Submit manuscript...
eISSN: 2373-6372

Gastroenterology & Hepatology: Open Access

Short Communication Volume 15 Issue 3

Splanchnic inflammatory syndrome and the not-so-silent risk of cancer

Richard C Semelka MD,1 Miguel Ramalho MD2

1Richard Semelka Consulting, PLLC, USA
2Department of Radiology, Hospital da Luz, Portugal

Correspondence: Richard Semelka MD, Richard Semelka Consulting, PLLC, 3901 Jones Ferry Road, Chapel Hill, NC 27516, USA

Received: May 20, 2024 | Published: June 20, 2024

Citation: Semelka RC, Ramalho M. Splanchnic inflammatory syndrome and the not-so-silent risk of cancer. Gastroenterol Hepatol Open Access. 2024;15(2):63‒64. DOI: 10.15406/ghoa.2024.15.00583

Download PDF

Short communication

For many years, and in many (all) organ systems, one of the primary risks for developing cancer is the presence of chronic inflammation.1-5 We have recently reported on the condition we term Splanchnic Inflammatory Syndrome (SIS), which we describe as the imaging findings of inflammation of the organs within the splanchnic system, with the two critical components being upper digestive tract inflammation and down-stream hepatic inflammation.6 Our theory is based on the observation that individuals with hepatosteatosis, virtually always have inflammation of some combination of the distal esophagus, stomach (usually antrum), duodenum (usually proximal), pan jejunum and pan ileum (not with the primary focus of the distal ileum, as this is where commonly Crohn's Disease appears). The majority of individuals are obese, and abdominal pain is extremely common, probably universally present, and can be generalized, in the right upper quadrant or left upper quadrant. The digestive tract component of the condition relates directly to the clinical conditions of leaky gut, irritable bowel syndrome, and the bowel component of the Metabolic Syndrome (our preferred designation: Splanchnic Metabolic Syndrome), and these may represent progressive states of inflammation, consecutively, but not necessarily with universal progression.

Often, these findings are present for years in sufferers, presumably principally because individuals generally do not alter their dietary regimen. So, the upper digestive tract, liver, pancreas, and gallbladder/biliary tree remain in constant chronic inflammation. Based on our work on the Splanchnic Inflammatory Syndrome, and the resultant chronic inflammation, our theory is that this chronic inflammation may be responsible for malignant disease in the digestive system.  The below describes our theory of the effects of malignancy induction, in the upper digestive tract segments individually:

Upper digestive tract: Esophageal cancer has been directly related to reflux disease for decades,7-9 and our contention is that many of these individuals have chronic inflammation as the principal cause of SIS. The same observation has been made for gastric cancer. Duodenal and jejunal cancers are rarer than esophageal and stomach cancers, but a principal cause is likely chronic inflammation.

Liver: Over the last decade, multiple publications have suggested that Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly nonalcoholic fatty liver disease, NAFLD) and primarily the inflammatory state of Metabolic dysfunction-associated steatohepatitis (MASH, formerly Nonalcoholic steatohepatitis [NASH])) is associated with the risk for the development of hepatocellular carcinoma (HCC), and may now be overtaking both alcohol-related and Hepatitis viral disease-related causes for HCC.10-15

Pancreas:  Over recent years, it has been recognized that the (Splanchnic) Metabolic Syndrome is often associated with pancreatic steatosis. This has been our experience interpreting MRI studies. Additionally, our current theory is that the now common observation of small pancreatic cysts may reflect a pancreatic response to inflammation tracking from the jejunum through the mesentery to the pancreas.   These pancreatic cysts are not related to known acute or chronic pancreatitis. They range in number and size from tiny individual or few cysts (the most common appearance) to numerous varying -sized cysts, with or without intraductal papillary mucinous neoplasms (IPMN). Our working theory is that they arise due to the pancreas being exposed to sustained chronic inflammation of SIS, and reflecting direct inflammatory spread from the duodenum, jejunum, and possibly the stomach. It is common practice to serially image patients with pancreatic cysts, and IPMNs, especially when they exceed 2.5 cm in diameter, because of the risk of cancer. Our current contention is that the risk of cancer does not stem from cysts, per se, rather due to chronic sustained inflammation of the pancreas in SIS. Therefore, pancreatic steatosis, pancreatic cysts/IPMNs, many cases of acute and chronic pancreatitis, and a number of cases of pancreatic cancer, all represent sequela of the chronic inflammation of SIS, as many published data indicate.16-21

Gallbladder and biliary tree: Our theory is that most cases of acalculous cholecystitis, and the various forms of biliary dyskinesia and ampullary dysfunctions are secondary/ sympathetic inflammation due to duodenal inflammation. Gallbladder cancer is most often observed in the setting of chronic inflammation associated with/ induced by chronic cholecystitis. Although we have not at present conjectured this, it is not unreasonable to consider that the impetus to develop gallstones may be due to the chronic inflammation of SIS. Cholangiocarcinoma and ampullary carcinoma seem more likely to arise secondary to SIS and duodenal inflammation that progresses in a retrograde fashion in the Common Bile Duct (CBD). Prior studies are reporting the connection between chronic inflammation and the development of cancers in the gallbladder and biliary tree.22-28

Treatment: The primary management for SIS and the downstream various chronic inflammation-related malignancies starts with prevention. The critical recognition of a healthy diet for essentially all diseases, from heart disease and neurocognitive disease to COVID-19 infection, was most recently emphasized. We would term such a diet as the umbrella term the Wholesome Diet (we will describe it in a future publication). Regarding choices in diet, for most individuals, the commonly recognized strategies are: cut down sugar, limit gluten, limit dairy, and stop smoking tobacco and other substances. It is also clear that it is paramount to avoid ultra-processed food altogether, due to the increased risk of cancer and cardiometabolic diseases.29-33 In a few subjects, more in-depth dietary evaluation is necessary to manage food allergies and intolerance, such as limiting nightshade vegetables (e.g., tomatoes, white potatoes), some nuts, strawberries, etc. Development of, or ameliorating, symptoms is the most straightforward finding to pay attention to in creating an optimal diet for those individuals with a complex history of chemical sensitivities.

Conclusion

Chronic inflammation of the Splanchnic Inflammatory Syndrome is likely a common cause of many cancers of the splanchnic system. Prevention is the most obvious and practical approach. The principal management, which is the safest, most effective, and most cost-efficient approach, is attention to diet.

Acknowledgments

None.

Conflicts of interest

None.

References

  1. Antonucci L, Karin M. The Past and Future of Inflammation as a Target to Cancer Prevention. Cancer Prev Res. 2024;17(4):141–155.
  2. Bouras E, Karhunen V, Gill D, et al. Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis. BMC Med. 2022;20(1):3.
  3. Greten FR, Eckmann L, Greten TF, et al. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis–associated cancer. Cell. 2004;118(3):285–296.
  4. Greten FR, Grivennikov SI. Inflammation and Cancer: Triggers, Mechanisms, and Consequences. Immunity. 2019;51(1):27–41.
  5. Nigam M, Mishra AP, Deb VK, et al. Evaluation of the association of chronic inflammation and cancer: Insights and implications. Biomed Pharmacother. 2023;164.
  6. Semelka RC, Elias Jr J, Pereira JC, et al. Hepatic steatosis: additional findings in the splanchnic system on magnetic resonance imaging. Gastroenterol Hepatol Open access. 2024;15(1):3–9.
  7. Arnal MJD. Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries. World J Gastroenterol. 2015;21(26).
  8. Akerstrom JH, Santoni G, von Euler Chelpin M, et al. Antireflux Surgery Versus Antireflux Medication and Risk of Esophageal Adenocarcinoma in Patients With Barrett's Esophagus. Gastroenterology. 2024;166(1):132–8 e3.
  9. Cook MB, Corley DA, Murray LJ, et al. Gastroesophageal reflux in relation to adenocarcinomas of the esophagus: a pooled analysis from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). PLoS One. 2014;9(7):e103508.
  10. Ramai D, Tai W, Rivera M, et al. Natural Progression of Non–Alcoholic Steatohepatitis to Hepatocellular Carcinoma. Biomedicines. 2021;9(2).
  11. Estes C, Razavi H, Loomba R, et al. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2017;67(1):123–133.
  12. Pfister D, Núñez NG, Pinyol R, et al. NASH limits anti–tumour surveillance in immunotherapy–treated HCC. Nature. 2021;592(7854):450–456.
  13. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nature Reviews Disease Primers. 2021;7(1).
  14. Asfari MM, Talal Sarmini M, Alomari M, et al. The association of nonalcoholic steatohepatitis and hepatocellular carcinoma. Eur J Gastroenterol Hepatol. 2020;32(12):1566–1570.
  15. Crane H, Eslick GD, Gofton C, et al. Global prevalence of MAFLD–related hepatocellular carcinoma: A systematic review and meta–analysis. Clin Mol Hepatol. 2024.
  16. Kolodecik T, Shugrue C, Ashat M, et al. Risk factors for pancreatic cancer: underlying mechanisms and potential targets. Front Physiol. 2014;4.
  17. Shadhu K, Xi C. Inflammation and pancreatic cancer: An updated review. Saudi J Gastroenterol. 2019;25(1).
  18. Greer JB, Whitcomb DC. Inflammation and pancreatic cancer: an evidence–based review. Curr Opin Pharmacol. 2009;9(4):411–418.
  19. Michaud DS. Role of bacterial infections in pancreatic cancer. Carcinogenesis. 2013;34(10):2193–2197.
  20. Desai V, Patel K, Sheth R, et al. Pancreatic Fat Infiltration Is Associated with a Higher Risk of Pancreatic Ductal Adenocarcinoma. Visc Med. 2020;36(3):220–226.
  21. Cayssials V, Buckland G, Crous–Bou M, et al. Inflammatory potential of diet and pancreatic cancer risk in the EPIC study. Eur J Nutr. 2022;61(5):2313–2320.
  22. Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383(9935):2168–2179.
  23. Valle JW, Kelley RK, Nervi B, et al. Biliary tract cancer. The Lancet. 2021;397(10272):428–444.
  24. Zhou M, Wang C, Lu S, et al. Tumor–associated macrophages in cholangiocarcinoma: complex interplay and potential therapeutic target. E Bio Medicine. 2021;67.
  25. Brindley PJ, Bachini M, Ilyas SI, et al. Cholangiocarcinoma. Nat Rev Dis Primers. 2021;7(1).
  26. Banales JM, Cardinale V, Carpino G, et al. Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS–CCA). Nature Reviews Gastroenterology & Hepatology. 2016;13(5):261–280.
  27. Grainge MJ, West J, Solaymani–Dodaran M, et al. The antecedents of biliary cancer: a primary care case–control study in the United Kingdom. Br J Cancer. 2008;100(1):178–180.
  28. Pérez–Moreno P, Riquelme I, García P, et al. Environmental and Lifestyle Risk Factors in the Carcinogenesis of Gallbladder Cancer. J Pers Med. 2022;12(2):234.
  29. Cordova R, Viallon V, Fontvieille E, et al. Consumption of ultra–processed foods and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study. The Lancet Regional Health – Europe. 2023;35.
  30. Chang K, Gunter MJ, Rauber F, et al. Ultra–processed food consumption, cancer risk and cancer mortality: a large–scale prospective analysis within the UK Biobank. EClinicalMedicine. 2023;56.
  31. Kliemann N, Rauber F, Bertazzi Levy R, et al. Food processing and cancer risk in Europe: results from the prospective EPIC cohort study. Lancet Planet Health. 2023;7(3):e219–e32.
  32. Kliemann N, Al Nahas A, Vamos EP, et al. Ultra–processed foods and cancer risk: from global food systems to individual exposures and mechanisms. Br J Cancer. 2022;127(1):14–20.
  33. Hang D, Du M, Wang L, et al. Ultra–processed food consumption and mortality among patients with stages I–III colorectal cancer: a prospective cohort study. EClinicalMedicine. 2024;71.
Creative Commons Attribution License

©2024 Semelka, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.