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Gomes-Porras M, Cárdenas-Salas J, Álvarez-Escolá C. Somatostatin Analogs in Clinical Practice: a Review. Int J Mol Sci 2020; 21:ijms21051682. [PMID: 32121432 PMCID: PMC7084228 DOI: 10.3390/ijms21051682] [Citation(s) in RCA: 134] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 02/22/2020] [Accepted: 02/25/2020] [Indexed: 12/14/2022] Open
Abstract
Somatostatin analogs are an invaluable therapeutic option in the diagnosis and treatment of somatotropinomas, thyrotropinomas, and functioning and non-functioning gastroenteropancreatic neuroendocrine tumors. They should also be considered an effective and safe therapeutic alternative to corticotropinomas, gonadotropinomas, and prolactinomas resistant to dopamine agonists. Somatostatin analogs have also shown to be useful in the treatment of other endocrine diseases (congenital hyperinsulinism, Graves’ orbitopathy, diabetic retinopathy, diabetic macular edema), non-endocrine tumors (breast, colon, prostate, lung, and hepatocellular), and digestive diseases (chronic refractory diarrhea, hepatorenal polycystosis, gastrointestinal hemorrhage, dumping syndrome, and intestinal fistula).
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Affiliation(s)
- Mariana Gomes-Porras
- Department of Endocrinology, “La Paz” University Hospital. Paseo de la Castellana, 261, 28046 Madrid, Spain;
| | - Jersy Cárdenas-Salas
- Department of Endocrinology, “Fundación Jiménez-Diaz” University Hospital. Av. de los Reyes Católicos, 2, 28040 Madrid, Spain;
| | - Cristina Álvarez-Escolá
- Department of Endocrinology, “La Paz” University Hospital. Paseo de la Castellana, 261, 28046 Madrid, Spain;
- Correspondence: ; Tel.: +34-917-277-209
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Ashkenazi I, Turégano-Fuentes F, Olsha O, Alfici R. Treatment Options in Gastrointestinal Cutaneous Fistulas. Surg J (N Y) 2017; 3:e25-e31. [PMID: 28825016 PMCID: PMC5553539 DOI: 10.1055/s-0037-1599273] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Accepted: 01/25/2017] [Indexed: 12/15/2022] Open
Abstract
Enterocutaneous fistulas occur most commonly following surgery. A minority of them is caused by a myriad of other etiologies including infection, malignancy, and radiation. While some fistulas may close spontaneously, most patients will eventually need surgery to resolve this pathology. Successful treatment entails adoption of various methods of treatment aimed at control of sepsis, protection of surrounding skin and soft tissue, control of fistula output, and maintenance of nutrition, with eventual spontaneous or surgical closure of the fistula. The aim of this article is to review the various treatment options in their appropriate context.
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Affiliation(s)
- Itamar Ashkenazi
- Department of Surgery, Hillel Yaffe Medical Center, Hadera, Israel
| | | | - Oded Olsha
- Department of Surgery, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Ricardo Alfici
- Department of Surgery, Hillel Yaffe Medical Center, Hadera, Israel
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Stevens P, Burden S, Delicata R, Carlson G, Lal S. Somatostatin analogues for treatment of enterocutaneous fistula. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2013. [DOI: 10.1002/14651858.cd010489] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Philip Stevens
- Salford Royal NHS Foundation Trust; Surgery; Stott Lane Salford UK M6 8HD
| | - Sorrel Burden
- University of Manchester; School of Nursing, Midwifery and Social Work; Room 6.32, Jean McFarlane Building, Oxford Road Manchester UK M13 9PL
| | - Raymond Delicata
- Gwent Healthcare NHS Healthboard ? Nevill Hall Hospital; General Surgery; Brecon Road Abergavenny UK NP7 7EG
| | - Gordon Carlson
- Salford Royal NHS Foundation Trust; General Surgery; Stott Lane Salford UK M6 8HD
| | - Simon Lal
- Salford Royal Foundation Trust; Intestinal Failure Unit; Salford UK M6 8HD
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A meta-analysis of outcomes following use of somatostatin and its analogues for the management of enterocutaneous fistulas. Ann Surg 2013; 256:946-54. [PMID: 22885696 DOI: 10.1097/sla.0b013e318260aa26] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Several randomized control trials (RCTs) have compared somatostatin and its analogues versus a control group in patients with enterocutaneous fistulas (ECF). This study meta-analyzes the literature and establishes whether it shows a beneficial effect on ECF closure. METHODS We searched MEDLINE, EMBASE, CINAHL, Cochrane, and PubMed databases according to PRISMA guidelines. Seventy-nine articles were screened. Nine RCTs met the inclusion criteria. Statistical analyses were performed using Review Manager 5.1. RESULTS Somatostatin analogues versus control. Number of fistula closed: A significant number of ECF closed in the somatostatin analogue group compared to control group, P = 0.002.Time to closure: ECF closed significantly faster with somatostatin analogues compared to controls, P < 0.0001.Mortality: No significant difference between somatostatin analogues and controls, P = 0.68.Somatostatin versus control. Number of fistula closed: A significant number of ECF closed with somatostatin as compared to control, P = 0.04.Time to closure: ECF closed significantly faster with somatostatin than controls, P < 0.00001.Mortality: No significant difference between somatostatin and controls, P = 0.63 CONCLUSIONS Somatostatin and octreotide increase the likelihood of fistula closure. Both are beneficial in reducing the time to fistula closure. Neither has an effect on mortality. The risk ratio (RR) for somatostatin was higher than the RR for analogues. This may suggest that somatostatin could be better than analogues in relation to the number of fistulas closed and time to closure. Further studies are required to corroborate these apparent findings.
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Ashkenazi I, Olsha O, Kessel B, Krausz MM, Alfici R. Uncommon acquired fistulae involving the digestive system: summary of data. Eur J Trauma Emerg Surg 2011; 37:259-267. [PMID: 26815108 DOI: 10.1007/s00068-011-0112-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2011] [Accepted: 04/16/2011] [Indexed: 10/18/2022]
Abstract
PURPOSE Most gastrointestinal fistulae commonly occur following surgery. A minority is caused by a myriad of other etiologies and is termed by some as "uncommon fistulae". The aim of this study was to review these fistulae and their treatment. METHODS A literature review was carried out. Searches were conducted in Pubmed and related references reviewed. RESULTS Except for Crohn's disease and diverticulitis, "uncommon fistulae" are described in case reports or very small case series. Most of the patients were treated by surgery. CONCLUSIONS The anatomic features of the fistula and the etiology usually dictate the approach. Most patients will eventually need surgery to resolve this pathology.
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Affiliation(s)
- I Ashkenazi
- Surgery B Department, Hillel Yaffe Medical Center, P.O. Box 169, Hadera, 38100, Israel.
| | - O Olsha
- Surgery Department, Shaare Zedek Medical Center, Jerusalem, Israel
| | - B Kessel
- Trauma Unit, Hillel Yaffe Medical Center, Hadera, Israel
| | - M M Krausz
- Surgery B Department, Hillel Yaffe Medical Center, P.O. Box 169, Hadera, 38100, Israel
| | - R Alfici
- Surgery B Department, Hillel Yaffe Medical Center, P.O. Box 169, Hadera, 38100, Israel
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Gupta M, Sonar P, Kakodkar R, Kumaran V, Mohanka R, Soin A, Nundy S. Small bowel enterocutaneous fistulae: the merits of early surgery. Indian J Surg 2008; 70:303-7. [PMID: 23133088 DOI: 10.1007/s12262-008-0087-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2008] [Accepted: 10/30/2008] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND The treatment of patients with small bowel enterocutaneous fistulas is complex and a challenge for every surgeon. The mortality and morbidity associated with only conservative management is often high and expensive because most patients cannot afford prolonged parenteral nutrition which itself carries a high incidence of complications. Although operations are difficult if performed early they may be lifesaving in our situation. The focus of our study was to determine whether, in patients with fistulae, early intervention resulted in low mortality and morbidity rates and to identify prognostic factors for fistula closure and mortality. PATIENTS AND METHODS Between August 1996 and July 2008 we treated 64 consecutive patients with small bowel enterocutaneous fistulae. There were 28 females and 36 males patients who had a mean age of 42.4 years. 49 (77%) of the fistulae resulted from surgical complications. Our policy was to intervene early once the patient was fit for a procedure. RESULTS In 4 patients (6.2%) the fistulae arose from the jejunum and in the remaining 94% from the ileum. Octreotide was administered in 49 (77%) patients. To maintain the nutrition of the patients enteral feeding was used in 47 (73%) while re-feeding of the proximal gut fistula output into the distal stoma was used in 7 patients. Spontaneous closure occurred in 10 patients (16%). There were 9 deaths (14%). Fifty-two patients (81%) required surgical intervention at some stage. A strong relationship was found between their preoperative albumin levels and and mortality. CONCLUSION Aggressive early surgical treatment with the judicious use of nutritional support, stoma care, octreotide, and control of sepsis results in a low mortality in patients with small intestinal fistulae. Preoperative hypoalbuminaemia is an important prognostic variable.
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Affiliation(s)
- Manoj Gupta
- Department of Surgical Gastroenteriology and Liver Transplantation, Sir Ganga Ram Hospital, New Delhi, India
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Small Intestine. Surgery 2008. [DOI: 10.1007/978-0-387-68113-9_50] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Abstract
BACKGROUND The management of enterocutaneous fistula is challenging, with significant associated morbidity and mortality. This article reviews treatment, with emphasis on the provision and optimal route of nutritional support. METHODS Relevant articles were identified using Medline searches. Secondary articles were identified from the reference lists of key papers. RESULTS AND CONCLUSION Management of enterocutaneous fistula should initially concentrate on correction of fluid and electrolyte imbalances, drainage of collections, treatment of sepsis and control of fistula output. The routine use of somatostatin infusion and somatostatin analogues remains controversial; although there are data suggesting reduced time to fistula closure, there is little evidence of increased probability of spontaneous closure. Malnutrition is common and adequate nutritional provision is essential, enteral where possible, although supplemental parenteral nutrition is often required for high-output small bowel fistulas. The role of immunonutrition is unknown. Surgical repair should be attempted when spontaneous fistula closure does not occur, but it should be delayed for at least 3 months.
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Affiliation(s)
- D A J Lloyd
- The Lennard-Jones Intestinal Failure Unit, St Mark's Hospital and Academic Institute, Harrow, UK.
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Qin HL, Su ZD, Zou Y, Fan YB. Effect of parenteral and enteral nutrition combined with octreotide on pancreatic exocrine secretion of patients with pancreatic fistula. World J Gastroenterol 2004; 10:2419-22. [PMID: 15285034 PMCID: PMC4576303 DOI: 10.3748/wjg.v10.i16.2419] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To evaluate the effect of parenteral and enteral nutrition combined with octreotide on pancreatic exocrine secretion of the patients with pancreatic fistula.
METHODS: Pancreatic juice, drained directly from the pancreatic fistula, was collected, and the volume, protein, amylase, HCO3-, K+, Na+ and Cl- were determined on d 1, 4 and 7 before and after 7-d treatment with octreotide, respectively.
RESULTS: No differences in exocrine pancreatic secretion were observed during the enteral and parenteral nutrition period (t = 2.03, P > 0.05); there were significant decreases in pancreatic juice secretion volume, protein, amylase, HCO3-, K+, Na+ and Cl- after parenteral and enteral nutrition combined with octreotide compared with octreotide pretreatment (t = 4.14, P < 0.05).
CONCLUSION: There is no stimulatory effect on the pancreatic secretion by intrajejunal nutrition and parenteral nutrition. Octreotide is effective on the reduction of pancreatic fistula output.
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Affiliation(s)
- Huan-Long Qin
- Department of Surgery, Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China.
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Abstract
During a period of six years, 17 cases of enterocutaneous fistulae arising from the small intestine were managed. Majority of the fistulae, (76%) resulted from surgical complications. There were 6 females and 11 male patients. The mean age of the patients was 40 years. In 9/17 patients (52%) the fistulae arose from the proximal small gut (duodenum and jejunum) and in the remaining 48% from the ileum. Octreotide was used in 11/17 patients (64%). Enteral nutrition was used in 9/17 patients (52%) while re-feed from the proximal gut fistulae was used in 4/9 patients (44%) to maintain the nutrition of the patients. Only one fistula (6%) closed spontaneously. There were 2 deaths (12%) in this study. 14/17 patients (82%) required surgical intervention at some stage for successful closure of intestinal fistula. Aggressive surgical treatment with judicious use of octreotide, nutritional support, stoma care and control of sepsis significantly improves the outcome of small intestinal fistulae.
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Affiliation(s)
- Rajan Chaudhry
- Senior Advisor (Surgery & Gastrointestinal Surgery), Command Hospital (Northern Command), C/o 56 APO
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Are Somatostatin Analogues (Octreotide and Lanreotide) Effective in Promoting Healing of Enterocutaneous Fistulas? J Wound Ostomy Continence Nurs 2002. [DOI: 10.1097/00152192-200209000-00005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Crook MA, Steger A. Abnormal liver function tests in a patient fed with total parenteral nutrition and treated with octreotide. Nutrition 2001; 17:152-4. [PMID: 11240342 DOI: 10.1016/s0899-9007(00)00515-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Octreotide is a long-acting analog of somatostatin, a hypothalamic release-inhibiting hormone. It is sometimes used therapeutically to relieve symptoms associated with acromegaly and gastroenteropancreatic endocrine tumors. It has also been used in the treatment of short-bowel syndrome and gastrointestinal and biliary fistulae. We report a patient with biliary leakage due to Marizzi's syndrome treated with total parenteral nutrition and octreotide who developed abnormal liver function tests that improved when the two treatments were stopped. We also review the literature regarding abnormal liver function tests in patients on total parenteral nutrition.
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Affiliation(s)
- M A Crook
- Department of Chemical Pathology, Guy's and St Thomas' and University Hospital Lewisham, London, UK.
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Li-Ling J, Irving M. Somatostatin and octreotide in the prevention of postoperative pancreatic complications and the treatment of enterocutaneous pancreatic fistulas: a systematic review of randomized controlled trials. Br J Surg 2001; 88:190-9. [PMID: 11167865 DOI: 10.1046/j.1365-2168.2001.01659.x] [Citation(s) in RCA: 125] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim of this study was to evaluate, through systematic review, the effectiveness of somatostatin and octreotide in the prevention of postoperative pancreatic complications and the treatment of established enterocutaneous pancreatic fistulas. METHODS Electronic databases, including Medline and EMBASE, were searched systematically by using keywords including 'somatostatin', 'octreotide', 'fistula' and 'randomiz(s)ed controlled trial'. In addition, citations of relevant primary and review articles were examined. Particular authors were contacted when necessary. Data on patient recruitment, intervention and outcome were extracted from the included trials and analysed. RESULTS Use of somatostatin or octreotide for the prevention of postpancreatectomy complications, including pancreatic fistulas, was identified in 14 randomized controlled trials, including one abstract and one conference proceeding, involving a total of 1686 patients. Use of somatostatin or octreotide for the treatment of established enterocutaneous pancreatic fistulas was identified in ten trials involving a total of 301 patients. Significant heterogeneity was found among the identified trials with regard to the definition of fistula, dosage of octreotide, starting time and duration of the treatment, among other factors. CONCLUSION There was major disagreement between the studies on whether use of the drugs in question is of value in preventing postoperative complications. This analysis suggests that, in units where the postoperative fistula rate following pancreaticoduodenectomy for neoplasia and other pancreatic conditions exceeds 10 per cent, somatostatin or octreotide administered before operation may significantly reduce the rate of major postoperative complications, particularly pancreatic fistulas. The identified evidence also suggests that there may be a limited role for such drugs in the treatment of established postoperative enterocutaneous pancreatic fistulas. A major conclusion is that further clarification of the roles of these drugs is still required through large, high-quality, randomized trials.
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Affiliation(s)
- J Li-Ling
- Department of Surgery, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, UK
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Hyon SH, Martinez-Garbino JA, Benati ML, Lopez-Avellaneda ME, Brozzi NA, Argibay PF. Management of a high-output postoperative enterocutaneous fistula with a vacuum sealing method and continuous enteral nutrition. ASAIO J 2000; 46:511-4. [PMID: 10926156 DOI: 10.1097/00002480-200007000-00028] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
A postoperative enterocutaneous fistula is one of the most complex medical problems. Its treatment may become long-lasting, wearisome, and its outcome often is disappointing. Here, we describe the use of a novel device to treat a 67-year-old patient with a postoperative, high-output enterocutaneous fistula. A semipermeable barrier was created over the fistula by vacuum packing a synthetic, hydrophobic polymer covered with a self-adherent surgical sheet. To set up the system, we constructed a vacuum chamber equipped with precision instruments that supplied subatmospheric pressures between 350 and 450 mm Hg. The intestinal content was, thus, kept inside the lumen, restoring bowel transit and physiology. The fistula output was immediately reduced from a median of 800 ml/day (range, 400-1,600 ml/day), to a median of 10 ml/day (range, 0-250 ml/day), which was readily collected by the apparatus. Oral feeding was reinitiated while both parenteral nutrition and octreotide were withdrawn. No septic complications occurred, and the perifistular skin stayed protected from irritating intestinal effluents. Both the fistula orifice and the wound defect fully healed after 50 days of treatment. We believe this method may serve as a useful tool to treat selected cases of high-output enterocutaneous fistulas without the need for octreotide or parenteral nutrition.
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Affiliation(s)
- S H Hyon
- Department of Surgery, Hospital Italiano de Buenos Aires, Argentina
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Cresci GA, Martindale RG. Metabolic and nutritional management of a patient with multiple enterocutaneous fistulas. Nutrition 1997; 13:446-8; discussion 448-9. [PMID: 9225338 DOI: 10.1016/s0899-9007(97)00094-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- G A Cresci
- Department of Surgery, Medical College of Georgia, Augusta 30912-4004, USA
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Invited commentary. World J Surg 1995. [DOI: 10.1007/bf00299183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Abstract
This chapter reviews the therapeutic use of octreotide in a variety of pancreatic disorders, including acute pancreatitis, in the prevention of postoperative and post-ERCP pancreatitis, in the control of postoperative pancreatic fistulae, and in chronic pancreatitis for the control of pain and of pseudocysts and ascites. The review also discusses the use of octreotide in intestinal disorders of motility, gastrointestinal bleeding, intestinal fistulae and refractory diarrhoea, including the diarrhoeas of AIDS, diabetes, short gut, chemotherapy, ileostomy and gastric surgery. The use of octreotide in neuroendocrine tumours, both for therapy and diagnostic imaging, is reviewed briefly. The paucity of adequately controlled studies in many of these situations is indicated and the potential usefulness of octreotide estimated.
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Affiliation(s)
- P N Maton
- Oklahoma Foundation for Digestive Research, OK City 73104
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