Skip to main content

First case report of neoadjuvant gemcitabine and S-1 for locally advanced unresectable duodenal adenocarcinoma

Abstract

Background

The usefulness of neoadjuvant chemotherapy for patients with duodenal adenocarcinoma remains unclear. We report the case of a successfully resected duodenal adenocarcinoma managed by neoadjuvant chemotherapy using gemcitabine and S-1.

Case presentation

A 72-year-old female presented with a one-week history of abdominal bloating and vomiting after meals. Esophagogastroduodenoscopy revealed a circumferential epithelial lesion in the second portion of the duodenum. Abdominal computed tomography scan revealed thickened walls and narrowing of the duodenum. Further, an adenocarcinoma was noted on biopsy. Though she was diagnosed with duodenal adenocarcinoma, pancreatic cancer could not be completely ruled out. Therefore, she underwent neoadjuvant chemotherapy using gemcitabine and S-1 after bypass surgery. After six chemotherapy cycles, the tumor significantly reduced in size. Further, lymph nodes and distant metastases were not noted on abdominal computed tomography. The patient underwent pancreaticoduodenectomy. Pathological examination revealed a 0.5-mm lesion and surrounding fibrosis at the duodenum, distal from the ampulla of Vater and the pancreas. Her postoperative course was almost uneventful, and she was discharged on the 31st postoperative day. The patient was followed up and had no tumor recurrence at 24 months after surgery.

Conclusion

Neoadjuvant chemotherapy with gemcitabine and S-1 was useful in reducing the size of a duodenal adenocarcinoma. This finding would aid physicians in managing patients that present with a similar presentation.

Background

Duodenal carcinoma (DC) is an uncommon malignancy, accounting for only 0.4% of gastrointestinal cancers [1]. Because patients with DCs present with nonspecific symptoms, its diagnosis is challenging, and patients often present with advanced disease. Its management includes complete surgical resection when feasible. Though adjuvant therapy is recommended in patients with DC [2], the role of neoadjuvant therapy remains unclear, especially in patients with locally advanced unresectable DC.

The usefulness of neoadjuvant chemotherapy has been reported in various types of cancers such as pancreatic and rectal cancers [3, 4]. We report a case of a successfully resected duodenal adenocarcinoma managed by neoadjuvant chemotherapy using gemcitabine and S-1.

Case presentation

A 72-year-old female presented with a one-week history of abdominal bloating and vomiting after meals. She was previously diagnosed with diabetes mellitus. Esophagogastroduodenoscopy revealed a circumferential epithelial lesion in the second portion of the duodenum (Fig. 1). Abdominal computed tomography (CT) scan revealed thickened walls and narrowing of the duodenum (Fig. 2a, b). Further, an adenocarcinoma was noted on biopsy. Though she was diagnosed with a duodenal adenocarcinoma, pancreatic cancer could not be completely ruled out. Therefore, she underwent neoadjuvant chemotherapy of gemcitabine and S-1 (GS) after bypass surgery (choledochojejunostomy and gastrojejunostomy). For each course, she received gemcitabine infusion (1000 mg/m2) on the first and eighth days. S-1 was administered orally twice daily (80 mg/day) for 2 weeks. The size of the tumor gradually decreased without any lymph nodes or distant metastases (Fig. 2c, d). After six courses of chemotherapy, an abdominal CT scan revealed that the tumor had significantly reduced in size (Fig. 2e, f). No adverse events were observed during her chemotherapy regimen. The patient then underwent pancreaticoduodenectomy. Pathological examination revealed a 0.5-mm lesion with surrounding fibrosis at the duodenum, distal from the ampulla of Vater and the pancreas (Fig. 3).

Fig. 1
figure 1

Esophagogastroduodenoscopy findings. a Circumferential epithelial lesion was found at the second portion of the duodenum (arrow). b The lumen was prominently narrowing and almost obstructed

Fig. 2
figure 2

Contrast enhanced abdominal computed tomography. a Before chemotherapy, axial view. The tumor was at the second portion of the duodenum (arrow). The lumen of the duodenum and the common bile duct was almost obstructed. b Before chemotherapy, coronal view. c After 3 courses of chemotherapy, axial view. The size of the tumor had decreased (arrow). d After 3 courses of chemotherapy, coronal view. e After 6 courses of chemotherapy, axial view. The tumor had extremely shrunken and was not detected (arrow). f After 6 courses of chemotherapy, coronal view

Fig. 3
figure 3

Specimen. a Macroscopic findings. The viable tumor was located at the duodenum away from the ampulla of Vater (arrow). b Cut surface of the specimen. (The tumor was pointed by arrow). c Microscopic findings. H.E. staining, 40 ×. A cluster of tumor cells was pointed by arrow. d H.E. staining, 400 ×

Except for the development of a postoperative grade B pancreatic fistula, her postoperative course was uneventful. She was discharged from the hospital on postoperative day 31 [5]. At a follow-up examination in the outpatient clinic at postoperative 24 months, no evidence of recurrence was detected.

Discussion

To the best of our knowledge, this is the first study reporting the use of neoadjuvant GS in patients with duodenal adenocarcinoma. Interestingly, it was markedly effective in a 72-year-old Japanese woman.

It was sometimes challenging for surgeons to differentiate duodenal adenocarcinoma from ampullary and pancreatic head cancers. Generally, it is pathologically impossible to differentiate these three cancers using biopsy alone. The only key feature differentiating the three would be the tumor location. Creating a preoperative diagnosis is essential because treatment plans for these tumors are different. In fact, we could not rule out pancreatic cancer preoperatively. Therefore, neoadjuvant GS treatment after bypass surgery was used in the case to manage pancreatic cancer, which had a worse prognosis [6].

Studies have shown that neoadjuvant chemotherapy or chemoradiotherapy has better clinical efficacy in patients with DC [7]. 5-FU, FOLFOX, and CAPOX were adopted as neoadjuvant regimens. However, there was scarce evidence of the utilization of S-1. S-1 is a relatively novel oral agent that has high efficacy and safety margin for advanced gastric and colorectal cancers [8, 9]. Today, S-1 is widely used for the treatment of gastrointestinal cancers and accepted as an alternative therapy to infused 5-FU, due to its administration convenience (oral intake) and less toxicity. Additionally, Fisherman et al. reported that chemotherapy including gemcitabine and irinotecan combinations appeared to have higher overall response rate compared to 5-FU-based regimen in a retrospective review of 113 patients with advanced small bowel adenocarcinoma [10]. We believe that GS was a suitable treatment regimen for the patient’s duodenal adenocarcinoma. However, the duration of this regimen is still unclear. In the present case, six courses of GS regimen were performed based on the preoperative treatment for pancreatic cancer in our institution.

Previous reports on the use of neoadjuvant chemotherapy with S-1 for patients with duodenal adenocarcinoma are listed in Table 1 [11,12,13,14,15,16]. A total of seven cases, including the present case, have been reported. The median age of the reported cases was 60 years (range, 48–72 years). Four patients were managed with S-1 and cisplatin, one patient was managed with S-1 with oxaliplatin in 1, one patient was managed with S-1 with gemcitabine, and one patient was managed with S-1 alone. Four patients had partial response treatment, and none of the patients experienced disease progression. The median follow-up period was 12 months (range, 6–23) with six patients alive. For patients with gastric cancer, neoadjuvant treatment with S-1 and cisplatin may also be performed [17]. According to the authors reported in Table 1, the regimen using S-1 and cisplatin was chosen because of its proximity to the stomach. Therefore, they followed neoadjuvant treatment for gastric cancer. However, there are no other reports that used S-1 with gemcitabine. In fact, duodenal adenocarcinoma is a relatively rare tumor. Thus, it is difficult to perform clinical trials on the usefulness of neoadjuvant chemotherapy. Further investigations such as multicenter study or using national database are necessary.

Table 1 Neoadjuvant chemotherapy with S-1 for duodenal adenocarcinoma

Neoadjuvant chemotherapy with gemcitabine and S-1 was useful in reducing the size of the duodenal adenocarcinoma. This finding would aid physicians in managing patients who present with a similar presentation.

Availability of data and materials

All data generated or analyzed during this study are included in the published article.

Abbreviations

DC:

Duodenal carcinoma

CT:

Computed tomography

GS:

Gemcitabine and S-1

References

  1. Shaib WL, Sharma R, Brutcher E, Kim S, Maithel SK, Chen Z, et al. Treatment utilization and surgical outcome of ampullary and duodenal adenocarcinoma. J Surg Oncol. 2014;109:556–60.

    Article  Google Scholar 

  2. Jabbour SK, Mulvihill D. Defining the role of adjuvant therapy: ampullary and duodenal adenocarcinoma. Semin Radiat Oncol. 2014;24:85–93.

    Article  Google Scholar 

  3. Müller PC, Frey MC, Ruzza CM, Nickel F, Jost C, Gwerder C, et al. Neoadjuvant chemotherapy in pancreatic cancer: an appraisal of the current high-level evidence. Pharmacology. 2021;106:143–53.

    PubMed  Google Scholar 

  4. Petrelli F, Trevisan F, Cabiddu M, Sgroi G, Bruschieri L, Rausa E, et al. Total neoadjuvant therapy in rectal cancer: a systematic review and meta-analysis of treatment outcomes. Ann Surg. 2020;271:440–8.

    Article  Google Scholar 

  5. Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, International Study Group on Pancreatic Surgery (ISGPS), et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery. 2017;161:584–91.

    Article  Google Scholar 

  6. Motoi F, Kosuge T, Ueno H, Yamaue H, Satoi S, Sho M, Study Group of Preoperative Therapy for Pancreatic Cancer (Prep) and Japanese Study Group of Adjuvant Therapy for Pancreatic cancer (JSAP), et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05). Jpn J Clin Oncol. 2019;49:190–4.

    Article  Google Scholar 

  7. Raghav K, Overman MJ. Small bowel adenocarcinomas–existing evidence and evolving paradigms. Nat Rev Clin Oncol. 2013;10:534–44.

    Article  CAS  Google Scholar 

  8. Mahlberg R, Lorenzen S, Thuss-Patience P, Heinemann V, Pfeiffer P, Möhler M. New perspectives in the treatment of advanced gastric cancer: S-1 as a novel oral 5-FU therapy in combination with cisplatin. Chemotherapy. 2017;62:62–70.

    Article  CAS  Google Scholar 

  9. Shimomura M, Shinozaki K, Hinoi T, Yoshimitsu M, Kurayoshi M, Sumitani D, Hiroshima Surgical study group of Clinical Oncology (HiSCO), et al. A multi-institutional feasibility study of S-1/oxaliplatin plus bevacizumab in patients with advanced/metastatic colorectal cancer: the HiSCO-02 prospective phase II study. Springerplus. 2016;5:1800.

    Article  Google Scholar 

  10. Fishman PN, Pond GR, Moore MJ, Oza A, Burkes RL, Siu LL, et al. Natural history and chemotherapy effectiveness for advanced adenocarcinoma of the small bowel: a retrospective review of 113 cases. Am J Clin Oncol. 2006;29:225–31.

    Article  CAS  Google Scholar 

  11. Egawa T, Ohashi M, Ito Y, Hayashi S, Doi M, Nagashima A. A partial response to combined S-1 and CDDP chemotherapy enabling a curative resection in a patient with locally advanced duodenal cancer. Gan To Kagaku Ryoho. 2008;35:2083–5.

    PubMed  Google Scholar 

  12. Kang SM, Murata A, Tendou M, Tezuka K, Nishino Y. A case report of primary duodenal adenocarcinoma with marked lymph node metastases responding to chemotherapy with S-1 plus CDDP combination. Gan To Kagaku Ryoho. 2009;36:1569–71.

    PubMed  Google Scholar 

  13. Mima K, Kakeji Y, Saeki H, Yoshida R, Yoshinaga K, Morita M, et al. Chemotherapy with TS-1+CDDP followed by curative operation for locally advanced duodenal cancer. Jpn J Gastroenterol Surg. 2011;44:836–41.

    Article  Google Scholar 

  14. Yamamoto S, Satou H, Endou I, Kubo M, Udaka T, Mizuta M, et al. A curatively resected giant mucinous adenocarcinoma of the duodenum successfully controlled by S-1 chemotherapy. Jpn J Gastroenterol Surg. 2014;47:490–8.

    Article  Google Scholar 

  15. Kanehira M, Futagawa Y, Furukawa K, Shiba H, Uwagawa T, Yanaga K. Radical resection of a primary unresectable duodenal cancer after chemotherapy using S-1 and cisplatin: report of a case. Surg Case Rep. 2017;3:34.

    Article  Google Scholar 

  16. Zhang GY, Mao J, Zhao B, Long B, Zhan H, Zhang JQ, et al. Duodenal bulb adenocarcinoma benefitted from neoadjuvant chemotherapy: a case report. Chemotherapy. 2017;62:290–4.

    Article  Google Scholar 

  17. Kochi M, Fujii M, Kanamori N, Kaiga T, Takahashi T, Kobayashi M, et al. Neoadjuvant chemotherapy with S-1 and CDDP in advanced gastric cancer. J Cancer Res Clin Oncol. 2006;132:781–5.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing.

Funding

This work was supported by Kochi Organization for Medical Reformation and Renewal Grants.

Author information

Authors and Affiliations

Authors

Contributions

JK drafted the manuscript. TO and JI edited the article. JK, KS, MT, TM, SS, and TO performed the preoperative investigation and operation. JI and MM diagnosed pathologically. TO provided academic consideration. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Takehiro Okabayashi.

Ethics declarations

Ethics approval and consent to participate

The ethics committee of Kochi Health Sciences Center approved the study design.

Consent for publication

Consent for publication has been obtained from the patient presented in this case report.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kimura, J., Sui, K., Tabuchi, M. et al. First case report of neoadjuvant gemcitabine and S-1 for locally advanced unresectable duodenal adenocarcinoma. surg case rep 8, 98 (2022). https://doi.org/10.1186/s40792-022-01453-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s40792-022-01453-2

Keywords