Long-term survival of a patient with liver metastases from gastric clear cell adenocarcinoma after multimodal treatment including interventional oncology techniques: a case report | BMC Gastroenterology

In December 2010, a 45-year-old, previously healthy man with no significant family medical history presented with a history of epigastric pain accompanied by a persistent nonproductive cough. A subsequent esophagogastroduodenoscopy identified a malignant gastric antrum lesion. Complementary imaging examinations (abdominal ultrasound and chest X-ray) did not reveal any distant metastases. The management of the patient at this stage as well as during all its subsequent stages has been determined by a multidisciplinary tumor board (MTB).

In February 2011, the patient underwent an R0 subtotal gastrectomy followed by a Billroth II gastrojejunostomy with a side-to-side jejunojejunal (Braun) anastomosis.

Subsequent histopathological examination revealed a sharply demarcated, exulcerated, moderately differentiated, invasive clear cell gut-like gastric AC (Fig. 1A–C). The 10 mm thick tumor, measuring 5 × 6 cm, infiltrated the serous surface and extensive lymphovascular invasion was also noted. The adjacent gastric mucosa showed signs of Helicobacter pylori gastritis with moderate intestinal metaplasia. All 18 dissected lymph nodes were negative for carcinoma. Based on this information and taking into account the 7th edition of the American Joint Committee on Cancer’s TNM staging classification for gastric cancer, the tumor described met the criteria for a stage IIb carcinoma (pT4aN0M0).

Fig. 1

A Macroscopic examination of the gastrectomy specimen revealed a clearly demarcated and ulcerated tumor. B Histological examination revealed clear cell adenocarcinoma with transmural infiltration of the gastric wall and extensive vascular invasion. VS At higher magnification, the tumor showed a tubular and cribriform architecture

From March to July 2011, the surgery was followed by postoperative chemoradiotherapy with capecitabine, the total radiation dose was 45 Gy delivered in 25 fractions over 5 weeks. In August 2012, two liver metastases 5 cm and 1 cm in diameter were discovered in the right lobe of the liver during follow-up imaging. From October 2012 to March 2013, first-line systemic chemotherapy was administered. The patient received 1 cycle of ECX (epirubicin, cisplatin, capecitabine); due to side effects, capecitabine was switched to fluorouracil after the first cycle. Computed tomography (CT) after 3 cycles showed a partial response (PR) which was maintained during regular follow-ups after treatment.

11 months after stopping treatment, a CT scan identified enlargement of the existing liver lesions (progressive disease). From March to May 2014, the patient received 3 cycles of TOF regimen (paclitaxel, oxaliplatin, fluorouracil) as second-line systemic therapy. This chemotherapy was stopped due to side effects (febrile neutropenia and stomatitis). In May 2014, a surveillance CT scan revealed only insignificant shrinkage of the liver metastases (stable disease), and the MTB suggested a right hepatectomy (Fig. 2A).

Figure 2
Figure 2

A Axial portal phase contrast computed tomography image shows hepatic metastases in segment VII. B Cone-beam computed tomography prior to application of superselective drug-eluting beads loaded with transarterial doxorubicin chemoembolization (as bridge therapy prior to planned portal vein embolization) confirmed complete absorption of contrast material in metastases

Due to an FLR of only 25%, immediate resection was not possible. Therefore, superselective DEBDOX-TACE was performed under the control of cone-beam computed tomography (CBCT) (Fig. 2B) in July and August 2014 with an interval of 4 weeks as bridging therapy before planned portal vein embolization (PVE) which was performed one week after the last DEBDOX-TACE. Tandem 100 (mathrm{mu m}) microspheres (Tandem®, Boston Scientific, Marlborough, MA, USA) loaded with 75 mg of doxorubicin were injected through a 2.4F microcatheter (Progreat®, Terumo Europe NV, Belgium).

Transhepatic ipsilateral right PVE using 250–1000 (mathrm{mu m}) particles (Embozene, Boston Scientific, Marlborough, MA, USA) and 6–10 mm embolization coils (Interlock-18 Fibered, Boston Scientific, Marlborough, MA, USA) were performed. Initially, smaller particles were infused to address smaller distal branches, followed by a gradual increase in microsphere caliber size until near complete stasis was achieved. Then the embolization coils were placed centrally to prevent recanalization (Fig. 3A,B).

Figure 3
picture 3

A Portography acquired immediately prior to portal vein embolization shows normal portal vein anatomy. B Control portography immediately after portal vein embolization with microspheres and coils shows successful occlusion of the right portal vein branches. VS CT scan images before portal vein embolization and 4 weeks after showing significant enlargement of the left hepatic lobe (future liver remnant increased from 25% to 41%)

Total functional liver volume (TFLV) and FLR volume were measured before and 4 weeks after PVE to assess FLR, TFLV and FLR/TFLV ratio using CT imaging. In October 2014, follow-up CT scan after DEBDOX-TACE and PVE demonstrated stabilization of ipsilateral disease burden and contralateral hepatic enlargement at sufficient interval (with an FLR of 41%) that allowed successful resection of the right hepatic lobe R0 (Fig. 3C). Histological examination of the resected liver metastases revealed histological features similar to those of the primary tumor (Fig. 4A).

Figure 4
number 4

A Liver metastases with histological features similar to those of the primary tumor

Following magnetic resonance imaging (MRI) in January 2015 which detected 2 small metastases in the remaining liver, the patient received 3 cycles of third-line systemic treatment containing FOLFIRI (folinic acid, fluorouracil and irinotecan) between January and May 2015. Response CT scan revealed growth of one of the metastases (Fig. 5A); and in July 2015, a superselective Y-90 SIRT (SIR-Spheres®; Sirtex Medical, North Sydney, NSW, Australia) with an activity of 522 MBq was performed under CBCT control (Fig. 5B). A complete response in the target lesion was maintained (Fig. 5C). In December 2015, 3 new metastases were detected on the control MRI. The patient was again treated with a superselective SIRT Y-90 (215 MBq + 241 MBq) under CBCT control, and a complete response until June 2016 was obtained. In July 2016, the CT scan showed new metastases and the last SIRT Y-90 procedure (459 MBq) was performed.

Figure 5
number 5

A Axial portal phase contrast computed tomography image shows hepatic metastases in segment VI. B Cone-beam computed tomography prior to selective superselective yttrium-90 internal radiotherapy confirmed complete uptake of contrast material in the metastases. VS Follow-up magnetic resonance image shows complete response by modified response endpoints in solid tumors

In December 2016, a new progression of liver disease was detected. This time, despite the MTB’s recommendation, another SIRT treatment was not approved by the insurance company. Therefore, liver-directed therapy with DEBDOX-TACE was performed using Tandem 100 (mathrm{mu m}) microspheres (Tandem®, Boston Scientific, Marlborough, MA, USA) loaded with 75 mg of doxorubicin in February 2017. In March 2017, the patient was started on fourth-line systemic therapy consisting of 3 cycles of Paclitaxel and Ramucirumab followed by Ramucirumab maintenance therapy until disease progression consisting of new liver metastases, ascites and pleural effusions was noted in November 2017.

In May 2018, 6 months after starting palliative care in December 2017, the patient died. His OS was 88 months, the last 69 months while he had metastatic disease.

Michael J. Chiaramonte