Benign cystic neoplasm and endocrine tumours of the pancreas – When and how to operate – An overview

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Review

Benign cystic neoplasm and endocrine tumours of the pancreas e When and how to operate e An overview Q7

H.G. Beger a, *, B. Poch b, C. Vasilescu c a

Department of General- and Visceral Surgery, c/o University of Ulm, Ulm, Germany Center of Oncologic, Endocrine and Minimal Invasive Surgery, Donouklinikum Neu-Ulm, Germany c Department of General Surgery and Liver Transplantation, Fundei Clinical Institute, Bucharest, Romania b

a r t i c l e i n f o

a b s t r a c t

Article history: Received 20 March 2014 Accepted 31 March 2014 Available online xxx

Background: The recent evolution of limited local operative procedures for benign pancreatic lesions shifted surgical treatment options to the application of local techniques, although major resections of pancreatic head and left resection are still the standard. Objectives: To evaluate the level of evidence of tumour enucleation (EN), pancreatic middle segment resection (PMSR) and duodenum preserving total/subtotal pancreatic head resection (DPPHRt/s), we focus based on present knowledge on indication to surgical treatment evaluating the questions, when and how to operate. Results: Tumour enucleation is recommended for all symptomatic neuro-endocrine tumours with size up to 2e3 cm and non-adherence to pancreatic main-ducts. EN has been applied predominantly in neuro-endocrine tumours and less frequently in cystic neoplasms. 20% of enucleation are performed as minimal invasive laparascopic procedure. Surgery related severe post-operative complications with the need of re-intervention are observed in about 11%, pancreatic fistula in 33%. The major advantage of EN are low procedure related early post-operative morbidity and a very low hospital mortality. PMSR is applied in two thirds for symptomatic cystic neoplasm and in one third for neuro-endocrine tumours. The high level of 33% pancreatic fistula and severe post-operative complications of 18% is related to management of proximal pancreatic stump. DPPHRt/s is used in 70% for symptomatic cystic neoplasms, for lesions with risk for malignancy and in less than 10% for neuro-endocrine tumours. DPPHRt with segment resection of peripapillary duodenum and intra-pancreatic common bile duct has been applied in one third of patients and in two thirds by complete preservation of duodenum and common bile duct. The level of evidence for EN and PMSR is low because of retrospective data evaluation and absence of RCT results. For DPPHR, 7 prospective, controlled studies underline the advantages compared to partial pancreaticoduodenectomy. Conclusion: The application of tumour enucleation, pancreatic middle segment resection and duodenum preserving subtotal or total pancreatic head resection are associated with low level surgery related early post-operative complications and a very low hospital mortality. The major advantage of the limited procedures is preservation of exo- and endocrine pancreatic functions. Ó 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Keywords: Cystic neoplasm Endocrine tumours of the pancreas Enucleation Pancreatic middle segment resection Duodenum preserving total pancreatic head resection

1. Introduction The most frequent benign lesions of the pancreas are cystic neoplasms and endocrine tumours [1,2]. Of cystic neoplasms frequent are intra-ductal papillary mucinous neoplasms (IPMN), mucinous cystic tumours (MCN) and serous cyst adenomas (SCA). Insulinoma are the predominant neuro-endocrine tumour [3]. Up to 50% of the reported benign lesions are clinically asymptomatic * Corresponding author. E-mail address: [email protected] (H.G. Beger).

detected by chance due frequent use of MD-CT, MRI, PET and EUS investigations of the abdomen. Patients who complain episodes of upper abdominal discomfort or have continuing clinical symptoms in association with a cystic neoplastic lesion or neuro-endocrine tumour are candidates for surgical treatment. In primary asymptomatic patients with yet undetermined risk for developing symptoms has been advocated to change to surgical treatment based on the size of the lesion and tumour growth [4]. Neuro-endocrine lesions (PNETs) are 10% of all benign tumorous lesions of the pancreas. Hormonal inactive and hormonal active PNETs develop from cellular compartment of islet cell parenchyma

http://dx.doi.org/10.1016/j.ijsu.2014.03.020 1743-9191/Ó 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: H.G. Beger, et al., Benign cystic neoplasm and endocrine tumours of the pancreas e When and how to operate e An overview, International Journal of Surgery (2014), http://dx.doi.org/10.1016/j.ijsu.2014.03.020

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which constitutes 2e10% of pancreatic tissue. In contrast to hormonal active PNETs, functional inactive endocrine tumours produce late in the course clinical signs which are mostly unspecific. Besides of well-established radiological investigations and EUS, the measurement of specific hormones in the peripheral blood, the Somatostatin Receptor Scintigraphy and the PET are diagnostic measures which establish in addition to specific hormone determination in blood in most patients the diagnosis, type and location of the tumour. Multifocality of PNETs is well-known particularly in case of hereditary syndromes like MEN-1. After performing a selective literature review, we focus in the following on the current knowledge about indication to surgical treatment and the present experience applying limited surgical techniques for benign cystic neoplasms and endocrine tumours. Based on recently published data of a systemic review and metaanalysis about use of tumour enucleation (EN), pancreatic middle segment resection (PMSR) and duodenum preserving total and subtotal pancreatic head resection (DPPHRt/s) for benign tumours, data of early and late post-operative outcome are specifically discussed [5,6]. 2. Natural history and treatment options of cystic neoplasm and endocrine tumours 2.1. Cystic neoplasm The natural clinical course of cystic neoplasm of the pancreas is incompletely understood. IPMN lesions of main duct (MD-IPMN), branch duct (BD-IPMN) and mixed type have variable clinical features and different risks for a malignant transformation. MD-IPMN are predominantly found in men and localised in pancreatic head. A transformation of benign adenoma to a cancerous process is observed in up to 70%. In BD-IPMN cancer has been found in up to 35%. The five year risk of developing an invasive cancer for MDIPMN is calculated on basis of the present data being 63%, for BDIPMN 15% [7]. High-grade dysplasias are detected in MD-IPMN in up to 62%; a carcinoma in situ, respectively an invasive carcinoma in operative specimens are found in up to 45% (Table 1). In small BDIPMN, which are Sendai negative, a cancerous process in surgical specimens found in up to 25% [19]. IPMN lesions show related to histologic subtype’s expression of mucine patterns. The intestinal sub-type contains MUC2 þ MUC5AC und CDX2, whereas the pancreato-biliary subtype is characterised by MUC1 and MUC5AC positivity but negativity for MUC2 and CDX2. The gastric-foveola histological type of IPMN shows positivity of MUC5AC but negativity for MUC1, MUC2 and CDX2 [20e22]. MCN lesions are predominant in female patients located frequently in body and tail of the pancreas. The differentiation of MCN from IPMN is based on multi-slice CT and MRT, but excluding a malignant process by imaging tools only is difficult [23]. MCN lesions are surrounded by a common capsula with a thick wall. Histologically, the diagnosis of MCN is established by presence of ovarian type stroma. The clinical feature of MCN differs whether they belong to the sub-group of mucinous cyst-adenoma or non-

Fig. 1. Main duct IPMN EM. 70 years, localised pancreatic head, max. diameter 4.8 cm, mural nodule in cystic cavity; Histology: carcinoma in-situ.

invasive, proliferative MCN lesion with dysplasia or mucinous cyst adeno-carcinoma. Mucinous cyst adenomas are 60% and noninvasive, proliferative MCNs 30% of all MCNs [24]. Serous cyst adenomas are clinically not a rare entity; they develop in different pathomorphological features: multiple microcystic adenomas, single macro-cystic lesions with multiple craplike structures and macro-cystic tumours with one single cavity [13]. SCA appear more frequently in the body and tail and are detected most frequently in female patients. SCA are considered to be rarely linked to malignancy. A malignant SCA and SCA in association with a remote ductal pancreatic cancer has been reported from several centres. Generally a malignant potential of SCA is considered to be low [2]. Solid pseudo-papillary neoplasms (SPN) develop almost exclusively in female patients in middle ages below 50 years. An advanced cancer is found in resected solid pseudopapillary tumours in up to 22% [26,27]. 2.2. Neuro-endocrine tumours Neuro-endocrine tumours of the pancreas are increasingly detected; the average size is 2e3 cm. However, tumour size below 1 cm in operative specimens are not rare. Up to 70% of all PNET’s are insulinoma which show most frequently functional activity. Insulinoma are in 90% benign, independently of the degree of clinical symptoms. Functional inactive are 30e50% of all PNET’s, usually late detected in clinical course. All gastroentero-pancreatic neuro-endocrine tumours are considered to be potentially malignant [28]. The risk of malignancy of tumours less than 2 cm in size, who show low degree of proliferation and have tumour marker Ki67/MIB1 positivity index of <3% and are not angio-invasive have a benign clinical course. PNET’s, which are histologically well-differentiated, but associated by a Ki67/MIB1 positivity index between 3 and 20% are considered having a distinct high risk for malignancy [29,30]. The vast majority of gastrinoma, glucagonoma, vipoma and ACTH-PNET’s are malignant. 6e7% of all PNET’s are low differentiated neuro-endocrine cancers [31].

Table 1 Risk of malignancy in cystic neoplastic lesions of the pancreas.

SCA IPMN-MD IPMN-BD MCN SPN

Q4,5

Tumour size borderline

High grade dysplasia

Carcinoma in-situ invasive carcinoma

Risk of cancer

>4 >3 >5 >4 >4

5.1% 57e62% 11% [17] 13.4% [11,12]

1.2% [13] 43e45% [10] 15% [16] 25% [19] 36% [12] 17.3% [11,12] 19.2% [26]

1.2%/5.1% [8,9] 63%/5 years [7] 14%/5 years [7] <15% [10]

cm cm cm cm cm

[15] [15] [15] >3 cm [18] [14,26]

Please cite this article in press as: H.G. Beger, et al., Benign cystic neoplasm and endocrine tumours of the pancreas e When and how to operate e An overview, International Journal of Surgery (2014), http://dx.doi.org/10.1016/j.ijsu.2014.03.020

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3. When to operate benign cystic neoplasms and neuroendocrine tumours? According to consensus guidelines of international expert meetings published 2006 and 2012 symptomatic and asymptomatic patients with MD-IPMN should have operative treatment in any case when they are surgically fit (Fig. 1) [10,32]. For BD-IPMN, surgery is recommended if tumour size is above 4e5 cm or the cyst present signs of malignancy; but tumour size maybe a misleading criteria for surveillance as recently has been shown [19] (Table 2). Mural nodules, pancreatic main duct dilation above >5e 9 mm, wall thickening, rapid tumour growth are signs of a malignant transformation and are indicators to change from surveillance to surgery [10,32]. Solid mass in a cystic lesion is associated with advanced IPMN cancer. Multifocality of IPMN lesions has become increasingly important for decision making in symptomatic patients. The incidence of synchronus and metachronus multifocal IPMNs are observed in up to 28% [33]. Branch duct-IPMNs have a higher risk of multifocality as main-duct IPMN (see Table 3). Surveillance of asymptomatic cystic neoplasms is recommended for branch duct IPMN tumours of a size up to 3 cm. The surveillance programme is based on use of MRT yearly for tumours below 2 cm in max. diameter; above 2 cm additionally multi-slice CT are indicated. In case of rapid tumour growth or development of mural nodules an EUS with fine needle aspiration is recommended to exclude development of a cancerous process. The risk of malignant transformation is high in MD-IPMN and lower in branch duct IPMN. The borderline tumour size for MCN is considered to be 5 cm in terms of decision making. Observation of asymptomatic serous cyst adenomas is recommended up to tumour size of 4 cm by yearly investigations. In serous pseudo-papillary neoplasia, carcinoma are found in 19% of resected tumours. Surgical treatment has been established for all patients suffering SPN because resection results in cure of patients.

3.1. Endocrine tumours Candidates for surgical treatment are patients with endocrine tumours who are clinically active lesions; asymptomatic PNETs below the size of 1 cm are cared by a surveillance programme [30]. Pathomorphologically, endocrine tumours demonstrate occasionally cystic changes, calcifications and intra-lesional bleeding. Most important criteria for decision making are clinical symptoms, tumour size above 2 cm and risk of malignancy. Tumorous lesions below 2 cm in diameter, who have a low proliferation index, are mostly of benign nature; but endocrine neoplasms, showing cellgrading G2 and a proliferation index Ki67/MIB1 >3e20% have a distinctly increased risk of malignancy as it is for PNETs of a tumour size above 2 cm, G1 cell grading and no signs of angioinvasion. PNETs of tumour size below 2 cm, which have histological gradings

Table 2 Indication to surgical treatment in symptomatic and asymptomatic cystic neoplasia of the pancreas. Clinical symptomatic cystsa: Asymptomatic cystsa: IPMN’s Main duct Branch duct MCN’s SCA SPsN

Surgical extirpation for all lesions

Surgery for all lesions Observation, TM > 4e5 cm surgery Surgery for all lesions Observation, cysts >4 cm surgery Surgery for all lesions

Surgery is a cancer preventive treatment. a International Consensus Guidelines, Tanaka et el. Pancreatology; 2006 [32] and 2012 [10].

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Table 3 Tumours of the pancreas, surveillance of asymptomatic lesions. Bd-IPMN:

TM

SCA

TM

<3 cm <1 cm <2e3 cm <4 cm

Observation MRT, MSeCT yearlya MRT/MRCP, MSeCT or EUS þ FNA yearlya Observation MSeCT yearlya

International Consensus Guidelines, Tanaka et al. Pancreatology 2012 [10]. a Change to surgical treatment in case of TM growth, mural nodule, cancer cell positive, CEA increase >200 mg/dL in cystic fluid.

G2 and Ki67/MIB1 index of >20% have a high probability to develop neuro-endocrine cancer [30,32]. Sporadic gastrinoma, glucagonoma and vipoma of the pancreas are, irrespective of tumour size, in >80% malignant lesions. About 10% of sporadic hormone active insulinoma are malignant [34]. MEN1-associated insulinoma show infrequently signs of malignancy. Multifocality of PNETs is observed in MEN1 and VHLsyndrome. 4. Options for surgical treatment of benign cystic neoplasms and endocrine tumours Most surgical institutions worldwide use for cystic lesions in the pancreatic head a KauscheWhipple-type resection; and for a benign cystic lesion in the body and tail of pancreas a spleen preserving left pancreatic resection. But major surgical procedures are burdened by additional sacrifice of normal functional pancreatic and extra-pancreatic tissues and a considerable high level of severe post-operative complications with a substantial risk of mortality. In the late outcome after a Whipple-type resection, procedure related late morbidity show an increase of exocrine insufficiency, a dysfunction of the glucose metabolism, respectively new onset of insuline dependent diabetes mellitus in about 20%. Episodes of cholangitis in the long-term course after a Whipple-type resection are underestimated. The recent evolution of limited surgical procedures established local resective techniques, but they are not yet used as standard surgical treatment modalities for benign pancreatic tumours (Table 4). Tumour enucleation [34], pancreatic middle segment resection [35] and duodenum preserving total or subtotal pancreatic head resection [36] have the potential of a local tumour extirpation associated with low procedure related post-operative morbidity and preservation of the endocrine and exocrine pancreatic functions compared to pre-operative status, respectively to results after standard procedures. 5. Indications and limitation of local surgical procedures for benign tumours of the pancreas 5.1. Tumour enucleation Tumour enucleation has been used predominantly for neuroendocrine tumours of the pancreas. Of 709 patients, who had Table 4 Options for surgical treatment of benign cystic and neuro-endocrine tumours of the pancreas. Limited surgical tumour extirpation  Enucleation  Pancreatic middle segment resection (central pancreatectomy)  Duodenum-preserving total/subtotal pancreatic head resection Presently standard procedures for benign TM’s Pancreatic left resection  spleen preservation Kausch-Whipple resection/Pylorus-preserving (Total duodeno-pancreatectomy  spleen preservation)

Please cite this article in press as: H.G. Beger, et al., Benign cystic neoplasm and endocrine tumours of the pancreas e When and how to operate e An overview, International Journal of Surgery (2014), http://dx.doi.org/10.1016/j.ijsu.2014.03.020

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tumour enucleation between 1991 and 2012 the mean tumours size was 2.4 cm [37e57]. 72% of the patients had enucleation of PNETs and 22% for cystic neoplasms. Besides of the minimal tissue trauma of pancreas, an additional benefit of EN is application of laparoscopic techniques, which has been used in 20% of all patients. 55% of enucleated endocrine tumours are located in pancreatic head, 45% in body and tail (Table 5). The major risk of application of EN technique for benign tumours lies in frequent development of pancreatic fistula above 30%. About half of the patients developed a ISGPF type B and C fistula. Pancreatic fistula grade B and C contribute significantly to postoperative morbidity. Severe post-operative complications as defined by Clavian-Dindo score 3 [59], after EN developed in 11%. The frequency of re-operation after enucleation of 4.7% and rehospitalisation of 11.8% may be related to the severity of type B and C fistula. The limitation of use of enucleation is size of lesion and tumour proximity to pancreatic main duct. In case of tumourwall adherence to pancreatic main duct, injuring of duct increases the risk of development of pancreatic fistula. To avoid duct injuring by enucleation, tumour size above 3 cm is a limiting criteria for application of enucleation technique, particularly in association with a pancreatic main duct dilation (Table 6).

5.2. Pancreatic middle segment resection Pancreatic middle segment resection has been applied in 64% for cystic neoplastic lesions and in 29% for neuro-endocrine tumours according to a systematic review including 826 patients reported between 1993 and 2010 [60e93] (see Table 7). The mean tumour size was 2.9 cm. Pancreatic middle segment resection produces in two resection surfaces of the pancreatic body. Resecting a cystic neoplasm in a size of 5e6 cm, necessitates in most cases additionally a tumour dissection close to walls of retro-pancreatic vessels. Cystic tumours particularly main duct IPMN and MCN are surrounded by a wall of inflammatory tissues, which frequently extends to the splenic vein respectively, splenic artery. Tumour encasement of vessels is associated with increased risk of blood loss during and after operation. The frequency of severe post-operative complications of 18% as well the high frequency of pancreatic fistula of 33% are related to management of the pancreatic stumps. The crucial point of pancreatic middle segment resection is surgical handling of the proximal pancreatic stump (Fig. 2). Whereas the left pancreas is secured by a pancreatico-jejunostomosis or more elegantly by pancreatico-gastrostomosis, the proximal pancreatic stump is mostly handled by simple closure using mechanical devices or by U-suturing of the tissue with isolated closure of the pancreatic main duct. However, simple closure rather causes than prevents local complications like fistula or peri-pancreatic fluid collections. The frequency of post-operative haemorrhage has been

Table 5 Tumour size, location and early post-operative morbidity and mortality after enucleation, pancreatic middle segment resection and duodenum preserving total/ subtotal pancreatic head resection for benign pancreatic tumours. Cystic neoplasm

ENa PMSRb DPPHRt/sc a b c d

21.7% 64% 71.1%

PNETd

72% 28.5% 7.9%

Table 6 Indication and contra-indication to tumour enucleation in cystic neoplasia and endocrine tumours of the pancreas. Indication: Cyst. TM

PNETa

Limitation of EN:

PNET e pancreas neuro-endocrine tumour. PMD e pancreatic main duct. a Kunz PL et al. Consensus guidelines for the management and treatment of neuro-endocrine tumours. Pancreas 2013; 42 : 557e577 [30] Ramage JK et al. Guidelines for the management of gastroenteropancreatic neuro-endocrine tumours. Gut 2005; 54 (IV) IV1-IV16 [117].

observed in 7% and the re-hospitalisation in 14%. The increased risk of severe type pancreatic fistula derived from the proximal pancreatic stump and frequency of haemorrhage contributes to the high level of re-operation and re-admission after pancreatic middle segment resection. Hospital mortality was with 0.8% very low (see Fig. 3). Applying pancreatic middle segment resection for large tumorous lesions of the body of the pancreas necessitating a resection of a pancreatic segment of more than 5e6 cm increases the risk for metabolic dys-functions. After extended middle segment resection of a large pancreatic segment, endocrine insufficiency in the long-term outcome is observed in up to 12% and exocrine insufficiency in about 20% compared to pre-operative levels [94]. For extended cystic neoplasms in the pancreas body a spleen preserving hemipancreatectomy may be an alternative procedure. However, the metabolic exo- and endocrine functions after pancreatic left resection are clinically relevant decreased, whereas the frequency of local complications found lower compared to pancreatic middle segment resection.

Table 7 Indication to duodenum preserving total/subtotal pancreatic head resection for cystic neoplasms and endocrine tumours of the pancreatic head. DPPHR total þ segment duodenum þ CBD

DPPHR total preservation of duodenum and CBD: DPPHR subtotal

Post-operative morbidity Severe complications

POPF

Hospital mortality

10.8% 17.7% 11.5%

33.1% 32.9% 19.9%

1.13% 0.81% 0.49%

Tumour enucleation [38e58]. Pancreatic middle segment resection [60e93]. Duodenum preserving total/subtotal pancreatic head resection [51,97e116]. Pancreatic neuro-endocrine tumours.

Clinical symptomatic cysts <2e3 cm Asymptomatic cysts <2e3 cm, age <50 years TM no abutment to PMD Absence of criteria of malignancy Clinical symptomatic TMs < 2 cm Asymptomatic TMs >1e2 cm Hormone-active TMs <2e3 cm PMD dilation Histo-pathology: high grade dysplasia, carcinoma (Multifocality) TM close proximity to PMD TM-size > 3 cm TM suspected to be invasive cancer

Limitation of DPPHRt

TM abutment to duodenal wall TM involving CBD Ligation of SPGDA þ IPPDA Ischaemia of peripapillary duodenum Cystic neoplasm þ carcinoma in-situ hi-PNEC > 2 cm TM extending to neck of pancreas PNET functional active >2 cm TM not including Duodenum þ CBD TM location in processus uncinatus (uncinetectomy) TM location in neck of pancreas CBD not involved Insulinoma >2 cm located in processus uncinatus Cystic neoplasm and advanced cancer Islet carcinoma TM > 2 cm

DPPHRt e total pancreatic head resection. DPPHRs e subtotal pancreatic head resection. SPGDA e superior posterior gastro-duodenal artery. IPPDA e inferior posterior pancreato-duodenal artery. hi-PNEC e hormone inactive pancreatic neuro-endocrine carcinoma.

Please cite this article in press as: H.G. Beger, et al., Benign cystic neoplasm and endocrine tumours of the pancreas e When and how to operate e An overview, International Journal of Surgery (2014), http://dx.doi.org/10.1016/j.ijsu.2014.03.020

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Fig. 2. Middle segment resection of the pancreatic body with two anastomoses. Ductto-duct anastomosis.

5.3. Duodenum preserving total/subtotal pancreatic head resection For benign tumours of the pancreatic head a total and subtotal head resection has been introduced in clinical practice between 1985 [95] and 1994 [96]. Location of the tumour within pancreatic head and size of lesion determine the use of a subtotal or total head resection. The surgical experience using duodenum preserving total pancreatic head resection is up to now limited [97e107]. Advantages are underlined by 7 prospective and controlled clinical trials, comparing duodenum preserving total pancreatic head resection with Whipple-type pancreatico-duodenectomy. Out of 405 patients reported between 1995 and 2003, one third had a total pancreatic head resection including peripapillary segment of duodenum and intra-pancreatic common bile duct. One third of patients experienced total head extirpation, but preservation of duodenum and common bile duct (Fig. 4a,b), one third had a subtotal resection conserving pancreatic tissue between intrapancreatic common bile duct and wall of duodenum as well tissue of the uncinate process (Fig. 5a,b). Surgical techniques of total head resection, with dissection of pancreatic tissue from peripapillary duodenum and preserving the posterior and anterior pancreatico-duodenal arcades are well established. Total pancreatic

Fig. 3. Islet cell carcinoma, 3 cm in max. diameter; operative specimen after total pancreatic head resection with segment resection of the duodenum and intrapancreatic common bile duct.

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head resection with segment resection of the peripapillary duodenum requires four anastomoses: end-to-end between proximal and distal duodenum; end-to-side of common bile duct and postpyloric duodenum and end-to-side between preserved pancreatic head or neck and the excluded jejunal loop and a Roux-en-Y anastomosis. The low frequency of re-operation of 1.8%, hospital mortality of 0.5% as well re-hospitalisation of 3.3% and 12.5% of severe early post-operative complications underlines the well standardised techniques of pancreatic head resection. Pancreatic fistula developed in 20% of patients, of them 47% grade B and C fistulas. A major advantage of duodenum preserving total and subtotal pancreatic head resection is preservation of exo- and endocrine functions compared to pre-operative level. In 7 prospective controlled trials comparing a duodenum preserving total head resection with a Whipple-type partial pancreaticoduodenectomy, the metabolic functions after DPPHRt were significant better preserved. An additional advantage of this technique is tailoring of head resection conserving neck of pancreas or uncinate process or parts of dorsal pancreatic head segment. DPPHRt with segment resection of peripapillary duodenum and common bile duct has been additionally applied in cystic neoplastic lesions with a carcinoma in-situ and T1 low risk cancer of the papilla, prepapillary common bile duct and peripapillary duodenal cancer. However, the indication for local, non-invasive cancers are to be proven by prospective controlled trials. 6. Comment Local surgical procedures for benign tumours of the pancreas are evolving operative techniques but presently not surgical standard. The evidence of tumour enucleation and pancreatic middle segment resection is low, because exclusively based on retrospective clinical trials without control groups. Two prospective controlled trials out of more than 30 retrospective studies have been published comparing PMSR with spleen preserving pancreatic left resection in patients suffering chronic pancreatitis but the authors did not include neoplastic tumours. PMSR exhibited advantages in regard to preservation of metabolic functions, but showed a higher level of surgery related early post-operative complications. Duodenum preserving total and subtotal pancreatic head resection is supported by 7 prospective controlled trials comparing early and late results after Whipple resection applied mostly for benign pancreatic head tumours. The controlled trials for DPPHRt/s

Fig. 4. OP situs after total pancreatic head resection with segment resection of peripapillary duodenum and intra-pancreatic common bile duct.

Please cite this article in press as: H.G. Beger, et al., Benign cystic neoplasm and endocrine tumours of the pancreas e When and how to operate e An overview, International Journal of Surgery (2014), http://dx.doi.org/10.1016/j.ijsu.2014.03.020

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oncologic resection with lymph node sampling and tissue resection to achieve an R0 status is recommended (Table 4). 7. Summary For benign cystic neoplasms and endocrine tumours the application of tumour enucleation, pancreatic middle segment resection and duodenum preserving subtotal and total pancreatic head resection offer advantages of a limited pancreatic and extrapancreatic tissue trauma compared to major oncological resection currently used as standard treatment. Tumour enucleation and pancreatic middle segment resection are burdened with a distinct risk of developing pancreatic fistula ISGPF grade B and C, but have advantage of a very low hospital mortality. The clinical evidence of tumour enucleation and pancreatic middle segment resection is low since the present knowledge is based only on retrospective uncontrolled studies. Duodenum preserving subtotal and total pancreatic head resection showed in comparison to a Whipple type head resection significant advantages in regard to maintenance of the exo- and endocrine pancreatic functions in the short- and longterm outcome. Prospective controlled trials are needed for evaluation of the proposed advantages of limited surgical procedures. Uncited reference [25].

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References

Fig. 5. a) Serous cyst adenoma of the uncinate process, 5 cm max. diameter, surgical procedure: sub-total pancreatic head resection, resection of processus uncinatus. b) Resection of cystic neoplasia of uncinate process. Subtotal pancreatic head resection, respective resection of uncinate process with conservation of CBD and periampullary duodenum.

exhibited advantages of a significant lower level of post-operative surgery-related complications, a very low hospital mortality <1% and full conservation of exo- and endocrine pancreatic functions early post-operatively and in late outcome of patients. Additional advantages of the local surgical procedures are application of laparoscopic or robotic techniques which are increasingly used for tumour enucleation. Tailoring extension of tissue resection yields limitation of sacrifice of pancreatic and extrapancreatic tissue. Applying subtotal pancreas head resection by tumour location in the processus uncinatus performing an uncinatectomy or in the dorsal part or neck of pancreas contributes to main goal of avoiding unnecessary sacrifice of pancreatic tissue. Tumour enucleation and pancreatic middle segment resection are burdened by a higher rate of pancreatic fistula above 30%, of them ISGPF B and C of 50%. The development of severe pancreatic fistula and the increased level of post-operative haemorrhage and frequency of re-hospitalisation after EN and PMSR are considered as limitation of use of these local resective techniques. In terms of the younger age of patients suffering cystic neoplasms of SCA and SPN and PNETs, limited surgical procedures are most beneficial because of the very low hospital mortality and full preservation of exo- and endocrine functions of pancreas. In case of advanced cancer developed from cystic neoplasms or invasive endocrine cancers, a standard major

[1] A.J. Megibow, F.P. Lombardo, A. Guarise, et al., Cystic masses: cross-sectional imaging observations and serial follow up, Abdominal Imaging 26 (2001) 640e642. [2] M.T. Barahat, K. Meeran, S.R. Bloom, Neuroendocrine tumors, Endocrinerelated Cancer 11 (2004) 1e18. [3] ThA Broughan, J.D. Leslie, J.M. Soto, R.E. Hermann, Pancreatic islet cell tumor, Surgery 99 (1998) 671e678. [4] B.M. Weinberg, M. Brennan, R. Spiegel, J.S. Tomlinson, J.J. Farrell, Asymptomatic pancreatic cystic neoplasms: maximizing survival and quality of life using Markow-based clinical nomograms, Gastroenterology 138 (2010) 531e540. [5] H.G. Beger, M. Siech, M. Schoenberg, B. Mayer, C. Vasilescu, Limited surgery for benign tumours of the pancreas e a systemic review and meta-analysis, World Journal of Surgery (2013) (submitted for publication). Q1 [6] H.G. Beger, A. Nakao, B. Mayer, B. Poch, Duodenum preserving total and subtotal pancreatic head resection for benign tumours e systematic review and meta-analysis, Surgery (2013) (submitted for publication). [7] P. Levy, V. Jouannad, D. O’Toole, et al., Natural history of intraductal papillary mucinous tumors of the pancreas: actuarial risk of malignancy, Clin. Gastroenterology and Hepatology 4 (2006) 460e468. [8] M.A. Khasab, E.J. Shin, S. Amateau, et al., Tumor size and location correlate with behaviour of pancreatic serous cystic neoplasm, Am J Gastroenterology 106 (2011) 1521e1526. [9] J.F. Tseng, A.L. Warshaw, V. Sahani, et al., Serous cystadenoma of the pancreas: tumor growth rates and recommendations for treatment, Annals of Surgery 242 (2005) 413e419. [10] M. Tanaka, C. Fernandez-del Castillo, V. Adsay, et al., International consensus guidelines 2012 for management of IPMN and MCN of the pancreas, Pancreatology: Official Journal of the International Association of Pancreatology 12 (2012) 183e197. [11] S. Crippa, R. Salvia, A.L. Warshaw, et al., Mucinous cystic neoplasm of the pancreas is not an aggressive entity: lessons from 163 resected patients, Annals of Surgery 247 (2008) 571e579. [12] K. Yamao, A. Yanagisawa, K. Takahashi, et al., Clinicopathological features and prognostics of mucinous cystic neoplasm with ovarian-type stroma, Pancreas 40 (2011) 67e71. [13] W. Kimura, T. Moriya, K. Hanada, et al., Multicenter study of serous cystic neoplams of the Japan Pancreas Society, Pancreas 41 (2012) 380e387. Q2 [14] I. Morikawa, T. Onogawa, S. Maeda, et al., Solid pseudopapillary neoplasms of the pancreas: an 18-year experience at a single Japanese Institution, Surgery Today (2012), http://dx.doi.org/10.1007/3 00595-012-0345-Z. [15] H. Kargozaran, B.S. Vuvu, P. Ray, et al., Invasive IPMN and MCN: same organ, different outcome? Annals of Surgical Oncology (2010) http://dx.doi.org/ 10.1245/s10434-010-1309-4. [16] R. Salvia, Crippa St, M. Falconi, et al., Branch-duct intraductal papillary mucinous neoplasms of the pancreas: to operate or not to operate? Gut 56 (2007) 1086e1090.

Please cite this article in press as: H.G. Beger, et al., Benign cystic neoplasm and endocrine tumours of the pancreas e When and how to operate e An overview, International Journal of Surgery (2014), http://dx.doi.org/10.1016/j.ijsu.2014.03.020

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65

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[17] R. Rohan-Rodriguez, R. Salvia, St Crippa, et al., Branch-duct intraductal papillary mucinous neoplasms: observations in 145 patients who underwent resection, Gastroenterology 133 (2007) 72e79. [18] R.P. Reddy, T.C. Smyrk, M. Zapiach, et al., Pancreatic mucinous cystic neoplasm defined by ovarian stroma: demographics, clinical features and prevalence of cancer, Clinical Gastroenterology and Hepatology: the Official Clinical Practice Journal of the American Gastroenterological Association 2 (2004) 1026e1031. [19] S. Fritz, M. Klauss, F. Bergmann, et al., Small (Sendai negative) branch-duct IPMN’s not harmless, Annals of Surgery 256 (2012) 313e320. [20] W.R. Brugge, G.U. Lanwers, D. Sohani, C. Fernandez-del Castillo, Cystic neoplasms of the pancreas, N Surg J Mod 351 (2004) 1218e1225. [21] N.V. Adsay, K. Marati, A. Audea, F. Sarkar, et al., The dichotomy in the preinvasive neoplasia to invasive carcinoma sequence in the pancreas differential expression of MUC1 and MUC2 supports the existence of two separate pathways of carcinogenetics, Modern Pathology 15 (2002) 1087e 1095. [22] N.V. Adsay, K. Merati, H. Nassar, et al., Pathogeneris of colloid (pure mucinous) carcinoma of exocrine organs, The American Journal of Surgical Pathology 27 (2003) 571e578. [23] C. Correa-Gallego, C.R. Ferrona, S.P. Thoya, et al., Incidental pancreatic cysts: do we really know what we are watching? Pancreatology: Official Journal of the International Association of Pancreatology 10 (2010) 144e150. [24] M.G. Sarr, M. Murr, T.C. Smyrk, et al., Primary cystic neoplasm of the pancreas. Neoplastic disorders of emerging importance e current state-ofthe-art and unanswered questions, Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 7 (2003) 417e428. [25] A. Formentini, D. Birk, M. Siech, et al., Serous cystadenocarcinoma of the pancreas and serous cystadenoma associated with ductal pancreatic adenocarcinoma, HPB Surgery 2 (2000) 41e45. [26] S.G. Tipton, T.C. Smyrk, M.G. Sarr, G.B. Thompson, Malignant potential of solid pseudopapillary neoplasm of the pancreas, The British Journal of Surgery 93 (2006) 733e737. [27] H.L. Huang, S.C. Shih, W.H. Chang, et al., Solid pseudopapillary tumor of the pancreas: clinical experience and literature review, World J Gastroenterology 11 (2005) 1403e1409. [28] M.B. Niederle, M. Hackl, K. Kaserer, et al., Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification, Endocrine-Related Cancer 17 (2010) 909e918. [29] G. Rindi, G. Glöppel, Ansman, et al., TNM staging of frequent (neuro) endocrine tumors: a concensus proposal including a grading system, Virchows Archiv: An International Journal of Pathology 449 (2006) 395e401. [30] P.L. Kunz, D. Reidy-Lagunes, L.B. Anthony, et al., Consensus guidelines for the management and treatment of neuroendocrine tumours, Pancreas 42 (2013) 557e577. [31] G. Rindi, G. Arndold, F.T. Bosman, et al., Nomenclature and classification of neurodendocrine neoplasm of the digestive system, in: Boshan, et al. (Eds.), WHO Classification of Tumours of the Digestive System, IARC Press, Lyon, 2010, pp. 14e15. [32] M. Tanaka, S. Chari, V. Adsay, et al., International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas, Pancreatology: Official Journal of the International Association of Pancreatology (2006) 17e22. [33] H. Mathai, Al Norris, A.C. Tsiatis, et al., Clinicopathological characteristics and molecular analyses of multifocal intraductal papillary mucinous neoplasms of the pancreas, Annals of Surgery 255 (2012) 326e333. [34] C. Donow, M. Pipeleers-Marichal, B. Stamm, et al., Pathologie des Insulinomas und Gastrinoms. Skalisation, Größe, Multizentrizität, Assoziation mit der multiplen endokrinen Neoplasie Tpy T und Malignität, Block Med Wochenzeitschrift 115 (1990) 1386e1391. [35] M.A. Talamini, R. Moesinger, C.J. Yeo, B. Poulose, R.H. Hruban, J.L. Cameron, H.A. Pitt, Cystadenomas of the pancreas: is enucleation an adequate operation? Annals of Surgery 227 (1998) 896e903. [36] C. Iacono, L. Bortolasi, G. Serio, Indications and technique of central pancreatectomyearly and late results, Langenbeck’s Archives of Surgery 390 (3) (2005) 266e271. [37] H.G. Beger, M. Schwarz, B. Poch, How I do it: duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions, Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 16 (2012) 2160e2166. [38] J.M. Kiely, A. Nakeeb, R.A. Komorowski, S.D. Wilson, H.A. Pitt, Cystic pancreatic neoplasms: enucleate or resect? Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 7 (2003) 890e897. [39] J.Y. Mabrut, L. Fernandez-Cruz, J.S. Azagra, C. Bassi, G. Delvaux, J. Weerts, J.M. Fabre, J. Boulez, J. Baulieux, J.L. Peix, J.F. Gigot, Hepatobiliary and Pancreatic Section (HBPS) of the Royal Belgian Society of Surgery, Belgian Group for Endoscopic Surgery (BGES), Club Coelio, Laparoscopic pancreatic resection: results of a multicenter European study of 127 patients, Surgery 137 (2005) 597e605. [40] S. Crippa, C. Bassi, R. Salvia, M. Falconi, G. Butturini, P. Pederzoli, Enucleation of pancreatic neoplasms, The British Journal of Surgery 94 (2007) 1254e 1259.

7

[41] P.A. Vagefi, O. Razo, V. Deshpande, et al., Evolving patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms: the Massachusetts General Hospital experience from 1977 to 2005, Archives of Surgery 142 (2007) 347e354. [42] L. Fernández-Cruz, L. Blanco, R. Cosa, H. Rendón, Is laparoscopic resection adequate in patients with neuroendocrine pancreatic tumors? World Journal of Surgery 32 (2008) 904e917. [43] B. Blanc, A. Sauvanet, A. Couvelard, P. Pessaux, S. Dokmak, M.P. Vullierme, P. Lévy, P. Ruszniewski, J. Belghiti, Limited pancreatic resections for intraductal papillary mucinous neoplasm, Journal de Chirurgie (Paris) 145 (6) (2008) 568e578. [44] S.C. Pitt, H.A. Pitt, M.S. Baker, K. Christians, J.G. Touzios, J.M. Kiely, S.M. Weber, S.D. Wilson, T.J. Howard, M.S. Talamonti, L.F. Rikkers, Small pancreatic and periampullary neuroendocrine tumors: resect or enucleate? Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 13 (2009) 1692e1698. [45] K.Y. Paik, S.H. Choi, Experience of limited pancreatic head resection for management of branch duct intraductal papillary mucinous neoplasm in a single center, World Journal of Gastroenterology: WJG 15 (2009) 2904e 2907. [46] H. Hwang, X. Dong, S.L. Gao, Y.L. Wu, Conservative resection for benign tumors of the proximal pancreas, World Journal of Gastroenterology: WJG 15 (32) (2009) 4044e4048. [47] A. Dedieu, A. Rault, D. Collet, et al., Laparoscopic enucleation of pancreatic neoplasm, Surgical Endoscopy 25 (2) (2011) 572e576. [48] R. Casadei, C. Ricci, D. Rega, M. D’Ambra, R. Pezzilli, P. Tomassetti, D. Campana, F. Nori, F. Minni, Pancreatic endocrine tumors less than 4 cm in diameter: resect or enucleate? A single-center experience, Pancreas 39 (2010) 825e828. [49] C. Ge, X. Luo, X. Chen, K. Guo, Enucleation of pancreatic cystadenomas, Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 14 (2010) 141e147. [50] M. Falconi, A. Zerbi, S. Crippa, et al., Parenchyma-preserving resections for small nonfunctioning pancreatic endocrine tumors, Annals of Surgical Oncology 17 (2010) 1621e1627. [51] S.E. Lee, J.Y. Jang, D.W. Hwang, K.U. Lee, S.W. Kim, Clinical efficacy of organpreserving pancreatectomy for benign or low-grade malignant potential lesion, Journal of Korean Medical Science 25 (2010) 97e103. [52] O. Turrini, C.M. Schmidt, H.A. Pitt, J. Guiramand, J.R. Aguilar-Saavedra, S. Aboudi, K.D. Lillemoe, J.R. Delpero, Side-branch intraductal papillary mucinous neoplasms of the pancreatic head/uncinate: resection or enucleation? Hpb: the Official Journal of the International Hepato Pancreato Biliary Association 13 (2011) 126e131. [53] T. Hackert, J. Werner, M.W. Büchler, Postoperative pancreatic fistula, Surgery 9 (2011) 211e217. [54] C. Brient, N. Regenet, L. Sulpice, L. Brunaud, S. Mucci-Hennekine, N. Carrère, J. Milin, A. Ayav, B. Pradere, A. Hamy, L. Bresler, B. Meunier, E. Mirallié, Risk factors for postoperative pancreatic fistulization subsequent to enucleation, Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 16 (2012) 1883e1887. [55] C.E. Cauley, H.A. Pitt, K.M. Ziegler, A. Nakeeb, C.M. Schmidt, N.J. Zyromski, M.G. House, K.D. Lillemoe, Pancreatic enucleation: improved outcomes compared to resection, Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 16 (2012) 1347e1353. [56] R. Cherif, S. Gaujoux, A. Couvelard, et al., Parenchyma-sparing resections for pancreatic neuroendocrine tumors, Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 16 (2012) 2045e2055. [57] S.M. Inchauste, B.J. Lanier, S.K. Libutti, et al., Rate of clinically significant postoperative pancreatic fistula in pancreatic neuroendocrine tumors, World Journal of Surgery 36 (2012) 1517e1526. [58] T. Zhang, Y. Mu, L. Qu, et al., Accurate combined preoperative localization of insulinomas aid the choice for enucleation: a single institution experience over 25 years, Hepato-Gastroenterology 59 (2012) 1282e1285. [59] P.A. Clavien, J. Borkun, M.L. da Oliveira, et al., The Clavien-Dindo classification of surgical complications: five-year experience, Annals of Surgery 250 (2009) 187e196. [60] N. Rotman, B. Sastre, P.L. Fagniez, Medial pancreatectomy for tumors of the neck of the pancreas, Surgery 113 (5) (1993) 532e535. [61] A.L. Warshaw, D.W. Rattner, C. Fernandez-del Castillo, K. Z’Graggen, Middle segment pancreatectomy: a novel technique for conserving pancreatic tissue, Archives of Surgery 133 (3) (1998) 327e331. [62] C. Partensky, D. Apa, F. Marchal, A. Méziat, F. Berger, Medial pancreatectomy with pancreatogastric anastomosis in pancreatic neoplasms, Chirurgie 123 (4) (1998 Sep) 363e367. [63] G. de Clavière, F. Paye, S. Fteriche, B. Terris, J. Belghiti, A. Sauvanet, Medial pancreatectomy: results of a series of 11 patients, Annales de Chirurgie 127 (1) (2002 Jan) 48e54. [64] A. Sauvanet, C. Partensky, B. Sastre, J.F. Gigot, P.L. Fagniez, J.J. Tuech, B. Millat, S. Berdah, B. Dousset, D. Jaeck, Y.P. Le Treut, C. Letoublon, Medial pancreatectomy: a multiinstitutional retrospective study of 53 patients by the French Pancreas Club, Surgery 132 (5) (2002) 836e843. [65] G. Balzano, A. Zerbi, P. Veronesi, M. Cristallo, V. Di Carlo, Surgical treatment of benign and borderline neoplasms of the pancreatic body, Digestive Surgery 20 (6) (2003) 506e510.

Please cite this article in press as: H.G. Beger, et al., Benign cystic neoplasm and endocrine tumours of the pancreas e When and how to operate e An overview, International Journal of Surgery (2014), http://dx.doi.org/10.1016/j.ijsu.2014.03.020

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65

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[66] M.J. Goldstein, J. Toman, J.A. Chabot, Pancreaticogastrostomy: a novel application after central pancreatectomy, Journal of the American College of Surgeons 198 (6) (2004) 871e876. [67] D.T. Etson, K.D. Lillemoe, J.L. Cameron, C.J. Yeo, Central pancreatectomy with pancreaticogastrostomy for benign pancreatic pathology, Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 8 (5) (2004) 532e538. [68] M.W. Muller, H. Friess, J. Kleeff, U. Hinz, M.N. Wente, D. Paramythiotis, P.O. Berberat, G.O. Ceyhan, M.W. Buchler, Middle segmental pancreatic resection: an option to treat benign pancreatic body lesions, Annals of Surgery 244 (6) (2006) 909e918 discussion 918e920. [69] K.M. Brown, M. Shoup, A. Abodeely, et al., Central pancreatectomy for benign pancreatic lesions, Hpb: the Official Journal of the International Hepato Pancreato Biliary Association 8 (2006) 142e147. [70] K.K. Roggin, U. Rudloff, L.H. Blumgart, et al., Central pancreatectomy revisited, Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 10 (2006) 804e812. [71] J.D. Christein, R.L. Smoot, M.B. Farnell, Central pancreatectomy: a technique for the resection of pancreatic neck lesions, Archives of Surgery 141 (2006) 293e299. [72] S. Crippa, C. Bassi, A.L. Warshaw, M. Falconi, S. Partelli, S.P. Thayer, P. Pederzoli, C. Fernandez-del Castillo, Middle pancreatectomy: indications, short- and long-term operative outcomes, Annals of Surgery 246 (1) (2007) 69e76. [73] J.D. Allendorf, B.A. Schrope, M.H. Lauerman, W.B. Inabnet, J.A. Chabot, Postoperative glycemic control after central pancreatectomy for mid-gland lesions, World Journal of Surgery 31 (1) (2007) 164e168 discussion 169e170. [74] B. Blanc, A. Sauvanet, A. Couvelard, et al., Résection limitées du pancréas pour tumeur intracanalaire papillaire et mucinous non invasive, Journal de Chirurgie (Paris) 145 (2008) 568e578. [75] H. Lavu, J.L. Knuth, M.S. Baker, C. Shen, N.J. Zyromski, M. Schmidt, A. Nakeeb, T.J. Howard, Middle segment pancreatectomy can be safely incorporated into a pancreatic surgeon’s clinical practice, Hpb: the Official Journal of the International Hepato Pancreato Biliary Association 10 (6) (2008) 491e497. [76] M. Adham, A. Giunippero, V. Hervieu, M. Courbiere, C. Partensky, Central pancreatectomy: single-center experience of 50 cases, Archives of Surgery 143 (2) (2008) 175e180 discussion 180e171. [77] M. Wayne, S. Neragi-Miandoab, F. Kasmin, et al., Central pancreatectomy without anastomosis, World Journal of Surgical Oncology 7 (2009 Aug 31) 67. [78] K. Shimada, Y. Sakamoto, M. Esaki, T. Kosuge, N. Hiraoka, Role of medial pancreatectomy in the management of intraductal papillary mucinous neoplasms and islet cell tumors of the pancreatic neck and body, Digestive Surgery 25 (1) (2008) 46e51. [79] L.M. Ocuin, J.M. Sarmiento, C.A. Staley, J.R. Galloway, C.D. Johnson, W.C. Wood, D.A. Kooby, Comparison of central and extended left pancreatectomy for lesions of the pancreatic neck, Annals of Surgical Oncology 15 (8) (2008) 2096e2103. [80] S. Hirano, M. Tani, M. Kawai, S. Ina, R. Nishioka, M. Miyazawa, A. Shimizu, K. Uchiyama, H. Yamaue, A central pancreatectomy for benign or low-grade malignant neoplasms, Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 13 (9) (2009) 1659e1665. [81] C. Sperti, C. Pasquali, A. Ferronato, et al., Median pancreatectomy for tumors of the neck and body of the pancreas, Journal of the American College of Surgeons 190 (2000) 711e716. [82] G. Cataldegirmen, C.G. Schneider, D. Bogoevski, A. Koenig, J.T. Kaifi, M. Bockhorn, L.S. Deutsch, Y. Vashist, J.R. Izbicki, E.F. Yekebas, Extended central pancreatic resection as an alternative for extended left or extended right resection for appropriate pancreatic neoplasms, Surgery 147 (3) (2009) 331e338. [83] T. Shikano, A. Nakao, Y. Kodera, S. Yamada, T. Fujii, H. Sugimoto, N. Kanazumi, S. Nomoto, S. Takeda, Middle pancreatectomy: safety and longterm results, Surgery 147 (1) (2009) 21e29. [84] C.J. Lee, J. Scheiman, M.A. Anderson, O.J. Hines, H.A. Reber, J. Farrell, M.L. Kochman, P.J. Foley, J. Drebin, Y.S. Oh, G. Ginsberg, N. Ahmad, N.B. Merchant, J. Isbell, A.A. Parikh, J.B. Stokes, T. Bauer, R.B. Adams, D.M. Simeone, Risk of malignancy in resected cystic tumors of the pancreas < or ¼3 cm in size: is it safe to observe asymptomatic patients? A multiinstitutional report, Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 12 (2008) 234e242. [85] G.M. Xiang, C.L. Tan, H. Zhang, et al., Central pancreatectomy for benign or borderline lesions of the pancreatic neck: a single centre experience and literature review, Hepato-Gastroenterology 59 (2012) 1286e1289. [86] J. DiNorcia, L. Ahmed, M.K. Lee, P.L. Reavey, E.A. Yakaitis, J.A. Lee, B.A. Schrope, J.A. Chabot, J.D. Allendorf, Better preservation of endocrine function after central versus distal pancreatectomy for mid-gland lesions, Surgery 148 (6) (2010) 1247e1254 discussion 1254e1246. [87] T. Sudo, Y. Murakami, K. Uemura, et al., Middle pancreatectomy with pancreaticogastrostomy: a technique, operative outcomes, and long-term pancreatic function, Journal of Surgical Oncology 101 (2010) 61e65. [88] J. LaFemina, P.A. Vagefi, A.L. Warshaw, C. Fernandez-del Castillo, Transgastric pancreaticogastric anastomosis: an alternative operative approach for middle pancreatectomy, Archives of Surgery 145 (5) (2010) 476e481. [89] C.M. Kang, J.M. Lee, M.W. Kim, et al., Experiences in central pancreatectomy, Digestive Surgery 28 (2011) 57e62.

[90] U. Boggi, G. Amorese, N. De Lio, et al., Central pancreatectomy with inframesocolic pancreatojejunostomy, Langenbeck’s Archives of Surgery 397 (2012) 1013e1021. [91] T. Dumitrascu, A. Scarlat, M. Ionescu, et al., Central pancreatectomy versus spleen-preserving distal pancreatectomy: a comparative analysis of early and late postoperative outcomes, Digestive Surgery 29 (2012) 400e407. [92] A. Li, P. Prasoon, W. Hong, et al., Pancreaticogastrostomy: a salvage procedure for pancreatic body and neck resection, Iranian Red Crescent Medical Journal 14 (2012) 731e736. [93] A. Venara, V. de Franco, S. Mucci, et al., Central pancreatectomy: comparison of results according to the type of anastomosis, Journal of Visceral Surgery 149 (2012) e153ee158. [94] M. Falconi, W. Mantovani, S. Crippa, et al., Pancreatic insufficiency after different resections for benign tumours, British Journal of Surgery 95 (2008) 85e91. [95] A. Schwarz, H.G. Beger, Modifikation der duodenumerhaltenden Pankreaskopfresektion mit Segmentresektion des Duodenums e Erfahrung mit 4 Patienten, Mittelrheinische Chirurgen, Jahrestagung, 1996, p. 5. [96] A. Nakao, S. Inona, M. Kajikawa, et al., Pancreatic head resection with segmental duodenectomy, Shujutsu 48 (1994) 635e638 (in Japanese). [97] T. Imaizumi, F. Hanyu, M. Suzuki, et al., Clinical experience with duodenum preserving total resection of the head of the pancreas with pancreaticocholedochoduodenostomy, Journal of Hepato-Biliary-Pancreatic Surgery 2 (1995) 38e44. [98] S. Isaji, Y. Kawarada, Pancreatic head resection with second-portion duodenectomy for benign lesions, low-grade malignancies, and early stage carcinomas involving the pancreatic head region, American Journal of Surgery 181 (2001) 172e176. [99] S. Miyakawa, A. Horiguchi, K. Mizuno, S. Ishihara, N. Niwamoto, K. Miura, Preservation of arterial arcades during duodenum-preserving total pancreatic head resection for intraductal papillary tumor, Hepato-Gastroenterology 50 (2003) 993e997. [100] Y.J. Ahn, S.W. Kim, Y.C. Park, J.Y. Jang, Y.S. Yoon, Y.H. Park, Duodenal-preserving resection of the head of the pancreas and pancreatic head resection with second-portion duodenectomy for benign lesions, low-grade malignancies, and early carcinoma involving the periampullary region, Archives of Surgery 138 (2003) 162e168. [101] S. Hirano, S. Kondo, Y. Ambo, E. Tanaka, T. Morikawa, S. Okushiba, H. Katoh, Outcome of duodenum-preserving resection of the head of the pancreas for intraductal papillary-mucinous neoplasm, Digestive Surgery 21 (2004) 242e 245. [102] Y. Murakami, K. Uemura, Y. Yokoyama, M. Sasaki, M. Morifuji, Y. Hayashidani, T. Sudo, T. Sueda, Pancreatic head resection with segmental duodenectomy for intraductal papillary mucinous tumors of the pancreas, Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 8 (2004) 713e719. [103] T. Takada, H. Yasuda, H. Amano, M. Yoshida, A duodenum-preserving and bile duct-preserving total pancreatic head resection with associated pancreatic duct-to-duct anastomosis, Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract 8 (2004) 220e224. [104] K. Ito, Duodenum preservation in pancreatic head resection to maintain pancreatic exocrine function (determined by pancreatic function diagnostant test and cholecystokinin secretion), Hepatobiliary & Pancreatic Surgery 12 (2005) 123e128. [105] L. Fernández-Cruz, C. Olvera, M.A. López-Boado, J. Bollo, J. Romero, J. Comas, Organ-preserving resection of the pancreaticoduodenal region in the treatment of intraductal papillary mucinous tumors, Cirugia Espanola 80 (2006) 295e300. [106] T. Imaizumi, T. Hatori, N. Harada, A. Fukuda, K. Takasaki, F. Hanyu, Intraductal papillary mucinous neoplasm of the pancreas; resection and cancer prevention, American Journal of Surgery 194 (2007) S95eS99. [107] T. Nakagohri, T. Kinoshita, M. Konishi, S. Takahashi, N. Gotohda, Surgical outcome of intraductal papillary mucinous neoplasms of the pancreas, Annals of Surgical Oncology 14 (2007) 3174e3180. [108] J.X. Xiong, C.Y. Wang, J. Tao, S.H. Zhang, Indication and choice of operation technique for duodenum-preserving resection of pancreatic head: 22 cases reports, Zhonghua Wai Ke Za Zhi [Chinese Journal of Surgery] 45 (2007) 24e 26. [109] T. Fuji, M. Kanda, Y. Kodera, et al., Comparison of pancreatic head resection with segmental duodenectomy and pylorus-preserving pancreatoduodenectomy for benign and low-grade malignant neoplasms of the pancreatic head, Pancreas 40 (2011) 1258e1263. [110] S. Pedrazzoli, S.A. Canton, C. Sperti, Duodenum-preserving versus pyloruspreserving pancreatic head resection for benign and premalignant lesions, Journal of Hepato-biliary-pancreatic Sciences 18 (2011) 94e102. [111] D.W. Hwang, J.Y. Jang, S.E. Lee, C.S. Lim, K.U. Lee, S.W. Kim, Clinicopathologic analysis of surgically proven intraductal papillary mucinous neoplasms of the pancreas in SNUH: a 15-year experience at a single academic institution, Langenbeck’s Archives of Surgery 397 (2012) 93e102. [112] D.J. Gong, J.M. Zhang, G.J. Mao, L.T. Xu, R.J. Wu, S.A. Yu, X.K. Wu, X.M. Li, W. Shen, Z.D. Zheng, Duodenum-preserving pancreatic head resection vs. pancreatoduodenectomy for benign lesions and low-grade malignancies of the pancreatic head, Hepato-Gastroenterology 60 (121) (2012), http:// dx.doi.org/10.5754/hge12407 (Epub ahead of print).

Please cite this article in press as: H.G. Beger, et al., Benign cystic neoplasm and endocrine tumours of the pancreas e When and how to operate e An overview, International Journal of Surgery (2014), http://dx.doi.org/10.1016/j.ijsu.2014.03.020

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H.G. Beger et al. / International Journal of Surgery xxx (2014) 1e9 [113] J. Busquets, J. Fabregat, F.G. Borobia, R. Jorba, C. Valls, T. Serrano, E. Ramos, N. Pelaez, A. Rafecas, Organ-preserving surgery for benign lesions and lowgrade malignancies of the pancreatic head: a matched case-control study, Surgery Today 40 (2010) 125e131. [114] A. Horiguchi, S. Miyakawa, S. Ishihara, M. Ito, Y. Asano, K. Furusawa, T. Shimizu, T. Yamamoto, Surgical design and outcome of duodenumpreserving pancreatic head resection for benign or low-grade malignant tumors, Journal of Hepato-biliary-pancreatic Sciences 17 (2010) 792e797. [115] S.W. Kim, K.H. Kim, J.Y. Jang, et al., Practical guidelines for the preservation of the pancreaticoduodenal arteries during duodenum-preserving resection of

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the head of the pancreas: clinical experience and a study using resected specimens from pancreaticoduodenectomy, Hepato-Gastroenterology 48 (2001 Jan) 264e269. [116] K. Yamaguchi, K. Yokohata, K. Nakano, et al., Which is a less invasive pancreatic head resection: PD, PPPD, or DPPHR? Digestive Diseases and Sciences 46 (2) (2001 Feb) 282e288. [117] J.K. Ramage, A.H.G. Davies, J. Ardill, et al., Guidelines for the management of gastroenteropancreatic neuroendocrine tumours, Gut 54 (IV) (2005) IV1e IV16.

Please cite this article in press as: H.G. Beger, et al., Benign cystic neoplasm and endocrine tumours of the pancreas e When and how to operate e An overview, International Journal of Surgery (2014), http://dx.doi.org/10.1016/j.ijsu.2014.03.020

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