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International Journal of Surgery 12 (2014) 606e614

REVIEW

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International Journal of Surgery

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Review

Benign cystic neoplasm and endocrine tumours of the pancreas e

When and how to operate e An overview

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

aDepartment of General- and Visceral Surgery, c/o University of Ulm, Ulm, GermanybCenter of Oncologic, Endocrine and Minimal Invasive Surgery, Donouklinikum Neu-Ulm, GermanycDepartment of General Surgery and Liver Transplantation, Fundei Clinical Institute, Bucharest, Romania

a r t i c l e i n f o

Article history:Received 20 March 2014Accepted 31 March 2014Available online 15 April 2014

Keywords:Cystic neoplasmEndocrine tumours of the pancreasEnucleationPancreatic middle segment resectionDuodenum preserving total pancreatic headresection

* Corresponding author.E-mail address: sekretariat@beger-ulm.de (H.G. Be

http://dx.doi.org/10.1016/j.ijsu.2014.03.0201743-9191/� 2014 Surgical Associates Ltd. Published

a b s t r a c t

Background: The recent evolution of limited local operative procedures for benign pancreatic lesionsshifted surgical treatment options to the application of local techniques, although major resections ofpancreatic head and left resection are still the standard.Objectives: To evaluate the level of evidence of tumour enucleation (EN), pancreatic middle segmentresection (PMSR) and duodenum preserving total/subtotal pancreatic head resection (DPPHRt/s), wefocus based on present knowledge on indication to surgical treatment evaluating the questions, whenand how to operate.Results: Tumour enucleation is recommended for all symptomatic neuro-endocrine tumours with sizeup to 2e3 cm and non-adherence to pancreatic main-ducts. EN has been applied predominantly inneuro-endocrine tumours and less frequently in cystic neoplasms. 20% of enucleation are performed asminimal invasive laparascopic procedure. Surgery related severe post-operative complications with theneed of re-intervention are observed in about 11%, pancreatic fistula in 33%. The major advantage of ENare low procedure related early post-operative morbidity and a very low hospital mortality. PMSR isapplied 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 tomanagement 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 withsegment resection of peripapillary duodenum and intra-pancreatic common bile duct has been appliedin 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 RCTresults. For DPPHR, 7 prospective, controlled studies underline the advantages compared to partialpancreaticoduodenectomy.Conclusion: The application of tumour enucleation, pancreatic middle segment resection and duodenumpreserving subtotal or total pancreatic head resection are associated with low level surgery related earlypost-operative complications and a very low hospital mortality. The major advantage of the limitedprocedures is preservation of exo- and endocrine pancreatic functions.

� 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

1. Introduction

The most frequent benign lesions of the pancreas are cysticneoplasms and endocrine tumours [1,2]. Of cystic neoplasmsfrequent are intra-ductal papillary mucinous neoplasms (IPMN),mucinous cystic tumours (MCN) and serous cyst adenomas (SCA).Insulinoma are the predominant neuro-endocrine tumour [3]. Upto 50% of the reported benign lesions are clinically asymptomatic

ger).

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detected by chance due frequent use of MD-CT, MRI, PET and EUSinvestigations of the abdomen. Patients who complain episodes ofupper abdominal discomfort or have continuing clinical symptomsin association with a cystic neoplastic lesion or neuro-endocrinetumour are candidates for surgical treatment. In primary asymp-tomatic patients with yet undetermined risk for developingsymptoms has been advocated to change to surgical treatmentbased on the size of the lesion and tumour growth [4].

Neuro-endocrine lesions (PNETs) are 10% of all benign tumorouslesions of the pancreas. Hormonal inactive and hormonal activePNETs develop from cellular compartment of islet cell parenchyma

.

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.

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which constitutes 2e10% of pancreatic tissue. In contrast to hor-monal active PNETs, functional inactive endocrine tumours pro-duce late in the course clinical signs which are mostly unspecific.Besides of well-established radiological investigations and EUS, themeasurement of specific hormones in the peripheral blood, theSomatostatin Receptor Scintigraphy and the PET are diagnosticmeasures which establish in addition to specific hormone deter-mination in blood in most patients the diagnosis, type and locationof the tumour. Multifocality of PNETs is well-known particularly incase of hereditary syndromes like MEN-1.

After performing a selective literature review, we focus in thefollowing on the current knowledge about indication to surgicaltreatment and the present experience applying limited surgicaltechniques for benign cystic neoplasms and endocrine tumours.Based on recently published data of a systemic review and meta-analysis about use of tumour enucleation (EN), pancreatic middlesegment resection (PMSR) and duodenum preserving total andsubtotal pancreatic head resection (DPPHRt/s) for benign tumours,data of early and late post-operative outcome are specifically dis-cussed [5,6].

2. Natural history and treatment options of cystic neoplasmand endocrine tumours

2.1. Cystic neoplasm

The natural clinical course of cystic neoplasm of the pancreas isincompletely understood. IPMN lesions of main duct (MD-IPMN),branch duct (BD-IPMN) and mixed type have variable clinical fea-tures and different risks for a malignant transformation. MD-IPMNare predominantly found inmen and localised in pancreatic head. Atransformation of benign adenoma to a cancerous process isobserved in up to 70%. In BD-IPMN cancer has been found in up to35%. The five year risk of developing an invasive cancer for MD-IPMN is calculated on basis of the present data being 63%, for BD-IPMN 15% [7]. High-grade dysplasias are detected in MD-IPMN inup to 62%; a carcinoma in situ, respectively an invasive carcinoma inoperative specimens are found in up to 45% (Table 1). In small BD-IPMN, which are Sendai negative, a cancerous process in surgicalspecimens found in up to 25% [19]. IPMN lesions show related tohistologic subtype’s expression of mucine patterns. The intestinalsub-type contains MUC2 þ MUC5AC und CDX2, whereas thepancreato-biliary subtype is characterised by MUC1 and MUC5ACpositivity but negativity for MUC2 and CDX2. The gastric-foveolahistological type of IPMN shows positivity of MUC5AC but nega-tivity for MUC1, MUC2 and CDX2 [20e22].

MCN lesions are predominant in female patients locatedfrequently in body and tail of the pancreas. The differentiation ofMCN from IPMN is based onmulti-slice CTandMRT, but excluding amalignant process by imaging tools only is difficult [23]. MCN le-sions are surrounded by a common capsula with a thick wall. His-tologically, the diagnosis of MCN is established by presence ofovarian type stroma. The clinical feature of MCN differs whetherthey belong to the sub-group of mucinous cyst-adenoma or non-

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

Tumour size borderline High grade dysplasia

SCA >4 cm [25] 5.1%IPMN-MD >3 cm [15] 57e62%IPMN-BD >5 cm [15] 11% [17]MCN >4 cm [15] >3 cm [18] 13.4% [11,12]SPN >4 cm [14,26]

invasive, proliferative MCN lesion with dysplasia or mucinouscyst adeno-carcinoma. Mucinous cyst adenomas are 60% and non-invasive, proliferative MCNs 30% of all MCNs [24].

Serous cyst adenomas are clinically not a rare entity; theydevelop in different pathomorphological features: multiple micro-cystic adenomas, single macro-cystic lesions with multiple crap-like structures and macro-cystic tumours with one single cavity[13]. SCA appear more frequently in the body and tail and aredetected most frequently in female patients. SCA are considered tobe rarely linked to malignancy. A malignant SCA and SCA in asso-ciation with a remote ductal pancreatic cancer has been reportedfrom several centres. Generally a malignant potential of SCA isconsidered to be low [2]. Solid pseudo-papillary neoplasms (SPN)develop almost exclusively in female patients in middle ages below50 years. An advanced cancer is found in resected solid pseudo-papillary tumours in up to 22% [26,27].

2.2. Neuro-endocrine tumours

Neuro-endocrine tumours of the pancreas are increasinglydetected; the average size is 2e3 cm. However, tumour size below1 cm in operative specimens are not rare.

Up to 70% of all PNET’s are insulinoma which show mostfrequently functional activity. Insulinoma are in 90% benign, inde-pendently of the degree of clinical symptoms. Functional inactiveare 30e50% of all PNET’s, usually late detected in clinical course. Allgastroentero-pancreatic neuro-endocrine tumours are consideredto be potentially malignant [28]. The risk of malignancy of tumoursless than 2 cm in size, who show low degree of proliferation andhave tumour marker Ki67/MIB1 positivity index of <3% and are notangio-invasive have a benign clinical course. PNET’s, which arehistologically well-differentiated, but associated by a Ki67/MIB1positivity index between 3 and 20% are considered having a distincthigh risk for malignancy [29,30]. The vast majority of gastrinoma,glucagonoma, vipoma and ACTH-PNET’s are malignant. 6e7% of allPNET’s are low differentiated neuro-endocrine cancers [31].

Carcinoma in-situ invasive carcinoma Risk of cancer

�1.2% [13] 1.2%/5.1% [8,9]43e45% [10] 63%/5 years [7]15% [16] 25% [19] 14%/5 years [7]36% [12] 17.3% [11,12] <15% [10]19.2% [26]

Table 3Tumours of the pancreas, surveillance of asymptomatic lesions.

Bd-IPMN: TM <3 cm<1 cm<2e3 cm

ObservationMRT, MSeCT yearlya

MRT/MRCP, MSeCT or EUS þ FNA yearlya

SCA TM <4 cm ObservationMSeCT 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.

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3. When to operate benign cystic neoplasms and neuro-endocrine tumours?

According to consensus guidelines of international expertmeetings published 2006 and 2012 symptomatic and asymptom-atic patients with MD-IPMN should have operative treatment inany case when they are surgically fit (Fig. 1) [10,32]. For BD-IPMN,surgery is recommended if tumour size is above 4e5 cm or thecyst present signs of malignancy; but tumour size maybe amisleading criteria for surveillance as recently has been shown [19](Table 2). Mural nodules, pancreatic main duct dilation above >5e9 mm, wall thickening, rapid tumour growth are signs of a malig-nant transformation and are indicators to change from surveillanceto surgery [10,32]. Solid mass in a cystic lesion is associated withadvanced IPMN cancer. Multifocality of IPMN lesions has becomeincreasingly important for decision making in symptomatic pa-tients. The incidence of synchronus and metachronus multifocalIPMNs are observed in up to 28% [33]. Branch duct-IPMNs have ahigher risk of multifocality as main-duct IPMN (see Table 3).

Surveillance of asymptomatic cystic neoplasms is recommendedfor branch duct IPMN tumours of a size up to 3 cm. The surveillanceprogramme is based on use of MRT yearly for tumours below 2 cmin max. diameter; above 2 cm additionally multi-slice CT are indi-cated. In case of rapid tumour growth or development of muralnodules an EUS with fine needle aspiration is recommended toexclude development of a cancerous process. The risk of malignanttransformation is high inMD-IPMN and lower in branch duct IPMN.The borderline tumour size for MCN is considered to be 5 cm interms of decision making. Observation of asymptomatic serous cystadenomas is recommended up to tumour size of 4 cm by yearlyinvestigations. In serous pseudo-papillary neoplasia, carcinoma arefound in 19% of resected tumours. Surgical treatment has beenestablished for all patients suffering SPN because resection resultsin cure of patients.

3.1. Endocrine tumours

Candidates for surgical treatment are patients with endocrinetumours who are clinically active lesions; asymptomatic PNETsbelow the size of 1 cm are cared by a surveillance programme [30].

Pathomorphologically, endocrine tumours demonstrate occa-sionally 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 lesionsbelow 2 cm in diameter, who have a low proliferation index, aremostly of benign nature; but endocrine neoplasms, showing cell-grading G2 and a proliferation index Ki67/MIB1 >3e20% have adistinctly increased risk of malignancy as it is for PNETs of a tumoursize above 2 cm, G1 cell grading and no signs of angioinvasion.PNETs of tumour size below 2 cm, which have histological gradings

Table 2Indication to surgical treatment in symptomatic and asymptomatic cystic neoplasiaof the pancreas.

Clinical symptomatic cystsa: Surgical extirpation for all lesionsAsymptomatic cystsa:IPMN’sMain duct Surgery for all lesions Observation,

TM > 4e5 cm surgeryBranch ductMCN’s Surgery for all lesionsSCA Observation, cysts >4 cm surgerySPsN Surgery for all lesions

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

2012 [10].

G2 and Ki67/MIB1 index of>20% have a high probability to developneuro-endocrine cancer [30,32]. Sporadic gastrinoma, glucago-noma and vipoma of the pancreas are, irrespective of tumour size,in >80% malignant lesions.

About 10% of sporadic hormone active insulinoma aremalignant[34]. MEN1-associated insulinoma show infrequently signs of ma-lignancy. Multifocality of PNETs is observed in MEN1 and VHL-syndrome.

4. Options for surgical treatment of benign cystic neoplasmsand endocrine tumours

Most surgical institutions worldwide use for cystic lesions in thepancreatic head a KauscheWhipple-type resection; and for abenign cystic lesion in the body and tail of pancreas a spleen pre-serving left pancreatic resection. But major surgical procedures areburdened by additional sacrifice of normal functional pancreaticand extra-pancreatic tissues and a considerable high level of severepost-operative complications with a substantial risk of mortality. Inthe late outcome after a Whipple-type resection, procedure relatedlate morbidity show an increase of exocrine insufficiency, adysfunction of the glucose metabolism, respectively new onset ofinsuline dependent diabetes mellitus in about 20%. Episodes ofcholangitis in the long-term course after a Whipple-type resectionare underestimated. The recent evolution of limited surgical pro-cedures established local resective techniques, but they are not yetused as standard surgical treatment modalities for benign pancre-atic tumours (Table 4). Tumour enucleation [34], pancreatic middlesegment resection [35] and duodenum preserving total or subtotalpancreatic head resection [36] have the potential of a local tumourextirpation associated with low procedure related post-operativemorbidity and preservation of the endocrine and exocrinepancreatic functions compared to pre-operative status, respectivelyto results after standard procedures.

5. Indications and limitation of local surgical procedures forbenign tumours of the pancreas

5.1. Tumour enucleation

Tumour enucleation has been used predominantly for neuro-endocrine tumours of the pancreas. Of 709 patients, who had

Table 4Options for surgical treatment of benign cystic and neuro-endocrine tumours of thepancreas.

Limited surgical tumour extirpation� Enucleation� Pancreatic middle segment resection (central pancreatectomy)� Duodenum-preserving total/subtotal pancreatic head resection

Presently standard procedures for benign TM’sPancreatic left resection � spleen preservationKausch-Whipple resection/Pylorus-preserving(Total duodeno-pancreatectomy � spleen preservation)

Table 6Indication and contra-indication to tumour enucleation in cystic neoplasia andendocrine tumours of the pancreas.

Indication:Cyst. TM Clinical symptomatic cysts <2e3 cm

Asymptomatic cysts <2e3 cm, age <50 yearsTM no abutment to PMDAbsence of criteria of malignancy

PNETa Clinical symptomatic TMs < 2 cmAsymptomatic TMs >1e2 cmHormone-active TMs <2e3 cm

Limitation of EN: PMD dilationHisto-pathology: high grade dysplasia, carcinoma(Multifocality)TM close proximity to PMDTM-size > 3 cmTM suspected to be invasive cancer

PNET e pancreas neuro-endocrine tumour.PMD e pancreatic main duct.

a Kunz PL et al. Consensus guidelines for the management and treatment ofneuro-endocrine tumours. Pancreas 2013; 42 : 557e577 [30] Ramage JK et al.Guidelines for the management of gastroenteropancreatic neuro-endocrine tu-mours. Gut 2005; 54 (IV) IV1-IV16 [117].

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tumour enucleation between 1991 and 2012 themean tumours sizewas 2.4 cm [37e57]. 72% of the patients had enucleation of PNETsand 22% for cystic neoplasms. Besides of the minimal tissue traumaof pancreas, an additional benefit of EN is application of laparo-scopic 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 tu-mours 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 post-operative morbidity. Severe post-operative complications asdefined by Clavian-Dindo score �3 [59], after EN developed in 11%.The frequency of re-operation after enucleation of 4.7% and re-hospitalisation of 11.8% may be related to the severity of type Band C fistula. The limitation of use of enucleation is size of lesionand tumour proximity to pancreatic main duct. In case of tumour-wall adherence to pancreatic main duct, injuring of duct increasesthe risk of development of pancreatic fistula. To avoid duct injuringby enucleation, tumour size above 3 cm is a limiting criteria forapplication of enucleation technique, particularly in associationwith a pancreatic main duct dilation (Table 6).

Table 7Indication to duodenum preserving total/subtotal pancreatic head resection forcystic neoplasms and endocrine tumours of the pancreatic head.

DPPHR total þ segmentduodenum þ CBD

TM abutment to duodenal wallTM involving CBDLigation of SPGDA þ IPPDA Ischaemia

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 tu-mours according to a systematic review including 826 patientsreported between 1993 and 2010 [60e93] (see Table 7). The meantumour size was 2.9 cm. Pancreatic middle segment resectionproduces in two resection surfaces of the pancreatic body. Resect-ing a cystic neoplasm in a size of 5e6 cm, necessitates in most casesadditionally a tumour dissection close to walls of retro-pancreaticvessels. Cystic tumours particularly main duct IPMN and MCN aresurrounded by a wall of inflammatory tissues, which frequentlyextends to the splenic vein respectively, splenic artery. Tumourencasement of vessels is associatedwith increased risk of blood lossduring and after operation. The frequency of severe post-operativecomplications of 18% as well the high frequency of pancreatic fistulaof 33% are related to management of the pancreatic stumps. Thecrucial point of pancreatic middle segment resection is surgicalhandling of the proximal pancreatic stump (Fig. 2). Whereas the leftpancreas is secured by a pancreatico-jejunostomosis or moreelegantly by pancreatico-gastrostomosis, the proximal pancreaticstump is mostly handled by simple closure using mechanical de-vices or by U-suturing of the tissue with isolated closure of thepancreatic main duct. However, simple closure rather causes thanprevents local complications like fistula or peri-pancreatic fluidcollections. The frequency of post-operative haemorrhage has been

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

Cystic neoplasm PNETd Post-operative morbidity

Severecomplications

POPF Hospitalmortality

ENa 21.7% 72.0% 10.8% 33.1% 1.13%PMSRb 64.0% 28.5% 17.7% 32.9% 0.81%DPPHRt/sc 71.1% 7.9% 11.5% 19.9% 0.49%

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

observed in 7% and the re-hospitalisation in 14%. The increased riskof severe type pancreatic fistula derived from the proximalpancreatic stump and frequency of haemorrhage contributes to thehigh level of re-operation and re-admission after pancreatic middlesegment resection. Hospital mortality was with 0.8% very low (seeFig. 3).

Applying pancreatic middle segment resection for largetumorous lesions of the body of the pancreas necessitating aresection of a pancreatic segment of more than 5e6 cm increasesthe risk for metabolic dys-functions. After extended middlesegment resection of a large pancreatic segment, endocrine insuf-ficiency in the long-term outcome is observed in up to 12% andexocrine insufficiency in about 20% compared to pre-operativelevels [94]. For extended cystic neoplasms in the pancreas body aspleen preserving hemipancreatectomy may be an alternativeprocedure. However, the metabolic exo- and endocrine functionsafter pancreatic left resection are clinically relevant decreased,whereas the frequency of local complications found lowercompared to pancreatic middle segment resection.

of peripapillary duodenumCystic neoplasm þ carcinoma in-situhi-PNEC > 2 cm

DPPHR total preservationof duodenum and CBD:

TM extending to neck of pancreasPNET functional active >2 cmTM not including Duodenum þ CBD

DPPHR subtotal TM location in processus uncinatus(uncinetectomy)TM location in neck of pancreasCBD not involvedInsulinoma >2 cm located in processus uncinatus

Limitation of DPPHRt Cystic neoplasm and advanced cancerIslet 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.

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

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5.3. Duodenum preserving total/subtotal pancreatic head resection

For benign tumours of the pancreatic head a total and subtotalhead resection has been introduced in clinical practice between1985 [95] and 1994 [96]. Location of the tumour within pancreatichead and size of lesion determine the use of a subtotal or total headresection. The surgical experience using duodenum preserving to-tal pancreatic head resection is up to now limited [97e107]. Ad-vantages are underlined by 7 prospective and controlled clinicaltrials, comparing duodenum preserving total pancreatic headresection with Whipple-type pancreatico-duodenectomy. Out of405 patients reported between 1995 and 2003, one third had a totalpancreatic head resection including peripapillary segment of duo-denum and intra-pancreatic common bile duct. One third of pa-tients experienced total head extirpation, but preservation ofduodenum and common bile duct (Fig. 4a,b), one third had a sub-total resection conserving pancreatic tissue between intra-pancreatic common bile duct and wall of duodenum as well tis-sue of the uncinate process (Fig. 5a,b). Surgical techniques of totalhead resection, with dissection of pancreatic tissue from peri-papillary duodenum and preserving the posterior and anteriorpancreatico-duodenal arcades arewell established. Total pancreatic

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

head resection with segment resection of the peripapillary duo-denum requires four anastomoses: end-to-end between proximaland distal duodenum; end-to-side of common bile duct and post-pyloric duodenum and end-to-side between preserved pancreatichead or neck and the excluded jejunal loop and a Roux-en-Yanastomosis. The low frequency of re-operation of 1.8%, hospitalmortality of 0.5% as well re-hospitalisation of 3.3% and 12.5% ofsevere early post-operative complications underlines the wellstandardised techniques of pancreatic head resection. Pancreaticfistula developed in 20% of patients, of them 47% grade B and Cfistulas. A major advantage of duodenum preserving total andsubtotal pancreatic head resection is preservation of exo- andendocrine functions compared to pre-operative level. In 7 pro-spective controlled trials comparing a duodenum preserving totalhead resection with a Whipple-type partial pancreatico-duodenectomy, the metabolic functions after DPPHRt were signif-icant better preserved. An additional advantage of this technique istailoring of head resection conserving neck of pancreas or uncinateprocess or parts of dorsal pancreatic head segment. DPPHRt withsegment resection of peripapillary duodenum and common bileduct has been additionally applied in cystic neoplastic lesions witha carcinoma in-situ and T1 low risk cancer of the papilla, pre-papillary common bile duct and peripapillary duodenal cancer.However, the indication for local, non-invasive cancers are to beproven by prospective controlled trials.

6. Comment

Local surgical procedures for benign tumours of the pancreasare evolving operative techniques but presently not surgical stan-dard. The evidence of tumour enucleation and pancreatic middlesegment resection is low, because exclusively based on retrospec-tive clinical trials without control groups. Two prospectivecontrolled trials out of more than 30 retrospective studies havebeen published comparing PMSRwith spleen preserving pancreaticleft resection in patients suffering chronic pancreatitis but the au-thors did not include neoplastic tumours. PMSR exhibited advan-tages in regard to preservation of metabolic functions, but showed ahigher level of surgery related early post-operative complications.Duodenum preserving total and subtotal pancreatic head resectionis supported by 7 prospective controlled trials comparing early andlate results after Whipple resection applied mostly for benignpancreatic head tumours. The controlled trials for DPPHRt/s

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

Fig. 5. a) Serous cyst adenoma of the uncinate process, 5 cm max. diameter, surgicalprocedure: 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 periampullaryduodenum.

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exhibited advantages of a significant lower level of post-operativesurgery-related complications, a very low hospital mortality <1%and full conservation of exo- and endocrine pancreatic functionsearly post-operatively and in late outcome of patients. Additionaladvantages of the local surgical procedures are application oflaparoscopic or robotic techniques which are increasingly used fortumour enucleation. Tailoring extension of tissue resection yieldslimitation of sacrifice of pancreatic and extrapancreatic tissue.Applying subtotal pancreas head resection by tumour location inthe processus uncinatus performing an uncinatectomy or in thedorsal part or neck of pancreas contributes to main goal of avoidingunnecessary sacrifice of pancreatic tissue. Tumour enucleation andpancreatic middle segment resection are burdened by a higher rateof pancreatic fistula above 30%, of them ISGPF B and C of 50%. Thedevelopment of severe pancreatic fistula and the increased level ofpost-operative haemorrhage and frequency of re-hospitalisationafter EN and PMSR are considered as limitation of use of theselocal resective techniques. In terms of the younger age of patientssuffering cystic neoplasms of SCA and SPN and PNETs, limitedsurgical procedures are most beneficial because of the very lowhospital mortality and full preservation of exo- and endocrinefunctions of pancreas. In case of advanced cancer developed fromcystic neoplasms or invasive endocrine cancers, a standard major

oncologic resectionwith lymph node sampling and tissue resectionto achieve an R0 status is recommended (Table 4).

7. Summary

For benign cystic neoplasms and endocrine tumours the appli-cation of tumour enucleation, pancreatic middle segment resectionand duodenum preserving subtotal and total pancreatic headresection offer advantages of a limited pancreatic and extra-pancreatic tissue trauma compared to major oncological resectioncurrently used as standard treatment. Tumour enucleation andpancreatic middle segment resection are burdened with a distinctrisk of developing pancreatic fistula ISGPF grade B and C, but haveadvantage of a very low hospital mortality. The clinical evidence oftumour enucleation and pancreatic middle segment resection islow since the present knowledge is based only on retrospectiveuncontrolled studies. Duodenum preserving subtotal and totalpancreatic head resection showed in comparison to aWhipple typehead resection significant advantages in regard to maintenance ofthe exo- and endocrine pancreatic functions in the short- and long-term outcome. Prospective controlled trials are needed for evalu-ation of the proposed advantages of limited surgical procedures.

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