Ann Surg Oncol https://doi.org/10.1245/s10434-017-6299-z

ORIGINAL ARTICLE – UROLOGIC ONCOLOGY

Peritoneal Carcinomatosis of Urachus Origin Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): An International Registry of 36 Patients Frederic Mercier, MD, MSc1, Guillaume Passot, MD, PhD1,2, Laurent Villeneuve, PhD2,3, Edward A. Levine, MD4, Yutaka Yonemura, MD, PhD5,6,7,8,9, Diane Goe´re´, MD, PhD10, Paul H. Sugarbaker, MD11, Christelle Marolho, MSc3, David L. Bartlett, MD12, Olivier Glehen, MD, PhD1,2, and On Behalf of the PSOGI and BIG RENAPE Groups 1

Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Pierre Be´nite, France; 2EMR 37-38, Lyon 1 University, Lyon, France; 3Poˆle Information Me´dicale Evaluation Recherche, Hospices Civils de Lyon, Unite´ de Recherche Clinique, Lyon, France; 4Section of Surgical Oncology, Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, NC; 5Asian School of Peritoneal Surface Oncology, Kyoto, Japan; 6NPO to support Peritoneal Surface Malignancy Treatment, Kyoto, Japan; 7Regional Cancer Therapies, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Osaka, Japan; 8Kutatsu General Hospital, Kusatsu, Shiga, Japan; 9Ikeda Hospital, Nagaizumi-cho, Shizuoka, Japan; 10Department of Surgery, Gustave Roussy, Universite´ Paris-Saclay, Villejuif, France; 11Center for Gastrointestinal Malignancies, Program in Peritoneal Surface Oncology, MedStar Washington Hospital Center, Washington, DC; 12Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA

ABSTRACT Purpose. Peritoneal carcinomatosis or pseudomyxoma peritonei from urachus is a rare form of presentation, often diagnosed at an advanced state of tumor burden. Because of its rarity, little is known about its natural history, prognosis, or optimal treatment. We searched a large international multicenter database of peritoneal surface disease to identify cases of peritoneal carcinomatosis of urachus that were treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) at expert centers. The aim is to improve knowledge and understanding of the disease and standardize its treatment. Methods. A prospective multicenter international database was retrospectively searched to identify all patients with urachus tumor and peritoneal metastases who

Collaborators (PSOGI and BIG-RENAPE Working Groups) are listed in the ‘‘Acknowledgement’’. Ó Society of Surgical Oncology 2017 First Received: 31 May 2017 O. Glehen, MD, PhD e-mail: [email protected]

underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI). Postoperative complications, long-term results, and principal prognostic factors were analyzed. Results. The analysis included 36 patients. After median follow-up of 48 months, median overall survival (OS) was 58.5 months. Three- and 5-year OS was 55.4 and 46.2%, respectively. Patients who underwent complete macroscopic CRS had significantly better survival than those treated with incomplete CRS, with median OS not achieved and of 20.1 months, respectively [95% confidence interval (CI) 4.4–30.5, p \ 0.001]. There were no postoperative deaths, and 37.9% of patients had major complications. Conclusion. CRS and HIPEC may increase long-term survival in selected patients with peritoneal metastases of urachus origin, especially when complete CRS is achieved.

Pseudomyxoma peritonei (PMP) is a clinical condition involving extensive intraperitoneal spread of mucin. PMP is associated with various mucinous tumors, each of which has distinct biologic behaviors.1–4 The most common primary tumor sites are the appendix and ovaries. Understanding of the pathological and physiopathological characteristics and natural evolution, as well as the

F. Mercier et al.

prognosis, of these rare tumors have improved over the last 20 years thanks to an expanding body of literature.5–7 As pathology methods used to classify tumor origin have evolved, other locations for primary tumors that lead to PMP have been identified, with urachus being one such site.8–10 It is challenging to confirm a diagnosis of urachusderived PMP, but there are three main indicators: midline mass visualized on computed tomography (CT) scan, complaints of mucosuria by the patient, and elevated cancer antigen (CA) 19-9.2,5,11 PMP presentation of urachus cancer is a rare occurrence.1 Standard treatment for appendiceal PMP has evolved dramatically over the last two decades, and the gold-standard treatment is now cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). These procedures, when performed at a high-volume center, can achieve long-lasting patient survival (5-year survival of around 80%) and can even cure a good proportion of patients.12,13 There are few reports of PMP of urachal origin, and most publications are case reports, although one single-center retrospective patient series reported nine cases.2–5,7–9 Due to the paucity of knowledge about these rare tumors, it is extremely difficult to define their natural evolution, physiopathological characteristics, and prognosis. Indeed, a single-center database simply cannot collect enough cases to help researchers better understand the tumor pathology. To collect data from more cases with this rare disease, an international database was created for rare peritoneal diseases using the Peritoneal Surface Oncology Group International (PSOGI) and BIG RENAPE working group databases as resources. We report herein the largest series of peritoneal carcinomatosis of urachus origin treated with CRS and HIPEC.

Sugarbaker score, which ranges from 0 to 39.14 Quality of CRS was defined according to Sugarbaker completeness of cytoreduction (CC) score: CC-0, no macroscopic residual tumor; CC-1, residual tumor \ 2.5 mm; CC-2, residual tumor between 2.5 and 25 mm; CC-3, residual tumor [ 25 mm.15 CRS was considered to be complete when CC-0 or CC-1 score was attained. Intraperitoneal treatment consisted of HIPEC performed by either open abdomen technique or closed abdomen technique, as described previously.16 Surgical complications were retrospectively graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.17 Recurrences were diagnosed based on clinical, radiological, or histological findings and were consistently confirmed in multidisciplinary team meetings. Statistical Analysis

PATIENTS AND METHODS

Descriptive data are expressed as mean (± SD) and median (range or 95% CI) for quantitative variables and as number (percentage) for qualitative data. Overall survival (OS) time was defined as time from first HIPEC procedure to date of death, date of last follow-up, or cutoff date, whichever came first. Perioperative deaths were not excluded from the survival analysis. Recurrence-free survival was defined as time from first HIPEC procedure until recurrence or last follow-up. Deceased patients were censored at date of death. Patients with recurrent disease at time of HIPEC procedure or patients who had undergone CC-2 resection were considered to have immediate relapse and were not included in recurrence-free survival analysis. Median survival times and survival rates were computed by Kaplan–Meier method. Hazard ratios and p values were obtained using the Cox proportional hazards model. SAS statistical software (v9.3) was used for all analyses.

Study Population

RESULTS

A prospective multicenter international database (a collaborative database of the PSOGI and BIG-RENAPE) was searched to identify all patients who underwent HIPEC for peritoneal metastases of urachus origin at all expert centers that are part of the PSOGI and BIG RENAPE working groups. The study was conducted in accordance with the tenets of the Declaration of Helsinki. For each patient included in the database, the following data were collected: sex, age at time of surgery, history of abdominal surgery, history of preoperative chemotherapy, extension of peritoneal disease, completeness of CRS, length of surgery, and postoperative morbidity and mortality. Extent of peritoneal metastasis was routinely measured using the peritoneal cancer index (PCI), formerly called the

Population Between December 1992 and December 2015, 36 patients underwent HIPEC for peritoneal metastases of urachal origin. These patients were treated at 14 specialized centers. Table 1 describes the clinicopathological characteristics and morbidity/mortality of these patients. Descriptive data are expressed as mean (± SD) and median (range). Median age at diagnosis was 42.7 years (20.6–61.1 years), and there was a 2:1 male:female ratio. Of the 36 patients, 17 received preoperative chemotherapy. Median PCI was 8.5 (1–33). Median surgical time was 434 min (150–966 min). In terms of HIPEC technique, open technique was used for 23 patients and closed

HIPEC in Urachus Peritoneal Carcinomatosis TABLE 1 Clinicopathological characteristics and morbidity/mortality of patients with urachus-derived carcinomatosis

TABLE 2 Median 3-year and 5-year overall survival and diseasefree survival of patients with urachus-derived carcinomatosis

Characteristic

n = 36

Overall survival (n = 35)

Age, median (range), years

42.7 (20.6–61.1)

Sex, n (%) Male

24 (66.7)

Female

12 (33.3) a

Preoperative chemotherapy , n (%) b

17 (50)

Peritoneal cancer index (PCI) , median (range)

8.5 (1–33)

[ 15 Median length of surgery (range)c, min

9 (37.5) 434 (150–966)

Median (months)

58.5

3-year (%)

55.4

5-year (%)

46.2

Disease-free survival (n = 28) Median (months)

60.5

3-year (%)

62.6

5-year (%)

55.6

Completeness of cytoreduction (CC) score, n (%) CC-0

24 (66.7)

CC-1

7 (19.4)

CC-2–3

5 (13.9)

HIPEC technique, n (%) Closed abdomen

13 (36.1)

Open abdomen (coliseum)

23 (63.9) d

Major surgical complications , n (%)

11 (37.9)

Hematologic

1 (3.4)

Cardiovascular

1 (3.4)

Gastrointestinal

4 (13.8)

Renal

1 (3.4)

Treatment, n (%) Interventional radiology Surgery

2 (6.9) 3 (11.5)

Death within 90 days of surgery, n (%)

0 (0)

Postoperative chemotherapye, n (%)

10 (40)

Lymph node involvementf, n (%)

3 (11.5)

Cancer differentiationg, n (%) Poor

2 (16.7)

Moderate

4 (33.3)

Well

6 (50)

Some patients were missing the following data: apreoperative chemotherapy, n = 2; bPCI, n = 12; clength of surgery, n = 8; d major complications, n = 7; epostoperative chemotherapy, n = 11; f lymph node involvement, n = 10; gcancer differentiation, n = 24

technique for 13 patients. The following drugs were used for HIPEC: cisplatin in 1 patient, mitomycin C in 15 patients, oxaliplatin in 3 patients, and melphalan in 2 patients. Four drug combinations were used: cisplatin/ mitomycin C for eight patients, oxaliplatin/irinotecan for four patients [with addition of systemic 5-fluorouracil (5FU)], cisplatin/doxorubicin for two patients, and doxorubicin/mitomycin C in one patient. The rate of macroscopically complete CRS (CC-0 or CC-1) was 86.1%. There were 11 major surgical complications (grade III–IV) in 29 patients, corresponding to a 37.9% rate of major complications. No postoperative deaths were reported. Lymph node involvement was observed in 3 of 26 patients. Tumor differentiation was reported in 12 patients,

being well differentiated in 6, moderately differentiated in 4, and poorly differentiated in 2. Survival Median follow-up was 48 months (95% CI 34.9–69.4 months). Median OS was 58.5 months (95% CI 11.2–105.9 months). Three-year OS was 55.4%, and 5-year OS was 46.2% for the entire study population. Disease-free survival (DFS) was calculated for 28 patients. Median DFS was 60.5 months (95% CI 20.6–100.3 months); Three-year DFS was 62.6%, and 5-year DFS was 55.6% (Table 2). There was a statistically significant difference in survival for patients who underwent complete macroscopic CRS (Fig. 1). The OS for optimal CRS (CC-0 and CC-1) was 100, 64.72, and 53.93% at 1, 3, and 5 years, respectively. In the incomplete CRS group (CC-2 and CC-3), OS was 75, 0, and 0% at 1, 3, and 5 years, respectively. Median OS of the CC0 subgroup was 58.5 months (7.8–109.2 months) and was not reached for the CC1 subgroup. There was no difference in OS between CC-0 and CC-1 group (p = 0.8785). When patients were categorized according to PCI B 14 versus PCI [ 14, OS was 100, 87.5, and 87.5% at 1, 3, and 5 years in the low-PCI group and 100, 50, and 33.3% at 1, 3, and 5 years in the high-PCI group. This difference in survival was not statistically significant (p = 0.078) (Fig. 2). OS and DFS Risk Factors for Death, Recurrence, and Adverse Events on Univariate Analysis For OS, CC score was the only risk factor associated with a statistically significant difference. Incomplete CRS (CC-2 and CC-3) was associated with negative outcome [hazard ratio (HR) = 7.04, 95% CI 1.95–25.34, p = 0.003]. PCI score category, i.e., PCI B 14 or PCI [ 14, was not associated with a statistically significant difference (p = 0.116) For DFS, PCI [ 14 was associated with negative outcome (recurrence) (HR 15.21, 95% CI 1.86–124.25,

DISCUSSION

0.5

0.75

CC0+CC1 CC2+CC3

p log rank<0.001

0

0.25

Overall survival

1

F. Mercier et al.

0

12

24

36

Time after surgery, months

48

60

CC0+CC1 0 12 24 36 48 60 Left 31 25 20 13 10 5 Failed 0 0 4 8 8 9 CC2 Left

0 12 24 36 48 60 4 3 1 0 0 0

Failed

0

1 3 4

4 4

0.75

PCI ≤ 14 PCI > 14

0.5

p log rank=0.077

0

0.25

Overall survival

1

FIG. 1 Overall survival for urachus-derived carcinomatosis according to completeness of cytoreduction (CC) score

0

12

24

36

Time after surgery, months

48

60

0-14

0

Left

15

11 10

6

4 1

0

0 0

1

1 1

Failed

12 24 36 48 60

>=15

0

Left

9

12 24 36 48 60 8 7

4

3 2

Failed

0

0 1

4

4 5

FIG. 2 Overall survival for urachus-derived carcinomatosis according to peritoneal cancer index (PCI)

p = 0.011). Lymph node involvement was also associated with earlier recurrence (HR 5.27, 95% CI 1.29–21.50, p = 0.021). None of the tested variables had statistically significant prognostic value for postoperative adverse events. No postoperative deaths were reported (Table 3).

We report herein the largest international multiinstitutional series of patients with peritoneal metastases of urachus origin. Urachus neoplasm with carcinomatosis is a very rare occurrence, with only 28 cases reported in English-language literature, excluding this series.2 The major finding of this study is that achievement of optimal CRS (CC-0 and CC-1) was the most important factor for longterm survival. Surprisingly, our analysis did not find that PCI score had a significant impact on OS. As reported by Liu et al., PMP of urachal origin probably originates from neoplastic cells via development of intestinal-type mucinous adenocarcinoma.2 This idea is based on findings using mucin-leaking visualization technology during surgery and on the observation that PMP of urachal origin has a similar immunohistochemistry pattern to appendiceal-origin carcinomatosis. Since there is a high probability that similar mechanisms are involved in the two diseases, it seemed likely to us that the impact of therapeutic treatment would be similar. The PSOGI has stated that HIPEC and optimal CRS are needed to maximize the survival rate of PMP of appendiceal mucinous neoplasm.18 Interestingly, the survival curves of the previous study18 show some similarities to the survival curve in this study. In both studies, achieving optimal CRS (CC-0 or CC-1) had a significant impact on survival. The survival curves differed significantly between macroscopic resection of all disease (CC-0 and CC-1) compared with debulking surgery (CC-2 and CC-3). As shown in Fig. 1, no patients survived beyond 30 months if optimal CRS was not obtained. This demonstrates the major impact of complete CRS on patient prognosis. Long-term (5-year) survival of more than 50% can be achieved with complete CRS for patients with advanced locoregional spread of the disease. On univariate analysis for OS, CC score was the only significant predictor of prognosis. In contrast to most previous carcinomatosis studies, PCI was not a statistically significant factor for poorer OS, even though the survival curves differed slightly between PCI B 14 and PCI [ 14. The cutoff of 14 was chosen to differentiate between groups with low and high disease burden. Even if the median was 8.5, the range was wide (1–33). The group stayed relatively well balanced at that cutoff, which is

TABLE 3 Prognostic factors for death and recurrence in patients with urachus-derived carcinomatosis Outcome

Associated factor

Death

CC score

7.04 (1.95–25.34)

0.003

a

15.21 (1.86–124.25)

0.011

5.27 (1.29–21.50)

0.021

Recurrence

PCI

Hazard ratio (95% CI)

Lymph node involvementb a

b

Some patients were missing the following data: PCI, n = 4; lymph node involvement, n = 3

p value

HIPEC in Urachus Peritoneal Carcinomatosis

sometimes used in colorectal carcinomatosis.19 Since CC score was the most important factor, this could be explained by the relationship between high PCI and CC-2 and CC-3.20 Even if PCI is generally a significant predictive factor for OS, several studies have found that PCI was not a prognostic factor for OS. In those series, as in ours, CC score was a significant predictive factor for OS.21–23 This absence of difference in OS could also be explained by the limited number in each group or missing data, when analyzed by PCI category. Since our study included data from multiple centers and from patients who received different chemotherapy regimens for HIPEC, it is difficult to draw conclusions regarding which regimen was the most effective. In literature, there is no single recommended chemotherapy regimen; indeed, most data have been published as case reports. Szarvas et al.24 performed a metaanalysis of 74 published case reports of metastatic urachus-derived carcinoma and categorized the chemotherapy regimens into four groups: cisplatin based, 5-FU based, combinations, and other. The 5-FU group achieved better radiologic response rate than the cisplatin group (44% vs 9%), but combination therapy was superior to both groups. Since chemotherapy used for colorectal cancer seems to have better efficacy and since these two types of cancer have similar cellular origins, it seems likely that the HIPEC regimen used to treat PMP of appendiceal origin should also be used for PMP of urachal origin. However, there are not enough data to support this recommendation. The same principle seems to apply to mucinous appendiceal tumor. HIPEC helps control the disease and was reported to be an independent predictor of better prognosis, but HIPEC may not be the most important factor compared with optimal CRS.18 Mitomycin C was the drug that was used most often in our series, and it is one of the most common drugs used for HIPEC to treat PMP of appendiceal origin.18 Even if no statistical analysis can be done to identify the best drug regimen, 13 patients survived for over 36 months in our series; of these patients, 5 received a combination of cisplatin/mitomycin C, 4 received mitomycin C, 1 received a combination of oxaliplatin/irinotecan, 1 received a combination of cisplatin/doxorubicin, and 1 received oxaliplatin (data not shown). These data could suggest optimal efficiency for either the combination of cisplatin/ mitomycin C or mitomycin C alone. This must be investigated further before a formal recommendation can be made. Several factors have been reported to be associated with prognosis. Lymphatic invasion in urachus carcinoma has poor prognosis, and survival appears to be similar for patients with nodal invasion and patients with distant metastasis.25,26 The metaanalysis by Szarvas et al. found a rate of lymphatic invasion of 17%.24 Even if lymphatic

node positivity carries poor prognosis, studies have not been able to demonstrate a survival benefit for lymph node dissection.25,27,28 In studies we conducted, the impact of nodal involvement was not associated with OS (p = 0.207), but nodal involvement was a statistically significant factor for DFS (HR 5.27, p = 0.021). Cellular differentiation was not often reported for pathology analysis, so we cannot draw any conclusions regarding those results. Signet ring differentiation was inconsistently reported as a prognostic factor in urachal carcinoma.28,29 This study has some limitations. First, the inclusion period was quite long (24 years; from 1992 to 2015), and survival improved over time as techniques improved.5 In 1992, only a few centers performed CRS, and survival after CRS may have been worse during this early period. Second, HIPEC regimens and time of exposure varied in different centers, meaning that patients were not treated with a standardized regimen. Third, this was a retrospective study with limited sample size that was subject to inclusion bias and that had missing data; these factors may have impacted the survival analysis. The median DFS was longer than the median since patients with CC score of 2 were considered to have progressed from date of surgery. Due to limited sample size, multivariate analysis could not be carried out. However, despite these limitations, this is the largest series to date and reports important follow-up data. CONCLUSIONS Peritoneal metastases or PMP of urachal origin should be managed the same way as PMP from mucinous appendiceal primary cancer. Patients should be referred to expert centers to evaluate resectability, since long-term survival is better when CRS is optimized. International databases are needed for rare diseases like these in order to collect information that could help improve their management. ACKNOWLEDGEMENT The authors thank Peggy Jourdan-Enfer and Anaı¨s Poulet for their expert help with data collection. The authors thank Lorna Saint Ange for help with editing the manuscript, and Evelyne Decullier for help with data analysis. The collaborators of the BIG-RENAPE Working Group include the following: J. Abba (Department of Surgical Oncology, CHU Grenoble University, Grenoble, France); K. Abboud (Department of Surgical Oncology, CHU St Etienne, St Etienne, France); M. Alyami (Department of Surgical Oncology, Centre Hospitalier Lyon Sud EMR 3738, Lyon 1 University, Lyon, France); C. Arvieux (Department of Surgical Oncology, CHU Grenoble University, Grenoble, France); N. Bakrin (Department of Surgical Oncology, Centre Hospitalier Lyon Sud - EMR 3738, Lyon 1 University, Lyon, France); J.-M. Bereder (Department of Surgical Oncology, CHU L’Archet 2, Nice, France); D. Bouzard (Department of Surgical Oncology, CHU Louis Mourier, Colombes, France); C. Brigand (Department of Surgical Oncology, CHRU Hautepierre, Strasbourg, France); S. Carre`re

F. Mercier et al. (Department of Surgical Oncology, Institut du Cancer de Montpellier, Montpellier, France); D. Delroeux (Department of Surgical Oncology, CHU Jean Minjoz, Besanc¸on, France); F. Dumont (Department of Surgical Oncology, ICO - Rene´ Gauducheau, St Herblain, France); C. Eveno (Department of Surgical Oncology, CHU Lariboisie`re, Paris, France); O. Facy (Department of Surgical Oncology, CHU Dijon, Dijon, France); F. Guyon (Department of Surgical Oncology, Institut Bergonie´, Bordeaux, France); G. Ferron (Department of Surgical Oncology, IUCT Oncopole, Toulouse, France); R. Kianmanesh (Department of Surgical Oncology, CHU Robert Debre´, Reims, France); R. Lo Dico (Department of Surgical Oncology, CHU Lariboisie`re, Paris, France); G. Lorimier (Department of Surgical Oncology, CHU Angers, Angers, France); F. Marchal (Department of Surgical Oncology, Institut de Cance´rologie de Lorraine, Vandoeuvre-le`s-Nancy, France); P. Mariani (Department of Surgical Oncology, Institut Curie, Paris, France); P. Meeus (Department of Surgical Oncology, Centre Le´on Be´rard, Lyon, France); S. Msika (Department of Surgical Oncology, CHU Louis Mourier, Colombes, France); P. Ortega-Deballon (Department of Surgical Oncology, CHU Dijon, Dijon, France); B. Paquette (Department of Surgical Oncology, CHU Jean Minjoz, Besanc¸on, France); P. Peyrat (Department of Surgical Oncology, Centre Le´on Be´rard, Lyon, France); N. Pirro (Department of Surgical Oncology, CHU La Timoˆne, Marseille, France); M. Pocard (Department of Surgical Oncology, CHU Lariboisie`re, Paris, France); J. Porcheron (Department of Surgical Oncology, CHU St Etienne, St Etienne, France); F. Quenet (Department of Surgical Oncology, Institut du Cancer de Montpellier, Montpellier, France); P. Rat (Department of Surgical Oncology, CHU Dijon, Dijon, France); O. Sgarbura (Department of Surgical Oncology, Institut du Cancer de Montpellier, Montpellier, France); E. Thibaudeau (Department of Surgical Oncology, ICO - Rene´ Gauducheau, St Herblain, France); J.-J. Tuech (Department of Surgical Oncology, CHU Charles Nicolle, Rouen, France); F. Zinzindohoue (Department of Surgical Oncology, Hoˆpital Europe´en Georges Pompidou, Paris, France). The collaborators of the PSOGI Working Group include the following: S. A. Ahrendt (Department of Surgery, University of Pittsburgh Medical Center Shadyside Hospital, Pittsburgh, USA); E. Akaishi (Department of Surgical Oncology, Centro de Oncologia Hospital Sirio Libanes, Sao Paolo, Brazil); S. H. Baik (Department of Surgery, Gangnam Severance Hospital - Yonsei University College of Medicine, Seoul, Korea); D. Baratti (Department of Gastrointestinal Surgery, San Raffaele Scientific Institute, Milan, Italy); A. Bhatt (Department of Surgical Oncology, Fortis Hospitals Limited, Bangalore, India); P. Cachin (Department of Surgery, Akademiska sjukhuset, Uppsala University Hospital, Uppasala, Sweden); W. Ceelen (Department of Gastrointestinal Surgery, Gent University Hospital, Ghent, Belgium); I. De Hingh (Department of Surgery, Catharina Ziekenhuis, Eindhoven, The Netherlands); M. De Simone (Department of Surgical Oncology, Candiolo Cancer Institute - FPO, IRCCS, Turin, Italy); P. Dube´ (Department of Surgery, University of Montreal, Montreal, Canada); R. P. Edwards (Department of Surgery, University of Pittsburgh Medical Center Shadyside Hospital, Pittsburgh, USA); J. Franko (Department of Surgical Oncology, Mercy Medical Center, Baltimore, USA); L. Gonzalez-Bayon (Department of Surgical Oncology, Hospital Gregorio Maran˜o´n, Madrid, Spain); V. Gushchin (Department of Surgical Oncology, Mercy Medical Center, Baltimore, USA); M. P. Holtzman (Department of Surgery, University of Pittsburgh Medical Center Shadyside Hospital, Pittsburgh, USA); M.-C. Hsieh (Department of General Surgery, WanFang Hospital, Taipei, Taiwan); D. Kecmanovic (Department of Surgery, First Surgical Clinic, Clinical Center of Serbia, Belgrade, Serbia); K. W. Lee (Department of Surgery, University of Pittsburgh Medical Center Shadyside Hospital, Pittsburgh, USA); K. Lehmann (Department of Surgery and Transplantation, University Hospital of Zurich, Zurich, Switzerland); Y. Liu (NPO to Support Peritoneal

Surface Malignancy Treatment, Kyoto, Japan); S. Mehta (Division of Peritoneal Surface Oncology, Saifee Hospital, Mumbai, India); D. L. Morris (Department of Surgery, University of New South Wales, Sydney, Australia); S. O’Dwyer (Department of Colorectal Surgery, Christie Cancer Center, Manchester, UK); E. Orsenigo (Department of Gastrointestinal Surgery, San Raffaele Scientific Institute, Milan, Italy); P. K. Pande (Department of Surgical Oncology, BLK Superspeciality Hospital, New Delhi, India); E. J. Park (Department of Surgery, Gangnam Severance Hospital - Yonsei University College of Medicine, Seoul, Korea); J. F. Pingpank (Department of Surgery, University of Pittsburgh Medical Center Shadyside Hospital, Pittsburgh, USA); P. Piso (Department of Surgery, University of Regensburg, Regensburg, Germany); F. Rajan (Department of Surgical Oncology, Kovai Medical Centre, Coimbatore, India); B. Rau (Department of Surgical Oncology, Charite Campus Mitte University of Berlin, Berlin, Germany); A. Sardi (Department of Surgical Oncology, Mercy Medical Center Baltimore, USA); L. Sideris (Department of Surgery, University of Montreal, Montreal, Canada); A. Sommariva (Melanoma and Sarcoma Unit, Istituto Oncologico Veneto, Padua, Italy); J. Spiliotis (First Department of Surgical Oncology, Metaxa Cancer Memorial Hospital, Piraeus, Greece); A. A. K. Tentes (Department of Surgery, Metropolitan Hospital, Athens, Greece); M. Teo (Department of Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore); R. Yarema (Department of Oncology and Medical Radiology Danylo Halytsky Lviv National Medical University, Lviv, Ukraine); R. Younan (Department of Surgery, Centre Hospitalier de l’Universite´ de Montre´al, Montreal, Canada); S. S. Zaveri (Department of Surgical Oncology, Manipal Hospital, Bangalore, India); H. J. Zeh (Department of Surgery, University of Pittsburgh Medical Center, Shadyside Hospital, Pittsburgh, USA). DISCLOSURE to this article.

The authors report no conflicts of interest relevant

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