Introduction

Long-term optimal clinical response in terms of weight loss and other outcomes remains a challenging topic for researchers working in the field of bariatric surgery. Significant weight regains at a long-term follow-up and is seen in up to 40% in patients with body mass index (BMI) > 50 kg/m2 and in up to 20% in severe obesity (BMI > 40 kg/m2) [1,2,3,4]. Tailoring the different limbs of the LRYGB is a major topic in bariatric research; yet, consensus on the optimal length of the biliopancreatic limb (BPL), Roux Limb (RL), and common channel (CC) seems far from being reached.

While the length of the common channel (CC) is thought to significantly impact the degree of malabsorption, current discussions on LRYGB limb length are primarily centered on the biliopancreatic limb (BPL) length [5,6,7,8,9,10,11,12]. Despite promising results from past studies [13,14,15,16,17], there has been a lack of well-performed randomized controlled trials (RCTs) that specifically investigate the effects of altering the common channel (CC) length by extending the Roux limb (RL) [18,19,20]. Excellent weight loss and low malabsorption revision rate found in the study by Thurnheer et al. triggered our group to design a randomized controlled trial on this subject [14].

In 2014, the multicenter Dutch Common Channel Trial (DUCATI) was initiated to further investigate on this topic [21]. Patients participating in this trial were randomized to receive either a very long Roux limb laparoscopic Roux-en-Y gastric bypass (VLRL-LRYGB) with a fixed 100-cm CC and variable length RL, or a standard laparoscopic Roux-en-Y gastric bypass (S-LRYGB) with a fixed 150-cm RL and variable length CC, with a fixed 60-cm BPL in both groups. First reports from this trial at a 1-year follow-up showed no significant difference in terms of weight loss and little nutritional deficiencies [22, 23]. However, at the 3-year follow-up, the VLRL-LRYGB group demonstrated a significantly greater weight loss compared to the S-LRYGB group [24]. With all enrolled trial patients being at least 5 years of post-surgery, a long-term analysis was conducted to assess weight loss, suboptimal clinical response rates, impacts on obesity-related medical conditions, re-operations, malnutrition side effects, and complication rates.

Methods

This double-blinded RCT included 444 patients to undergo either VLRL-RYGB or S-LRYGB (1:1 ratio randomization). Stratification was applied for participating center, age, gender, type 2 diabetes mellitus (T2DM), and BMI. Two Dutch bariatric centers participated in this RCT, being the Franciscus Gasthuis and Vlietland in Rotterdam (271 patients enrolled) and the Bariatric Center South-West Netherlands, Bravis Hospital, Bergen op Zoom (174 patients enrolled), both performing more than 1000 bariatric cases yearly. Previous publications from this group described more extended details regarding the trial protocol and technical aspect about the surgical procedures as well [21, 23]. In all patients, total small bowel length was measured.

The primary outcome measure of this, long-term (5 years) follow-up, investigation is weight loss expressed as percentage total weight loss (%TWL) and percentage excess weight loss (%EWL). Secondary outcome assessments are effects on obesity-related medical conditions, re-operation rate, and malnutrition side effects. For analysis of difference between bowel movements between both procedures, we used the following definition: mild diarrhea was defined as having one to three stools per day more than normal and soft to mushy consistency of the stool. Severe diarrhea was defined as having more than three stools per day more than normal and a mushy to liquid consistency of the stool, despite using medication.

Suboptimal clinical response is defined as achieving or maintaining less than 20% of %TWL [25].

Statistical Analysis

Both intention-to-treat and per-protocol analyses were used to analyze weight loss results. Per-protocol analysis was conducted to explore the effects on obesity-related medical conditions, compare suboptimal clinical response rates, and assess micronutrient and vitamin deficiencies. An intention-to-treat analysis was conducted to assess the re-operation rate. The same statistical tests were utilized as reported in our previous publication [23]. Results were considered significant at p < 0.05 (two-sided).

Results

Patient and Procedure Characteristics

No significant differences regarding baseline characteristics were observed between both groups (Table 1). Technical aspects of both procedures as well as conversion rate and correlation analysis between patient characteristics and the length of the small bowel have been previously published [23]. Important early findings which should be emphasized is the higher number of conversions to other procedures, and the higher rate of early (< 30 days) re-interventions in the VLRL-LRYGB group. This is related to the fact that the VLRL-LRYGB was considered to be a technically and ergonomically more challenging procedure by all participating surgeons despite adjusting positioning of the patient and change in trocar placement.

Table 1 Baseline characteristics of participants by group
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Conversion to other procedure (e.g., S-LRYGB, laparoscopic sleeve gastrectomy, or mini gastric bypass—one anastomosis gastric bypass (MGB-OAGB)) was required in 26 patients (11.7%) in the VLRL-LRYGB group compared to 11 patients (5.0%) in the S-LRYGB group (p = 0.007). As outlined in a prior publication authored by our group, the decision to convert to MGB-OAGB was made at the discretion of the surgeon [23]. In every instance, a short mesentery of the small intestinal limb hindered the creation of a safe, tension-free gastro-jejunostomy. Among these six patients, four also presented with GERD, rendering sleeve gastrectomy unsuitable as an escape. Mean RL length was 422 cm (range, 210–730 cm) in VLRL-LRYGB group, compared to 150 cm in the S-LRYGB group (Fig. 1). However, the total alimentary tracts (TAT = RL + CC) were quite similar between both groups, with lengths of 522 cm (± 114 cm) and 533 cm (± 109 cm), respectively (p = 0.315).

Fig. 1
figure 1

Limb lengths. After correction for conversion VLRL-LRYGB (n = 196) and S-LRYGB (n = 211). BPL, biliopancreatic limb; RL, Roux limb; CC, common channel; TAT, total alimentary tract (= RL + CC). A single asterisk (*) indicates that in 13 patients it was not possible to adequately measure the length of the common channel due to adhesions at the terminal ileum

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Total overall loss to follow up at 5 years was 149 (33.6%) patients (Table 2).

Table 2 Total number of patients at follow-up
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Weight Loss

At 5 years of follow-up (FU), a significant difference in %TWL (32.2% vs. 28.6%, p = 0.002) and %EWL (79.2% vs. 70.9%, p = 0.004) in favor of VLRL-LRYGB group was found in intention-to-treat analysis (Fig. 2a and Table 3).

Fig. 2
figure 2figure 2

a %EWL ands %TWL at 1 to 5 years follow up, Intention-to-treat analysis. b %EWL and %TWL at a 1- to 5-year follow-up, per-protocol analysis.

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Table 3 %EWL and %TWL at a 1- to 5-year follow-up, intention-to-treat analysis
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Per protocol analysis at 5 years of FU also shows a significant difference in %TWL (32.7% vs. 28.1%, p = 0.001), and %EWL (81.2% vs. 70.3%, p = 0.002) (Fig. 2b and Table 4).

Table 4 %EWL and %TWL at a 1- to 5-year follow-up, per-protocol analysis
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In VLRL-LRYGB group patients with short total small bowel length achieved 34.4% vs. 25.1% %TWL (p = 0.001) and 85.1% vs. 70.9% %EWL (p = 0.008) at 5 years, compared to long total small bowel length. To conduct this correlation analysis, we employed a cut-off of 580 cm as the modus of total small bowel length, categorizing lengths as either long (> 580 cm) or short (< 580 cm). Per-protocol analysis was used while excluding patients with unknown total small bowel lengths.

A statistically significant higher suboptimal clinical response rate was found in S-LRYGB group compared to VLRL-LRYGB group (22.0% versus 8.3%, p = 0.001) at 5 years of follow-up (p = 0.001).

Effect on Obesity-related Medical Conditions

For all investigated obesity-related medical conditions, no differences were found between both groups (see further details in Table 5).

Table 5 Effect on obesity related medical conditions
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Morbidity and Mortality at 5 Years of FU

The overall > 30 days after surgery complication rate at 5 years of follow-up was 19.8% in the VLRL-LRYGB group compared to 10.4% in the S-LRYGB group (p = 0.007) (Table 6). Modification surgery for malabsorption was required in eight patients (3.6%) in the VLRL-LRYGB group versus two patients (0.9%) in the S-LRYGB group (p = 0.055). On average, these procedures were performed 18.3 months after the initial operation, with a range of 5 to 33 months. The primary reason for modification surgery for malabsorption was severe diarrhea (seven patients in the VLRL-LRYGB group versus one in the S-LRYGB group). Treatment involved revising to S-LRYGB in all cases in the VLRL-LRYGB group and by reversing to normal anatomy in the S-LRYGB group patient. A total of seven out of these ten patients had a long (> 580 cm) total small bowel length. More details about these patients and their laboratory results have been previously published [24]. Among this particular subset of patients requiring modification surgery, the mean %EWL at 5 years was 91.7% (± 31.6% SD) and the mean %TWL was 31.9% (± 8.5% SD). At 5 years, a total of nine patients reported mild diarrhea of which seven in VLRL-LRYGB group and two in standard LRYGB group (p = 0.081) and one patient reported severe diarrhea in VLRL-LRYGB group versus 0 in standard LRYGB group.

Table 6 Morbidity and mortality after 30 days (≤ 5 years)
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Four patients had passed away at 5 years of follow-up. Three patients in VLRL-RYGB group died of which one died due to a cerebrovascular accident at 4 years and 2 months after surgery, one died due to stage 4 gastric cancer in remnant stomach at 4 years and 6 months after surgery, and one died due to sepsis following necrotizing fasciitis at 4 years and 11 months after surgery. One patient from the S-LRYGB group passed away due to an unknown cause at approximately 3 years of follow up.

Nutrient and Vitamin Deficiencies at 5 Years of Follow-up

Information regarding usage of multivitamin was accessible for 102 patients (48.3%) in the VLRL-LRYGB group and 113 (57.7%) in the S-LRYGB group. In the VLRL-LRYGB group, 21 patients (10.7%) used bariatric supplements and additional specific supplements (such as iron supplements, vitamin B12, and/or vitamin D) versus ten patients (4.7%) in the S-LRYGB group at 5 years of follow-up. In the VLRL-LRYGB group, 61 patients (31.1%) used bariatric supplements alone, while in the S-LRYGB group, this number was 58 (27.5%). Twenty-eight patients (14.3%) in the VLRL-LRYGB group and also 28 patients (13.3%) in the S-LRYGB group used non-bariatric supplements. In the VLRL-LRYGB group, three patients reported no multivitamin usage, compared to six patients in the S-LRYGB group.

Following the exclusion of patients who underwent escape or modification surgery for malabsorption, available laboratory results at the 5-year follow-up for per-protocol analysis were accessible for a total of 107 patients (57.5%) in the VLRL-LRYGB group and 103 patients (49.3%) in the S-LRYGB group. No statistically significant differences were observed when comparing micronutrient and vitamin deficiencies (see Fig. 3). Nevertheless, a notable percentage of patients in both groups showed deficiencies for iron, ferritin, and vitamin D.

Fig. 3
figure 3

Deficiency rates in micronutrients and vitamin at a 5-year postoperative. Deficiency for micronutrient or vitamin was defined by laboratory value below lower threshold of normal value. Normal value range used was as follows: albumin 35–52 g/L, calcium 2.15–2.65 mmol/L, ferritin 22–204 µg/L, folic acid 7.0–46.4 nmol/L, iron 9.0–30.4 µmol/L, potassium 3.5–5.1 mmol/L, magnesium 0.66–1.07 mmol/L, sodium 135–145 mmol/L, transferrin 1.80–3.82 g/L, vitamin B1 70–185 nmol/L, vitamin B6 35–110 nmol/L, vitamin B12 130–700 pmol/L or active vitamin B12 > 32 pmol/L, vitamin D 50–250 nmol/L

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Discussion

The role of the total alimentary tract (TAT) or total alimentary limb length (TALL) has been poorly investigated so far; yet, a recent systematic review by Wang et al. reports some evidence that shortening TALL affects weight loss [26]. However, these results should be interpreted with caution, as most of the studies included in this systematic review were retrospective cohort studies, and the majority did not have follow-up periods exceeding 2 years. Recently, two new reviews regarding optimal small bowel limb length in gastric bypass were published [27, 28]. Both studies provide an overview of the existing literature on altering limb lengths and reach similar conclusions: a longer BPL leads to greater weight loss and improved glycemic control for patients with diabetes, but it also increases the risk of micronutrient deficiencies. These studies also illustrate how the discussion is predominantly focused on the BPL length because of better weight loss results. The precise mechanism behind this effect remains unclear. It is suggested that lengthening of the BPL leads to increased release of incretins, such as glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) induced by the rapid release of bile and nutrients to the L cells of the ileum [29].

In 2014, Nergaard et al. published the first RCT to describe better weight loss with longer BPL by comparing a 200-cm BPL and 60-cm RL with a 60-cm BPL and 200–cm RL LRYGB [30]. At 5 years, weight loss expressed as percentage excess BMI loss (EBMIL%) was approximately 83% which is comparable to the 5-year result of the VLRL-LRYGB group, assuming that the formula used for calculating EBMIL% yields the same results as the formula used for %EWL used in the current investigation. In contrary to the 5-year results of the current investigation, Nergaard described higher percentages of patients with micronutrient deficiencies requiring adjustment of their supplementation during follow-up. This difference might be explained by the use of specialized bariatric multivitamins during follow-up in the DUCATI study groups [22]. The Dutch ELEGANCE trial, randomizing patients to a 150-cm BPL with 75-cm RL or a 75-cm BPL with a 150-cm RL managed to achieve a 98% total follow-up at 4 years [5]. Weight loss in terms of %EWL was significantly better in the long BPL group at 4 years with 72%, but no difference in %TWL was observed and weight regain in both groups was observed. Results in VLRL-LRYGB group seem better when compared to these results with less profound recurrent weight gain over the years.

Other series describing very long RL type LRYGB show excellent weight loss results at 2–3 years, but long-term results are lacking [14,15,16,17]. One other study reporting a comparable very long RL LRYGB reports 5-year weight loss results (78% %EWL and 42% %TWL) [14]. Results in VLRL-LRYGB group at 5 years are similar for %EWL. %TWL seems a lot higher in the study by Thurnheer et al. which might be explained by a higher pre-operative BMI in this study when compared to the pre-operative BMI in VLRL-LRYGB group. Süsstrunk et al. describes 10-year results of a retrospective cohort of 232 patients undergoing a very-very long limb Roux-en-Y gastric bypass which is almost identical to the VLRL-RYGB in the DUCATI study [17]. Effect on weight at 5 years is comparable to VLRL-LRYGB group at 5 years and modification surgery for malnutrition as well. At 5 years, an interesting finding was observed when looking at total small bowel length. Patients with relatively short (< 580 cm) total small bowel length had a significantly higher impact on the statistically significant difference in weight loss results in favor of VLRL-LRYGB group compared to standard LRYGB group. This is in line with findings in literature stating that a shorter TALL yields better weight loss results than a long TALL [26,27,28, 31, 32].

At a 3-year follow-up, a significantly higher percentage of patients showed resolution of T2DM in the VLRL-LRYGB group [24]. Although we found a similar higher percentage of T2DM resolution at 5 years in favor of VLRL-LRYGB group when compared to standard LRYGB (75% vs. 51%), analysis did not yield a statistically significant difference due to a higher percentage of missing data in S-LRYGB group. Modification surgery for malabsorption was performed more, although not statistically significant, in VLRL-LRYGB group in 3.6% of patients compared to 0.9% in standard LRYGB group. This is comparable to modification surgery rates described in literature from similar very long RL gastric bypasses, ranging between 1.1 and 5% [14,15,16,17]. At 5 years, nutritional deficiencies rates in VLRL-LRYGB group were overall relatively high when compared to the results reported by Thurnheer et al. from Swiss especially when looking at ferritin deficiency but with a very lower rate of albumin deficiency reported in VLRL-LRYGB group [14]. This difference in ferritin deficiency rate is unknown but a possible explanation might be higher daily dosage of iron and perhaps earlier switch to intravenous therapy in the Thurnheer group when deficiency persisted. The higher rate of protein and albumin deficiency described in the 355 Swiss patients at 5 years is remarkably different from the current results from the VLRL-LRYGB group. This difference is hard to explain and the authors feel that the 25-cm extra CL length is too short to provide the difference between both studies; nevertheless, only 11 patients had lab results in the Turnheer study at 5 years, and therefore these differences should be interpreted with caution [14]. Vitamin and micronutrient deficiencies seem lower at 5 years in both DUCATI study groups when compared to data from long BPL studies [10, 30] which might be attributed to a relatively longer TALL [27, 28, 31].

The authors fixed BPL in both DUCATI study groups at 60 cm to eliminate contributing factor of BPL length in order to fully focus on the effect of elongating RL. Recent systematic reviews on limb length all draw similar conclusions regarding RL and CC length, stating keeping CC of at least 200 cm to reduce risk of vitamin and micronutrient deficiency and lengthening RL does not improve weight loss outcome [26, 27, 31]. This is in contrast to what was observed at a 5-year follow-up in VLRL-LRYGB group, as well as in the study by Süsstrunk et al. and suggests that this statement regarding RL lengthening is not correct [17]. In fact, when looking at the long-term results derived from both “long RL” studies (i.e., DUCATI study and the Süsstrunk cohort) and comparing these to “long BPL” studies shows great weight loss results for both types of procedure but with less protein malnutrition in both “long RL” studies [30, 31]. Weight loss results at 5 years are excellent and appear to show better preservation of weight loss over the years without inducing significant micronutrient and vitamin deficiencies when compared to standard type LRYGB. Another interesting finding is that most patients requiring modification surgery for malabsorption had a long total small bowel length. This finding in combination with better weight loss results in patients with short (< 580 cm) total small bowel length might suggest that VLRL-LRYGB might be a better option in patients with relatively short total small bowel length. The difference between weight loss results at 1 year and 3 to 5 years is hypothesized to be caused by initial restrictive effect of the procedure caused by the stoma size and calibrated gastric pouch, rather than the (hypothesized) metabolic effects of the different limb lengths on weight loss. This may be reflected in the better weight loss outcomes in the group with relatively short total small bowel length [24].

The overall loss to follow-up of 34% is a limitation of this current investigation. Despite this, the absolute number of patients with available results is still significant enough to draw conclusions, especially when compared to the number of patients in other studies.

Conclusion

Contrary to current insights in optimum Roux-en-Y gastric bypass limb lengths, lengthening of the Roux limb shows good sustainable weight loss results at 5 years without significant additional nutritional side effects. However, a higher risk of overall complications is observed in the first years after surgery. Nevertheless, the additional risk of malnutrition seems acceptable due to the relative low incidence reported during follow up in the VLRL-LRYGB group. An important other factor to consider is the fact that the surgeons who performed the VLRL-LRYGB in the DUCATI study all report that this procedure is technically more challenging due to a number of factors which could contribute to this higher risk of overall complications. With that in mind, it is an interesting question if, and in which form, the VLRL-LRYGB could have a place in the clinical practice of the bariatric surgeon.

The relatively low percentage of patients requiring modification surgery due to severe diarrhea and no significant differences in nutritional deficiencies at 5 years suggests that a 100-cm common channel in combination with a relatively long Roux limb can still be sufficient for adequate micronutrient uptake in the total alimentary tract with adequate micronutrient supplementation use. These results should therefore be considered in the discussion on optimum Roux-en-Y limb length which has been focused on varying BPL and disregarding RL due to the inferior results of comparative studies looking at small variations in RL length.

Total small bowel length in relation to total alimentary tract seems an important factor in tailoring the limb lengths and should be a relevant subject in future studies.