Late-onset peritoneal recurrence of advanced gastric cancer 20 years after primary resection
© Okugawa et al; licensee BioMed Central Ltd. 2010
Received: 31 August 2010
Accepted: 24 November 2010
Published: 24 November 2010
Late onset of peritoneal recurrence of gastric cancer more than 10 years after surgery is extremely rare, and only three cases have been reported. We present the case of a 61-year-old man who was diagnosed finally with peritoneal recurrence of gastric cancer 20 years after primary curative resection. As a result of small-bowel obstruction caused by peritoneal recurrence, diverting ileostomy with partial ileal resection was performed. The resected specimen revealed tubular adenocarcinoma that resembled the primary gastric cancer. The clinical course after the second operation was unfavorable and systemic chemotherapy had no effect. He died at 62 years of age, 21 years and 7 months after initial gastrectomy. Immunohistochemical analysis using antibodies against proliferating cell nuclear antigen (PCNA), Ki-67, and p53 was performed to investigate the phenotype of primary and recurrence cancer. Protein expression of proliferation markers such as PCNA and Ki-67 was down-regulated, but p53 was overexpressed at the site of recurrence. These data suggest that late peritoneal recurrence has a low proliferation rate and is resistant to chemoradiotherapy. In conclusion, we present late onset of peritoneal recurrence of gastric cancer more than 20 years after primary surgery, and speculate on the mechanism of late-onset recurrence in our case.
Gastric cancer is a leading cause of tumor-related deaths, with approximately 50,000 individuals dying of gastric cancer each year in Japan. Death from gastric cancer is almost entirely caused by recurrent disease. Peritoneal recurrence represents one of the most common causes of failure after curative surgery for gastric cancer [1–4]. The median survival rate after peritoneal recurrence is only about 6 months . The prognosis of peritoneal recurrence is so poor that standard treatment has not been established. Usually, peritoneal recurrence occurs within 5 years after surgery, especially during the first 2 years [5, 6], and late-onset peritoneal recurrence of gastric cancer more than 10 years after surgery is extremely rare.
We report a case of peritoneal recurrence of gastric cancer that occurred more than 20 years after curative surgery, and review previous reports of these cases. Furthermore, by using immunohistochemical analysis, we also investigated how expression of several proteins, such as proliferating cell nuclear antigen (PCNA), Ki67 (cell proliferation), and p53 (resistance to chemoradiotherapy), differ between primary and secondary resection samples, and speculate on the mechanism of late-onset recurrence in our case.
A 41-year-old man with no remarkable medical history was referred to our department with a two-month history of difficulty on swallowing and appetite loss. A barium study and endoscopic examination showed type 4 advanced gastric cancer in the lesser curvature of the upper body of the stomach. On admission, the tumor markers, such as carcinoembryonic antigen(CEA) and gastrointestinal cancer antigen 19-9 were within normal limits. He underwent total gastrectomy (D2 dissection) with splenectomy and distal pancreatectomy for advanced gastric cancer in the greater curvature of the corpus. Histological examination of the resected specimen revealed tubular adenocarcinoma of the moderately differentiated type with partial signet-ring cell carcinoma. The depth of tumor invasion was confirmed as exposed-serosal (se). There was mild lymphatic invasion (ly1), no venous invasion (v0), and lymph node metastasis (n2). The patient received adjuvant chemotherapy with oral 5-fluorouracil for 1 year, and was followed up for 5 years on an outpatient basis without any sign of recurrence.
Systemic reevaluation, including total colonoscopy and systemic computed tomography, could not confirm another primary tumor as the cause of the recurrence, therefore, peritoneal recurrence of gastric cancer more than 20 years after primary surgery was diagnosed. Follow-up systemic computed tomography at 1 year after the second operation could not showed primary other lesion responsible for peritoneal dissemination. The patient's general condition after secondary surgery took a gradual turn for the worse, despite 5-fluorouracil-based systemic chemotherapy, and he died at 62 years of age, 21 years and 7 months after initial gastrectomy.
Although sites of recurrence of gastric cancer include the peritoneum, liver, bone marrow and lymph nodes, peritoneal dissemination is the most common site of recurrence [7, 8]. Peritoneal recurrence in gastric cancer has been reported in 17% of patients who underwent curative resection . Especially in advanced gastric cancer, peritoneal recurrence is more frequent. Peritoneal recurrence of gastric cancer is thought to occur by spreading through the serosa or the lymphatic or vascular systems [4, 9]. Then, peritoneal recurrence is involved closely with advanced invasion of the serosa and lymph node metastasis.
Shiraishi et al have compared early and late recurrence after gastrectomy for gastric cancer patients, and have reported that tumor size, lymphatic invasion, level of lymph node metastasis, stage of disease, and extent of lymph node dissection are the factors associated most significantly with early recurrence within 2 years after gastrectomy . In contrast, Moon et al  have recently reported the changing pattern of prognostic indicators during 15 years' follow-up of advanced gastric cancer after gastrectomy and adjuvant chemotherapy. They have suggested that tumor factors, including stage, were clinical prognostic indicators within 5 years post-gastrectomy, but there were no such indicators after 10 years.
Late onset peritoneal recurrence of gastric cancer over 10 years after curative resection
TNM stage at initial operation
Recurrence free survival
With or without distant metastasis
Moon YW, 200711)
II or IIIA
With distant metastasis
Moon YW, 200711)
II or IIIA
Without distant metastasis
Aihara R, 200712)
Without distant metastasis
Our Case, 2010
Without distant metastasis
We also assessed both the organ specificity of disseminated lesion and the mechanism of late-onset recurrence of gastric cancer by immunohistochemistry using pan-CK, CK-7, and CK-20 as a indicator of epithelial differentiation [13–16], p53 as a chemo-radioresistance marker , PCNA, and Ki-67 as a cell proliferation marker [18, 19]. CK-7 and CK-20 have been used for immunophenotyping of metastases and primary adenocarcinomas a the study by Wauters et al . In our case, primary gastric cancer showed the same CK-7/CK-20 expression pattern as disseminated lesion. The CK-7-/CK-20- pattern was reported to be found from 10% to 25% of gastric carcinoma [15, 16], and these data might support the diagnosis of the peritoneal dissemination of gastric cancer 20 years after curative resection. Furthermore, recurrent cancer cells expressed Ki-67 and PCNA at a lower level than the primary lesion in each specimen. On the other hand, staining with antibodies against p53 revealed that recurrent cancer cells had higher expression of mutant p53 than primary cancer cells did. The clinical course corroborated these findings, which suggest that recurrent cancer cells have slow proliferation and are resistant to chemotherapy.
In conclusion, we report an extremely rare case of peritoneal recurrence detected 20 years after curative surgery for advanced gastric cancer. Regardless of the advanced stage, peritoneal recurrence should be considered as one of the recurrence patterns of gastric cancer during long follow-up in patients for more than 10 years after curative gastrectomy.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
We thank M. Ue-eda for technical assistance.
- Moriguchi S, Maehara Y, Korenaga D, Sugimachi K, Nose Y: Risk factors which predict pattern of recurrence after curative surgery for patients with advanced gastric cancer. Surg Oncol. 1992, 1 (5): 341-346. 10.1016/0960-7404(92)90034-I.View ArticlePubMedGoogle Scholar
- Averbach AM, Jacquet P: Stategies to decrease the incidence of intra-abdominal recurrence in resectable gastric cancer. Br J Surg. 1996, 83 (6): 726-733. 10.1002/bjs.1800830605.View ArticlePubMedGoogle Scholar
- Yoo CH, Noh SH, Shin DW, Choi SH, Min JS: Recurrence following curative resection for gastric carcinoma. Br J Surg. 2000, 87 (2): 236-242. 10.1046/j.1365-2168.2000.01360.x.View ArticlePubMedGoogle Scholar
- Maehara Y, Hasuda S, Koga T, Tokunaga E, Kakeji Y, Sugimachi K: Postoperative outcome and sites of recurrence in patients following curative resection of gastric cancer. Br J Surg. 2000, 87 (3): 353-357. 10.1046/j.1365-2168.2000.01358.x.View ArticlePubMedGoogle Scholar
- Roviello F, Marrelli D, de Manzoni G, Morgagni P, Di Leo A, Saragoni L, De Stefano A, Italian Research Group for Gastric Cancer: Prospective study of peritoneal recurrence after curative surgery for gastric cancer. Br J Surg. 2003, 90 (9): 1113-1119. 10.1002/bjs.4164.View ArticlePubMedGoogle Scholar
- Iwanaga T, Koyama H, Furukawa H, Taniguchi H, Wada A, Tateishi R: Mechanism of late recurrence after radical surgery for gastric carcinoma. Am J Surg. 1978, 135 (5): 637-640. 10.1016/0002-9610(78)90126-5.View ArticlePubMedGoogle Scholar
- Adachi Y, Mori M, Maehara Y, Sugimachi K: Long-term survival after resection for advanced gastric carcinoma. J Clin Gastroenterol. 1995, 21 (3): 208-210. 10.1097/00004836-199510000-00008.View ArticlePubMedGoogle Scholar
- Bonenkamp JJ, Hermans J, Sasako M, van de Velde CJ, Welvaart K, Songun I, Meyer S, Plukker JT, Van Elk P, Obertop H, Gouma DJ, van Lanschot JJ, Taat CW, de Graaf PW, von Meyenfeldt MF, Tilanus H, Dutch Gastric Cancer Group: Extended lymph node dissection for gastric cancer. N Engl J Med. 1999, 340 (12): 908-914. 10.1056/NEJM199903253401202.View ArticlePubMedGoogle Scholar
- Maehara Y, Oshiro T, Baba H, Ohno S, Kohnoe S, Sugimachi K: Lymphatic invasion and potential for tumor growth and metastasis in patients with gastric cancer. Surgery. 1995, 117 (4): 380-385. 10.1016/S0039-6060(05)80056-X.View ArticlePubMedGoogle Scholar
- Shiraishi N, Inomata M, Osawa N, Yasuda K, Adachi Y, Kitano S: Early and late recurrence after gastrectomy for gastric cancer. Univariate and multivariate analyses. Cancer. 2000, 89 (2): 255-261. 10.1002/1097-0142(20000715)89:2<255::AID-CNCR8>3.0.CO;2-N.View ArticlePubMedGoogle Scholar
- Moon YW, Jeung HC, Rha SY, Yoo NC, Roh JK, Noh SH, Kim BS, Chung HC: Changing patterns of prognosticators during 15-year follow-up of advanced gastric cancer after radical gastrectomy and adjuvant chemotherapy: a 15-year follow-up study at a single korean institute. Ann Surg Oncol. 2007, 14 (10): 2730-2737. 10.1245/s10434-007-9479-4.View ArticlePubMedGoogle Scholar
- Aihara R, Mochiki E, Ohotake S, Kamiyama Y, Ohono T, Kuwano H, Kurokawa K, Suzuki K: Peritoneal recurrence of gastric cancer with mucin phenotype 12 years after curative resection: report of a case. Surg Today. 2007, 37 (4): 325-329. 10.1007/s00595-006-3392-5.View ArticlePubMedGoogle Scholar
- Gupta A, Malati T, Gupta PD: Altered expression of keratin in epithelioid tumours. Curr Sci. 1992, 62: 2882-2893.Google Scholar
- Wauters CC, Smedts F, Gerrits LG, Bosman FT, Ramaekers FC: Keratins 7 and 20 as diagnostic markers of carcinomas metastatic to the ovary. Hum Pathol. 1995, 26 (8): 852-855. 10.1016/0046-8177(95)90006-3.View ArticlePubMedGoogle Scholar
- Wang NP, Zee S, Zarbo RJ, Bacchi CE, Gown AM: Coordinate expression of cytokeratins 7 and 20 defines unique subsets of carcinomas. Appl Immunohistochem. 1995, 3: 99-107.Google Scholar
- Chu P, Wu E, Weiss LM: Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol. 2000, 13 (9): 962-972. 10.1038/modpathol.3880175.View ArticlePubMedGoogle Scholar
- Levine AJ: p53, the cellular gatekeeper for growth and division. Cell. 1997, 88 (3): 323-331. 10.1016/S0092-8674(00)81871-1.View ArticlePubMedGoogle Scholar
- Hall PA, Levinson DA, Wood AL, Yu CC, Kellock DB, Watkins JA, Barnes DM, Gillett CE, Camplejohn R, Dover R: Proliferating cell nuclear antigen(PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol. 1990, 162 (4): 285-294. 10.1002/path.1711620403.View ArticlePubMedGoogle Scholar
- Schlüter C, Duchrow M, Wohlenberg C, Becker MH, Key G, Flad HD, Gerdes J: The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. J Cell Biol. 1993, 123 (3): 513-522. 10.1083/jcb.123.3.513.View ArticlePubMedGoogle Scholar
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