Abstract
Gastric cancer with portal vein tumor thrombosis (GC-PVTT) is a rare condition with a very poor prognosis. A 64-year-old man with GC-PVTT was admitted to our hospital. His carcinoembryonic antigen level was slightly elevated (17.4 ng/ml). Upper gastrointestinal endoscopy showed a type-2 gastric lesion (45 mm × 40 mm) in the gastric antrum. The PVTT originated from the main gastric tumor and continued to the superior mesenteric vein. Fluorodeoxyglucose-positron emission tomography showed high uptake both by the main tumor and PVTT. A distal gastrectomy with D2 lymphadenectomy was performed with simultaneous removal of the PVTT. Pathological examination showed a poorly differentiated adenocarcinoma with neuroendocrine differentiation. Adjuvant chemotherapy with S-1 was administered for 1 year. The patient survived for >5 years with no recurrence. Surgical gastrectomy and complete removal of the PVTT followed by S-1 chemotherapy could be a treatment option that offers improved long-term survival for patients with GC-PVTT.
Gastric cancer with portal vein tumor thrombosis (GC-PVTT) is a rare condition that is treated with chemotherapy and/or surgery; however, its prognosis is very poor (1-12). Both the role of chemotherapy and surgery for patients with GC-PVTT has yet to be established. Recently, several reports have suggested that gastrectomy with removal of the PVTT in combination with perioperative chemotherapy may be beneficial in selected cases (3-12). In East Asians, S-1 (TS-1; Taiho Pharmaceutical) is widely administered as an adjuvant therapy for patients who have undergone curative resection for locally advanced gastric cancer (13, 14).
Herein, we present a case involving an advanced GC-PVTT patient who survived for >5 years without recurrence. The patient underwent distal gastrectomy with removal of the PVTT that extended to the superior mesenteric vein (SMV) trunk followed by adjuvant chemotherapy with S-1.
Case Report
A 64-year-old man was referred to our hospital because of epigastric pain. Physical examination showed no abnormality. Laboratory testing gave slightly abnormal results: aspartate aminotransferase, 75 IU/l; alanine aminotransferase, 77 IU/l; blood sugar, 189 mg/dl; and HbA1c, 6.9%. Carcinoembryonic antigen was slightly elevated 17.4 ng/ml (normal range, ≤5.0 ng/ml), whereas carbohydrate antigen 19-9 and serum α-fetoprotein were within the normal range. Upper gastrointestinal endoscopy showed a type 2 gastric lesion (45 mm × 40 mm) in the gastric antrum (Figure 1). The pathological diagnosis of biopsy specimens revealed a poorly differentiated adeno-carcinoma. On T2-weighted magnetic resonance imaging, a PVTT with hyperintensity spreading from the gastroepiploic vein to the SMV trunk was observed (Figure 2). Abdominal computed tomography (CT) showed the main tumor and PVTT. Three-dimensional CT angiography clearly showed PVTT via the gastrocolic trunk (Figure 3). Fluorode-oxyglucose-positron emission tomography showed abnormal uptake both of the main tumor and PVTT (Figure 4). The diagnostic images did not show distant metastasis or peritoneal dissemination; therefore, surgical intervention was selected as an initial therapy. In February 2014, we performed an open distal gastrectomy with D2 lymphadenectomy and Roux-en-Y reconstruction. The main tumor was egg sized and had distinct serosal invasion. Lymph node, liver, and peritoneal metastases were not detected during surgery. The non-invasive PVTT occupied an area from the right gastroepiploic vein to the SMV. Initially, the SMV was clamped up- and down-stream at the point where the PVTT protruded into the SMV, and the PVTT was completely removed followed by minimal portal vein wall resection (Figure 5A). The defect of the portal vein was closed by using a transverse continuous suture with 5-0 Prolene® (Figure 5B). The operative time was 403 min, the blood loss amount was 780 g, and no blood product was needed. Macroscopically, the resected specimen appeared to show complete removal of the main tumor and the PVTT (Figure 6). Pathological examination of the resected specimen showed a poorly differentiated adenocarcinoma with neuroendocrine differentiation (Figure 7). By immunostaining, obvious staining of chromogranin A and synaptophysin was observed. AFP immunostaining was negative, and no hepatoid features were identified. Ki67 was positive in 20% to 30% of the tumor cells. The final pathological tumor stage according to the Union for International Cancer Control TNM Classification of Malignant Tumors, 8th Edition (15) was stage IIIA [pT4a, pN2 (5/38), and pM0]. In the postoperative course, the patient developed delayed gastric emptying, but he promptly recovered after receiving medication and was discharged from the hospital on postoperative day 25. Adjuvant chemotherapy with S-1 was started on the 52nd postoperative day and continued for 1 year. S-1 therapy was administered orally at a dose of 120 mg/day for 14 days, followed by a 7-day drug-free interval. Obvious side effects to delay the chemotherapy were not observed. The patient is alive without recurrence after 5 years at this writing.
Discussion
To our knowledge, this is the first case of a GC-PVTT patient who lived >5 years without recurrence. He was treated with distal gastrectomy and surgical excision of PVTT followed by 12 months of adjuvant chemotherapy with S-1. The previous largest series of GC-PVTT cases (n=51) found that the median survival time was 5.4 months, and the 5-year survival rate was <10% with only one actual 5-year survivor (2). Surgical removal of the PVTT was not performed for all patients. Female sex and hepatic mass type of the PVTT were defined as independent poor prognostic factors. When the PVTT appeared to originate from the hepatic mass, it was classified as the hepatic mass type. In that cohort, operations for gastric cancer and systemic chemotherapy were performed for 12 (23.5%) and 43 (84.3%) patients, respectively; however, ‘operations for gastric cancer’ and ‘application of chemotherapy’ were not determined as prognostic factors.
GC- PVTT is known to be an aggressive phenotype with poor prognosis accompanied by high levels of AFP and a high incidence of liver metastasis (9, 16). PVTT is considered to be an early step in liver metastasis because metastasis is established when cancer cells are released from the primary tumor. However, formation of PVTT need not always represent the first step toward liver metastasis. It has been reported that an aggressive approach followed by appropriate chemotherapy may delay the recurrence and prolong the survival time for patients with no liver metastasis (3).
In our case, PVTT showed expanded growth even in the pathological findings, and a small portion existed in the SMV trunk. Therefore, we were able to easily remove the PVTT without simultaneous resection of the extensive SMV wall. The SMV wall was primarily closed subsequently. Intraoperative assessments, including intraoperative ultrasonography, are very useful to determine the extent of portal vein resection. In cases with invasive growth of PVTT, simultaneous resection of the portal vein wall is required. In a previous case with SMV invasion by a PVTT, pancreatoduodenectomy was applied (3).
A literature review showed 11 GC-PVTT patients who were treated with surgical intervention, including our case (Table I) (3-12). Among them, 5 patients survived for >3 years; all were males, and 4 were diagnosed as having moderately to poorly differentiated adenocarcinomas. One of those 5 patients was AFP-positive and the other showed liver metastasis. Gastrectomy was performed for all patients, and the PVTT was removed in 2 patients. In the other 2 patients, PVTT disappeared by induction chemotherapy with S-1 + cisplatin; therefore, no surgical treatment of the PVTT was needed. Adjuvant chemotherapy, including S-1, was administered to all 5 patients. Among the 3-year survivors, only 2 patients survived for >5 years, and our patient is the only recurrence-free survivor as of this report. The other 5-year survivor was treated with total gastrectomy without PVTT removal followed by adjuvant therapy of S-1. Aggressive chemotherapy, including fluorouracil plus leucovorin with oxaliplatin (termed FOLFOX) and fluorouracil plus leucovorin with irinotecan (termed FOLFIRI) (11), was additionally performed for recurrences. On the other hand, in GC-PVTT patients treated with chemotherapy alone, there has been only 1 other report of a 5-year survivor (2). A 67-year-old male GC-PVTT patient without liver metastasis was treated with systemic chemotherapy and lived for 7 years; however, the details of his chemotherapy regimen are unknown.
Previous studies have reported on the effectiveness of chemotherapy for GC-PVTT; however, the regimens used differed across the studies, and the theoretical basis for the use of these regimens has not been described (1-4, 5-7, 9-12). In the current case, we selected S-1 as an adjuvant chemotherapy. As described in the Japanese guidelines (17), S-1 has been a key drug in adjuvant chemotherapy for advanced gastric cancer and was reported to be more effective for the undifferentiated type of gastric cancer than for the differentiated type (13). Presently, more effective adjuvant chemotherapies of capecitabine plus oxaliplatin and S-1 plus docetaxel are available (18, 19).
The long recurrence-free survival of our patient can be possibly explained by the following reasons. First, R0 resection of the primary tumor and complete extirpation of PVTT was achieved. The patient showed normal AFP-level and had no liver metastasis. Second, the patient was male and the PVTT did not originate from the hepatic mass. Third, adjuvant chemotherapy with S-1 may also have contributed to the long-term recurrence-free survival.
In conclusion, gastrectomy together with complete removal of PVTT followed by S-1 chemotherapy could be a treatment option that offers improved long-term survival for patients with GC-PVTT. Accumulation of more cases in which this treatment approach is used are needed to confirm our speculation.
Footnotes
Authors' Contributions
Conception and design: Y. Yoshida, T. Beppu; Acquisition of data: Y. Yoshida, S. Saito; Writing, review, and/or revision of the manuscript: All Authors; Supervision: T. Beppu.
Conflicts of Interest
The Authors declare no conflicts of interest regarding this study.
- Received March 15, 2019.
- Revision received March 27, 2019.
- Accepted March 28, 2019.
- Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved