Benefits of Supplemental Jejunostomy Tube Feeding During Neoadjuvant Therapy in Patients with Locally Advanced,Potentially Resectable Esophageal Cancer

Abstract

Background:

Standard treatment for locally advanced esophageal cancer includes neoadjuvant therapy followed by surgical resection. However, many patients experience a period of decreased oral intake during neoadjuvant treatment and are at risk for malnutrition. We hypothesize that use of jejunostomy tube (j-tube) feedings during neoadjuvant therapy in selected patients may be associated with better perioperative outcomes.

Methods:

A prospectively collected database at a single institution was retrospectively analyzed. The study period was from 2005 to 2015. Patients who underwent j-tube placement before neoadjuvant therapy before definitive resection for esophageal cancer were included in the analysis. Perioperative outcomes were compared between patients who adhered to recommended tube feeds during neoadjuvant therapy (users) and patients who did not adhere (nonusers).

Results:

During the study period, 94/301 patients received a j-tube before or during neoadjuvant therapy for esophageal cancer. Seventy-three patients utilized tube feeds regularly during the neoadjuvant phase, while 21 patients did not. The groups did not differ significantly with respect to clinical factors such as dysphagia on presentation, postneoadjuvant therapy performance status, or Charlson Comorbidity Index. Perioperative pneumonia rates were lower in j-tube users compared to nonusers (6.8% [5 of 73] versus 23.8% [5 of 21]), respectively, P = .036); this difference remained significant with adjustment for type of surgery (odds ratio = 0.16, P = .018).

Conclusions:

j-Tube users had a significantly lower incidence of pneumonia within 30 days of curative resection when compared to nonusers. j-Tube feedings during neoadjuvant therapy for selected patients with locally advanced esophageal cancer should be encouraged.

Introduction

Concurrent Chemotherapy and Radiation (CRT) followed by surgical resection has become standard of care for locally advanced esophageal and gastroesophageal junction (GEJ) cancer supported by the results of large randomized controlled trials.¹ Patients with locally advanced esophageal and GEJ tumors may present with significant dysphagia or weight loss leading to malnutrition at the time of diagnosis. A decrease in oral intake during neoadjuvant CRT can lead to further weight loss, in addition to treatment interruptions, increased morbidity, and poor long-term outcomes.^2–4 Recently, the practice at our center has been to place a laparoscopic feeding jejunostomy tube (j-tube) in patients who are scheduled to undergo neoadjuvant therapy and who presented with significant dysphagia to solids, any dysphagia to liquids, and/or significant weight loss. We recommend that enteral feedings should be initiated during neoadjuvant therapy if the patient's ability to eat or drink worsens or if the patient continues to lose weight during neoadjuvant therapy. However, enteral feeding recommendations are not always adhered to, even in these circumstances. The reason for this noncompliance is not well described, but it is often due to patient reluctance to use tube feedings or reluctance of the physicians conducting the neoadjuvant therapy to initiate tube feedings. This study aims to identify benefits of j-tube placement before neoadjuvant therapy in esophageal cancer patients with significant dysphagia or weight loss by comparing the clinical outcomes of those patients who actually received enteral feedings through their j-tube with those who did not.

Materials and Methods

Institutional review board approval (IRB# 16-9022) was obtained. A retrospective analysis of a prospectively collected, single- institution database was then performed. All patients who underwent esophagogastrectomy for mid-distal esophageal or GEJ cancer, cT2-4, N0-2, and M0, from January 2005 through December 2015 at our institution were considered. Patients who underwent j-tube placement before neoadjuvant therapy were included in the analysis. Patients who did not undergo j-tube placement before neoadjuvant therapy or did not receive neoadjuvant therapy were excluded. Patients who adhered to recommended tube feedings during neoadjuvant therapy (>1 can per day) were defined as users, and patients who did not adhere to the recommended tube feeding regimen were nonusers. Tube feeding recommendations were made based on collaboration between the surgical and nutritional teams.

Pretreatment symptoms, including dysphagia, unintentional weight loss >5% of body weight in 6 months before presentation, and comorbidities by Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS) and Charlson Comorbidity Index (CCI) were examined. Complications due to j-tube placement were analyzed. Major morbidities from j-tube placement were defined as a need for reoperation or readmission to hospital.

Esophagogastrectomy was performed in both minimally invasive and open approaches (Ivor Lewis, modified McKeown, and transhiatal). Perioperative outcomes were defined as occurring within 30 days of resection. Perioperative complications were defined as grade ≥1 adverse event per the Common Terminology Criteria for Adverse Events Version 4.03 or any event requiring surgical intervention within 30 days of resection. Pneumonia was defined as pulmonary infiltrate on chest radiograph with clinical features of pulmonary infection (fever, leukocytosis, and increased oxygen requirement) or a positive sputum culture. All pneumonias were treated with antimicrobial agents.

Pretreatment symptoms and perioperative outcomes were each compared by j-tube usage with Fisher's exact tests for categorical variables, t-test for age, and the Wilcoxon rank sum test for CCI. For each perioperative complication, logistic regression was used to estimate odds ratios (ORs) and confidence intervals for j-tube users versus nonusers. We used multivariable logistic regression to control for type of surgery (minimally invasive or open approach); other covariates were not included as they did not differ by j-tube use (P > .20).

Results

During the study period, 301 patients underwent esophagogastrectomy. Ninety-four of these patients met our criteria for placement of a j-tube before or during neoadjuvant therapy for esophageal cancer. Seventy-three patients utilized tube feeds as recommended during the neoadjuvant phase (users), while 21 patients did not (nonusers) (21/94 = 22%). Patient demographics, comorbidities, and surgical data are outlined in Table 1. The groups did not differ significantly for dysphagia on presentation, preneoadjuvant treatment performance status, CCI, or unintentional pretreatment weight loss of >5% of body weight within 6 months.

Table 1.

Preneoadjuvant Therapy Demographics, Jejunostomy Tube Users Versus Nonusers

	Users (N = 73)	Nonusers (N = 21)	P value^*
Sex			.75
Male	59 (80.8%)	18 (85.7%)
Female	14 (19.2%)	3 (14.3%)
Race			.84
Black	2 (2.7%)	1 (4.8%)
White	67 (91.8%)	20 (95.2%)
Hispanic	3 (4.1%)	0 (0.0%)
Other	1 (1.4%)	0 (0.0%)
Age, years			.67
Mean (std)	62.4 (9.0)	61.4 (9.5)
Pretreatment ECOG PS			.28
0	45 (61.6%)	13 (61.9%)
1	28 (38.4%)	7 (33.3%)
2	0 (0.0%)	1 (4.8%)
CCI (total)
Median (25th, 75th percentiles)	3 (2,4)	2 (2,4)	1.00
By CCI category
0	4 (5.6%)	1 (4.8%)	.99
1	11 (15.5%)	3 (14.3%)
2–3	35 (49.3%)	11 (52.4%)
4–11	21 (29.6%)	6 (28.6%)
CCI incomplete	2	0
Dysphagia			.31
Yes	63 (86.3%)	16 (76.2%)
No	10 (13.7%)	5 (23.8%)
Weight loss			.27
Yes	39 (53.4%)	9 (42.9%)
No	34 (46.6%)	12 (57.1%)

p > 0.05 = Not significantly different.

CCI, Charlson Comorbidity Index; ECOG PS, Eastern Cooperative Oncology Group performance status.

The vast majority of patients in both groups had neoadjuvant CRT with a small minority receiving only chemotherapy. The decrease in body mass index preneoadjuvant and postneoadjuvant therapy was similar for j-tube users (0.6) versus nonusers (0.8).The two groups did not differ significantly in response to neoadjuvant therapy pathologic stage or need for adjuvant treatment (Table 2). j-Tube users had higher rates of open surgery compared to nonusers (18% versus 5%), but the difference was not statistically significant (P = .18).

Table 2.

Treatment Parameters, Users Versus Nonusers

	Users (N = 73)	Nonusers (N = 21)	P value
Neoadjuvant CRT	70 (95.8%)	19 (90.5%)	.58
Response to neoadjuvant therapy			.46
Downstaged	45 (61.6%)	14 (66.7%)
Stable	21 (28.8%)	5 (23.8%)
Upstaged	6 (8.2%)	2 (9.5%)
Surgery type			.18
Minimally invasive	60 (82.2%)	20 (95.2%)
Open	13 (17.8%)	1 (4.8%)
Pathologic staging (yp stage)			.96
Complete response (pCR)	22 (30.1%)	6 (28.6%)
I	12 (16.4%)	4 (19.0%)
II	22 (30.1%)	7 (33.3%)
III	17 (23.3%)	4 (19.0%)
Adjuvant CRT
Received adjuvant chemotherapy	15 (20.5%)	5 (23.8%)	.77
Received adjuvant radiation	3 (4.1%)	1 (4.8%)	1.00

CRT, chemotherapy and radiation; pCR, pathologic complete response.

Complication rates after esophagogastrectomy in the perioperative setting are shown in Table 3. The incidence of perioperative pneumonia was significantly lower in users (6.8% versus 23.8%, OR = 0.24, P = .036) and this association remained significant on multivariable analysis yielding an OR = 0.16 (P = .018). Pneumonia had a borderline association with needing a second operation within 30 days (40% of patients with pneumonia had reoperation compared to 14% of those without pneumonia, P = .063). Reoperations within 30 days after esophagogastrectomy consisted of upper endoscopy (n = 4), vocal cord injection (n = 3), thoracic duct ligation (n = 2), and dilation of the pylorus (n = 2) or anastomotic stricture (n = 5).

Table 3.

Perioperative Complications After Esophagogastrectomy, Jejunostomy Tube Users Versus Nonusers

			Logistic regression outcome = complication (yes/no)
			Odds ratio, j-tube users versus nonusers
			Unadjusted		Adjusted for type of surgery
	Users (N = 73)	Nonusers (N = 21)	OR (95% CI)	P value	OR (95% CI)	P value^*
Median LOS, days (25th, 75th percentiles)	11 (9,15)	10 (8,13)
Perioperative complication
Pneumonia	5 (6.8%)	5 (23.8%)	0.24 (0.06–0.91)	.036	0.16 (0.04–0.73)	.018
30-day readmission	9 (12.3%)	1 (4.8%)	2.81 (0.3–23.56)	.34	3.02 (0.36–25.52)	.31
Reoperation within 30 days	15 (20.5%)	1 (4.8%)	5.18 (0.64–41.70)	.23	4.41 (0.54–36.18)	.36
30-day mortality (all)	3 (4.1%)	1 (4.8%)	0.86 (0.08–8.70)	.90	0.28 (0.02–4.97)	.39
30-day mortality (2008–2015)	1/66 (1.5%)	1/20 (5.0%)	0.29 (0.02–4.90)	.39	—
Ventilator >48 hours	5 (6.8%)	1 (4.8%)	1.47 (0.16–13.33)	.73	0.70 (0.06–8.18)	.77
Anastomotic leak	9 (12.3%)	2 (9.5%)	1.34 (0.27–6.72)	.73	1.44 (0.28–7.31)	.66
Anastomotic stricture	2 (2.7%)	1 (4.8%)	0.56 (0.05–6.54)	.65	0.66 (0.06–7.64)	.74
ARDS	2 (2.7%)	1 (4.8%)	0.56 (0.05–6.54)	.65	0.21 (0.01–4.11)	.31
Arrhythmia	15 (20.5)	6 (28.6%)	0.65 (0.21–1.95)	.44	0.56 (0.18–1.74)	.32

ARDS, adult respiratory distress syndrome; CI, confidence interval; j-tube, jejunostomy tube; LOS, length of stay; OR, odds ratio.

There were six j-tube-related complications among users during the neoadjuvant phase (6/73 = 8.2%). Five j-tube users (6.9%) experienced tube-related wound infection, while two j-tube users (2.7%) underwent reoperation (one for wound infection and one for small bowel obstruction). Among nonusers, there were five j-tube-related complications during the neoadjuvant phase (5/21 = 23.8%), including two infections and three dislodgments. None of the nonusers required reoperation for j-tube-related complications.

No significant difference was seen in locoregional recurrences (5.5% versus 14.3%, P = .34) or distant recurrences (20.6% versus 28.6%, P = .55) comparing users to nonusers. Mortality within 30 days of surgery was also comparable between patients early and late in our experience.

Discussion

While a number of studies have examined enteral feeding methods postesophagectomy,^5,6 few studies have evaluated the benefit of supplemental j-tube feedings during neoadjuvant treatment. Huerter et al. showed that providing enteral access in the neoadjuvant period was associated with overall improved nutrition, but was not associated with improved postesophagectomy outcomes compared to those who had no enteral access.⁷ However, the authors compared patients who had enteral access with those who did not have access, while noting that 28% of their patients with enteral access did not use it consistently.

In general, significant weight loss at diagnosis (>5% from baseline) or dysphagia are common reasons for placement of a j-tube before neoadjuvant treatment at our center, although not all the patients in this analysis received those feedings. In our experience, initiation of neoadjuvant CRT may worsen existing dysphagia/odynophagia at first, with improvement later as the tumor responds to the treatment. The reasons for not using the j-tube for feedings were not captured in the database, although some combination of physician and/or patient preference is possible in most cases. This is a potential source of bias in our analysis, as this was a single-center retrospective review of prospectively collected data.

We attempted to isolate the benefits of supplemental enteral feeding during neoadjuvant therapy by comparing perioperative complications and short-term outcomes of patients receiving supplemental feeding through a j-tube with those who did not from a group of patients, all of whom had jejunostomy feeding tubes placed before neoadjuvant therapy for similar indications of weight loss and dysphagia. Our 22% incidence of nonusers appears to match the 28% rate reported by Huerter et al.⁷

We believe our study is the first to show a decreased incidence of postoperative pneumonia in selected patients receiving supplementary nutrition during neoadjuvant treatment for esophageal or GEJ cancer. Postoperative pneumonia is also an important cause of morbidity and mortality in patients undergoing esophagectomy. A recent database study found the incidence of pneumonia to be 12.2% after esophageal cancer resection.⁸ We report a lower rate in j-tube users (6.8%), but an increased rate in nonusers (23.8%). Pulmonary complications have been reported to be the most common reason for readmission after esophagogastrectomy.⁹ This study reported a rate of postoperative pneumonia of 22%, which is concordant with our nonuser population. Other retrospective studies have shown a link between surgical complications after esophagogastrectomy.^10,11 Postoperative pneumonia can result from immunodeficiency, respiratory muscle weakness, and overall frailty, all of which may occur in the setting of suboptimal nutrition.²

In general, significant weight loss at diagnosis (>5% from baseline) is a common reason for placement of a j-tube before neoadjuvant treatment at our center. In our experience, initiation of CRT may worsen dysphagia/odynophagia at first, with improvement later as the tumor responds to the treatment. Progressive dysphagia during neoadjuvant therapy places patients at an increased risk of further weight loss unless supplemental nutrition is provided—this in addition to the risk of severe dehydration, which could lead to treatment-related complications and delays in completion of neoadjuvant treatment. A recent study in lung cancer patients revealed weight loss during CRT can be detrimental to survival. A retrospective study of 151 patients showed those who lost >5% of body weight in the first 3 weeks after initiation of CRT had a significantly decreased median overall survival (13 versus 23 months, P = .017) compared to those patients who did not experience weight loss.⁴ We were not able to capture similar data regarding weight loss during CRT because many of our surgical patients received induction therapy outside of our institution. Weight loss has been shown to influence overall survival in esophageal cancer as well. A retrospective study including over 900 patients showed significantly decreased overall survival in patients with esophageal cancer who had lost >10% of body weight before diagnosis.¹² It is unclear if this finding reflects poorer prognostic features due to more aggressive tumor biology or more symptomatic obstruction, but it does support the argument that weight loss worsens outcomes for esophageal cancer patients. We are differentiating the well-described negative effects of pretreatment weight loss, which may be related to tumor biology or other factors,¹² from subsequent weight loss that may occur during neoadjuvant therapy.

j-Tube placement before neoadjuvant therapy has shown to be a generally safe procedure.^13,14 Major morbidity of j-tube ranges from 1.1% to 2.7% and mortality rates from 0.4% to 2.4%.¹⁴ Our series is in agreement with 2.1% (n = 2/143) major morbidity and no mortalities related to the j-tube.¹⁵ However, given the inherent risk of j-tube use and placement, we recommend the selective placement of j-tubes to minimize the risk to patients unlikely to need supplemental nutrition during CRT (no or minimal dysphagia or weight loss at the time of presentation).

A study randomizing selected patients with esophageal or GEJ cancer to j-tube or no j-tube before neoadjuvant therapy would be well suited to address the efficacy of supplemental tube feedings during neoadjuvant therapy, but no such trial has been performed. Despite the lack of a randomized trial and because of the possibility of decreased oral intake during neoadjuvant therapy, we currently recommend placement of a pretreatment j-tube in patients with locally advanced, potentially resectable esophageal or GEJ cancer, who present with either an unintentional loss of >5% of body weight or dysphagia to some solids or liquids.

Conclusions

In a group of patients with similar indications for the placement of a feeding j-tube, those who received nutrition through the j-tube during neoadjuvant therapy (j-tube users) had a significantly decreased incidence of pneumonia within 30 days of curative resection when compared to nonusers. Provision of supplemental j-tube feedings in patients with decreased oral intake during neoadjuvant therapy may decrease perioperative complications in esophagogastrectomy patients.

Footnotes

Disclosure Statement

No competing financial interests exist.

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