Ostomy

All patients over the age of 18 with colon cancer in UICC stages I and II who underwent a resection of the tumor at the Medical University of Innsbruck, Department of Visceral, Transplant, and Thoracic Surgery between 2007 and 2016 were evaluated for this retrospective study. Patients with rectal cancer were excluded because of the rather complex multimodal treatment (e.g., neoadjuvant radiochemotherapy, ostomy creation, and reversal) and the higher risk of local recurrence, to create a patient collective as homogenous as possible. Patients who received adjuvant chemotherapy (recommended by the interdisciplinary tumor-board despite UICC stages I or II due to additional risk factors such as bowel perforation, high grading 3/4, positive vascular-, lymphangio-, or perineural-status) were excluded. Further exclusion criteria were endoscopic resection, R1- or R2- resection, and mucinous carcinoma. Figure 1 shows the flowchart of included and excluded patients.Fig. 1

Flowchart of the included and excluded patients. VTT, Visceral, Transplant, and Thoracic Surgery; UICC, Union internationale contre le cancer; CRC, colorectal cancer; DF, disease free

The surveillance time was 5 years, according to the follow-up protocol at the Medical University of Innsbruck, Department of Visceral, Transplant, and Thoracic Surgery, based on the recommendations of NCCN (National Comprehensive Cancer Network), ESMO (European Society for Medical Oncology), and ACO ASSO (Austrian Society for Surgical Oncology) (Table 1).Table 1

The surveillance protocol at the Medical University of Innsbruck, Department of Visceral, Transplant, and Thoracic Surgery based on the recommendations of NCCN (National Comprehensive Cancer Network), ESMO (European Society for Medical Oncology), and ACO ASSO (Austrian Society for Surgical Oncology)

	1st year				2nd year				3rd year				4th year				5th year
Months	3	6	9	12	15	18	21	24	27	30	33	36	39	42	45	48	51	54	57	60
CEA	x	x	x	x	x	x	x	x	-	x	-	x	-	x	-	x	-	x	-	x
Clinical examination	x	x	x	x	x	x	x	x	-	x	-	x	-	x	-	x	-	x	-	x
Colonoscopy	(xa)	-	-	x	-	-	-	-	-	-	-	-	-	-	-	Xb	-	-	-	-
CT scan	-	-	-	x	-	-	-	x	-	-	-	x	-	-	-	x	-	-	-	x

In case of curative treatment of distant metastases, CT scans are repeated in 6-monthly intervals during the first 2 years, and the surveillance period is prolonged for further 5 years

CEA carcinoembryonic antigen, CT computed tomography

^aIf not performed preoperatively

^bIf normal findings are to be repeated regularly according to national screening protocols

Data were collected from medical reports, operative reports, anesthesia protocols, and histopathological findings, by using electronic health records (Klinisches Informationssystem, KIS, Powerchart, Cerner). Demographic variables were age and gender. Clinical variables included the physical status classification system ASA (American Society of Anesthesiologists), surgical resection, histopathology evaluation, and the TNM classification. Outcome variables included surveillance drop-out, 5-year disease-free survival (DFS), and 5-year overall survival (OS). Recurrence was defined as clear radiological or endoscopic suspicion with or without histological proof. Tumor recurrence was divided into local recurrence and metastases (e.g., liver or lung metastases). Additionally, metachronous colorectal cancer was documented. Finally, the therapeutic approach of recurrence was analyzed.
Statistical analyses were performed with the software SPSS (IBM SPSS Statistics 20; International Business Machines Corporation; Armonk, New York, USA). The Kaplan–Meier method was used to calculate the DFS and OS.
The local ethics committee approved the study (Votum 1437/2021).

Subjects are initially evaluated in a screening visit (Day -3) during which they will be screened for eligibility, including baseline clinical and physical assessments (Fig 1). At screening, the investigator or designee will review the subject’s medical history to determine eligibility, explain the study to the subject and the subject’s parent or legal guardian, and if eligible, obtain informed consent (S3 File). Informed consent and assent will be obtained from study investigators and authorized personnel and the discussion will be documented in the patient’s electronic medical record. If consent is given and the subject is deemed eligible based on the results of the screening visit, they will be enrolled in the study and pre-baseline assessments will be performed, which will include physical examination, nutritional assessment, vital signs, and laboratory evaluations (Fig 1). The subject’s parent or guardian will also receive education from a registered dietitian on recording caloric intake and composition in oral and enteral feeds, and PN. As part of this education, the dietitian will review how to record daily oral and enteral intake via paper dairy or with a HIPAA-compliant nutrition/food tracking phone application. If the latter, the subject’s parent or guardian will receive access to a nutrition/food tracking phone application.
The subject’s parent or guardian will then be asked to collect all stool for 72-hours over Day -3 to Day -1 and to record caloric intake and composition in oral and enteral feeds, and PN during that time. The collected stool will be submitted to the Boston Children’s clinical laboratory for total fat quantification. To evaluate the degree of fat malabsorption, the intake data and stool fat quantification will be used to measure the baseline CFA, as previously described [15 (link)].
Treatment will be administered on study Day 1, followed by daily use of the RELiZORB enzyme cartridge whenever EN is administered, for a total of 90 days. During the treatment period, all EN will be administered through the RELiZORB enzyme cartridge. Nutritional intake (24-hour enteral dietary and PN volume intake), stool consistency/amount/frequency (if applicable) or ostomy (if applicable) output, study device use, and incidence of symptom changes will be recorded daily, in an electronic or paper diary, by the subject’s parent or guardian. Access to the nutrition/food tracking phone application along with a daily phone call from a study coordinator will be used to ensure accurate recording and completion of these tasks.
Subjects will return to the clinic on Days 7, 14, 28, 60, and 90 of the treatment period (Fig 1). The final clinic visit will be preceded by a repeat 72-hour stool collection and measurement of CFA to determine the change (if any) in intestinal fat absorption. During the clinic visits, staff will review the information in the subject’s diary, review compliance with the use of the study device and discuss relevant observations with the subject during the visit. Upon review, information contained in the diary will be entered in the electronic database. In addition to a daily study coordinator phone call, the study staff will have weekly telephone contact with families during interim weeks after the day 14 visit. Prior to these visits, subjects will be weighed at home by their parent or guardian using a standardized weight scale. At the in-person clinic and weekly telephone visits, study staff will monitor safety, diaries, weight data, stool composition (Bristol scale) and output, changes in caloric intake, changes in urine output, and will make adjustments to PN and enteral feeding accordingly (Fig 2). Adjustments will be based on the subject’s nutritional needs, weekly weights, height, hydration status and investigator’s medical judgement. If necessary, unscheduled visits can be arranged in place of the telephone contacts.
At each clinic visit, vital signs, physical examination, clinical evaluations, AEs, concomitant medications, medical/surgical procedures, and blood tests to determine the levels of liver enzymes will also be performed. Blood samples will be collected to analyze lipid profiles. All AEs post-baseline that occur will be recorded. Participants will meet with a study dietitian during each visit to assess nutritional needs and address issues or concerns.