Duodenal obstruction due to malignant pancreaticobiliary and duodenal cancers has become more common with the development of chemotherapy and other palliative therapies. Historically, duodenal obstruction has been known to occur in 2% to 25% of patients without surgery. However, a recent study reported nearly twice the obstruction rate (38%).¹ Gastric outlet obstruction (GOO) is reported to be a marker for poor survival, regardless of the type of cancer,² and its management is important for the patient’s quality of life and further management of the malignancy. The palliative management of GOO includes duodenal self-expandable metallic stent (SEMS) placement, surgical gastrojejunostomy (GJ), or endoscopic ultrasound-guided GJ (EUS-GJ).^3,4 A meta-analysis showed the superiority of surgical GJ for patients with a long life expectancy and good performance compared to duodenal stenting.⁵ The American Society for Gastrointestinal Endoscopy recommends surgical GJ in patients with a life expectancy of >6 months and a good performance status.⁶ However, many patients are not suitable for surgical approaches, and even with a good performance status and life expectancy of >6 months, many endoscopists prefer duodenal SEMS insertion. EUS-GJ has shown comparable clinical outcomes to other methods but has technical barriers with instrument and cost issues.^7,8

Duodenal stenting has several advantages over other management techniques. This skill is intuitive, and the time to the resumption of oral intake is shorter than that involving surgical GJ.⁶ It also requires a shorter hospital stay and provides a lower procedure-related bleeding rate compared to other techniques. However, its disadvantage is the high reintervention rate.⁹ The reintervention rate of duodenal stents is approximately 20%.¹⁰

The management of obstructed duodenal stents includes secondary duodenal SEMS placement by stent-in-stent method, surgical GJ, and EUS-GJ. Similar to the first strategy, the management strategy here should be selected based on the patient’s life expectancy, performance, and endoscopist’s preference. However, information regarding the management of duodenal SEMS obstruction is insufficient. Previous studies regarding secondary stent insertion using the stent-in-stent method mostly included gastric cancers.^11-15 Sasaki et al.¹⁵ included more patients with pancreatic cancer; however, the number of patients included in their study was small (n=16). Therefore, we aimed to review the clinical results of secondary duodenal stent insertion for salvaging obstructed duodenal SEMS in pancreaticobiliary and duodenal malignancies.

1. Patients

We reviewed the databases of two tertiary hospitals (Asan Medical Center, Seoul, Korea, and Pusan National University Hospital, Busan, Korea) for patients who underwent secondary duodenal stent insertion for the management of obstructed duodenal stents in cases of pancreaticobiliary and duodenal malignancies between January 2016 and December 2021. We excluded: (1) patients diagnosed with GOO caused by gastric cancer, considering its location and disease characteristics; (2) patients who experienced obstruction of the first stent within 1 week, as we assessed them as having clinical failure of the first stent; and (3) patients with limited information. This study was approved by the Ethics Committee of each hospital (IRB numbers: Asan Medical Center 2023-1209, Pusan National University Hospital 2303-041-125). Written informed consent was waived.

2. Procedure

All procedures were performed in a stent-in-stent manner by four experienced endoscopists (T.J.S., O.D.W., S.Y.H., and D.U.K.). Computed tomography was performed before the procedures. The causes of the first stent obstruction were evaluated using endoscopy and radiocontrast medium injections under fluoroscopy. The obstruction site was negotiated with a guidewire, and an SEMS was deployed under fluoroscopic guidance. The length and type (uncovered or partially covered) of the SEMS were selected at the endoscopist's discretion. If the stent could not cover the entire stricture, an additional stent was deployed. All stents had a diameter of 20 mm and lengths of 6, 8, 10, or 12 cm. They were manufactured by Taewoong Medical, Seoul, Korea, or Standard Sci-Tech Inc., Seoul, Korea.

3. Assessment of clinical outcomes

The primary outcome was stent patency. Data regarding the baseline patient characteristics (age, sex, diagnosis, Eastern Cooperative Oncology Group (ECOG) performance status, prior biliary drainage, prior chemotherapy before stent insertion, serum albumin before stent insertion, and first stent patency) and clinical outcomes (technical success, clinical success, obstruction site, adverse event, chemotherapy after stent insertion, stent patency, cause of stent dysfunction, and overall survival) were collected. Stent patency was calculated from the insertion date to the date of reintervention. In cases where there was no evidence of stent dysfunction during the follow-up period, the duration of stent patency was considered to be equal to the survival time of the patient, and they were censored. The prior stent patency was calculated and classified as less or greater than 180 days, as the American Society for Gastrointestinal Endoscopy guideline suggests a 6-month cutoff for choosing between duodenal stenting or surgical GJ. We postulated that the duration of the secondary duodenal stent might be indicated by the preceding stent patency. A prolonged initial stent patency could suggest a slower progression of the tumor or a more favorable response to chemotherapy, potentially resulting in an extended secondary stent patency. Conversely, a shorter primary stent patency might indicate the aggressive nature of the tumor or a suboptimal response to chemotherapy. The obstruction site was classified into above-ampulla, ampulla-involved, and below-ampulla. Technical success was reached when the secondary stent successfully covered the stricture by tumor ingrowth or overgrowth. The gastric outlet obstruction scoring system (GOOSS) was used to assess the severity of duodenal obstruction before and after secondary stent insertion, and clinical success was defined as any improvement of the GOOSS score. Adverse events were recorded based on a lexicon for endoscopic adverse events.¹⁶

4. Statistical analysis

Descriptive statistics, including means or medians, standard deviations, and interquartile ranges, were used for continuous variables, as appropriate. Categorical parameters are expressed as frequencies and proportions and were compared using the chi-square or Fisher exact test. We used the Kaplan-Meier method and the Cox hazard regression test to estimate the time-to-event data. Multivariable Cox regression was performed to identify factors associated with patency and overall survival. Using a backward elimination, variables with p-value <0.2 on univariable regression were included as covariates for multivariable Cox regression. Outcomes are reported as percentages with a 95% confidence interval (CI). All reported p-values were two-sided, and a p‐value of <0.05 was considered to indicate statistical significance. The data were analyzed using the R program, version 4.2.1 (R Foundation for Statistical Computing, Vienna, Austria, http://www.R-project.org).

1. Patient characteristics

During the study period, 694 cases of duodenal stenting were performed at Asan Medical Center and Pusan National University Hospital. Among those cases, a total of 128 patients (108 Asan Medical Center and 20 Pusan National University Hospital) underwent secondary duodenal SEMS placement to salvage an obstructed duodenal SEMS between January 2016 and December 2021. Eighteen patients were excluded for the following reasons: gastric cancer (n=4), first stent patency ≤7 days (n=9), and limited information (n=5). Among the 110 patients, secondary stent insertion failed in one. Therefore, 109 patients were included in the final analysis. The mean age was 64.4±11.2 years, and the male-to-female ratio was 63:46. The most common diagnosis was pancreatic cancer (n=70), followed by biliary cancer (n=22), duodenal cancer (n=5), and other metastatic cancers (n=12). Other metastatic cancer cases included hepatocellular carcinoma (n=3), breast cancer (n=2), lung cancer (n=1), liposarcoma (n=1), colon cancer (n=1), renal cancer (n=1), cancer of unknown primary (n=1), bladder cancer (n=1), and neuroendocrine cancer (n=1). The baseline characteristics, including the ECOG performance status, prior biliary drainage, prior chemotherapy, serum albumin level before the procedure, and first stent patency, are summarized in Table 1.

Table 1 . Baseline Characteristics of the Included Patients.

Characteristic	Value (n=109)
Age, yr	64.4±11.2
Sex
Male	63 (57.8)
Female	46 (42.2)
Primary cancer
Pancreatic cancer	70 (64.2)
Biliary cancer	22 (20.2)
Duodenal cancer	5 (4.6)
Other metastatic cancers*	12 (11.0)
Cause of the first stent dysfunction
Tumor ingrowth	69 (63.3)
Tumor overgrowth	40 (36.7)
ECOG performance status
1	53 (48.6)
2	35 (32.1)
3	17 (15.6)
4	4 (3.7)
Prior biliary drainage	80 (73.4)
Prior chemotherapy	82 (75.2)
Albumin, g/dL	2.6±0.5
First stent patency, day	152.1±158.0
First stent patency <180 day	32 (29.4)

Data are presented as mean±SD or number (%)..

ECOG, Eastern Cooperative Oncology Group..

*Other metastatic cancers included hepatocellular carcinoma (n=3), lung cancer (n=1), liposarcoma (n=1), breast cancer (n=2), colon cancer (n=1), renal cancer (n=1), cancer of unknown primary (n=1), bladder cancer (n=1), and neuroendocrine cancer (n=1)..

2. Technical and clinical outcomes of secondary duodenal SEMS placement

Technical success was achieved in 109 out of 110 patients (99.1%). In one patient, the procedure failed because the guidewire could not be placed through a severe long tight stricture. EUS-GJ was performed for the patient. Among 109 patients with successful secondary stenting, clinical success was observed in 94 (86.2%) (Fig. 1). Out of 109 patients, 95 (87.2%) achieved success with a single stent, while the remaining 14 required multiple stents. Specifically, 13 patients required two stents, and one patient required three stents to cover the stricture. The distribution of the GOOSS scores before the procedure was as follows: 0 (n=39), 1 (n=39), and 2 (n=31). The distribution of the GOOSS scores after the procedure was as follows: 0 (n=5), 1 (n=12), 2 (n=46), and 3 (n=46). Uncovered stents and partially covered stents were used in 65 (59.6%) and 44 (40.4%) cases, respectively. Adverse events occurred in five (4.6%) patients, and these included cholangitis (n=2), pancreatitis (n=1), perforation (n=1), and bleeding (n=1) (Table 2). They occurred within a week after stent insertion. Cholangitis was managed with percutaneous transhepatic biliary drainage. All adverse events were successfully managed conservatively. Twenty-three patients experienced a stent dysfunction. The overall median stent patency was 231 days (95% CI, 169 to not available) (Fig. 2). Stent dysfunction was managed with additional stent insertion. The overall survival was 90 days (95% CI, 74 to 125) (Fig. 3).

Figure 1. Flowchart regarding this study. SEMS, self-expandable metallic stent.

Figure 2. Kaplan-Meier curve for the patency of the secondary duodenal stent.

Figure 3. Kaplan-Meier curve for patient survival after secondary duodenal stenting.

Table 2 . Technical and Clinical Outcomes of Secondary Duodenal Stenting for Duodenal Stent Obstruction (n=109).

Outcome	Value
Technical success rate, No. (%)	109/110 (99.1)
Clinical success rate, No. (%)	94 (86.2)
Pre-GOOSS score, 0/1/2/3	39/39/31/0
Post-GOOSS score, 0/1/2/3	5/12/46/46
Location, No. (%)
Above ampulla	28 (25.7)
Ampulla involved	49 (45.0)
Beyond ampulla	32 (29.4)
Stent type, No. (%)
Uncovered	65 (59.6)
Partially covered	44 (40.4)
Adverse event, No. (%)	5 (4.6)
Cholangitis	2
Pancreatitis	1
Perforation	1
Bleeding	1
Stent patency, median (95% CI), day	231 (169–NA)
Cause of stent dysfunction, No. (%)	23 (21.1)
Ingrowth	14
Overgrowth	7
Migration	2
Overall survival, median (IQR), day	90 (74–125)

GOOSS, gastric outlet obstruction scoring system; CI, confidence interval; NA, not available; IQR, interquartile range..

3. Factors related to clinical failure

Compared to the clinical success group, the clinical failure group (n=15) showed lower serum albumin level (2.3±0.3 g/dL vs 2.6±0.5 g/dL, p=0.007) and a higher ECOG score (2.6±1.0 vs 1.6±0.8, p<0.001). Only 6.7% (1/15) of those who experienced clinical failure were able to receive chemotherapy after secondary duodenal stenting because, generally, cytotoxic chemotherapy is not recommended for decompensated states (ECOG scale >2). Patients who experienced clinical failure showed significantly shorter survival than those who experienced clinical success (28 days, 95% CI [13 to 74] vs 101 days, 95% CI [84 to 138]; p<0.001) (Table 3).

Table 3 . Factors Related to Clinical Failure.

Factor	Clinical failure (n=15)	Clinical success (n=94)	p-value
Age, yr	69.3±9.1	63.6±11.3	0.066
Male sex	7 (46.7)	56 (59.6)	0.510
Pancreatic cancer	11 (73.3)	59 (62.8)	0.615
Chemotherapy after procedure	1 (6.7)	34 (36.2)	0.048
GOOSS before procedure	1.1±0.8	0.9±0.8	0.469
Albumin, g/dL	2.3±0.3	2.6±0.5	0.007
ECOG performance status	2.6±1.0	1.6±0.8	<0.001
Survival after procedure, day	28 (13–74)	101 (84–138)	<0.001

Data are presented as mean±SD, number (%), or median (95% CI)..

GOOSS, gastric outlet obstruction scoring system; ECOG, Eastern Cooperative Oncology Group..

4. Multivariable Cox hazard analysis for stent patency and survival

The multivariable Cox hazard analysis was performed to identify the factors associated with stent patency and survival. Age, sex, diagnosis (pancreatic cancer vs others), first stent patency (≥6 months vs <6 months), stent type (uncovered vs partially covered), location, GOOSS score before and after the procedure, albumin level before the procedure, and the type of chemotherapy after the secondary stent insertion were included in the analysis. Regarding stent patency, the ECOG performance status (hazard ratio, 2.46; 95% CI, 1.38 to 4.39; p=0.024) and first stent patency ≥6 months (hazard ratio, 0.30; 95% CI, 0.10 to 0.91; p=0.033) remained significant associated factors (Table 4). Regarding survival, the first stent patency ≥6 months, chemotherapy after the procedure, GOOSS score after the procedure, albumin level before the procedure, and ECOG performance remained significant associated factors (Table 5).

Table 4 . Multivariable Cox Proportional Analysis for Patency.

Variable	Univariable analysis			Multivariable analysis
	HR (95% CI)	p-value		HR (95% CI)	p-value
Age	0.98 (095–1.02)	0.370
Male sex	0.98 (0.43–2.25)	0.974
Pancreatic cancer	0.60 (0.26–1.38)	0.232
First patency ≥6 mo	0.31 (0.10–0.92)	0.034		0.30 (0.10–0.91)	0.033
Partially covered stent	1.55 (0.66–3.63)	0.315
Chemotherapy after procedure	0.84 (0.36–1.93)	0.672
Location
Ampulla involved	Reference
Above ampulla	0.91 (0.33–2.47)	0.800
Beyond ampulla	0.80 (0. 28–2.31)	0.700
GOOSS before procedure	0.64 (0.38–1.10)	0.110
GOOSS after procedure	0.53 (0.27–1.04)	0.653
Albumin	0.82 (0.33–2.10)	0.683
ECOG performance status	2.31 (1.24–3.92)	0.007		2.46 (1.38–4.39)	0.024

HR, hazard ratio; CI, confidence interval; GOOSS, gastric outlet obstruction scoring system; ECOG, Eastern Cooperative Oncology Group..

Table 5 . Multivariable Cox Proportional Analysis for Survival.

Variable	Univariable analysis			Multivariable analysis
	HR (95% CI)	p-value		HR (95% CI)	p-value
Age	1.01 (0.99–1.02)	0.603
Male sex	1.03 (0.69–1.51)	0.898
Pancreatic cancer	0.84 (0.56–1.25)	0.393
First patency ≥6 mo	0.64 (0.42–0.99)	0.044		0.52 (0.33–0.81)	0.004
Partially covered stent	1.24 (0.83–1.83)	0.290
Chemotherapy after procedure	0.48 (0.32–0.73)	<0.001		0.68 (0.43–1.07)	0.092
Location
Ampulla involved	Reference
Above ampulla	1.10 (0.68–1.77)	0.694
Beyond ampulla	0.94 (0.59–1.47)	0.772
GOOSS before procedure	0.90 (0.71–1.13)	0.364
GOOSS after procedure	0.35 (0.26–0.47)	<0.001		0.47 (0.33–0.65)	<0.001
Albumin	0.53 (0.34–0.83)	0.066		0.65 (0.41–1.03)	0.066
ECOG performance status	2.03 (1.59–2.58)	<0.001		1.53 (1.14–2.04)	0.004

HR, hazard ratio; CI, confidence interval; GOOSS, gastric outlet obstruction scoring system; ECOG, Eastern Cooperative Oncology Group..

Many studies have reported clinical data regarding first duodenal SEMS placement. However, those regarding the outcomes of secondary duodenal SEMS placement for obstructed duodenal SEMS are limited, especially for pancreaticobiliary and duodenal malignancies. To the best of our knowledge, this is the largest retrospective study regarding secondary duodenal SEMS placement for obstructed duodenal SEMS in patients with pancreaticobiliary and duodenal malignancies.

Our study showed a technical success rate of approximately 99.1%, which was comparable to that of the first stent insertion. A second stent insertion could be easier, as a previously inserted stent can help place the guidewire under fluoroscopy. Although secondary duodenal insertion was technically successful, it did not lead to total clinical success (86.2%). This means that although luminal patency is secured after secondary stent insertion, clinical success is not guaranteed. Several factors can contribute to clinical failures, such as advanced malignancy causing anorexia and peritoneal carcinomatosis affecting gastrointestinal motility.¹⁷ In our study, 15 patients with clinical failure had lower serum albumin levels and higher ECOG scores than those with clinical success. Their survival rates were significantly lower. We believe that these patients would not have benefited from surgery or EUS-GJ. Therefore, duodenal stenting is an attractive option for these patients, considering its cost or associated morbidity.

In our study, the dysfunction rate of the secondary duodenal stent was 21.1%, with a median patency of 231 days (95% CI, 169 to not available). The dysfunction rate appeared to be similar to that of the first stent. Patency was similar to the previous reports.^11,12,18 The patency can be exaggerated due to short survival time (median 90 days). However, as median patency is longer than the median survival, secondary stenting would be a good option for obstructed duodenal stent. Stent ingrowth was the most common reason for dysfunction, and was managed with a third duodenal stent insertion.

We performed multivariable analysis to identify factors related to stent patency, and ECOG performance status and first stent patency ≥6 months remained significant factors. Currently the American Society for Gastrointestinal Endoscopy guideline suggests surgical GJ for more than 6-month life expectancy. However, duodenal stenting also can achieve longer patency, and we thought the longer the previous stent functions, the longer the secondary stent will function, as this could imply better response to chemotherapy or slow progression. As the results imply, secondary stenting would be a good salvage option if the first stent functions long enough. If the patency of the first stent is short, it would be better to choose surgery or EUS-GJ.

We also analyzed factors related to patient survival. The first stent patency ≥6 months, chemotherapy after the procedure, GOOSS score after the procedure, albumin level before the procedure, and ECOG performance were significantly related to the patient’s survival. Albumin levels are usually low in states of malnutrition and inflammation and are known to be associated with cancer survival.¹⁹ These related factors imply that good performance status, better nutritional status, and chemotherapy are critical for patient survival. Therefore, optimal management of duodenal obstruction should be prioritized for patients with pancreaticobiliary and duodenal malignancies to provide better nutritional support, which could lead to better performance status. Palliative chemotherapy should also be recommended if patients can tolerate longer survival after the secondary stenting.

Overall, adverse events occurred in five patients (4.6%). Cholangitis was the most common adverse event (n=2). Since most patients may have previously undergone biliary drainage, endoscopists should be aware of the risk of biliary obstruction. Even though the secondary stent was located across the ampulla in 45% of the patients, only one case of pancreatitis occurred. Previously inserted stents may decrease the risk of pancreatitis due to the remodeling of the tumor. Sasaki et al.¹⁵ reported perforation as a major complication (13.8%) of secondary gastroduodenal stenting, however, we observed this in one case, which was managed conservatively. Therefore, secondary duodenal stenting can be considered safe.

The choice between covered and uncovered stents is another issue associated with secondary duodenal stent insertion. According to a recent meta-analysis, covered stents were reported to show longer patency and a higher risk of migration than uncovered stents, and there was no statistical difference in the technical and clinical success rates and overall adverse events.²⁰ Regarding secondary stenting, Park et al.¹² reported that covered and uncovered stents were equally acceptable based on patency and adverse events. However, their study mostly included gastric cancer (90.9%), and the locations were mostly prepyloric lesions or anastomotic sites after subtotal gastrectomy (90.9%). Regarding primary stenting in pancreaticobiliary cancer, Woo et al.²¹ reported a higher complication rate with covered stents, primarily due to a significantly higher stent migration rate with a tendency for shorter patency compared with uncovered stents. In our study, we found no statistical differences in patency and adverse events between the two types of stents. Further study for optimal stent for secondary stenting should be carried in the future.

The strength of our study is the large number of patients with pancreaticobiliary and duodenal malignancies. However, this study had several limitations. First, there was selection bias owing to the retrospective design. Moreover, the high technical success rate may have resulted from a selection bias. Second, different types of cancers and chemotherapies were included, which may have affected the stent patency and survival. Particularly, life expectancy influences the dysfunction rate. Since stent dysfunction is calculated from insertion to reintervention, individuals with a shorter remaining lifespan may contribute to a lower dysfunction rate. However, we believe that these data may provide real-world information. Third, different sizes, designs, numbers, and types of stents were used and the strategy of selection was not standardized; however, their effects on the results may not be significant. Fourth, safety might have been underestimated, as late adverse events (>14 days) could not be reliably distinguished from complications arising from tumor progression. In conclusion, secondary duodenal stent insertion is a viable option for first duodenal stent obstruction. Moreover, further comparative studies involving surgery or EUS-GJ for obstructed duodenal stents are warranted.

No potential conflict of interest relevant to this article was reported.

Study concept and design: T.J.S. Data acquisition: H.D.J., S.Y.H., D.U.K., H.S.L., S.H.C. Data analysis and interpretation: H.S., H.D.J. Drafting of the manuscripts: H.S., H.D.J. Critical revision of the manuscript for important intellectual content: D.O., D.W.S. Statistical analysis: H.S., S.W.K. Study supervision: T.J.S. Approval of final manuscript: all authors.