{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:56:12Z","timestamp":1788850572388,"version":"build-2803163510"},"reference-count":89,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T00:00:00Z","timestamp":1572480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with peritoneal metastasis (PM) of gastrointestinal and gynecological origin present with a nutritional deficit characterized by increased resting energy expenditure (REE), loss of muscle mass, and protein catabolism. Progression of peritoneal metastasis, as with other advanced malignancies, is associated with cancer cachexia anorexia syndrome (CAS), involving poor appetite (anorexia), involuntary weight loss, and chronic inflammation. Eventual causes of mortality include dysfunctional metabolism and energy store exhaustion. Etiology of CAS in PM patients is multifactorial including tumor growth, host response, cytokine release, systemic inflammation, proteolysis, lipolysis, malignant small bowel obstruction, ascites, and gastrointestinal side effects of drug therapy (chemotherapy, opioids). Metabolic changes of CAS in PM relate more to a systemic inflammatory response than an adaptation to starvation. Metabolic reprogramming is required for cancer cells shed into the peritoneal cavity to resist anoikis (i.e., programmed cell death). Profound changes in hexokinase metabolism are needed to compensate ineffective oxidative phosphorylation in mitochondria. During the development of PM, hypoxia inducible factor-1\u03b1 (HIF-1\u03b1) plays a key role in activating both aerobic and anaerobic glycolysis, increasing the uptake of glucose, lipid, and glutamine into cancer cells. HIF-1\u03b1 upregulates hexokinase II, phosphoglycerate kinase 1 (PGK1), pyruvate dehydrogenase kinase (PDK), pyruvate kinase muscle isoenzyme 2 (PKM2), lactate dehydrogenase (LDH) and glucose transporters (GLUT) and promotes cytoplasmic glycolysis. HIF-1\u03b1 also stimulates the utilization of glutamine and fatty acids as alternative energy substrates. Cancer cells in the peritoneal cavity interact with cancer-associated fibroblasts and adipocytes to meet metabolic demands and incorporate autophagy products for growth. Therapy of CAS in PM is challenging. Optimal nutritional intake alone including total parenteral nutrition is unable to reverse CAS. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) stabilized nutritional status in a significant proportion of PM patients. Agents targeting the mechanisms of CAS are under development.<\/jats:p>","DOI":"10.3390\/ijms20215444","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T12:38:23Z","timestamp":1572525503000},"page":"5444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Cachexia Anorexia Syndrome and Associated Metabolic Dysfunction in Peritoneal Metastasis"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-7723","authenticated-orcid":false,"given":"Rami","family":"Archid","sequence":"first","affiliation":[{"name":"Department of General &amp; Transplant Surgery, University Hospital T\u00fcbingen, D-72076 T\u00fcbingen, Germany"},{"name":"National Center for Pleura and Peritoneum, University Hospital T\u00fcbingen, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6639-1935","authenticated-orcid":false,"given":"Wiebke","family":"Solass","sequence":"additional","affiliation":[{"name":"National Center for Pleura and Peritoneum, University Hospital T\u00fcbingen, D-72076 T\u00fcbingen, Germany"},{"name":"Institute of Pathology and Neuropathology, University Hospital T\u00fcbingen, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Tempfer","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Ruhr-University Bochum, 44625 Herne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2301-4080","authenticated-orcid":false,"given":"Alfred","family":"K\u00f6nigsrainer","sequence":"additional","affiliation":[{"name":"Department of General &amp; Transplant Surgery, University Hospital T\u00fcbingen, D-72076 T\u00fcbingen, Germany"},{"name":"National Center for Pleura and Peritoneum, University Hospital T\u00fcbingen, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Adolph","sequence":"additional","affiliation":[{"name":"Nutrition Unit, Department of Anesthesiology, University Hospital T\u00fcbingen, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Reymond","sequence":"additional","affiliation":[{"name":"Department of General &amp; Transplant Surgery, University Hospital T\u00fcbingen, D-72076 T\u00fcbingen, Germany"},{"name":"National Center for Pleura and Peritoneum, University Hospital T\u00fcbingen, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7408-4695","authenticated-orcid":false,"given":"Robert B.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Upper Gastrointestinal Surgery, UNSW, Liverpool Hospital, Sydney, NSW 2170, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.21037\/apm.2018.08.07","article-title":"Measuring cachexia-diagnostic criteria","volume":"8","author":"Dev","year":"2019","journal-title":"Ann. 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