Skip to main content
Top
Published in: Virchows Archiv 2/2016

01-08-2016 | Original Article

Peritoneal dissemination in early gastric cancer: importance of the lymphatic route

Authors: Masao Yoshida, Takashi Sugino, Kimihide Kusafuka, Takashi Nakajima, Rie Makuuchi, Masanori Tokunaga, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Masanori Terashima, Noboru Kawata, Masaki Tanaka, Naomi Kakushima, Kohei Takizawa, Hiroyuki Ono

Published in: Virchows Archiv | Issue 2/2016

Login to get access

Abstract

The current paradigm concerning the mechanism of peritoneal dissemination of gastric cancer is that it occurs through an invasive process in which cancer cells directly penetrate the gastric wall and exfoliate into the peritoneal cavity. However, some experimental studies suggest the lymphatic route as an alternative. We present five early gastric cancer cases, which support this alternative pathway of peritoneal dissemination without direct invasion in the serosa. We investigated all patients with early gastric cancer who underwent curative gastrectomy between September 2002 and February 2015 at the Shizuoka Cancer Center, Japan. We examined them by intraoperative peritoneal lavage cytology and frozen section diagnosis of peritoneal nodules during laparotomy. Peritoneal dissemination was defined as peritoneal metastasis by positive cytology or histological diagnosis. Among 1509 early gastric cancers, five cases (0.3 %, 95 % CI 0.1–0.8 %) presented peritoneal dissemination detected by lavage cytology and frozen section diagnosis of peritoneal nodules. Histological examination revealed that the primary tumors invaded the submucosal layer using the lymphatic route, through which they metastasized to regional lymph nodes. Our data indicate that gastric cancer may give rise to peritoneal dissemination even at an early stage, probably through the lymphatic route without direct invasion into the serosa.
Literature
3.
go back to reference Boku N (2011) Past and present achievements, and future direction of the Gastrointestinal Oncology Study Group (GIOSG), a Division of Japan Clinical Oncology Group (JCOG). Jpn J Clin Oncol 41(12):1315–1321CrossRefPubMed Boku N (2011) Past and present achievements, and future direction of the Gastrointestinal Oncology Study Group (GIOSG), a Division of Japan Clinical Oncology Group (JCOG). Jpn J Clin Oncol 41(12):1315–1321CrossRefPubMed
4.
go back to reference Thomassen I, van Gestel Y, van Ramshorst B, Luyer M, Bosscha K, Nienhuijs S, Lemmens V, de Hingh I (2014) Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. Int J Cancer 134(3):622–628CrossRefPubMed Thomassen I, van Gestel Y, van Ramshorst B, Luyer M, Bosscha K, Nienhuijs S, Lemmens V, de Hingh I (2014) Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. Int J Cancer 134(3):622–628CrossRefPubMed
5.
go back to reference Bando E, Yonemura Y, Takeshita Y, Taniguchi K, Yasui T, Yoshimitsu Y, Fushida S, Fujimura T, Nishimura G, Miwa K (1999) Intraoperative lavage for cytological examination in 1,297 patients with gastric carcinoma. Am J Surg 178(3):256–262CrossRefPubMed Bando E, Yonemura Y, Takeshita Y, Taniguchi K, Yasui T, Yoshimitsu Y, Fushida S, Fujimura T, Nishimura G, Miwa K (1999) Intraoperative lavage for cytological examination in 1,297 patients with gastric carcinoma. Am J Surg 178(3):256–262CrossRefPubMed
6.
go back to reference Bang Y-J, Van Cutsem E, Feyereislova A, Chung H, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang Y-K (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet (London, England) 376(9742):687–697CrossRef Bang Y-J, Van Cutsem E, Feyereislova A, Chung H, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang Y-K (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet (London, England) 376(9742):687–697CrossRef
7.
go back to reference Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O’Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M (1997) Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15(1):261–267CrossRefPubMed Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O’Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M (1997) Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15(1):261–267CrossRefPubMed
8.
go back to reference Wagner A, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, Fleig W (2010) Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 3:CD004064PubMed Wagner A, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, Fleig W (2010) Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 3:CD004064PubMed
9.
go back to reference Ajani J, Moiseyenko V, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Marabotti C, Van Cutsem E (2007) Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: the V-325 Study Group. J Clin Oncol 25(22):3205–3209CrossRefPubMed Ajani J, Moiseyenko V, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Marabotti C, Van Cutsem E (2007) Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: the V-325 Study Group. J Clin Oncol 25(22):3205–3209CrossRefPubMed
10.
go back to reference Yang X-J, Huang C-Q, Suo T, Mei L-J, Yang G-L, Cheng F-L, Zhou Y-F, Xiong B, Yonemura Y, Li Y (2011) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol 18(6):1575–1581CrossRefPubMedPubMedCentral Yang X-J, Huang C-Q, Suo T, Mei L-J, Yang G-L, Cheng F-L, Zhou Y-F, Xiong B, Yonemura Y, Li Y (2011) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol 18(6):1575–1581CrossRefPubMedPubMedCentral
11.
go back to reference Gill R, Al Adra D, Nagendran J, Campbell S, Shi X, Haase E, Schiller D (2011) Treatment of gastric cancer with peritoneal carcinomatosis by cytoreductive surgery and HIPEC: a systematic review of survival, mortality, and morbidity. J Surg Oncol 104(6):692–698CrossRefPubMed Gill R, Al Adra D, Nagendran J, Campbell S, Shi X, Haase E, Schiller D (2011) Treatment of gastric cancer with peritoneal carcinomatosis by cytoreductive surgery and HIPEC: a systematic review of survival, mortality, and morbidity. J Surg Oncol 104(6):692–698CrossRefPubMed
12.
go back to reference Glockzin G, Piso P (2012) Current status and future directions in gastric cancer with peritoneal dissemination. Surg Oncol Clin N Am 21(4):625–633CrossRefPubMed Glockzin G, Piso P (2012) Current status and future directions in gastric cancer with peritoneal dissemination. Surg Oncol Clin N Am 21(4):625–633CrossRefPubMed
13.
go back to reference Glehen O, Gilly F, Arvieux C, Cotte E, Boutitie F, Mansvelt B, Bereder J, Lorimier G, Quenet F, Elias D (2010) Peritoneal carcinomatosis from gastric cancer: a multi-institutional study of 159 patients treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy. Ann Surg Oncol 17(9):2370–2377CrossRefPubMed Glehen O, Gilly F, Arvieux C, Cotte E, Boutitie F, Mansvelt B, Bereder J, Lorimier G, Quenet F, Elias D (2010) Peritoneal carcinomatosis from gastric cancer: a multi-institutional study of 159 patients treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy. Ann Surg Oncol 17(9):2370–2377CrossRefPubMed
14.
go back to reference Kodera Y, Yamamura Y, Shimizu Y, Torii A, Hirai T, Yasui K, Morimoto T, Kato T (1999) Peritoneal washing cytology: prognostic value of positive findings in patients with gastric carcinoma undergoing a potentially curative resection. J Surg Oncol 72(2):60–64CrossRefPubMed Kodera Y, Yamamura Y, Shimizu Y, Torii A, Hirai T, Yasui K, Morimoto T, Kato T (1999) Peritoneal washing cytology: prognostic value of positive findings in patients with gastric carcinoma undergoing a potentially curative resection. J Surg Oncol 72(2):60–64CrossRefPubMed
15.
go back to reference Hagiwara A, Takahashi T, Sawai K, Taniguchi H, Shimotsuma M, Okano S, Sakakura C, Tsujimoto H, Osaki K, Sasaki S (1993) Milky spots as the implantation site for malignant cells in peritoneal dissemination in mice. Cancer Res 53(3):687–692PubMed Hagiwara A, Takahashi T, Sawai K, Taniguchi H, Shimotsuma M, Okano S, Sakakura C, Tsujimoto H, Osaki K, Sasaki S (1993) Milky spots as the implantation site for malignant cells in peritoneal dissemination in mice. Cancer Res 53(3):687–692PubMed
16.
go back to reference Yamamoto M, Taguchi K, Baba H, Endo K, Kohnoe S, Okamura T, Maehara Y (2006) Peritoneal dissemination of early gastric cancer: report of a case. Surg Today 36(9):835–838CrossRefPubMed Yamamoto M, Taguchi K, Baba H, Endo K, Kohnoe S, Okamura T, Maehara Y (2006) Peritoneal dissemination of early gastric cancer: report of a case. Surg Today 36(9):835–838CrossRefPubMed
17.
go back to reference Kakushima N, Kamoshida T, Hirai S, Hotta S, Hirayama T, Yamada J, Ueda K, Sato M, Okumura M, Shimokama T, Oka Y (2003) Early gastric cancer with Krukenberg tumor and review of cases of intramucosal gastric cancers with Krukenberg tumor. J Gastroenterol 38(12):1176–1180CrossRefPubMed Kakushima N, Kamoshida T, Hirai S, Hotta S, Hirayama T, Yamada J, Ueda K, Sato M, Okumura M, Shimokama T, Oka Y (2003) Early gastric cancer with Krukenberg tumor and review of cases of intramucosal gastric cancers with Krukenberg tumor. J Gastroenterol 38(12):1176–1180CrossRefPubMed
18.
go back to reference Japanese gastric cancer treatment guidelines 2010 (ver. 3) (2011). Gastric Cancer 14 (2):113-123 Japanese gastric cancer treatment guidelines 2010 (ver. 3) (2011). Gastric Cancer 14 (2):113-123
20.
go back to reference Koike H, Ichikawa D, Kitamura K, Tsuchihashi Y, Yamagishi H (2004) Perinodal involvement of cancer cells in gastric cancer patients. Surgery 135(3):266–272CrossRefPubMed Koike H, Ichikawa D, Kitamura K, Tsuchihashi Y, Yamagishi H (2004) Perinodal involvement of cancer cells in gastric cancer patients. Surgery 135(3):266–272CrossRefPubMed
21.
go back to reference Etoh T, Sasako M, Ishikawa K, Katai H, Sano T, Shimoda T (2006) Extranodal metastasis is an indicator of poor prognosis in patients with gastric carcinoma. Br J Surg 93(3):369–373CrossRefPubMed Etoh T, Sasako M, Ishikawa K, Katai H, Sano T, Shimoda T (2006) Extranodal metastasis is an indicator of poor prognosis in patients with gastric carcinoma. Br J Surg 93(3):369–373CrossRefPubMed
22.
go back to reference Yoo CH, Noh SH, Shin DW, Choi SH, Min JS (2000) Recurrence following curative resection for gastric carcinoma. Br J Surg 87(2):236–242CrossRefPubMed Yoo CH, Noh SH, Shin DW, Choi SH, Min JS (2000) Recurrence following curative resection for gastric carcinoma. Br J Surg 87(2):236–242CrossRefPubMed
23.
go back to reference Shimada S, Yagi Y, Shiomori K, Honmyo U, Hayashi N, Matsuo A, Marutsuka T, Ogawa M (2001) Characterization of early gastric cancer and proposal of the optimal therapeutic strategy. Surgery 129(6):714–719CrossRefPubMed Shimada S, Yagi Y, Shiomori K, Honmyo U, Hayashi N, Matsuo A, Marutsuka T, Ogawa M (2001) Characterization of early gastric cancer and proposal of the optimal therapeutic strategy. Surgery 129(6):714–719CrossRefPubMed
24.
go back to reference Moriguchi S, Maehara Y, Korenaga D, Sugimachi K, Nose Y (1992) Risk factors which predict pattern of recurrence after curative surgery for patients with advanced gastric cancer. Surg Oncol 1(5):341–346CrossRefPubMed Moriguchi S, Maehara Y, Korenaga D, Sugimachi K, Nose Y (1992) Risk factors which predict pattern of recurrence after curative surgery for patients with advanced gastric cancer. Surg Oncol 1(5):341–346CrossRefPubMed
25.
go back to reference Sasako M, Sano T, Yamamoto S, Kurokawa Y, Nashimoto A, Kurita A, Hiratsuka M, Tsujinaka T, Kinoshita T, Arai K, Yamamura Y, Okajima K (2008) D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med 359(5):453–462CrossRefPubMed Sasako M, Sano T, Yamamoto S, Kurokawa Y, Nashimoto A, Kurita A, Hiratsuka M, Tsujinaka T, Kinoshita T, Arai K, Yamamura Y, Okajima K (2008) D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med 359(5):453–462CrossRefPubMed
26.
go back to reference Farley DR, Donohue JH, Nagorney DM, Carpenter HA, Katzmann JA, Ilstrup DM (1992) Early gastric cancer. Br J Surg 79(6):539–542CrossRefPubMed Farley DR, Donohue JH, Nagorney DM, Carpenter HA, Katzmann JA, Ilstrup DM (1992) Early gastric cancer. Br J Surg 79(6):539–542CrossRefPubMed
27.
go back to reference Guadagni S, Reed PI, Johnston BJ, De Bernardinis G, Catarci M, Valenti M, di Orio F, Carboni M (1993) Early gastric cancer: follow-up after gastrectomy in 159 patients. Br J Surg 80(3):325–328CrossRefPubMed Guadagni S, Reed PI, Johnston BJ, De Bernardinis G, Catarci M, Valenti M, di Orio F, Carboni M (1993) Early gastric cancer: follow-up after gastrectomy in 159 patients. Br J Surg 80(3):325–328CrossRefPubMed
28.
go back to reference Roviello F, Marrelli D, de Manzoni G, Morgagni P, Di Leo A, Saragoni L, De Stefano A (2003) Prospective study of peritoneal recurrence after curative surgery for gastric cancer. Br J Surg 90(9):1113–1119CrossRefPubMed Roviello F, Marrelli D, de Manzoni G, Morgagni P, Di Leo A, Saragoni L, De Stefano A (2003) Prospective study of peritoneal recurrence after curative surgery for gastric cancer. Br J Surg 90(9):1113–1119CrossRefPubMed
29.
go back to reference Huang B, Sun Z, Wang Z, Lu C, Xing C, Zhao B, Xu H (2013) Factors associated with peritoneal metastasis in non-serosa-invasive gastric cancer: a retrospective study of a prospectively-collected database. BMC Cancer 13:57CrossRefPubMedPubMedCentral Huang B, Sun Z, Wang Z, Lu C, Xing C, Zhao B, Xu H (2013) Factors associated with peritoneal metastasis in non-serosa-invasive gastric cancer: a retrospective study of a prospectively-collected database. BMC Cancer 13:57CrossRefPubMedPubMedCentral
30.
go back to reference Thomassen I, van Gestel Y, van Ramshorst B, Luyer M, Bosscha K, Nienhuijs S, Lemmens V, de Hingh I (2014) Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. Int J Cancer 134(3):622–628 Thomassen I, van Gestel Y, van Ramshorst B, Luyer M, Bosscha K, Nienhuijs S, Lemmens V, de Hingh I (2014) Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. Int J Cancer 134(3):622–628
31.
go back to reference Guadagni S, Catarci M, Kinoshitá T, Valenti M, De Bernardinis G, Carboni M (1997) Causes of death and recurrence after surgery for early gastric cancer. World J Surg 21(4):434–439CrossRefPubMed Guadagni S, Catarci M, Kinoshitá T, Valenti M, De Bernardinis G, Carboni M (1997) Causes of death and recurrence after surgery for early gastric cancer. World J Surg 21(4):434–439CrossRefPubMed
Metadata
Title
Peritoneal dissemination in early gastric cancer: importance of the lymphatic route
Authors
Masao Yoshida
Takashi Sugino
Kimihide Kusafuka
Takashi Nakajima
Rie Makuuchi
Masanori Tokunaga
Yutaka Tanizawa
Etsuro Bando
Taiichi Kawamura
Masanori Terashima
Noboru Kawata
Masaki Tanaka
Naomi Kakushima
Kohei Takizawa
Hiroyuki Ono
Publication date
01-08-2016
Publisher
Springer Berlin Heidelberg
Published in
Virchows Archiv / Issue 2/2016
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-016-1960-7

Other articles of this Issue 2/2016

Virchows Archiv 2/2016 Go to the issue