The Impact of Pancreatic Resection on Exocrine Homeostasis

Patients undergoing pancreatic resection are at risk for developing postoperative exocrine dysfunction. We sought to determine the incidence of and clinical factors associated with exocrine dysfunction after pancreatectomy. A retrospective review of a prospective database composed of patients undergoing pancreatic resection between 2004 and 2013 was performed. Logistic regression was used to identify preoperative factors that influenced postoperative exocrine insufficiency. One hundred sixty-one patients with complete follow-up were identified. The mean age was 64.1 ± 12.65 years. The majority were: female (51%), white (66%), tobacco users (61%), nondrinkers (68%), nondiabetic (71%), and without preoperative exocrine dysfunction (96%). Average body mass index was 27.8 ± 6.32 kg/m2. Most underwent a pancreaticoduodenectomy (67.3%) for pancreatic cancer (59.6%). Pancreatic fistula occurred in 6.8 per cent. Seven patients were on enzyme replacement therapy preoperatively. Forty-four patients (27%) had postoperative exocrine dysfunction (five of whom were on enzyme replacement therapy preoperatively). Two of seven (29%) of patients with preoperative exocrine dysfunction had complete resolution of their exocrine dysfunction. On univariate analysis, only the type of operation (Whipple) was significantly associated with exocrine dysfunction ( P = 0.04). On multivariate analysis, both female gender and type of operation were independently associated with postoperative exocrine dysfunction ( P = 0.05). Pancreatic exocrine dysfunction occurred less frequently in this population than what is commonly reported in the literature. Female patients undergoing resection of the pancreatic head have significantly increased risk of exocrine dysfunction.

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Pancreatic Exocrine Insufficiency as a Complication of Gastrointestinal Surgery and the Impact of Pancreatic Enzyme Replacement Therapy

Digestive Diseases ◽

10.1159/000501675 ◽

2019 ◽

Vol 38 (1) ◽

pp. 53-68 ◽

Cited By ~ 6

Author(s):

Adarsh Chaudhary ◽

J. Enrique Domínguez-Muñoz ◽

Peter Layer ◽

Markus M. Lerch

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pancreatic Enzyme ◽

Pancreatic Exocrine Insufficiency ◽

Exocrine Insufficiency ◽

Metabolic Complications ◽

Enzyme Replacement ◽

Pancreatic Enzyme Replacement Therapy ◽

Pancreatic Exocrine ◽

The Impact

Background: Pancreatic exocrine insufficiency (PEI) is characterized by inadequate production, insufficient secretion, and/or inactivation of pancreatic enzymes, resulting in maldigestion. The aim of this review was to analyze the prevalence and pathophysiology of PEI resulting from gastrointestinal (GI) surgery and to examine the use of pancreatic enzyme replacement therapy (PERT) for effectively managing PEI. Summary: A targeted PubMed search was conducted for studies examining the prevalence and pathophysiology of PEI in patients following GI surgery and for studies assessing the effects of PERT in these patients. PEI is a common complication following GI surgery that can lead to nutritional deficiencies, which may contribute to morbidity and mortality in patients. Timely treatment of PEI with PERT can prevent malnutrition, increase quality of life, and possibly reduce the associated mortality. Treatment of PEI should aim not only to alleviate symptoms but also to achieve significant improvements in nutritional parameters. Dose optimization of PERT is required for effective management of PEI, in addition to regular assessment of nutritional status, appropriate patient education, and reassessment if symptoms return. Key Messages: Difficulties in detecting PEI following GI surgery can result in undiagnosed and untreated maldigestion, leading to metabolic complications and increased morbidity. Both are preventable by early administration and monitoring for optimal doses of PERT.

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Nutritional Therapy, Pancreatic Exocrine Insufficiency, and Pancreatic Enzyme Replacement Therapy in Cystic Fibrosis

Clinical Pancreatology for Practising Gastroenterologists and Surgeons ◽

10.1002/9781119570097.ch48 ◽

2021 ◽

pp. 379-387

Author(s):

Jefferson N. Brownell ◽

Laura Padula ◽

Elizabeth Reid ◽

Virginia A. Stallings ◽

Asim Maqbool

Keyword(s):

Cystic Fibrosis ◽

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pancreatic Enzyme ◽

Nutritional Therapy ◽

Pancreatic Exocrine Insufficiency ◽

Exocrine Insufficiency ◽

Enzyme Replacement ◽

Pancreatic Enzyme Replacement Therapy ◽

Pancreatic Exocrine

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Enzyme replacement therapy in mice lacking arylsulfatase B targets bone-remodeling cells, but not chondrocytes

Human Molecular Genetics ◽

10.1093/hmg/ddaa006 ◽

2020 ◽

Vol 29 (5) ◽

pp. 803-816 ◽

Cited By ~ 1

Author(s):

Gretl Hendrickx ◽

Tatyana Danyukova ◽

Anke Baranowsky ◽

Tim Rolvien ◽

Alexandra Angermann ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Bone Remodeling ◽

Cell Types ◽

Skeletal Growth ◽

Enzyme Replacement ◽

Mps Vi ◽

Arylsulfatase B ◽

The Impact ◽

Deficient Mice

Abstract Mucopolysaccharidosis type VI (MPS-VI), caused by mutational inactivation of the glycosaminoglycan-degrading enzyme arylsulfatase B (Arsb), is a lysosomal storage disorder primarily affecting the skeleton. We have previously reported that Arsb-deficient mice display high trabecular bone mass and impaired skeletal growth. In the present study, we treated them by weekly injection of recombinant human ARSB (rhARSB) to analyze the impact of enzyme replacement therapy (ERT) on skeletal growth and bone remodeling. We found that all bone-remodeling abnormalities of Arsb-deficient mice were prevented by ERT, whereas chondrocyte defects were not. Likewise, histologic analysis of the surgically removed femoral head from an ERT-treated MPS-VI patient revealed that only chondrocytes were pathologically affected. Remarkably, a side-by-side comparison with other cell types demonstrated that chondrocytes have substantially reduced capacity to endocytose rhARSB, together with low expression of the mannose receptor. We finally took advantage of Arsb-deficient mice to establish quantification of chondroitin sulfation for treatment monitoring. Our data demonstrate that bone-remodeling cell types are accessible to systemically delivered rhARSB, whereas the uptake into chondrocytes is inefficient.

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Pancreatic Enzyme Replacement Therapy in Pancreatic Cancer

Cancers ◽

10.3390/cancers12020275 ◽

2020 ◽

Vol 12 (2) ◽

pp. 275 ◽

Cited By ~ 6

Author(s):

Raffaele Pezzilli ◽

Riccardo Caccialanza ◽

Gabriele Capurso ◽

Oronzo Brunetti ◽

Michele Milella ◽

...

Keyword(s):

Pancreatic Cancer ◽

Weight Loss ◽

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pancreatic Enzyme ◽

Exocrine Insufficiency ◽

Enzyme Replacement ◽

Pancreatic Enzyme Replacement Therapy ◽

Literature Evidence ◽

Industrialised Countries

Pancreatic cancer is an aggressive malignancy and the seventh leading cause of global cancer deaths in industrialised countries. More than 80% of patients suffer from significant weight loss at diagnosis and over time tend to develop severe cachexia. A major cause of weight loss is malnutrition. Patients may experience pancreatic exocrine insufficiency (PEI) before diagnosis, during nonsurgical treatment, and/or following surgery. PEI is difficult to diagnose because testing is cumbersome. Consequently, PEI is often detected clinically, especially in non-specialised centres, and treated empirically. In this position paper, we review the current literature on nutritional support and pancreatic enzyme replacement therapy (PERT) in patients with operable and non-operable pancreatic cancer. To increase awareness on the importance of PERT in pancreatic patients, we provide recommendations based on literature evidence, and when data were lacking, based on our own clinical experience.

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P0067PREDICTORS OF LONG-TERM OUTCOME IN A SPANISH COHORT OF PATIENTS WITH FABRY DISEASE ON ENZYME REPLACEMENT THERAPY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0067 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Marian Goicoechea ◽

Francisco Gomez-Preciado ◽

Silvia Benito ◽

Joan Torras ◽

Roser Torra ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Fabry Disease ◽

Replacement Therapy ◽

Left Ventricular ◽

Response To Therapy ◽

Clinical Event ◽

Enzyme Replacement ◽

Clinical Events ◽

The Impact

Abstract Background and Aims Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in Fabry disease patients on ERT. Method Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). Results In 69 patients (42 males, 27 females, mean age 44.6 ±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242 to 128 mg/g (p = 0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR ≤60 ml/min/1.73 m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043), being these differences more relevant in females (log Rank 18.514, p<0.001) than males (logRank: 3.442, p=0.064). Lower baseline eGFR was associated with a 3- to 7-fold increase in the risk of clinical events in different Cox models. Conclusion GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes. For the first time, we show that initiation of ERT in women before renal function deteriorates has a similar or even larger impact as in Fabry males to prevent clinical events.

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Changing Patterns of Mortality in Gaucher Disease Prior to and Following the Advent of Enzyme Replacement Therapy.

Blood ◽

10.1182/blood.v104.11.3799.3799 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3799-3799

Author(s):

Neal J. Weinreb ◽

Robert E. Lee

Keyword(s):

Cardiovascular Disease ◽

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Cause Of Death ◽

Gaucher Disease ◽

Age At Death ◽

Enzyme Replacement ◽

Number Of Patients ◽

Changing Patterns ◽

The Impact

Abstract Enzyme replacement therapy (ERT) with exogenous glucosylceramide β-glucosidase (alglucerase, [Ceredase®] or imiglucerase, [Cerezyme®]) has been shown to improve anemia, thrombocytopenia, hepatosplenomegaly, bone symptoms and quality of life in patients with Gaucher disease. However, the impact of ERT on mortality has not been assessed since the inception of ERT in 1991. Data from the epoch prior to the availability of ERT were obtained from the University of Pittsburgh Gaucher Disease Registry. Data from the time period following the advent of ERT were obtained from the International Collaborative Gaucher Group (ICGG) Gaucher Registry and the Ceredase/Cerezyme pharmacovigilance database (Genzyme Corporation). Age of death was obtained for patients with reported Type 1 (non-neuronopathic) Gaucher disease. Only patients with a known cause of death were included in this analysis. Pre-ERT Era (R.E.L.) Post-ERT Era Number of patients 31 137 Treated with ERT No Yes Mean age at death (years) 53.2 55.6 Range of age at death (years) 3–85 0.2–89 Cause of death due to: n % n % • Gaucher disease 4 12.9% 1 0.7% • Leukemia 3 9.7% 7 5.1% • Lymphoma 1 3.2% 3 2.2% • Myeloma 3 9.7% 1 0.7% • Solid tumor 12 38.7% 17 12.4% • Hemorrhage 1 3.2% 14 10.2% • Thromboembolism 0 0.0% 4 2.9% • Other cardiovascular disease 2 6.5% 26 19.0% • Infectious disease 3 9.7% 6 10.9% • Other causes 2 6.5% 49 35.8% These descriptive data collected prior to the advent of ERT and following approval of ERT in 1991 raise intriguing questions about the changing pattern of mortality in Gaucher disease. Any direct comparison of these populations must be qualified by the possibility of detection bias or a cohort effect. Therefore, pending further information, it is difficult to attribute significance to the difference in mean age at death between the two populations. However, there have been shifts in the pattern of the causes of death. Most notably, deaths due to the primary manifestations of Gaucher disease and to hematologic cancers and solid tumors appear substantially less common in the post-ERT era whereas the proportion of deaths due to cardiovascular disease and other causes appears to be increasing. More accurate estimates of the patterns of mortality in Gaucher disease remain to be determined, particularly for the pre-ERT era. Additional studies of the changing patterns of mortality in Gaucher disease are ongoing.

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