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Extended resection in pancreatic metastases: feasibility, frequency, and long-term outcome: a retrospective analysis

Extended resection in pancreatic metastases: feasibility, frequency, and long-term outcome: a... Background: Metastases to the pancreas are rare, accounting for less then 2 % of all pancreatic malignancies. However, both the benefit of extended tumor resection and the ideal oncological approach have not been established for such cases; therefore, we evaluated patients with metastasis to the pancreas who underwent pancreatic resection. Methods: Between 1994 and 2012, 676 patients underwent pancreatic surgery in our institution. We retrospectively reviewed patients’ medical records according to survival, and surgical and non-surgical complications. Student’s t-test and the log-rank test were used for statistical analysis. Results: Eighteen patients (2.7 %) received resection for pancreatic metastases (12 multivisceral resections and 6 standard resections). The pancreatic metastases originated from renal cell carcinoma (n = 10), malignant melanoma (n = 2), neuroendocrine tumor of the ileum (n = 1), sarcoma (n = 1), colon cancer (n = 1), gallbladder cancer (n =1), gastrointestinal stromal tumor (n = 1), and non-small cell lung cancer (n = 1). The median time between primary malignancy resection to metastasectomy was 83 months (range, 0–228 months). Minor surgical complications (Grade I-IIIa) occurred in six patients (33.3 %) whereas major surgical complications (Grade IIIb-V) occurred in three patients (16.6 %). No patients died during hospitalization. The median follow-up was 76 months (range, 10–165 months). One-year, 3-year and 5-year survival for standard resection versus multivisceral resection was 83, 50, and 56 % versus 83, 66, and 50, respectively. Twelve patients died after a median of 26 months (range, 5–55 months). Conclusions: A surgical approach with curative intent is justified in select patients suffering from metastases to the pancreas and offers good long-term survival. The resection of pancreatic metastases of different tumor types was associated with favorable morbidity and mortality when compared with resection of the primary pancreatic malignancies. Our findings also demonstrated that multivisceral resection was feasible, with acceptable long term outcomes, even though morbidity rates tended to be higher after multivisceral resection than after standard resection. Keywords: Multivisceral resection, Metastases to the pancreas, Pancreaticoduodenectomy * Correspondence: [email protected] Equal contributors Department of Visceral, Transplantation, Thoracic, and Vascular Surgery, University Hospital Leipzig, 04103 Leipzig, Germany Full list of author information is available at the end of the article © 2015 Wiltberger et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wiltberger et al. BMC Surgery (2015) 15:126 Page 2 of 8 Background morbidity according to Clavien-Dindo classification [10], Metastases to the pancreas are rare and account only for presence of pancreatic fistulae according to the Inter- 1–2 % of all pancreatic malignancies [1]. Most primaries national Study Group for Pancreatic Fistula criteria [11], that spread to the pancreas are renal cell carcinomas hospital mortality defined as death within the first (RCC), lung cancers, malignant melanomas, and malig- 60 days after resection, overall survival rate, disease-free nancies of the gastrointestinal tract [2, 3]. However, at survival, and histopathological data. Patients who died the time of diagnosis, patients often present with within the first 90 days after resection were excluded widespread systemic disease and therefore, no curative from further statistical analysis. MVR was defined as re- treatment is applicable. Several studies have demon- section of one additional organ, excluding the spleen. stratedsurvivalbenefit andimprovedqualityof life after complete metastasectomy for isolated lung or Statistics liver metastases [4, 5]. Therefore, extended surgical Data are presented as median (range) unless otherwise intervention is a well-established approach in a multi- specified. Statistical differences between groups were disciplinary concept for select patients suffering from determined by Student’s t-test. Student’s t-test and the colorectal or pulmonary metastases in the liver [6]. log-rank test were used to analyze continuous variables However, extended surgery for pancreatic metastasectomy and overall survival excluding in-hospital mortality, re- is rare and remains debatable as there have been few spectively. All statistical analyses were performed with studies on the procedure, all of which have reported SPSS for Windows (version 12.0, SPSS Inc., Chicago, controversial results [7–9]. Patients with localized IL, USA). extrapancreatic disease appear to be suitable for pan- creatic resection but the ideal oncological approach Results has not been established and the benefit of multivisc- Patient characteristics and preoperative symptoms eral resection (MVR) remains undetermined. Our aim Between 1994 and 2012, 676 patients were scheduled for was to assess the frequency and feasibility of MVR pancreatic surgery, of which 18 (2.6 %) received resec- for metastases to the pancreas. We also analyzed the tion for metastatic disease of the pancreas (Table 1). influence of MVR on perioperative and long-term Eight of the patients were men and 10 were woman outcomes compared with standard resection. with a median age of 65 years (range, 22–75 years) and a median body mass index of 25.4 kg/m (range, Methods 18–31 kg/m ). Four patients (22.2 %), had diabetes We retrospectively analyzed the medical records of mellitus type II and 13 (72.2 %) patients received patients who underwent pancreatic resection at the medication for high blood pressure (Table 2). At the Department of Visceral, Transplant, Thoracic, and time of diagnosis of pancreatic metastases, eight patients Vascular Surgery, University Hospital Leipzig, Leipzig, (44.4 %) had one or more tumor-related symptoms includ- Germany, between 1994 and 2012. ing weight loss (n = 8), abdominal pain (n = 8), decrease in For this study ethical approval was obtained from general performance (n = 5), obstructive jaundice (n =2), the institutional local ethical committee (AZ 318-14- or absence of appetite (n = 1). Ten patients (55.5 %) 06102014, Ethical committee of the University Clinic had no specific symptoms and the diagnosis of pancreatic Leipzig, Leipzig). Due to the retrospective design of metastases was obtained through routine follow-up the study and accordingly national guidelines, the examinations. local ethic committee confirmed, that informed con- sent was not necessary from participants. Primary tumor characteristics All patients were operated on with curative intent. We The majority of pancreatic metastases originated from included patients with extrapancreatic spread in this renal cell carcinoma (n = 10; 55.5 %), malignant melan- study only when extrapancreatic disease appeared to be oma (n = 2), and neuroendocrine tumor of the ileum resectable, and we excluded patients with primary tu- (n = 1). Other primaries included sarcoma (n =1), mors that had infiltrated the pancreas through direct colon cancer (n = 1), gallbladder cancer (n =1), gastro- extension. intestinal stromal tumor (n = 1), and non-small cell We assessed the following patient characteristics: sex, lung cancer (n = 1). Metastases to the pancreas were age, body mass index, preoperative symptoms, comor- located mainly in the pancreatic head (n = 10) bidities, type of resection, duration of operation, re- followed by the total pancreas (n = 3) and the cauda quired units of fresh frozen plasma and/or packed red region (n = 3). In two patients, metastases were simul- blood cells, median length of stay on the intensive care taneously located in the corpus and cauda region. unit, total length of stay, time between surgery for the Eleven patients (61 %) had simultaneous metastases in primary tumor and pancreatic resection, postoperative other organs and seven of these patients underwent Wiltberger et al. BMC Surgery (2015) 15:126 Page 3 of 8 Table 1 Patient characteristics Case No. Primary Malignancy Location in the pancreas Time interval Type of Operation further metastases at detection tumor recurrence/ (sync./metac.) (months)* of pancreatic metastasis□ survival status 1 RCC Head (sync.) 0 PPPD + Nephrectomy no no/alive 2 Lung-Cancer Cauda (metac.) 83 DP + Gastrectomy + Splenectomy + vertebral body resection Vertebral body (s) no/TRD 3 RCC Head (metac.) 142 PPPD no no/Non-TRD 4 RCC Head (sync.) 0.8 PPPD no Local recurrence/alive 5 RCC Head/Corpus/Cauda (metac.) 120 Enucleation in pancreatic head + DP + Splenectomy Lung (s) Thyroid/TRD 6 RCC Head/Corpus/Cauda (metac.) 132 TP + Spleenectomy + distal Gastrectomy Thyroid (s) no/TRD 7 Gallblader-Cancer Head (sync.) 0 PPPD + Liver resection (SII SIII) Liver (a) yes/TRD 8 RCC Corpus/Cauda (sync.) 17 DP + Spleen + Colon +Jejunom Pulmo (s) no/TRD 9 GIST Head (metac.) 34 PPPD + Hemicolectomy Liver (a) yes/alive 10 RCC Head (metac.) 106 Whipple no Lung/TRD 11 Sarcoma Head (sync.) 0 Whipple + Hemihepatectomy + Hemicolectomy Liver (s) Liver/TRD 12 RCC Head/Corpus/Cauda (metac.) 66 TP + Spleen no Cerebral/TRD 13 Melanoma Head/Corpus/Cauda (metac.) 90 TP + Segemental liver resection Liver (a) Liver/alive 14 RCC Cauda (metac.) 123 DP Pulmo (s) Thyroid/TRD 15 Melanoma Head (metac.) 228 PPPD + Hemihepatectomy Liver (a) Liver/TRD 16 RCC Head (sync.) 0 DP + Spleen + Nephrctomy no no/alive 17 Colon-Cancer Head (metac.) 29 PPPD + Liver resection (Lobus caudatus) Liver (s) no/alive 18 NET Ileum Head (sync.) 78 PPPD + Jejunum Jejunum (s) no/alive sync. indicates synchronous metastases to the pancreas; metac. indicates metachronous metastases to the pancreas; * interval from resection of primary tumor to resection of pancreatic metastasis; □ excluding pancreas (a, after; s, synchronous; p, prior); † at time of study; RCC indicates renal cell carcinoma; NET indicates neuroendocrine tumor; PPPD indicates pylorus-preserving pancreaticoduodenectomy; DP indicates distal pancreatectomy; TP indicates total pancreatectomy; TRD indicates tumor-related death Wiltberger et al. BMC Surgery (2015) 15:126 Page 4 of 8 Table 2 Demographic data Characteristics Total (n = 18) Standard Resection (n = 6) Multivisceral resection (MVR; n = 12) p-value* Age (median; Range) 65 (22–75) 70 (49–75) 58 (22–72) 0.074 Gender (%) Female 10 (55.6) 4 (22.2) 6 (33.3) 0.548 Male 8 (44.4) 2 (11.1) 6 (33.3) 0.548 BMI (median; Range) 25.4 (18–31.1) 26 (21.7–30.4) 24.4 (18–31.1) 0.264 Comorbidities (%) Diabetes mellitus 4 (22.2) 2 (11.1) 2 (11.1) 0.932 Arterial hypertension 13 (72.2) 5 (33.3) 8 (44.4) 0.817 Metabolic syndrome 3 (16.7) 1 (5.6) 2 (11.1) 0.932 COPD* 2 (11.1) 0 (0) 2 (11.1) 0.104 CAD 5 (27.8) 1 (5.6) 4 (22.2) 0.374 Preoperative symptoms (%) Asymptomatic 10 (55.6) 4 (22.2) 6 (33.3) 0.548 Symptomatic Weight loss 8 (44.4) 3 (16.7) 5 (33.3) 0.984 Abdominal pain 7 (38.9) 3 (16.7) 4 (33.3) 0.682 obstructive jaundice 2 (11.1) 0 (0) 2 (11.1) 0.103 decrease in general performance 3 (16.7) 1 (5.6) 2 (11.1) 0.742 absence of appetite 1 (5.6) 1 (5.6) 0 (0) 0.170 Sleep hyperhidrosis 1 (5.6) 0 (0) 1 (5.6) 0.166 New onset of diabetes 1 (5.6) 0 (0) 1 (5.6) 0.166 COPD indicates chronic obstructive pulmonary disease; CAD indicates coronary artery disease simultaneous resection of the extrapancreatic masses. The (66.6 %) patients. Five patients who received Whipple- other four patients received a subsequent procedure procedure/PPPD or total pancreatectomy also required (metastasectomy of the lungs in three cases and one thy- additional liver resection to remove synchronous extra- roidectomy). In four patients, the diagnosis of pancreatic pancreatic metastases. Two of these patients underwent metastases coincided with that of the primary malignancy, additional bowel resection and three patients received which was RCC in all cases. In three of these patients, pri- additional gastric or bowel resection. In two patients who mary tumor and metastatic resection was performed as underwent PPPD or DP, simultaneous nephrectomy was one procedure. In one patient, an intraoperative biopsy of performed and one patient received simultaneous verte- the pancreatic head during tumor-nephrectomy con- bral body resection for solitary bone metastasis. The me- firmed metastatic disease and metastasectomy was per- dian operation time for all procedures was 322 min formed four weeks later. In three patients (30 %) with (range, 193–591 min). Ten patients received intraopera- RCC multifocal lesions in the resected specimens were tive fresh frozen plasma (median 3, range 0–18 units) detected. and/or packed red blood cells (median 2, range, 0–10 units). Microscopically-free resection margins (R0) were Surgical procedures achieved in 77.7 % of the patients. The median time between resection of the primary ma- lignancies to resection of the pancreatic metastases was Perioperative outcome 83 months (range, 0–228 months). The most frequently Length of stay in the intensive care unit and total length used surgical procedures were Whipple-procedure/pyl- of stay were 2 days (range, 1–50 days) and 21.5 days orus-preserving pancreaticoduodenectomy (PPPD) in 10 (range, 12–55 days), respectively (Table 3). No patients patients and distal pancreatectomy (DP) in five patients. died during hospitalization. Postoperative complications In four patients, DP was performed with and, in one occurred in 11 patients (61.1 %), of which 81 % were patient, without splenectomy. In three patients, total surgical and 18 % were non-surgical complications. pancreatectomy was performed, with simultaneous Minor surgical complications (Grade I-IIIa, n = 6) were: splenectomy in two cases. MVR was performed in 12 new onset of diabetes in two patients; wound infection Wiltberger et al. BMC Surgery (2015) 15:126 Page 5 of 8 Table 3 Perioperative data Data Total (n = 18) StandardResection (n = 6) Multivisceral resection (n = 12) p-Value Operative Data Length of operation (min) 322 (193–591) 261 (193–462) 346 (216–591) 0.137 FFPs and/or pRBCs 3 (0–18) 2 (0–10) 3 (0– 3) 1 (0–8) 3 (0–18) 4 (1–10) 0.291/0.838 Perioperative Data LOS-ICU 2 (1–50) 1 (1–3) 3 (1–50) 0.205 T-LOS 21 (12–55) 20 (16– 2) 23 (12–55) 0.898 Time interval* 72 (0–228) 113 (0–142) 31.5 (0–228) 0.259 Follow-up 76 (10–165) 59 (28–95) 53 (10–165) 0.104 1-year/3-year/5-year survival 84/66/55 83/50/56 83/66/50 Histopathological data RO/R1/R2 15/3/0 (83.3/16.7/0) 7/0/0 (38.9/0/0) 8/3/0 (44.4/16.7/0) 0.081 Negative/positive LN 13/5 (72.2/27.8) 6/1 (33.3/5.6) 7/4 (38.9/22.2) 0.278 Postoperative Complications (Clavien-Dindo classification) Non-Surgical related complications Minor (Grade I-IIIa) 0 (0) 0 (0) 0 (0) 0 Major (Grade IIIb – IV) 2 (11.1) 1 (5.6) 1 (5.6) 0.681 Surgical related complications Minor (Grade I-IIIa) 6 (33.3) 2 (11.1) 4 (22.2) 0.781 Major (Grade IIIb – IV) 3 (16.7) 1 (5.6) 2 (11.1) 0.932 Overall Morbidity Mortality (60 days) 0 (0) 0 (0) 0 (0) 0 Overall-Mortality Follow up Local recurrence 1 (5.6) 1 (5.6) 0 (0) 0.166 Extrapancreatic Recurrence 9 (50) 4 (22.2 5 (33.3) 0.565 Further surgical interventions 6 (33.3) 2 (11.1) 4 (22.2) 0.781 FFP, fresh frozen plasma; pRBC, packed red blood cells; LOS-ICU, length of stay in intensive care unit; T-LOS; total length of stay (n = 2), which was managed conservatively; and pancre- tumor-related in one case. During follow-up, nine pa- atic fistula grade B with prolonged use of abdominal tients suffered from extrapancreatic recurrence. Five drainage (n = 2). Major surgical complications (Grade patients received further surgical treatment including IIIb-V, n = 3) were: leakage from the hepaticojejunost- thyroidectomy, liver resection, or metastasectomy of the omy site with the need for relaparotomy, bowel perfor- lungs. In one patient, cerebral metastasis was treated by ation with the need for relaparotomy, biliary leakage stereotactic irradiation. Local recurrence of pancreatic after combined liver and pancreas resection that had to disease was seen in one patient and was successfully be treated with an interventional drain, and a wound controlled by total resection of the pancreatic remnant. infection that required re-operation under general In our sample, the time interval between resection of anesthesia, with each complication occurring in one the primary malignancy and detection of metastatic dis- case. Major non-surgical complications (Grade IIIb-V, ease did not correlate significantly with overall survival n = 2) occurred in two patients and both developed after resection of the pancreatic metastases. Kaplan- pneumonia requiring readmission to the intensive care Meier curve for survival with standard resection versus unit. MVR are shown in Fig. 1. One-, 3- and 5-year survival for standard resection versus MVR was 83, 50, and 56 %, Follow-up and survival versus 83, 66, and 50 %, respectively. No patient was lost to follow-up and the median follow- up time was 76 months (range, 10–165 months) with 12 Discussion patients dying after a median of 26 months (range, 5–55 Surgical interventions for metastatic disease have in- months). Death was tumor-related in 11 cases and non- creased over the last decade, concurrent with considerable Wiltberger et al. BMC Surgery (2015) 15:126 Page 6 of 8 Fig. 1 Kaplan–Meier survival curve showing survival for patients who underwent standard resection (solid line) versus multivisceral resection (dotted line) (in months) improvement in quality of life and long-term survival of complete resection of colorectal liver metastases, which up to 10 years following resection for the most common emphasizes the importance of this therapeutic option (liver or lung) metastases [12, 13]. As a result, surgical re- [12]. In our study, the rate of microscopically-free resec- section of metastases is now an integral part of a multidis- tion margins (77.7 %) did not differ from other studies ciplinary oncological approach [6]. In contrast, metastases reporting positive resection margins for pancreatic can- to the pancreas are uncommon and the majority of pa- cer of 17–30 % [17–19]. tients present with no specific symptoms [14] and with Because of the high incidence of metastatic disease non-resectable widespread disease at the time of diagnosis. originating from RCC, the most valid conclusions can be However, in cases of isolated disease, surgical intervention provided for this tumor type. Consequently, most re- may be beneficial in terms of overall survival, even in pa- ported data refer to RCC and are comparable with our tients with localized extrapancreatic metastases, and in results in terms of incidence and overall survival [1, 8, 20]. terms of the need for MVR to obtain complete tumor-free In our study, 10 patients (55.5 %) had pancreatic metasta- resection margins. ses from RCC and the overall survival of this subgroup Based on our experience, surgical intervention is justi- was 60 %. In a recently published review, Tanis et al. re- fied in select patients diagnosed with metastases to the ported a 5-year survival rate of 72.6 % in 311 cases follow- pancreas. Our data showed that surgical resection for ing pancreatic surgery for RCC metastases [21]. In this pancreatic metastases is feasible and provides good long context, time of metastatic onset is discussed as a prog- term results, even in patients undergoing MVR. Peri- nostic marker for long-term survival. A small number of operative morbidity and in-hospital mortality were studies have observed a trend to better overall survival in comparable to studies evaluating standard pancreatic patients with long disease-free interval when evaluating resection for primary malignancies [15]. In our study, primary tumor resection and onset of metastases to the morbidity after MVR tended to be higher than after pancreas. We did not see a similar effect in our patients standard resection. However, MVR for pancreatic me- because overall survival did not differ significantly be- tastases should not be considered an absolute contra- tween patients with longer disease-free interval. These indication for surgery, because our results indicated findings are supported by the results of a meta-analysis equivalent overall survival in the MVR group. which identified 15 studies addressing pancreatic The limitations of our study are the small cohort and metastasectomy for RCC [1]. In the univariate analysis, the absence of a control group treated by other thera- time from resection of the primary tumor did not affect peutic strategies. Therefore, general recommendations overall survival. cannot be made based on our data, even though Many changes have been made, regarding the onco- complete resection (R0) is generally considered a good logical treatment for metastatic RCC. Individualized im- prognostic marker for patients’ overall survival [16]. For munotherapy based on immunoreactive cytokines and/ instance, long-term survival of 10 years can be seen after or antiangiogenetic agents (e.g. bevacizumab, sunitinib, Wiltberger et al. BMC Surgery (2015) 15:126 Page 7 of 8 and sorafenib) have showed encouraging results. There- In total, nine of our patients (50 %) developed extra- fore, surgical resection should not be considered as the pancreatic recurrence, of which five (33.3 %) had under- only therapeutic option: An interdisciplinary approach gone previous MVR. Four patients received primarily including visceral surgeons, urologists and oncologists combined liver and pancreas resection for metastases of should be performed for the treatment against pancre- sarcoma or gallbladder cancer (n = 1 for each cancer) atic metastases to obtain sufficient synergistic antitumor and for metastases of malignant melanoma in two cases. effects. However, the best way to combine surgery with In the latter patients, hepatic recurrence occurred and oncological treatment has to be evaluated addressed by further surgical intervention was performed in one pa- future studies. tient, who is still alive. These results are consistent with Pancreatic metastases can occur after a long disease- other reports showing a survival rate of 50 % after liver free interval, with a median time between resection of resection for malignant melanoma [23]. Therefore, the the primary tumor and detection of pancreatic metasta- type of the primary tumor should also be considered ses of 72 months (range, 0–228 months). This biological when deciding on surgery and the patient should be in- tumor behavior reflects the importance of a prudent formed of the risk of recurrence. long-term follow-up in these patients, even if specific symptoms are missing. This point is supported by our Conclusions findings, which revealed that only 44.4 % of the patients A surgical approach with curative intent is justified in had specific symptoms. We recommend that regular select patients suffering from metastases to the pan- follow-up including radiological imaging should be per- creas and offers good long-term survival. Our results formed even after a long disease-free interval. showed that resection of pancreatic metastases of dif- Very few data are available regarding the potential im- ferent tumor types was associated with favorable mor- pact of MVR for pancreatic metastases on morbidity and bidity and mortality when compared with resection of mortality because of the low proportion of patients with the primary pancreatic malignancies. Our findings also MVR in most of the published studies [20]. However, in demonstrated that MVR was feasible, with acceptable our study, the majority of patients (66.6 %) were treated long term outcomes, even though morbidity tended to by a multivisceral approach. In a retrospective analysis, be higher than with standard resection. Strobel et al. compared patients who received either Abbreviations standard resection or MVR for pancreatic metastases of DP: distal pancreatectomy; MVR: multivisceral resection; PPPD: pylorus-preserving different tumor types [22]. The authors reported no sig- pancreaticoduodenectomy; RCC: renal cell carcinoma. nificant difference for morbidity and mortality between Competing interests groups, although morbidity in the MVR group tended to The authors declare that they have no competing interests. be higher. Also, the majority of complications were sur- Authors’ contributions gical, with one patient dying in each group. These results GW, JB, HMH and MB were responsible for the study conception and design; are comparable to our results where the majority of GW, CB, JB, FK, GA, and HMH were responsible for data acquisition; GW, JB, postoperative complications were also surgical. We also HMH, and MB analyzed and interpreted the data; GW, JB, and HMH drafted the manuscript; and FK, JB, CB, MS, HMH and MB critically revised the saw that major surgical complications occurred more manuscript. All authors read and approved the final manuscript. frequently in the MVR group, although this result was not statistically significant. Because of its potentially Acknowledgements The authors declare that no funding was received for the study. beneficial impact on long-term survival, we do not con- sider that MVR is an absolute contraindication but that Author details the increased operative risk should be considered in the Department of Visceral, Transplantation, Thoracic, and Vascular Surgery, University Hospital Leipzig, 04103 Leipzig, Germany. Department of Surgery, decision making process. The overall morbidity in our University Hospital Großhadern (LMU), Munich, Germany. Department of study was not increased compared with the reported General, Visceral, and Transplant Surgery, Charité - Universitätsmedizin Berlin, morbidity rate for resection of primary pancreatic malig- Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. nancies of up to 58.5 %, even though major surgical Received: 6 May 2015 Accepted: 7 December 2015 complications occurred more frequently in our study [15]. This might be attributable to the high proportion of patients who underwent MVR. References 1. Reddy S, Wolfgang CL. The role of surgery in the management of isolated During our study follow-up, only one patient suf- metastases to the pancreas. Lancet Oncol. 2009;10:287–93. fered from tumor recurrence in the pancreas and this 2. Eidt S, Jergas M, Schmidt R, Siedek M. Metastasis to the pancreas–an was successfully treated by resection of the pancreatic indication for pancreatic resection? 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Extended resection in pancreatic metastases: feasibility, frequency, and long-term outcome: a retrospective analysis

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Springer Journals
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Copyright © 2015 by Wiltberger et al.
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Medicine & Public Health; Surgery; Internal Medicine
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1471-2482
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10.1186/s12893-015-0114-1
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Abstract

Background: Metastases to the pancreas are rare, accounting for less then 2 % of all pancreatic malignancies. However, both the benefit of extended tumor resection and the ideal oncological approach have not been established for such cases; therefore, we evaluated patients with metastasis to the pancreas who underwent pancreatic resection. Methods: Between 1994 and 2012, 676 patients underwent pancreatic surgery in our institution. We retrospectively reviewed patients’ medical records according to survival, and surgical and non-surgical complications. Student’s t-test and the log-rank test were used for statistical analysis. Results: Eighteen patients (2.7 %) received resection for pancreatic metastases (12 multivisceral resections and 6 standard resections). The pancreatic metastases originated from renal cell carcinoma (n = 10), malignant melanoma (n = 2), neuroendocrine tumor of the ileum (n = 1), sarcoma (n = 1), colon cancer (n = 1), gallbladder cancer (n =1), gastrointestinal stromal tumor (n = 1), and non-small cell lung cancer (n = 1). The median time between primary malignancy resection to metastasectomy was 83 months (range, 0–228 months). Minor surgical complications (Grade I-IIIa) occurred in six patients (33.3 %) whereas major surgical complications (Grade IIIb-V) occurred in three patients (16.6 %). No patients died during hospitalization. The median follow-up was 76 months (range, 10–165 months). One-year, 3-year and 5-year survival for standard resection versus multivisceral resection was 83, 50, and 56 % versus 83, 66, and 50, respectively. Twelve patients died after a median of 26 months (range, 5–55 months). Conclusions: A surgical approach with curative intent is justified in select patients suffering from metastases to the pancreas and offers good long-term survival. The resection of pancreatic metastases of different tumor types was associated with favorable morbidity and mortality when compared with resection of the primary pancreatic malignancies. Our findings also demonstrated that multivisceral resection was feasible, with acceptable long term outcomes, even though morbidity rates tended to be higher after multivisceral resection than after standard resection. Keywords: Multivisceral resection, Metastases to the pancreas, Pancreaticoduodenectomy * Correspondence: [email protected] Equal contributors Department of Visceral, Transplantation, Thoracic, and Vascular Surgery, University Hospital Leipzig, 04103 Leipzig, Germany Full list of author information is available at the end of the article © 2015 Wiltberger et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wiltberger et al. BMC Surgery (2015) 15:126 Page 2 of 8 Background morbidity according to Clavien-Dindo classification [10], Metastases to the pancreas are rare and account only for presence of pancreatic fistulae according to the Inter- 1–2 % of all pancreatic malignancies [1]. Most primaries national Study Group for Pancreatic Fistula criteria [11], that spread to the pancreas are renal cell carcinomas hospital mortality defined as death within the first (RCC), lung cancers, malignant melanomas, and malig- 60 days after resection, overall survival rate, disease-free nancies of the gastrointestinal tract [2, 3]. However, at survival, and histopathological data. Patients who died the time of diagnosis, patients often present with within the first 90 days after resection were excluded widespread systemic disease and therefore, no curative from further statistical analysis. MVR was defined as re- treatment is applicable. Several studies have demon- section of one additional organ, excluding the spleen. stratedsurvivalbenefit andimprovedqualityof life after complete metastasectomy for isolated lung or Statistics liver metastases [4, 5]. Therefore, extended surgical Data are presented as median (range) unless otherwise intervention is a well-established approach in a multi- specified. Statistical differences between groups were disciplinary concept for select patients suffering from determined by Student’s t-test. Student’s t-test and the colorectal or pulmonary metastases in the liver [6]. log-rank test were used to analyze continuous variables However, extended surgery for pancreatic metastasectomy and overall survival excluding in-hospital mortality, re- is rare and remains debatable as there have been few spectively. All statistical analyses were performed with studies on the procedure, all of which have reported SPSS for Windows (version 12.0, SPSS Inc., Chicago, controversial results [7–9]. Patients with localized IL, USA). extrapancreatic disease appear to be suitable for pan- creatic resection but the ideal oncological approach Results has not been established and the benefit of multivisc- Patient characteristics and preoperative symptoms eral resection (MVR) remains undetermined. Our aim Between 1994 and 2012, 676 patients were scheduled for was to assess the frequency and feasibility of MVR pancreatic surgery, of which 18 (2.6 %) received resec- for metastases to the pancreas. We also analyzed the tion for metastatic disease of the pancreas (Table 1). influence of MVR on perioperative and long-term Eight of the patients were men and 10 were woman outcomes compared with standard resection. with a median age of 65 years (range, 22–75 years) and a median body mass index of 25.4 kg/m (range, Methods 18–31 kg/m ). Four patients (22.2 %), had diabetes We retrospectively analyzed the medical records of mellitus type II and 13 (72.2 %) patients received patients who underwent pancreatic resection at the medication for high blood pressure (Table 2). At the Department of Visceral, Transplant, Thoracic, and time of diagnosis of pancreatic metastases, eight patients Vascular Surgery, University Hospital Leipzig, Leipzig, (44.4 %) had one or more tumor-related symptoms includ- Germany, between 1994 and 2012. ing weight loss (n = 8), abdominal pain (n = 8), decrease in For this study ethical approval was obtained from general performance (n = 5), obstructive jaundice (n =2), the institutional local ethical committee (AZ 318-14- or absence of appetite (n = 1). Ten patients (55.5 %) 06102014, Ethical committee of the University Clinic had no specific symptoms and the diagnosis of pancreatic Leipzig, Leipzig). Due to the retrospective design of metastases was obtained through routine follow-up the study and accordingly national guidelines, the examinations. local ethic committee confirmed, that informed con- sent was not necessary from participants. Primary tumor characteristics All patients were operated on with curative intent. We The majority of pancreatic metastases originated from included patients with extrapancreatic spread in this renal cell carcinoma (n = 10; 55.5 %), malignant melan- study only when extrapancreatic disease appeared to be oma (n = 2), and neuroendocrine tumor of the ileum resectable, and we excluded patients with primary tu- (n = 1). Other primaries included sarcoma (n =1), mors that had infiltrated the pancreas through direct colon cancer (n = 1), gallbladder cancer (n =1), gastro- extension. intestinal stromal tumor (n = 1), and non-small cell We assessed the following patient characteristics: sex, lung cancer (n = 1). Metastases to the pancreas were age, body mass index, preoperative symptoms, comor- located mainly in the pancreatic head (n = 10) bidities, type of resection, duration of operation, re- followed by the total pancreas (n = 3) and the cauda quired units of fresh frozen plasma and/or packed red region (n = 3). In two patients, metastases were simul- blood cells, median length of stay on the intensive care taneously located in the corpus and cauda region. unit, total length of stay, time between surgery for the Eleven patients (61 %) had simultaneous metastases in primary tumor and pancreatic resection, postoperative other organs and seven of these patients underwent Wiltberger et al. BMC Surgery (2015) 15:126 Page 3 of 8 Table 1 Patient characteristics Case No. Primary Malignancy Location in the pancreas Time interval Type of Operation further metastases at detection tumor recurrence/ (sync./metac.) (months)* of pancreatic metastasis□ survival status 1 RCC Head (sync.) 0 PPPD + Nephrectomy no no/alive 2 Lung-Cancer Cauda (metac.) 83 DP + Gastrectomy + Splenectomy + vertebral body resection Vertebral body (s) no/TRD 3 RCC Head (metac.) 142 PPPD no no/Non-TRD 4 RCC Head (sync.) 0.8 PPPD no Local recurrence/alive 5 RCC Head/Corpus/Cauda (metac.) 120 Enucleation in pancreatic head + DP + Splenectomy Lung (s) Thyroid/TRD 6 RCC Head/Corpus/Cauda (metac.) 132 TP + Spleenectomy + distal Gastrectomy Thyroid (s) no/TRD 7 Gallblader-Cancer Head (sync.) 0 PPPD + Liver resection (SII SIII) Liver (a) yes/TRD 8 RCC Corpus/Cauda (sync.) 17 DP + Spleen + Colon +Jejunom Pulmo (s) no/TRD 9 GIST Head (metac.) 34 PPPD + Hemicolectomy Liver (a) yes/alive 10 RCC Head (metac.) 106 Whipple no Lung/TRD 11 Sarcoma Head (sync.) 0 Whipple + Hemihepatectomy + Hemicolectomy Liver (s) Liver/TRD 12 RCC Head/Corpus/Cauda (metac.) 66 TP + Spleen no Cerebral/TRD 13 Melanoma Head/Corpus/Cauda (metac.) 90 TP + Segemental liver resection Liver (a) Liver/alive 14 RCC Cauda (metac.) 123 DP Pulmo (s) Thyroid/TRD 15 Melanoma Head (metac.) 228 PPPD + Hemihepatectomy Liver (a) Liver/TRD 16 RCC Head (sync.) 0 DP + Spleen + Nephrctomy no no/alive 17 Colon-Cancer Head (metac.) 29 PPPD + Liver resection (Lobus caudatus) Liver (s) no/alive 18 NET Ileum Head (sync.) 78 PPPD + Jejunum Jejunum (s) no/alive sync. indicates synchronous metastases to the pancreas; metac. indicates metachronous metastases to the pancreas; * interval from resection of primary tumor to resection of pancreatic metastasis; □ excluding pancreas (a, after; s, synchronous; p, prior); † at time of study; RCC indicates renal cell carcinoma; NET indicates neuroendocrine tumor; PPPD indicates pylorus-preserving pancreaticoduodenectomy; DP indicates distal pancreatectomy; TP indicates total pancreatectomy; TRD indicates tumor-related death Wiltberger et al. BMC Surgery (2015) 15:126 Page 4 of 8 Table 2 Demographic data Characteristics Total (n = 18) Standard Resection (n = 6) Multivisceral resection (MVR; n = 12) p-value* Age (median; Range) 65 (22–75) 70 (49–75) 58 (22–72) 0.074 Gender (%) Female 10 (55.6) 4 (22.2) 6 (33.3) 0.548 Male 8 (44.4) 2 (11.1) 6 (33.3) 0.548 BMI (median; Range) 25.4 (18–31.1) 26 (21.7–30.4) 24.4 (18–31.1) 0.264 Comorbidities (%) Diabetes mellitus 4 (22.2) 2 (11.1) 2 (11.1) 0.932 Arterial hypertension 13 (72.2) 5 (33.3) 8 (44.4) 0.817 Metabolic syndrome 3 (16.7) 1 (5.6) 2 (11.1) 0.932 COPD* 2 (11.1) 0 (0) 2 (11.1) 0.104 CAD 5 (27.8) 1 (5.6) 4 (22.2) 0.374 Preoperative symptoms (%) Asymptomatic 10 (55.6) 4 (22.2) 6 (33.3) 0.548 Symptomatic Weight loss 8 (44.4) 3 (16.7) 5 (33.3) 0.984 Abdominal pain 7 (38.9) 3 (16.7) 4 (33.3) 0.682 obstructive jaundice 2 (11.1) 0 (0) 2 (11.1) 0.103 decrease in general performance 3 (16.7) 1 (5.6) 2 (11.1) 0.742 absence of appetite 1 (5.6) 1 (5.6) 0 (0) 0.170 Sleep hyperhidrosis 1 (5.6) 0 (0) 1 (5.6) 0.166 New onset of diabetes 1 (5.6) 0 (0) 1 (5.6) 0.166 COPD indicates chronic obstructive pulmonary disease; CAD indicates coronary artery disease simultaneous resection of the extrapancreatic masses. The (66.6 %) patients. Five patients who received Whipple- other four patients received a subsequent procedure procedure/PPPD or total pancreatectomy also required (metastasectomy of the lungs in three cases and one thy- additional liver resection to remove synchronous extra- roidectomy). In four patients, the diagnosis of pancreatic pancreatic metastases. Two of these patients underwent metastases coincided with that of the primary malignancy, additional bowel resection and three patients received which was RCC in all cases. In three of these patients, pri- additional gastric or bowel resection. In two patients who mary tumor and metastatic resection was performed as underwent PPPD or DP, simultaneous nephrectomy was one procedure. In one patient, an intraoperative biopsy of performed and one patient received simultaneous verte- the pancreatic head during tumor-nephrectomy con- bral body resection for solitary bone metastasis. The me- firmed metastatic disease and metastasectomy was per- dian operation time for all procedures was 322 min formed four weeks later. In three patients (30 %) with (range, 193–591 min). Ten patients received intraopera- RCC multifocal lesions in the resected specimens were tive fresh frozen plasma (median 3, range 0–18 units) detected. and/or packed red blood cells (median 2, range, 0–10 units). Microscopically-free resection margins (R0) were Surgical procedures achieved in 77.7 % of the patients. The median time between resection of the primary ma- lignancies to resection of the pancreatic metastases was Perioperative outcome 83 months (range, 0–228 months). The most frequently Length of stay in the intensive care unit and total length used surgical procedures were Whipple-procedure/pyl- of stay were 2 days (range, 1–50 days) and 21.5 days orus-preserving pancreaticoduodenectomy (PPPD) in 10 (range, 12–55 days), respectively (Table 3). No patients patients and distal pancreatectomy (DP) in five patients. died during hospitalization. Postoperative complications In four patients, DP was performed with and, in one occurred in 11 patients (61.1 %), of which 81 % were patient, without splenectomy. In three patients, total surgical and 18 % were non-surgical complications. pancreatectomy was performed, with simultaneous Minor surgical complications (Grade I-IIIa, n = 6) were: splenectomy in two cases. MVR was performed in 12 new onset of diabetes in two patients; wound infection Wiltberger et al. BMC Surgery (2015) 15:126 Page 5 of 8 Table 3 Perioperative data Data Total (n = 18) StandardResection (n = 6) Multivisceral resection (n = 12) p-Value Operative Data Length of operation (min) 322 (193–591) 261 (193–462) 346 (216–591) 0.137 FFPs and/or pRBCs 3 (0–18) 2 (0–10) 3 (0– 3) 1 (0–8) 3 (0–18) 4 (1–10) 0.291/0.838 Perioperative Data LOS-ICU 2 (1–50) 1 (1–3) 3 (1–50) 0.205 T-LOS 21 (12–55) 20 (16– 2) 23 (12–55) 0.898 Time interval* 72 (0–228) 113 (0–142) 31.5 (0–228) 0.259 Follow-up 76 (10–165) 59 (28–95) 53 (10–165) 0.104 1-year/3-year/5-year survival 84/66/55 83/50/56 83/66/50 Histopathological data RO/R1/R2 15/3/0 (83.3/16.7/0) 7/0/0 (38.9/0/0) 8/3/0 (44.4/16.7/0) 0.081 Negative/positive LN 13/5 (72.2/27.8) 6/1 (33.3/5.6) 7/4 (38.9/22.2) 0.278 Postoperative Complications (Clavien-Dindo classification) Non-Surgical related complications Minor (Grade I-IIIa) 0 (0) 0 (0) 0 (0) 0 Major (Grade IIIb – IV) 2 (11.1) 1 (5.6) 1 (5.6) 0.681 Surgical related complications Minor (Grade I-IIIa) 6 (33.3) 2 (11.1) 4 (22.2) 0.781 Major (Grade IIIb – IV) 3 (16.7) 1 (5.6) 2 (11.1) 0.932 Overall Morbidity Mortality (60 days) 0 (0) 0 (0) 0 (0) 0 Overall-Mortality Follow up Local recurrence 1 (5.6) 1 (5.6) 0 (0) 0.166 Extrapancreatic Recurrence 9 (50) 4 (22.2 5 (33.3) 0.565 Further surgical interventions 6 (33.3) 2 (11.1) 4 (22.2) 0.781 FFP, fresh frozen plasma; pRBC, packed red blood cells; LOS-ICU, length of stay in intensive care unit; T-LOS; total length of stay (n = 2), which was managed conservatively; and pancre- tumor-related in one case. During follow-up, nine pa- atic fistula grade B with prolonged use of abdominal tients suffered from extrapancreatic recurrence. Five drainage (n = 2). Major surgical complications (Grade patients received further surgical treatment including IIIb-V, n = 3) were: leakage from the hepaticojejunost- thyroidectomy, liver resection, or metastasectomy of the omy site with the need for relaparotomy, bowel perfor- lungs. In one patient, cerebral metastasis was treated by ation with the need for relaparotomy, biliary leakage stereotactic irradiation. Local recurrence of pancreatic after combined liver and pancreas resection that had to disease was seen in one patient and was successfully be treated with an interventional drain, and a wound controlled by total resection of the pancreatic remnant. infection that required re-operation under general In our sample, the time interval between resection of anesthesia, with each complication occurring in one the primary malignancy and detection of metastatic dis- case. Major non-surgical complications (Grade IIIb-V, ease did not correlate significantly with overall survival n = 2) occurred in two patients and both developed after resection of the pancreatic metastases. Kaplan- pneumonia requiring readmission to the intensive care Meier curve for survival with standard resection versus unit. MVR are shown in Fig. 1. One-, 3- and 5-year survival for standard resection versus MVR was 83, 50, and 56 %, Follow-up and survival versus 83, 66, and 50 %, respectively. No patient was lost to follow-up and the median follow- up time was 76 months (range, 10–165 months) with 12 Discussion patients dying after a median of 26 months (range, 5–55 Surgical interventions for metastatic disease have in- months). Death was tumor-related in 11 cases and non- creased over the last decade, concurrent with considerable Wiltberger et al. BMC Surgery (2015) 15:126 Page 6 of 8 Fig. 1 Kaplan–Meier survival curve showing survival for patients who underwent standard resection (solid line) versus multivisceral resection (dotted line) (in months) improvement in quality of life and long-term survival of complete resection of colorectal liver metastases, which up to 10 years following resection for the most common emphasizes the importance of this therapeutic option (liver or lung) metastases [12, 13]. As a result, surgical re- [12]. In our study, the rate of microscopically-free resec- section of metastases is now an integral part of a multidis- tion margins (77.7 %) did not differ from other studies ciplinary oncological approach [6]. In contrast, metastases reporting positive resection margins for pancreatic can- to the pancreas are uncommon and the majority of pa- cer of 17–30 % [17–19]. tients present with no specific symptoms [14] and with Because of the high incidence of metastatic disease non-resectable widespread disease at the time of diagnosis. originating from RCC, the most valid conclusions can be However, in cases of isolated disease, surgical intervention provided for this tumor type. Consequently, most re- may be beneficial in terms of overall survival, even in pa- ported data refer to RCC and are comparable with our tients with localized extrapancreatic metastases, and in results in terms of incidence and overall survival [1, 8, 20]. terms of the need for MVR to obtain complete tumor-free In our study, 10 patients (55.5 %) had pancreatic metasta- resection margins. ses from RCC and the overall survival of this subgroup Based on our experience, surgical intervention is justi- was 60 %. In a recently published review, Tanis et al. re- fied in select patients diagnosed with metastases to the ported a 5-year survival rate of 72.6 % in 311 cases follow- pancreas. Our data showed that surgical resection for ing pancreatic surgery for RCC metastases [21]. In this pancreatic metastases is feasible and provides good long context, time of metastatic onset is discussed as a prog- term results, even in patients undergoing MVR. Peri- nostic marker for long-term survival. A small number of operative morbidity and in-hospital mortality were studies have observed a trend to better overall survival in comparable to studies evaluating standard pancreatic patients with long disease-free interval when evaluating resection for primary malignancies [15]. In our study, primary tumor resection and onset of metastases to the morbidity after MVR tended to be higher than after pancreas. We did not see a similar effect in our patients standard resection. However, MVR for pancreatic me- because overall survival did not differ significantly be- tastases should not be considered an absolute contra- tween patients with longer disease-free interval. These indication for surgery, because our results indicated findings are supported by the results of a meta-analysis equivalent overall survival in the MVR group. which identified 15 studies addressing pancreatic The limitations of our study are the small cohort and metastasectomy for RCC [1]. In the univariate analysis, the absence of a control group treated by other thera- time from resection of the primary tumor did not affect peutic strategies. Therefore, general recommendations overall survival. cannot be made based on our data, even though Many changes have been made, regarding the onco- complete resection (R0) is generally considered a good logical treatment for metastatic RCC. Individualized im- prognostic marker for patients’ overall survival [16]. For munotherapy based on immunoreactive cytokines and/ instance, long-term survival of 10 years can be seen after or antiangiogenetic agents (e.g. bevacizumab, sunitinib, Wiltberger et al. BMC Surgery (2015) 15:126 Page 7 of 8 and sorafenib) have showed encouraging results. There- In total, nine of our patients (50 %) developed extra- fore, surgical resection should not be considered as the pancreatic recurrence, of which five (33.3 %) had under- only therapeutic option: An interdisciplinary approach gone previous MVR. Four patients received primarily including visceral surgeons, urologists and oncologists combined liver and pancreas resection for metastases of should be performed for the treatment against pancre- sarcoma or gallbladder cancer (n = 1 for each cancer) atic metastases to obtain sufficient synergistic antitumor and for metastases of malignant melanoma in two cases. effects. However, the best way to combine surgery with In the latter patients, hepatic recurrence occurred and oncological treatment has to be evaluated addressed by further surgical intervention was performed in one pa- future studies. tient, who is still alive. These results are consistent with Pancreatic metastases can occur after a long disease- other reports showing a survival rate of 50 % after liver free interval, with a median time between resection of resection for malignant melanoma [23]. Therefore, the the primary tumor and detection of pancreatic metasta- type of the primary tumor should also be considered ses of 72 months (range, 0–228 months). This biological when deciding on surgery and the patient should be in- tumor behavior reflects the importance of a prudent formed of the risk of recurrence. long-term follow-up in these patients, even if specific symptoms are missing. This point is supported by our Conclusions findings, which revealed that only 44.4 % of the patients A surgical approach with curative intent is justified in had specific symptoms. We recommend that regular select patients suffering from metastases to the pan- follow-up including radiological imaging should be per- creas and offers good long-term survival. Our results formed even after a long disease-free interval. showed that resection of pancreatic metastases of dif- Very few data are available regarding the potential im- ferent tumor types was associated with favorable mor- pact of MVR for pancreatic metastases on morbidity and bidity and mortality when compared with resection of mortality because of the low proportion of patients with the primary pancreatic malignancies. Our findings also MVR in most of the published studies [20]. However, in demonstrated that MVR was feasible, with acceptable our study, the majority of patients (66.6 %) were treated long term outcomes, even though morbidity tended to by a multivisceral approach. In a retrospective analysis, be higher than with standard resection. Strobel et al. compared patients who received either Abbreviations standard resection or MVR for pancreatic metastases of DP: distal pancreatectomy; MVR: multivisceral resection; PPPD: pylorus-preserving different tumor types [22]. The authors reported no sig- pancreaticoduodenectomy; RCC: renal cell carcinoma. nificant difference for morbidity and mortality between Competing interests groups, although morbidity in the MVR group tended to The authors declare that they have no competing interests. be higher. Also, the majority of complications were sur- Authors’ contributions gical, with one patient dying in each group. These results GW, JB, HMH and MB were responsible for the study conception and design; are comparable to our results where the majority of GW, CB, JB, FK, GA, and HMH were responsible for data acquisition; GW, JB, postoperative complications were also surgical. We also HMH, and MB analyzed and interpreted the data; GW, JB, and HMH drafted the manuscript; and FK, JB, CB, MS, HMH and MB critically revised the saw that major surgical complications occurred more manuscript. All authors read and approved the final manuscript. frequently in the MVR group, although this result was not statistically significant. Because of its potentially Acknowledgements The authors declare that no funding was received for the study. beneficial impact on long-term survival, we do not con- sider that MVR is an absolute contraindication but that Author details the increased operative risk should be considered in the Department of Visceral, Transplantation, Thoracic, and Vascular Surgery, University Hospital Leipzig, 04103 Leipzig, Germany. Department of Surgery, decision making process. The overall morbidity in our University Hospital Großhadern (LMU), Munich, Germany. Department of study was not increased compared with the reported General, Visceral, and Transplant Surgery, Charité - Universitätsmedizin Berlin, morbidity rate for resection of primary pancreatic malig- Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. nancies of up to 58.5 %, even though major surgical Received: 6 May 2015 Accepted: 7 December 2015 complications occurred more frequently in our study [15]. This might be attributable to the high proportion of patients who underwent MVR. References 1. Reddy S, Wolfgang CL. The role of surgery in the management of isolated During our study follow-up, only one patient suf- metastases to the pancreas. Lancet Oncol. 2009;10:287–93. fered from tumor recurrence in the pancreas and this 2. Eidt S, Jergas M, Schmidt R, Siedek M. Metastasis to the pancreas–an was successfully treated by resection of the pancreatic indication for pancreatic resection? 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J Surg Oncol. 2013;108(2):129–35. � Convenient online submission � Thorough peer review � Inclusion in PubMed and all major indexing services � Maximum visibility for your research Submit your manuscript at www.biomedcentral.com/submit

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BMC Surgery – Springer Journals

Published: Dec 11, 2015

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