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The Drain Debate: A Prospective Controlled Trial on Criteria-Based Prophylactic Drain Use in Total Gastrectomy for Esophagogastric Junctional or Gastric Cancer (The DRAG Study)
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Submitted:
05 November 2024
Posted:
06 November 2024
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Abstract
Background: Total gastrectomy with D2 lymph node dissection is standard for resectable esophagogastric junctional and gastric cancer, but high morbidity challenges perioperative care. ERAS guidelines advise against routine drains, yet conflicting evidence leads to inconsistent practice. Methods: The DRAG (DRains After Gastrectomy) Trial is a prospective, non-randomized study conducted from February 2020 to March 2023 at the 1st Propaedeutic Surgery Department, Hippocration General Hospital, Athens. Patients undergoing open D2 total gastrectomy had perianastomotic drains placed based on newly established criteria, offering a more tailored approach. Immediate and short-term postoperative outcomes, including recovery milestones and complications, were assessed. Results: Sixty patients were included, with 40 receiving a drain. The non-drain group had significantly lower pain scores, earlier mobilization, less postoperative nausea and vomiting, and a shorter hospital stay. Among those with complications, significant differences in surgical site infections, delayed mobilization, extra-abdominal issues, length of stay, readmissions, and reoperations suggest that drain use may increase complications and hinder recovery. Conclusion: Our study suggests that routine prophylactic drain use can be avoided in gastrectomy for esophagogastric junctional and gastric cancer when experienced surgeons in high-volume centers follow clearly defined criteria. Implementing these criteria may improve patient outcomes and reduce complications.
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Medicine and Pharmacology - Surgery1. Introduction
Gastric cancer ranks as the fifth most common and fifth most lethal cancer globally [1]. For patients with AJCC (American Joint Committee on Cancer) stages IB to IIIC, representing the majority of cases, the current gold standard of surgical treatment involves total gastrectomy combined with D2 lymph node dissection, followed by gastrointestinal tract reconstruction [2,3]. The survival rates following R0 resection vary significantly, ranging from 88% for stage IB to 25.3% for stage IIIC, as reported in the 7th edition of the TNM classification [4]. Given the significant morbidity and mortality associated with this extensive surgical procedure, there has been a growing focus on improving perioperative management and quality of life for these patients over the past two decades [5,6].
It has long been established that minimizing surgical intervention correlates with faster patient recovery [5,6,7]. The Enhanced Recovery After Surgery (ERAS) guidelines provide globally recognized perioperative recommendations for a variety of surgical procedures, grounded in research, audits, and evidence-based practice [6]. In 2014, Mortensen et al. [8] introduced ERAS guidelines specifically tailored for gastrectomy in gastric cancer. These guidelines include both procedure-specific and general recommendations applicable to the perioperative management of abdominal surgeries. However, much of the data underpinning these guidelines have been extrapolated from research on perioperative management in pancreaticoduodenectomy and colectomy for malignancies [9,10].
Since the publication of ERAS guidelines, evidence suggests limited and inconsistent global adherence to the protocol in gastrectomy, particularly regarding surgical drain use. Historically, drain placement during gastrectomy was routine [11], with literature reporting usage rates ranging from 57.7% to 62.8% [12,13,14]. The ERAS guidelines advise against drain placement to reduce complications like pain, delayed mobilization, and infections. This recommendation, based on two meta-analyses (400 cases) and two prospective trials, lacked robustness due to heterogeneity in surgery type and data collection [15,16,17,18] . These studies found no significant differences in hospital stay, morbidity, mortality, or complications between patients with and without drains, leading many to view the data as insufficient. Although the ERAS guidelines provide clear direction on drain use in surgeries such as pancreaticoduodenectomies and colectomies, recommending drains for the former but not the latter [9,10], the debate for gastrectomy remains unresolved. Japanese guidelines support routine use of intraperitoneal drains after total gastrectomy, with removal by the fifth postoperative day [19]. Studies from Japan further investigate the prognostic value of drain contents post-gastrectomy, reinforcing this practice [11,20,21,22,23,24]. In contrast, Western guidelines, such as those from the American College of Surgeons, advise against routine drain use, suggesting placement only in selected cases [25]. This divergence among experts contributes to uncertainty regarding drain use in gastrectomy, resulting in limited adherence to ERAS recommendations in Western practices [26,27].
This prospective, non-randomized controlled clinical trial aims to assess the impact of one perianastomotic drain when it is placed under specific, predefined criteria. The trial evaluates the immediate and short-term postoperative outcomes in patients who underwent D2 total gastrectomy for esophagogastric junctional and gastric cancer. The resections were performed in a high-volume centre and under the care of a highly experienced team. To our knowledge, this is the first study to propose specific recommendations tailored to the question of routine prophylactic drain use in total gastrectomy. This novel approach aims to fill an existing gap in the literature, offering a structured framework for clinical decision-making in high-volume centres.
2. Materials and Methods
The DRAG (DRains After Gastrectomy) Trial is a prospective, non-randomized, controlled clinical trial involving patients diagnosed with esophagogastric junctional or gastric neoplasm. All surgeries were performed by a single, highly experienced surgeon in the 1st Propaedeutic Surgery Department at Hippocration General Hospital in Athens, Greece. The patients underwent open total gastrectomy with D2 lymph node dissection, followed by Roux-en-Y gastrointestinal tract reconstruction, in accordance with a predefined, ERAS-compliant perioperative departmental protocol. Our institution’s protocol does not routinely incorporate exploratory laparoscopy or peritoneal cytology.
The participants were divided into two groups. The first group followed the department's standard practice, with a drain placed near the esophagojejunal anastomosis (drain group). In contrast, the second did not have a drain placed (non-drain group). The decision to place a drain was based on the following criteria:
a) Pulmonary diseases under oxygen therapy
b) Chronic oral steroid use (≥5mg/day prednisone equivalent for >1month)
c) Intraoperative hemodynamic instability requiring vasopressors
d) Intraoperative blood loss exceeding 250 mL
e) Vessel injury (celiac axis or its branches)
f) Injury to adjacent structures (pancreas, spleen, duodenum)
g) Tension of the anastomosis
h) Concerns about the integrity of the duodenal stump arising from potential staple misfiring or compromised tissue quality.
These criteria were informed by existing literature on gastrectomy and their presence denotes increased risk for postoperative complications [11,28,29,30,31,32,33,34,35,36,37,38,39,40].
All patients meeting the eligibility criteria (Table 1) underwent comprehensive preoperative evaluations, including clinical examinations, blood tests, imaging studies, and consultations with other specialties. The detailed preoperative assessment is outlined in Appendix A.
| ELIGIBILITY CRITERIA |
| INCLUSION CRITERIA |
| Age over 18 years old |
| Histologically proven EGJ (Siewert II or III) or non-EGJ gastric adenocarcinoma (intestinal, diffuse, or mixed Lauren type) |
| Surgical candidates for total gastrectomy plus D2 lymph node dissection |
| ECOG performance status 0 or 1 |
| Signed informed consent from |
| Preoperative evaluation of cTanyNanyM0 according to the American Joint Committee on Cancer Staging Manual, 7th edition |
| EXCLUSION CRITERIA |
| M1 disease |
| Other unplanned organ excision |
| Massive ascites or cachexia |
| Current participation in any other clinical trial |
| Severe cardiovascular, respiratory tract, kidney, liver, or psychiatric disease. |
| Poor compliance to the clinical protocol |
| Pregnancy |
Per our departmental protocol, patients were gradually mobilized starting directly after surgery, when feasible. On the second postoperative day, an oral gastrografin study was conducted for each patient to detect any early anastomotic leaks. Following a normal radiological study, patients were initiated on a liquid diet, which was then advanced to pureed food on the third postoperative day, and a soft diet on the fourth day. For patients in the drain group, the drain was removed on the fifth postoperative day, provided that the drainage volume was less than 50 mL over the preceding 48 hours, in line with departmental protocol. A descriptive timeline of the protocol is presented in Appendix B.
The primary outcomes measured in this study were: a) pain levels, assessed using the Visual Analog Scale (VAS) during the first 5 postoperative days, b) postoperative nausea and vomiting (PONV) within the first 5 days, c) initiation of feeding, d) postoperative bowel mobilization, e) patient mobilization, f) length of hospital stay (LOS)
Secondary outcomes included: a) mortality, b) surgically related readmissions and c) reoperations
This study was conducted in accordance with the principles outlined in the Helsinki Declaration of Human Rights [41] and with the Guidelines of Good Clinical Practice [42]. The final study protocol and the informed consent form for participant inclusion received approval from the Institutional Review Board (IRB). The IRB also conducted regular assessments, as required, to ensure the ongoing compliance with lawful medical practice throughout the trial.
The statistical analysis was performed using the R software (R foundation for Statistical Computing) version 4.3.0 for Windows. Descriptive characteristics for the quantitative data were expressed as median and Quartile 1 (Q1) to Quartile 3 (Q3) range and for completeness reasons the mean ± standard deviation (SD), for the qualitative data was reported the frequency of occurrence and the relevant percentage. Comparisons were preformed between patients with drainage and those without drainage; for the qualitative parameters statistical tests were performed via the chi-square test (and if required a Fisher exact test) and for the arithmetic data (as normality was not possible to be ensured using the Shapiro Wilk test), were applied not parametric tests, specifically the Mann Whitney U test. The significance level (p-value) was set to 0.05, thus statistically significant difference between compared groups was for p<0.05 and all tests were two sided.
3. Results
The study was conducted from February 2020 to March 2023. Among the 60 eligible participants, 40 were assigned to the drain group, while 20 were included in the non-drain group. The mean age of the patients was 71 ± 9.6 years, ranging from 48 to 87 years. Among the participants, 32 (53.33%) were male. The preoperative histological diagnosis primarily identified intestinal-type gastric cancer in 46.6% of the cases, with the most common lesion location being the body of the stomach (43.3%). Additionally, 25% of the patients had undergone preoperative chemotherapy due to node positivity at diagnosis (N≥1) or unresectability on exploratory laparotomy. Detailed descriptive statistics, categorized by various factors, are provided in Table 2.
The mean duration of the gastrectomy was 197 ± 37 minutes. Blood transfusion was required in 13.3% of patients, while 8.3% received only fresh frozen plasma (FFP). Among patients in the drain group, the most common indications for drain placement were significant blood loss (33.3%) and tension of the anastomosis (18.3%). A very small percentage of patients exhibited preoperative risk factors that would typically warrant drain placement. Further details on the intraoperative characteristics are provided in Table 2.
Postoperatively, 23.3% (n=14) of patients revealed deranged vital signs, with 9 patients in the drain group exhibiting concerning findings in their drains. Full blood counts (FBC) and biochemical abnormalities were detected within the first 3 days. Approximately 56% of patients experienced severe pain during the first 5 postoperative days, while postoperative nausea and vomiting were also common. Surgical site infections (SSI) were identified in 12 patients (20%).
Mobilization was impeded in 37% of patients, and feeding initiation was delayed in 28.3%, contrary to protocol. Bowel movement began on average at 3.58 ± 1 days. Two patients required postoperative ICU admission: one due to comorbidities and the other due to extended operative time. The mean length of hospital stay was 9 ± 9 days.
Fifteen percent (n=9) of patients experienced intra-abdominal complications, and 8.3% had extra-abdominal complications. These complications resulted in a 3% mortality rate, 5% readmission rate, and 6% reoperation rate within the first 30 postoperative days.
In specific, four patients developed anastomotic leaks two of which underwent reoperation with hybrid intraoperative stent suturing [43]. The third patient received endoscopic stenting, while the fourth was managed conservatively. All four patients belonged in the drain group.
Postoperative bleeding occurred in two patients. The first patient experienced bleeding on day zero, evident in the drain, and required reoperation. The second patient exhibited delayed bleeding on the 9th postoperative day and was treated conservatively. One patient was diagnosed with duodenal stump leak on the 7th postoperative day by means of computed tomography (CT). One patient in the non-drain group developed necrotizing pancreatitis due to a postoperative pancreatic fistula, detected on the 3rd postoperative day and necessitating reoperation; unfortunately, this patient passed away. Finally, one patient developed postoperative ileus requiring nasogastric tube placement. Table 2 provides a detailed summary of these findings.
Demographic and intraoperative characteristics between the two groups were compared to identify any potential differences that could impact the study outcomes. The results of these comparisons are detailed in Table 3. Statistical tests with p-values <0.05 indicated significant differences between the groups. However, no statistically significant differences were observed between the two groups overall.
Similar comparisons were conducted for intraoperative characteristics. Specifically, the duration of the operation, red blood cell (RBC) and FFP transfusion rates, drug allergies, and intraoperative incidents did not differ significantly between the two groups (see Table 4).
Postoperative characteristics and outcomes were assessed using various factors, and Fisher's exact tests were applied for comparisons. The percentage of patients reporting high pain (VAS) scores was significantly lower in the no-drain group (15%) compared to the drain group (77.5%). Additionally, delays in mobilization and oral feeding were notably less frequent in the no-drain group, occurring in only 10% of cases for each, versus 50% and 37.5% in the drain group, respectively (p=0.0038 and p=0.0340).
Significant differences were also observed in postoperative nausea and vomiting (PONV), with a lower incidence in the no-drain group (25%) compared to the drain group (60%, p=0.0142, OR: 0.22), indicating approximately five times higher odds of PONV in the drain group.
Moreover, the initiation of bowel movement and length of hospital stay were significantly shorter in the no-drain group. The median time of gut motility start was 3 days in the no-drain group compared to 4 days in the drain group (p=0.0142). The median length of stay (LOS) was also shorter for the no-drain group, at 5 days, compared to 7 days for the drain group (p=0.0001).
Box and whisker plots illustrating these results are presented in Figure 1. No significant differences were found in mortality, reoperations, or readmissions (see Table 5).
A characteristic diagram for the LOS is depicted in Figure 2.
As previously reported, nine patients experienced intra-abdominal complications, with seven in the drain group and two in the no-drain group. The most common complication was anastomotic leak, occurring in four cases, followed by two cases of bleeding. These complications significantly affected both the length of hospital stay (LOS) and reoperation rates. The median day of complication detection was 5.8 (range: 1 to 11). Although the number of cases in this subgroup is relatively small, for the sake of completeness the statistical analysis was performed and the outcomes are presented in Table 9. As anticipated, no statistically significant differences were found regarding the detection of anastomotic leaks, the postoperative day of complication detection, diagnosis based on drain content, hospitalization duration, reoperation rates, or mortality.
With regards to the complications only in the drain group, four cases were identified through drain content analysis, while three were detected based on clinical presentation and blood tests. The statistical analysis showed no significant differences regarding the method of complication detection, the postoperative day of diagnosis, LOS, or mortality rates among these patients (Table 10).
4. Discussion
The use of drains after elective total D2 gastrectomy remains a contentious issue in surgical practice. The ERAS guidelines generally recommend avoiding drains when possible, citing benefits such as faster recovery, reduced hospital stay, and quicker return to daily activities [5,6,8,9,10,45]. Despite this, many surgeons continue to use drains to manage abdominal fluid collections and detect postoperative complications such as intra-abdominal abscesses, anastomotic leaks, bleeding, and pancreatic fistulas. In cases of severe complications (Clavien-Dindo II to IV) [44], drains can also play a therapeutic role. This study aimed to delineate specific criteria that would guide the appropriate use of drain placement after total gastrectomy for gastric cancer.
Our study yielded no significant differences between patients with and without drains in terms of preoperative or demographic characteristics, nor between patients who developed complications and those who did not. While this study's sample size is relatively small, these findings should be considered in decisions about drain placement. Larger studies are warranted for more definitive conclusions.
Interestingly, patients who required FFP transfusion during reoperation developed a higher incidence of complications, particularly anastomotic leaks. It is well-established that blood transfusions can adversely affect postoperative outcome [46,47,48]. Recent research suggests that FFP transfusion may also provoke an immunomodulatory response, leading to altered cytokine profiles with reduced pro-inflammatory and increased anti-inflammatory cytokines [46,49].
In this analysis, vessel injury was identified as a significant risk factor for postoperative complications, while other commonly evaluated factors showed no notable differences. This finding highlights the need to carefully consider vessel injury when deciding on drain placement during gastrectomies. The literature identifies various risk factors associated with postoperative complications, including advanced age (>65 years), male sex, cardiopulmonary comorbidities, diffuse tumor histology, extensive lymphadenectomy, intraoperative blood loss, anastomotic tension, and impaired blood supply [28,29,30,31,32,33]. Although we observed no differences in these factors, they warrant careful consideration due to their established relevance in larger studies.
With regards to the VAS score, we found marginal statistical significance in pain levels between the drain and no-drain groups when complications were present, but significant difference when the complication was absent, suggesting that drain placement may be avoidable in the absence of complications. This finding aligns with the literature, which indicates that drains can significantly influence postoperative pain and may exacerbate it [16,17,45].
The current analysis revealed a significant difference in PONV between the drain and no-drain groups in uncomplicated patients. This suggests that prophylactic drain use might be unnecessary and could contribute to PONV. Although numerous studies have investigated postoperative nausea and vomiting (PONV) in bariatric surgery [50,51], there is limited research specifically addressing gastrectomy for gastric cancer. Given that PONV contributes to prolonged hospital stays, it is important to consider and attempt to mitigate this complication.
Evidence from our study showed no overall difference in surgical site infections (SSIs) between the drain and no-drain groups. However, in patients with postoperative complications, the drain group experienced a significantly higher rate of SSIs. The relationship between drains and SSIs remains debatable; while several studies report no association ([14,17,18,52], others suggest that retrograde bacterial contamination or leakage of protein-rich ascitic fluid may play a role [12]. Therefore, careful consideration of drain use in patients with complications is warranted to minimize the risk of SSIs
Our research demonstrated that extra-abdominal complications, particularly respiratory tract infections, were more prevalent in patients with drains when intra-abdominal complications occurred. This finding suggests that drain irritation may facilitate the dissemination of pathogens, although the literature on this relationship remains limited [12,53]
In this analysis, we found that drain placement was associated with delays in mobilization and oral feeding, although the differences were marginal when complications were present. Our study observed that gastrointestinal tract mobility was negatively impacted by drains, supporting the notion that prophylactic drains may be unnecessary, despite the lack of significant differences in the presence of complications. The literature presents mixed results regarding the impact of drains on mobilization and gastrointestinal function, with some studies reporting no significant differences between drain and no-drain groups while others suggest that drains may hinder recovery [11,12,14,15,45].
The presence of drains in this study significantly impacted the length of stay (LOS), as patients who experienced delays in mobilization, dietary resumption, and restoration of gastrointestinal motility were less likely to be discharged in a timely manner. This correlation is well-documented in the literature [15,16,17,18,45,54]. Furthermore, the authors believe that daily management of drains can present considerable challenges, especially in regions with limited community healthcare services. The occurrence of complications further complicates this situation, often resulting in extended hospital stays due to concerns from both patients and surgeons, as well as the ongoing need for regular drain monitoring.
From a financial perspective, extended hospital stays significantly increase healthcare costs globally, placing a burden on hospital resources and reducing the availability of beds for other patients. Prolonged admissions not only escalate direct costs, such as staffing and resource utilization, but also indirectly affect the overall efficiency and capacity of healthcare systems worldwide [55,56]
Data from our trial indicated that both readmissions and reoperations were statistically significant only among patients in the drain group who developed complications. This suggests that the use of drains may be associated with an increased risk of additional complications when they occur. The existing literature supports this finding in relation to reoperations [11]. However, regarding readmissions, the evidence presents a contrasting view [54,57]. These two meta-analyses demonstrated higher readmission rates in the non-drain groups, primarily due to undetected complications during the initial hospital stay. The authors attribute the observed findings to the predefined criteria employed in selecting patients for whom it was deemed safe to omit the perianastomotic drain.
In this study, mortality was only marginally significant in patients with intra-abdominal complications, which aligns with our expectations. Importantly, no significant difference in mortality rates was observed between the drain and no-drain groups. Unfortunately, the existing literature on mortality differences between these groups is limited. The two extensive studies [17,18] that reported on mortality also found no statistically significant differences between the drain and non-drain groups.
A final key consideration in minimizing the use of unnecessary drains is the incorporation of green surgery principles. In recent decades, there has been a concerted effort to minimize CO₂ and CO₂-equivalent emissions through education and actionable strategies. The implementation of theatre checklists that include parameters for improvement before, during, and after surgery is a step in this direction [58,59]. While specific guidelines for intraoperative drain use are lacking, similar to recommendations for urinary catheters, which advocate for their avoidance when not clinically necessary, a parallel approach could be applied to drains [60]. Despite these recommendations, adherence to minimizing unnecessary catheterization remains unsatisfactory [61]. Avoiding clinically unnecessary interventions, including drains, can significantly reduce the carbon footprint of surgical procedures and promote environmental sustainability. This approach not only benefits the environment but also mitigates financial costs associated with excessive use of medical resources [62].
The authors acknowledge the limitations of this study. Firstly, the sample size is relatively small for a study of this nature, largely due to constraints imposed by the COVID-19 pandemic. This confined sample size may have precluded the detection of statistical significance in areas where differences could potentially exist. Larger studies may provide more definitive insights. Additionally, no information regarding Helicobacter pylori (H. pylori) information was available in the histopathology reports, it is, however reasonable to assume, that H. pylori positive cases have been already detected and treated by the preceding preoperative gastroscopies. Given the ongoing debate regarding the relationship between H. pylori, prognosis, and disease relapse, the authors emphasize the importance of considering H. pylori status in future research, as the literature presents mixed findings on the impact of negative H. pylori status [63,64,65,66,67]
5. Conclusions
Our study suggests that routine prophylactic drain use may be unnecessary in gastrectomy for esophagogastric junctional or gastric cancer when performed by experienced surgeons at high-volume centres, provided the criteria introduced in this study are applied. To our knowledge, no other studies have proposed such parameters to address this clinical question, underscoring the novelty of our approach. However, larger-scale studies are needed to further validate these guidelines and strengthen the recommendation.
Author Contributions
Conceptualization: M.M.E and D.T, methodology: M.M.E, software: D.K and A.P, validation: D.K and T.T., formal analysis: M.M.E and T.T., data curation: K.T and G.Z, writing—original draft preparation: M.M.E, writing—review and editing: MD, supervision: D.T All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding
Institutional Review Board Statement
This study was conducted in accordance with the principles outlined in the Helsinki Declaration of Human Rights and with the Guidelines of Good Clinical Practice. The final study protocol received approval from the Institutional Review Board (IRB) of Hippocration General Hospital (1678 / 31-01-2020).
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement
Clinical Trials.gov.
Acknowledgments
None
Conflicts of Interest
The authors declare no conflicts of interest.
Abbreviations
AJCC: American Joint Committee on Cancer, aPTT: activated partial thromboplastin time, CA 125: Cancer antigen 125, CA 153: Cancer antigen 153, CA 19-9:Cancer antigen 19-9, CEA: Cancer embryonic antigen, CT: computed tomography DRAG: DRain After Gastrectomy, ECOG: Eastern Cooperative Oncology Group, EGJ: Esophago-gastric Junction, ERAS: Enhanced Recovery After Surgery, FBC: Full Blood Count, FFP: Fresh Frozen Plasma, ICU: Intensive Care Unit, INR: international normalised ratio, IRB: Institutional Review Board, LOS: Length of Stay, LFTs: Liver Function tests, POD: Postoperative Day, PONV: Postoperative Nausea and Vomiting, PT: prothrombin time, RFTs: Renal function Tests, SSI: Surgical Site Infection, TNM: Tumor- Nodes- Metastasis, U&E: Urea and Electrolytes, VAS: Visual Analogue Score
Appendix A
| PREOPERATIVE EVALUATION | |||
| History and physical examination | |||
| Blood exams | FBC, RFTs, LFTs, U&E, blood sugar, albumin and total protein levels | ||
| Blood clotting sufficiency | PT, INR, aPTT | ||
| Thyroid function | T3, T4, TSH, FT3, FT4 | ||
| Hepatitis virulence | anti- HCV antibodies, anti- HBV antibodies, HBs antigen | ||
| Blood type cross-match | |||
| Chest x-ray | |||
| Anesthesiologist check | Incentive spirometry, Mallabati score evaluation, ASA score, necessity for ICU stay after the operation | ||
| Electrocardiogram and cardiology examination | |||
| Previous colonoscopy to exclude secondary/second primary tumor in colon | |||
| aPTT: activated partial thromboplastin time, FBC: Full Blood Count, HBV: hepatitis B virus, HCV: hepatitis C virus, INR: international normalised ratio, LFTs: Liver Function tests, PT: prothrombin time, RFTs: Renal function Tests, T3: Triiodothyronine , T4,: Thyroxine ,TSH: thyroid stimulating hormone, U&E: Urea and Electrolytes. | |||
Appendix B. Timeline of Study Protocol
| STUDY PERIOD | |||||||||
| ENROLLMENT DAYS | DAY OF SURGERY | POSTOPERATIVE DAYS | |||||||
| TIMEPOINT | -7 TO -2 | -1 | 0 | 1 | 2 | 3 | 4 | 5 | Ω |
| ENROLLMENT | |||||||||
| PATIENT SELECTION | X | ||||||||
| PREOP CHECK | X | ||||||||
| CONSENT SIGN | X | ||||||||
| PROTOCOL EDUCATION | X | ||||||||
| INTERVENTION | |||||||||
| DRAIN PLACEMENT | X | ||||||||
| INTRAOPERATIVE DATA RECORDING | X | ||||||||
| MONITORING | |||||||||
| CLIN. EXAMINATION &VITALS | X | X | X | X | X | X | |||
| LABS | X | X | X | X | X | X | |||
| DRAIN CONTENT MONITORING | X | X | X | X | X | X | X | ||
| ORAL CONTRAST STUDY | X | ||||||||
| PONV | X | X | X | X | X | ||||
| PAIN (VAS SCORE) | X | X | X | X | X | X | |||
| SSI | X | X | X | X | X | ||||
| MOBILIZATION | X | X | X | X | X | ||||
| ORAL FEEDING | X | X | X | X | X | ||||
| GUT MOTILITY | X | X | X | X | X | X | |||
| EXTRAABDOMINAL COMPLICATIONS | X | X | X | X | X | ||||
| LOS | X | X | X | X | X | X | |||
| MORTALITY | X | X | X | X | X | X | |||
| READMISSIONS | X | X | X | X | X | X | |||
| REOPERATIONS | |||||||||
|
LOS: length of stay, SSI: surgical site infection, VAS score: visual analogue score Ω:time between POD#5 and discharge | |||||||||
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Figure 1.
Box and whisker plots for gut mobilization days (left) and length of hospital stay (right). In each diagram, the box limits indicate the lower (1st) and higher (3rd) quartiles (Q1 & Q3 respectively), horizontal lines within the boxes indicate median value, while the limits of the whiskers indicate minimum and maximum values after excluding outliers. Mean values are big circles and smaller circles outside the whisker areas indicate outliers. In the right picture not all outliers are visible due to vertical axis crop to enhance the dynamic range of the figure.
Figure 1.
Box and whisker plots for gut mobilization days (left) and length of hospital stay (right). In each diagram, the box limits indicate the lower (1st) and higher (3rd) quartiles (Q1 & Q3 respectively), horizontal lines within the boxes indicate median value, while the limits of the whiskers indicate minimum and maximum values after excluding outliers. Mean values are big circles and smaller circles outside the whisker areas indicate outliers. In the right picture not all outliers are visible due to vertical axis crop to enhance the dynamic range of the figure.
Figure 2.
Box and whisker plots for LOS in patients with and without intra-abdominal complications.
Table 2.
Descriptive statistics of perioperative characteristics.
| Group | Characteristic | Value |
| Demographics and patient characteristics | Age | 71±9.6, median (Q1-Q3): 73 (65-77.5), min: 48, max: 87 |
| Gender (male) | 32 (53.33%) | |
| Charlson score | 2.45±0.85, median (Q1-Q3): 2 (2-2.5), min:2, max: 5 | |
| ECOG | 8 patients (13.3%) had score 1, 52 patients had score 0 | |
| Histology | Diffuse | 22 (36.67%) |
| Intestinal | 28 (46.67%) | |
| Other | 7 (11.67%) | |
| Location | EGJ | 12 (20%) |
| Fundus | 5 (8.33%) | |
| Body | 26 (43.33%) | |
| Prepyloric antrum | 16 (26.67%) | |
| Pylorus | 1 (1.67%) | |
| Preoperative chemotherapy | Positive | 15 (25.42%) |
| Laboratory results abnormality | FBC | 6 (10%) |
| Biochemical | 4 (6.67%) | |
| Clotting | none | |
| Cancer antigens positivity * | CA 19.9 | 8 (13.33%) |
| CA 15.3 | 6 (10%) | |
| CA 125 | 3 (5%) | |
| CEA | 7 (12%) | |
| Intraoperative characteristics | Duration of operation (min) | 197.5±37.2, median (Q1-Q3): 200 (180-227.5), min 120, max 180 |
| Blood transfusion | 8 (13.33%) | |
| FFP transfusion | 5 (8.33%) | |
| Allergic reaction to drugs | 0 (%) | |
| Intraoperative incidents | 7 (11.67%) | |
| Criteria for drain placement | Blood loss >250mls | 20 (33.33%) |
| Vessel injury | 3 (5%) | |
| Anastomosis concerns | 11 (18.33%) | |
| Adjacent structures injury | None | |
| Stump integrity concerns | 3 (5%) | |
| Chronic respiratory comorbidity | 3 (5%) | |
| Post-operative characteristics | Derangements of vital signs | 14 (23.33%) |
| Drain quantity abnormality | 4 (9.76%) | |
| Drain quality abnormality | 5 (11.9%) | |
| FBC abnormality | 16 (26.67%) | |
| FBC abnormality day (POD) | 1.1±2.3, median (Q1-Q3): 1 (0-1), min 0, max 11 Day 0: 71.7%, day 1: 10%, after day 1: 18.3% |
|
| Biochemical abnormality | 15 (25%) | |
| Biochemical abnormality day (POD) | 0.7±1.8, median (Q1-Q3): 0 (0-1), min 0, max 11 Day 0: 73.3%, day 1: 10%, after day 1: 16.7% |
|
| Clotting abnormality (POD) | 1 (1.67%) | |
| Swallow test negative | 58 (96.67%) | |
| VAS score (high) | 34 (56.67%) | |
| SSI | 12 (20%) | |
| Mobilization delay | 22 (36.67%) | |
| Oral feeding delay | 17 (28.33%) | |
| Intra-abdominal complication | 9 (15%) | |
| Extra-abdominal complication | 5 (8.33%) | |
| ICU treatment | 2 (3.33%) | |
| PONV | 29 (48.33%) | |
| Bowel movement start (POD) | 3.58±1.04, median (Q1-Q3): 3 (3-4), min: 2, max 6 | |
| LOS (post-op to exit) | 9.5±9.01, median (Q1-Q3): 6.5 (5-8), min: 5, max: 59 | |
| Outcomes | Mortality | 3 (5%) |
| Re-admission | 5 (8.33%) | |
| Re-operation | 6 (10%) |
CA 125: Cancer antigen 125, CA 153: Cancer antigen 153, CA 19-9: Cancer antigen 19-9, CEA: Cancer embryonic antigen, ECOG: Eastern Cooperative Oncology Group, EGJ: Esophago-gastric Junction, FBC: Full Blood Count, FFP: Fresh Frozen Plasma, ICU: Intensive Care Unit, LOS: Length of Stay, POD: Postoperative Day, PONV: Postoperative Nausea and Vomiting, SSI: Surgical Site Infection, VAS: Visual Analogue Score. * Cancer antigen test normal values: CA 125 (0-31 U/ml), CA 153 (0-36 U/ml), CA 19-9 (0-37 U/ml), CEA: 0-5ng/ml.
Table 3.
Comparison of demographics and preoperative characteristics between the two groups.
| Group of characteristics | Characteristic | Without drain= 20 | With drain= 40 | p- value |
| Demographics and patient characteristics | Age(years) | 73 (66.5-77.5) | 73.5 (63-78) | 0.8138 |
| Gender (male) | 9/45% | 23/57.5% | 0.4180 | |
| Charlson score | 2 (2-2) | 2 (2-3) | 0.1567 | |
| ECOG | 0 (0-0) | 0 (0-0) | 0.5943 | |
| Histology | Diffuse | 7/35% | 15/37.5% | 1.0000 |
| Intestinal | 11/55% | 17/42.5% | 0.4180 | |
| Mixed | 1/5% | 6/15% | 0.4065 | |
| Location | EGJ | 6/30% | 6/15% | 0.1893 |
| Fundus | 3/15% | 2/5% | 0.3216 | |
| Body | 7/35% | 19/47.5% | 0.4162 | |
| Pre-pyloric antrum | 4/20% | 12/30% | 0.5408 | |
| Pylorus | 1/5% | 0/0% | 0.3333 | |
| Preoperative chemotherapy | Positive | 5/25% | 10/25.64% | 1.0000 |
| Laboratory results abnormality | FBC | 2/10% | 4/10% | 1.0000 |
| Biochemical | 2/10% | 2/5% | 0.5948 | |
| Clotting | None | None | NA | |
| Cancer antigens positivity* | CA 19.9 | 2/10% | 6/15% | 0.7068 |
| CA 15.3 | 1/5% | 5/12.5% | 0.6532 | |
| CA 125 | 0/0% | 3/7.5% | 0.5441 | |
| CEA | 3/ 15% | 4/10% | 0.6760 |
CA 125: Cancer antigen 125, CA 153: Cancer antigen 153, CA 19-9: Cancer antigen 19-9, CEA: Cancer embryonic antigen, ECOG: Eastern Cooperative Oncology Group, EGJ: Esophago-gastric Junction; *Cancer antigen test normal values: CA 125 (0-31 U/ml), CA 153 (0-36 U/ml), CA 19-9 (0-37 U/ml), CEA: 0-5ng/ml.
Table 4.
Comparison of intraoperative characteristics between the two groups.
| Characteristic | Without drainage device n=20 | With drainage device n=40 | p | OR and 95% CI* |
| Duration of operation (minutes) | 195 (160-205) | 200 (180-230) | 0.2095 | NA |
| Blood transfusion | 4/20% | 4/10% | 0.4218 | 2.25 (0.5-10.14) |
| FFP transfusion | 2/10% | 3/7.5% | 1.0000 | 1.37 (0.21-8.94) |
| Allergic reaction to drugs | None | None | NA | NA |
| Intraoperative incidents | 2/10% | 5/12.5% | 1.0000 | 0.78 (0.14-4.41) |
FFP: Fresh Frozen Plasma, NA: not applicable;*OR: Odds Ratio, CI: Confidence Interval
Table 5.
Comparison of postoperative characteristics and short-term outcomes between the two groups.
Table 5.
Comparison of postoperative characteristics and short-term outcomes between the two groups.
| Group of characteristics | Characteristic | Without drain (n=20) | With drain (n=40) | p | OR and 95% CI* |
| Post operative characteristics | Derangements of vital signs | 4/20% | 10/25% | 0.7556 | 0.75 (0.2-2.78) |
| Drain quantity abnormality | 0/0% | 4/10% | 1.0000 | NA | |
| Drain quality abnormality | 0/0% | 5/12.5% | 1.0000 | NA | |
| FBC abnormality | 3/15% | 13/32.5% | 0.2182 | 0.37 (0.09-1.48) | |
| FBC abnormality on day 0 | 17/85% | 26/65% | 0.1051 | 3.1 (0.76 - 12.23) | |
| Biochemical abnormality | 4/20% | 11/27.5% | 0.7529 | 0.66 (0.18-2.41) | |
| Biochemical abnormality on day 0 | 15/75% | 29/72.5% | 0.8365 | 1.1 (0.33 - 3.89) | |
| Clotting abnormality | 0/0% | 1/2.5% | 1.0000 | NA | |
| Swallow test positive | 0/100% | 2/5% | 0.5480 | NA | |
| VAS score (high) | 3/15% | 31/77.5% | <0.0001 | 19.52 (4.65-81.91) | |
| SSI | 4/20% | 8/20% | 1.0000 | 1 (0.26-3.83) | |
| Mobilization delay | 2/10% | 20/50% | 0.0038 | 0.11 (0.02-0.54) | |
| Oral feeding delay | 2/10% | 15/37.5% | 0.0340 | 0.19 (0.04-0.91) | |
| Intra-abdominal complication | 2/10% | 7/17.5% | 0.704 | 0.52 (0.1-2.79) | |
| Extra-abdominal complication | 2/10% | 3/7.5% | 1.0000 | 1.37 (0.21-8.94) | |
| ICU treatment | 1/5% | 1/2.5% | 1.0000 | 2.06 (0.12 -34.62) | |
| PONV | 5/25% | 24/60% | 0.0142 | 0.22 (0.07-0.73) | |
| Bowel movement start(POD) | 3 (2-4) | 4 (3-4) | 0.0141 | NA | |
| LOS (post-op to exit) | 5 (5-6) | 7 (6-10) | 0.0001 | NA | |
| Short- Term outcomes | Mortality | 2/10% | 1/2.5% | 0.2554 | 4.33 (0.37-50.95) |
| Re-admission | none | 5/12.5% | 0.1588 | NA | |
| Re-operation | 2/10% | 4/10% | 1.0000 | 1 (0.17-5.98) |
FBC: Full Blood Count, ICU: Intensive Care Unit, LOS: Length of Stay, POD: Postoperative Day, PONV: Postoperative Nausea and Vomiting, SSI: Surgical Site Infection, VAS: Visual Analogue Score, NA: not applicable;* OR: Odds Ratio, CI: Confidence Interval
Table 9.
Statistical analysis outcomes for the subgroup of patients with intra-abdominal complications.
Table 9.
Statistical analysis outcomes for the subgroup of patients with intra-abdominal complications.
| Without drain (n=2) | With drain (n=7) | P-value | |
| Anastomotic leak detection | |||
| No | 2 (100%) | 3 (42.9%) | 0.444 |
| Yes | 0 (0%) | 4 (57.1%) | |
| POD | |||
| Mean (SD) | 5.00 (2.83) | 6.14 (2.73) | 0.445 |
| Median [Min, Max] | 5.00 [3.00, 7.00] | 7.00 [1.00, 9.00] | |
| Drain relation | |||
| (-) | 1 (50.0%) | 3 (42.9%) | 1 |
| (+) | 1 (50.0%) | 4 (57.1%) | |
| Diagnosis by drain content | |||
| No | 1 (50.0%) | 3 (42.9%) | 1 |
| Yes | 1 (50.0%) | 4 (57.1%) | |
| Diagnosis by vitals | |||
| No | 1 (50.0%) | 2 (28.6%) | 1 |
| Yes | 1 (50.0%) | 5 (71.4%) | |
| Diagnosis by fbc | |||
| No | 2 (100%) | 4 (57.1%) | 0.5 |
| Yes | 0 (0%) | 3 (42.9%) | |
| Prolonged hospitalization | |||
| No | 1 (50.0%) | 1 (14.3%) | 0.417 |
| Yes | 1 (50.0%) | 6 (85.7%) | |
| Reoperation | |||
| No | 1 (50.0%) | 4 (57.1%) | 1 |
| Yes | 1 (50.0%) | 3 (42.9%) | |
| Death | |||
| No | 1 (50.0%) | 6 (85.7%) | 0.417 |
| Yes | 1 (50.0%) | 1 (14.3%) |
POD: postoperative day
Table 10.
Statistical analysis outcomes for the drain group with intra-abdominal complications to examine if diagnosis by drain content was a differentiation factor.
Table 10.
Statistical analysis outcomes for the drain group with intra-abdominal complications to examine if diagnosis by drain content was a differentiation factor.
| Diagnosis by other means(n=3) | Diagnosis by drain content(n=4) | P-value | |
| Anastomotic leak | |||
| No | 1 (33.3%) | 2 (50.0%) | 1 † |
| Yes | 2 (66.7%) | 2 (50.0%) | |
| POD | |||
| Mean (SD) | 6.67 (2.52) | 5.75 (3.20) | 0.714 |
| Median [Min, Max] | 7.00 [4.00, 9.00] | 7.00 [1.00, 8.00] | |
| Diagnosis by vitals | |||
| No | 1 (33.3%) | 1 (25.0%) | 1 † |
| Yes | 2 (66.7%) | 3 (75.0%) | |
| Diagnosis by labs | |||
| No | 2 (66.7%) | 2 (50.0%) | 1 † |
| Yes | 1 (33.3%) | 2 (50.0%) | |
| Prolonged hospitalization | |||
| Yes | 3 (100%) | 3 (75.0%) | 1 † |
| No | 0 (0%) | 1 (25.0%) | |
| Reoperation | |||
| No | 1 (33.3%) | 3 (75.0%) | 0.486 † |
| Yes | 2 (66.7%) | 1 (25.0%) | |
| Death | |||
| No | 3 (100%) | 3 (75.0%) | 1 † |
| Yes | 0 (0%) | 1 (25.0%) |
POD: postoperative day; †: Fisher’s exact test
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