Basic characteristics of included studies
| Study | Country | Design | ExoPI diagnostic method/definition | Pancreatic disease/disorder | Main surgical procedure | Total no. of patients (ExoPI event/no ExoPI event) | Age, mean ± SD, yr |
|---|---|---|---|---|---|---|---|
| Ke et al.,11 2018 | China | RCS | ExoPI defined as fecal elastase level < 200 μg/g, or presence of steatorrhea, or need for pancreatic enzyme replacement therapy (> 1-yr history; overt steatorrhea without treatment). | Chronic pancreatitis | PD, PPPD, Beger procedure, Berne procedure, Frey procedure, Partington–Rochelle procedure | 297 (36/58) | 47.00 ± 12.40 |
| Hallac et al.,5 2020 | USA | PCS | De novo postoperative ExoPI defined as development of symptoms (steatorrhea, bloating, colicky abdominal pain, weight loss) after resection, and commencement of pancreatic enzyme replacement therapy leading to resolution of symptoms. | Chronic pancreatitis, IPMN, MCN, paraganglioma, PDAC, PNET, SPEN | DP | 324 (38/264) | 60.60 ± 13.40 |
| Hirono et al.,12 2015 | Japan | PCS | Exocrine function evaluated with 13C-labelled mixed triglyceride breath test. ExoPI defined as cumulative dosage of 13CO2 at 7 h < 5%, calculated from time course of 13CO2 excretion. | Chronic pancreatitis, pancreatic cancer, bile duct cancer, IPMN, PNET, SPEN, gallbladder cancer, duodenal cancer, metastatic pancreatic cancer, SCN, stomach cancer, malignant lymphoma, bile duct dysplasia | PD, PPPD, PrPD | 189 (92/97) | 65.85 ± 11.22 |
| Kusakabe et al.,13 2019 | USA | BCS | ExoPI defined as need for new pharmacologic intervention in form of supplemental pancreatic enzymes in patients with excessive gas, bloating and steatorrhea on clinical judgment. | Chronic pancreatitis, malignant tumour, benign tumour | PD, DP | 1717 (622/1095) | 62.62 ± 12.79 |
| Riediger et al.,14 2007 | Germany | PCS | ExoPI defined as presence of steatorrhea and/or need for oral pancreatic enzyme supplementation without any routine measurements of exocrine function parameters (e.g., stool elastase level). | Chronic pancreatitis | PD, DPPHR, DP | 224 (75/149) | 44.58 ± 9.38 |
| Mackay et al.,15 2018 | The Netherlands | RCS | ExoPI defined as presence of steatorrhea and/or pancreatic enzyme supplementation at least 1 mo after (partial) pancreatic resection or enucleation. | NF-pNET, insulinoma, gastrinoma, glucagonoma, vipoma | PD, enucleation, central pancreatectomy, DP, central and distal pancreatectomy, total pancreatectomy | 112 (51/53) | 53.90 ± 12.40 |
| Nordback et al.,16 2007 | Finland | PCS | Pancreatic exocrine function measured by fecal elastase-1 assay with ELISA; ExoPI considered to be present if fecal elastase-1 concentration ≤ 200 μg/g | Chronic pancreatitis, PDAC, bile ductal adenocarcinoma, duodenal adenocarcinoma in papilla, pancreatic islet cell carcinoma, mucinous cystadenoma, serous cystadenoma | PrPD, PD with antrectomy, Beger procedure | 26 (26/0) | 62.00 ± 11.75 |
| Falconi et al.,17 2008 | Italy | PCS | ExoPI defined as presence of steatorrhea and weight loss, and positive result of 72-h stool chymotrypsin test (< 6 U/g) in absence of tumour recurrence. | Ampullary adenoma, serous cystadenoma, mucinous cystadenoma, IPMN, SPEN, endocrine and other neoplasms | PD, AR, LP | 162 (26/109) | 51.37 ± 19.56 |
| Rault et al.,18 2005 | France | PCS | Clinical steatorrhea defined as > 3 stools/d, > 200 g/d fecal output for ≥ 3 consecutive d, nauseating smell, pale or yellow stools, and appearance of stools as pasty or greasy. | Pancreatic neoplasm | PD | 52 (22/30) | 59.63 ± 11.51 |
| Nakamura et al.,19 2009 | Japan | PCS | Exocrine function evaluated by 13C-labelled mixed triglyceride breath test. ExoPI defined as cumulative dosage of 13CO2 at 7 h < 5%, calculated from time course of 13CO2 excretion. | IPMN, ampullary carcinoma, pancreatic carcinoma, distal cholangioma, carcinoma of gallbladder, SCN/MCN | PPPD, PD with antrectomy | 61 (38/23) | 67.47 ± 10.53 |
| Neophytou et al.,4 2018 | France | PCS | ExoPI defined as new onset of steatorrhea ≥ 3 times/d, 3 d/wk, with weight loss or malabsorption signs, excluding other causes or pharmacologic requirement of pancreatic enzymes that persists beyond discharge after initial surgery. | Adenoma, cyst, endocrine tumour, IPMN, pancreatic hamartoma, SPEN | PD, LP, enucleation | 92 (54/38) | 58.52 ± 14.03 |
| Okano et al.,20 2016 | Japan | RCS | Exocrine function evaluated by 13C-labelled mixed triglyceride breath test. ExoPI defined as cumulative dosage of 13CO2 at 7 h < 5%, calculated from time course of 13CO2 excretion. | Chronic pancreatitis, pancreatic carcinoma, IPMN, ampullary carcinoma, distal cholangioma, MCN, SPEN | PD, LP | 227 (128/99) | 65.91 ± 13.69 |
| Maignan et al.,21 2018 | France | PCS | ExoPI defined as fecal elastase level < 200 g per gram of stool. | Adenocarcinoma, IPMN, ampulloma, degenerated ampulloma, SPEN, endocrine tumour, cholangiocarcinoma, benign tumour | PD, LP, Whipple procedure, pyloric preservation | 91 (63/20) | 64.53 ± 13.40 |
| Kachare et al.,22 2014 | USA | PCS | ExoPI defined as any subjective symptoms of steatorrhea, postprandial abdominal pain, unexplained weight loss and diarrhea that improve with enzyme replacement therapy or reappear with cessation of enzyme replacement therapy. | Chronic pancreatitis, pancreatic adenocarcinoma, pancreatic neuroendocrine carcinoma, benign pancreatic tumour, ampullary tumour, duodenal mass, metastatic disease, cholangiocarcinoma, accessory spleen | Whipple procedure, DPS | 161 (44/117) | 64.10 ± 12.65 |
| Lim et al.,23 2016 | USA | PCS | ExoPI defined as need for new pharmacologic intervention such as pancreatic enzyme replacement therapy. | Benign neoplasm (e.g., IPMN, serous cystadenoma, mucinous cystadenoma, GIST) and malignant neoplasm (PDAC, ampullary adenocarcinoma, neuroendocrine carcinoma, cholangiocarcinoma, duodenal adenocarcinoma, metastasis) | PD, DP, enucleation | 227 (94/120) | 62.00 ± 11.00 |
| Miyamoto et al.,24 2020 | Japan | RCS | NA | PDAC | DP | 61 (23/38) | 62.10 ± 11.80 |
| Sikkens et al.,3 2014 | The Netherlands | PCS | ExoPI defined as fecal elastase-1 level < 0.2 μg per gram of feces. | Pancreatic cancer, ampullary carcinoma, bile duct carcinoma | PD, DP | 29 (24/5) | 60.70 ± 12.10 |
| Yuasa et al.,2 2012 | Japan | Cross-sectional | Exocrine function evaluated with 13C-labelled mixed triglyceride breath test. ExoPI defined as cumulative dosage of 13CO2 at 7 h < 5%, calculated from time course of 13CO2 excretion. | Chronic pancreatitis, IPMN, pancreatic carcinoma, ampullary carcinoma, distal cholangiocarcinoma, SCN/ MCN | PD, DP | 110 (60/45) | 66.70 ± 11.10 |
| Belyaev et al.,25 2013 | Germany | RCS | ExoPI defined as fecal elastase-1 level < 200 μg per gram of feces and/or serum β-carotene level < 50 μg/dL. | Chronic pancreatitis, pancreatic malignant tumour, benign lesion | PD, DP, total pancreatectomy | 221 (102/119) | 60.50 ± 11.90 |
| Jang et al.,26 2002 | South Korea | Cross-sectional | ExoPI defined as fecal elastase-1 level ≤ 200 μg/g. | Bile duct cancer, ampulla of Vater cancer, pancreas head cancer | PD | 34 (33/1) | 57.80 ± 11.25 |
AR = atypical resection; BCS = bidirectional cohort study; DP = distal pancreatectomy; DPPHR = duodenum-preserving pancreatic head resection; DPS = distal pancreatectomy with splenectomy; ELISA = enzyme-linked immunosorbent assay; ExoPI = exocrine pancreatic insufficiency; GIST = gastrointestinal stromal tumour; IPMN = intraductal papillary mucinous neoplasm; LP = left pancreatectomy; MCN = mucinous cystic neoplasm; NA = not available; NF-pNET = nonfunctional pancreatic neuroendocrine tumour; PCS = prospective cohort study; PD = pancreaticoduodenectomy; PDAC = pancreatic ductal adenocarcinoma; PNET = primitive neuroectodermal tumour; PPPD = pylorus-preserving pancreaticoduodenectomy; PrPD = pylorus-resecting pancreaticoduodenectomy; RCS = retrospective cohort study; SCN = serous cystic neoplasm; SD = standard deviation; SPEN = solid pseudopapillary epithelial neoplasm.