, Claire L. Rutherford, Ahmed K. Mirza, Taha Lazim, Henry C.C. Lim, Diana Duke, Talat Ahmed, William D. Beasley, Marc D. Wilkinson, Geta Maharaj, Cathy Malcolm, Timothy H. Brown, Guy M. Shingler, Nicholas Mowbray, Rami Radwan, Paul Morcous, Simon Wood, Abbas Kadhim, Duncan J. Stewart, Andrew L. Baker, Nicola Tanner, and Hrishikesh Shenoy

Subjects
Male, Databases, Factual, medicine.medical_treatment, 0302 clinical medicine, Risk Factors, Odds Ratio, Prospective Studies, Prospective cohort study, Framingham Risk Score, Gastroenterology, Age Factors, Gallbladder, Middle Aged, Conversion to Open Surgery, Treatment Outcome, Cholecystectomy, Laparoscopic, 030220 oncology & carcinogenesis, Predictive value of tests, 030211 gastroenterology & hepatology, Female, Original Article, Risk assessment, Dilatation, Pathologic, Adult, medicine.medical_specialty, Digestive System Diseases, MEDLINE, Risk Assessment, 03 medical and health sciences, Sex Factors, Predictive Value of Tests, medicine, Humans, Aged, Common Bile Duct, Chi-Square Distribution, Hepatology, Laparoscopyc cholecystectomy, business.industry, General surgery, Reproducibility of Results, Odds ratio, United Kingdom, Surgery, preoperative assessment, Logistic Models, Multivariate Analysis, Cholecystectomy, business, Chi-squared distribution, risk factors
Abstract

Laparoscopic cholecystectomy is commonly performed, and several factors increase the risk of open conversion, prolonging operating time and hospital stay. Preoperative stratification would improve consent, scheduling and identify appropriate training cases. The aim of this study was to develop a validated risk score for conversion for use in clinical practice.Preoperative patient and disease-related variables were identified from a prospective cholecystectomy database (CholeS) of 8820 patients, divided into main and validation sets. Preoperative predictors of conversion were identified by multivariable binary logistic regression. A risk score was developed and validated using a forward stepwise approach.Some 297 procedures (3.4%) were converted. The risk score was derived from six significant predictors: age (p = 0.005), sex (p 0.001), indication for surgery (p 0.001), ASA (p 0.001), thick-walled gallbladder (p = 0.040) and CBD diameter (p = 0.004). Testing the score on the validation set yielded an AUROC = 0.766 (p 0.001), and a score6 identified patients at high risk of conversion (7.1% vs. 1.2%).This validated risk score allows preoperative identification of patients at six-fold increased risk of conversion to open cholecystectomy.

Published
2016

3. Hepatic portal venous gas complicating Bickerstaff's encephalitis with Guillain Barré overlap

Author

Stephen J. Pettit, Pat G. Casey, Corinna Slawinski, and Ed Parkin

Subjects
Intestinal pseudo-obstruction, Adult, Male, Flaccid paralysis, Ischemia, Guillain-Barre Syndrome, Article, Intensive care, Intestine, Small, Paralysis, medicine, Humans, Guillain-Barre syndrome, Bacteria, business.industry, Portal Vein, Intestinal Pseudo-Obstruction, General Medicine, medicine.disease, Parenteral nutrition, Liver, Anesthesia, Bacterial Translocation, Immunology, Encephalitis, Gases, medicine.symptom, business
Abstract

Hepatic portal venous gas (HPVG) is a radiological finding often associated with intestinal ischaemia and high mortality.1 We report a 34-year-old male patient who developed flaccid paralysis of all four limbs, areflexia and ophthalmoplegia after a short viral illness. A diagnosis of Bickerstaff's encephalitis with Guillain Barre overlap was made.2 He was ventilated, treated with immunoglobulins and received enteral nutrition via a nasogastric tube. Some neurological improvement was noted on day 22 in intensive care. On day 23 he developed marked abdominal distention with large volume faeculant nasogastric aspirates. CT …

Published
2015

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