**Core tip:** Endoscopic positioning of self-expandable metal stents (SEMSs) has an established role in the palliation of obstructing metastatic colorectal cancers (CRCs).  More controversial is the management of re-obstruction due to intrastent tumor ingrowth.  In our case, a patient with obstructing, metastatic, carcinomatous CRC, primary palliated with SEMS placement, experienced two different episodes of intrastent tumor in-growth.  This occurred along with a long-lasting history of partial efficacy of chemotherapy, including bevacizumab.  Both these episodes were successfully treated through subsequent stent-in-stent placement, with immediate symptom relief, no procedure-related complications (notwithstanding different negative prognostic factors), no need for chemotherapy discontinuation and, ultimately, a good quality of life. 

INTRODUCTION
============

Colorectal cancer (CRC) is one of the most commonly encountered neoplasms, especially in Western countries, with an increasing incidence over the last years\[[@B1],[@B2]\].  More than a quarter of CRC patients are diagnosed with stage IV disease, and about ten percent of CRC patients present with large bowel occlusion\[[@B3]-[@B5]\], involving a management regimen (endoscopic *vs* surgical) that is still debated\[[@B3],[@B6]-[@B8]\].  The application of self-expandable metal stents (SEMSs) for CRC obstruction has been increasingly used over time in the setting of palliation of inoperable cases as an alternative to emergency surgery\[[@B9]\].  Surgical procedures are burdened by a high mortality rate in this setting\[[@B4],[@B10],[@B11]\], are not oncologically indicated in advanced disease, and require a time interval before undertaking chemotherapy\[[@B12]\].  This represents the only possibility of disease control for these patients.  On the contrary, endoscopic procedures, despite being less invasive\[[@B13]\] and requiring shorter hospitalization times\[[@B11],[@B14]-[@B16]\], suffer from a suboptimal technical success rate (particularly for tortuous colorectal flexures\[[@B17]\]) and from the possibility of these complications\[[@B6],[@B10],[@B17]-[@B22]\]: colonic perforation (10%), stent migration (9%) and re-obstruction (18%)\[[@B10]\].  The issue of complications is even more noteworthy when patients are candidates for chemotherapy with antiangiogenic agents (*e.g*.,  bevacizumab), a described risk factor for colonic perforation in the presence of a SEMS\[[@B23],[@B24]\].  While some complications need to be treated by surgery, re-obstruction can be treated by stent-in-stent deployment\[[@B25]\].  Nevertheless, technical success and clinical efficacy are scarcely reported, yet are still lower than primary stenting\[[@B3],[@B25]\].  Moreover, the issue of the stent-in-stent patency and the possible management of an additional intra-stent neoplastic ingrowth has never been assessed. 

We describe the case of a man with occluding splenic flexure CRC that was treated by SEMS positioning due to metastatic, carcinomatous disease, with chemotherapy starting immediately after the first stent positioning.  However, in two different occasions (6 mo and 22 mo after primary stenting), the patients experienced symptoms of a radiologically confirmed bowel occlusion due to endoscopically-diagnosed intra-stent tumor ingrowth.  Nevertheless, systemic disease was substantially under control with chemotherapy.  Despite the presence of negative prognostic factors (splenic-flexure location, carcinomatosis, bevacizumab subsequently added to chemotherapy regimen, previously positioned SEMS and SEMS-in-SEMS), both of the two episodes were successfully treated with positioning of additional stent-in-stents, which allowed for substantial chemotherapeutic continuity and lasting partial disease control of carcinomatous disease. 

CASE PRESENTATION
=================

A 66-year-old man was diagnosed in March 2016 with occluding colonic cancer, immediately proximal to and partially involving the splenic flexure.  Due to the presence of liver metastasis and peritoneal carcinomatosis with ascites, a 22 mm/6 cm through-the-scope (TTS) SEMS (Wallflex^TM^, Boston Scientific) was placed through the stenosis, and chemotherapy with fluorouracil/folinic acid/irinotecan was immediately started.  Six months later, an occluding intra-stent tumor ingrowth (with responsive systemic disease) was treated by the placement of a colonic stent-in-stent (22 mm/9 cm TTS SEMS; Wallflex^TM^, Boston Scientific), and chemotherapy resumed 2 d after. 

After more than 1 year of substantial disease stability (although bevacizumab was added to the chemotherapy regimen 18 mo after diagnosis), the patient experienced symptoms of intestinal occlusion in January 2018 (+16 mo from the second stent).  Physical examination revealed abdominal distension, hyper-tympanism on percussion, and tinkling bowel sounds.  An abdominal X-ray showed ileocolic dilation proximal to the correctly located previous stents (Figure [1A](#F1){ref-type="fig"}), and colonoscopy showed new intrastent tumor ingrowths (Figure [2A](#F2){ref-type="fig"}). 

![ Abdominal X-ray before and after the positioning of the third stent.  A: Large bowel massive distention (long arrows) without apparent stent migration; curves highlight the profiles of the proximal edges of the first and second previously placed stents; B: The third stent placed within the two previously placed stents (short arrows indicating some of the radiopaque markers), with detention of proximal loops.](WJGE-11-61-g001){#F1}

![ Endoscopic appearance of neoplastic stenosis before and after the third stent.  A: Tumor ingrowth inside the two completely hidden previously placed stents; B: A small diameter hole inside the stenotic tract immediately after deployment of the third stent.](WJGE-11-61-g002){#F2}

FINAL DIAGNOSIS
===============

The conclusive diagnosis was bowel occlusion due to intrastent tumor ingrowth in a patient with previously positioned multiple SEMS for the palliation of an obstructing, metastatic, carcinomatous CRC with partial disease control under chemotherapy, including bevacizumab. 

TREATMENT
=========

Considering the presence of carcinosis and ascites, as well as the patient's willingness to avoid a stoma, an additional TTS 22 mm/8 cm SEMS (Hanarostent^®^, M.I.Tech) was successfully positioned within the two previous stents (Figure [3](#F3){ref-type="fig"}) using fluoroscopic guidance and deep sedation.  This procedure was performed after multidisciplinary discussion and informed consent. 

![ Intraprocedural radiological appearance of the three stents bypassing the lesion above the splenic flexure.  Curves highlight the proximal edges of the first and second previously placed stents; arrows indicate some of the radiopaque markers of the third recently positioned and gradually expanding stent.](WJGE-11-61-g003){#F3}

OUTCOME AND FOLLOW-UP
=====================

Despite that the stent opening appeared endoscopically not brilliant (Figure [2B](#F2){ref-type="fig"}), the patient experienced immediate relief of occlusive symptoms, the following X-ray showed no residual bowel dilation (Figure [1B](#F1){ref-type="fig"}) and chemotherapy was resumed 8 d after. 

No SEMS-related adverse events occurred until June 2018 (+150 d from the last procedure and +27 mo from diagnosis), when the patient died due to systemic complications related to disease progression. 

DISCUSSION
==========

This 66-year-old patient with metastatic, carcinomatous, occluding CRC was successfully treated with multiple endoscopic procedures (1 SEMS and 2 SEMS-in-SEMS placements), without procedure-related complications and with clinical benefit, good quality of life and partial systemic disease control for more than 2 years. 

Some aspects made us consider this case of interest for endoscopy, gastroenterology and oncology practitioners.  Firstly, to our knowledge, the possibility of positioning a third stent-in-stent for recurrent intrastent tumor ingrowth has never been considered and described.  Moreover, some presumptive technical difficulties and negative prognostic factors\[[@B26]\] did not interfere with the success and efficacy of the endoscopic palliation.  For example, a significantly lower technical success of SEMS placement\[[@B27]\] and patency after SEMS placement\[[@B25]\] has been demonstrated in patients with carcinomatosis (83% *vs* 93% for technical success\[[@B27]\] and 118 d *vs* 361 d for SEMS patency\[[@B25]\]).  Carcinomatosis and the proximal location of the obstruction were found to be independent predictors of technical failure\[[@B27]\].  Moreover, concomitant chemotherapy with bevacizumab has been preliminary associated with increased perforation risk when compared to either chemotherapy without bevacizumab or no chemotherapy\[[@B23],[@B24],[@B28]-[@B30]\].  However, in our case, neither the presence of peritoneal carcinomatosis with ascites, the splenic flexure location, nor subsequent chemotherapy that included bevacizumab affected the technical success or lasting clinical benefits of the procedures.  In fact, the patient has remained asymptomatic, on a varied fiber-free diet and with an acceptable quality of life until death, which was due to disease progression. 

In one study focusing on secondary stent-in-stent placement\[[@B25]\], the rate of technical success was not reported (patients with attempted but failed secondary SEMS placement were excluded).  In this study, overall clinical success after secondary positioning was achieved in 75% of patients (which is lower than reported in the setting of primary stenting), and long-term clinical failure was reported in 52% of patients with initially successful secondary positioning.  In addition, the presence of carcinomatosis was associated with reduced long-term clinical success.  However, in our case, the presence of the two previously positioned SEMS did not hamper the successful positioning and clinical efficacy of the third stent-in-stent. 

The same authors also compared, for the first time, the clinical outcomes of an endoscopic re-stenting *vs* palliative surgery after a first stent failure in 115 patients, which was due to malignant re-obstruction.  They demonstrated that among patients undergoing secondary SEMS placement, the overall mortality rate and median duration of hospital stay were significantly lower than in the surgery group, where the median lumen patency was higher (7.9 mo *vs* 3.4 mo for the stent patency).  Notably, no significant differences were registered in overall and progression-free survival between the two groups\[[@B31]\].  In this scenario, we report one case with an extraordinary stent patency of 480 d after secondary stenting and of 150 d after tertiary stenting. 

All these data highlight the need for a cautious evaluation of the solution best suited for one specific patient with stent re-obstruction. 

CONCLUSION
==========

In this case, despite the presence of negative prognostic factors and technical difficulties, tertiary stenting was technically successful.  The patient experienced immediate relief of symptoms, has not encountered any SEMS-related adverse events, and has maintained a good quality of life during the 150 d following the last stent positioning, without the need for chemotherapy discontinuation.  Despite the fact that the evidence on multiple stenting is controversial, and that data on tertiary stent-in-stenting are lacking, this report suggests that the positioning of a third stent-in-stent in patients with recurrent intra-stent tumor in-growth should be considered and might be a reasonable and effective option.  Further research is needed to confirm the safety and reproducibility of this approach compared with surgical options, not only in terms of technical feasibility, but also regarding quality of life and long-term outcomes. 

EXPERIENCES AND LESSONS
=======================

SEMS positioning is an established treatment for the palliation of occluding unresectable CRCs.  Even in the presence of negative prognostic factors, the feasibility of endoscopic palliation may be discussed in multidisciplinary tumor boards in facilities with high endoscopic expertise and prompt surgical back-up. 

SEMS re-obstruction is the most frequent complication of the endoscopic palliation of occluding CRCs, and SEMS-in-SEMS placement has proven to be a valid option in this setting. 

Even after secondary failure of SEMS-in-SEMS due to recurrent tumor ingrowth, a tertiary SEMS-in-SEMS placement is technically feasible and might be an option in referral centers. 

ACKNOWLEDGMENTS
===============

The authors would like to thank the nursing staff of the Endoscopy Unit and the medical staff of Oncological Division of Regina Elena Cancer Institute, which has collaborated in retrieving clinical information during the procedure and during patient follow-up. 

Informed consent statement: The patient gave informed consent prior to the procedure. 

Conflict-of-interest statement: The authors declare that they have no conflicts of interest. 

CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016). 

Manuscript source: Unsolicited manuscript

Peer-review started: October 30, 2018

First decision: November 29, 2018

Article in press: December 13, 2018

Specialty type: Gastroenterology and hepatology

Country of origin: Italy

Peer-review report classification

Grade A (Excellent): 0

Grade B (Very good): B

Grade C (Good): C

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P- Reviewer: Iliescu EL, Sipos F S- Editor: Wang XJ L- Editor: Filipodia E- Editor: Song H

[^1]: Author contributions: Vanella G, Assisi D and Lapenta R were involved in the procedure and in concept of the report; Vanella G and Coluccio C were involved in retrieving useful information from clinical charts and writing the manuscript; Vanella G, Coluccio C and Di Giulio E were involved in literature review; Di Giulio E, Assisi D and Lapenta R were involved in critical revision of the manuscript; all authors had access and approved the last version of the manuscript. 

    Corresponding author: Emilio Di Giulio, MD, Professor, Department of Digestive Endoscopy, Sant'Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1035-1039, Rome 00189, Italy.  <emilio.digiulio@uniroma1.it>

    Telephone: +39-6-33776151 Fax: +39-6-33776692
