Therapeutic physical factors as part of outpatient medical rehabilitation for patients after colorectal cancer surgery: а randomized controlled trial

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BACKGROUND

In Russia, as worldwide, there is an increasing incidence of cancer, including gastrointestinal malignancies, occupying leading positions in the mortality structure of malignant neoplasms [1–4]. According to Kaprin [1], the prevalence of colorectal cancer in Russia increases by 3–4% annually, with the colon cancer accounting for 7.1% of malignant neoplasms in the morbidity structure. Osombaev et al. [5] classify Russia among countries with growing or stable incidence and mortality rates for colon cancer (colorectal cancer).

For localized and locally advanced colorectal cancer (T1-3N0M0), surgical treatment (right/left hemicolectomy, lymph node dissection) is recommended, followed by rehabilitation to facilitate recovery of impaired body functions, including the patient’s mental functioning [6–8]. Overall, according to Krutov et al. [6], medical rehabilitation for patients after surgical intervention for colorectal cancer should be conducted in accordance with the fast-track surgery concept and aimed at alleviating pain syndrome, increasing patient activity, restoring intestinal peristalsis, and stabilizing emotional status. In this context, therapeutic physical modalities with sanogenetic effects appears appropriate [9–14]. Specifically, therapeutic exercise helps enhance the body’s adaptive capabilities through gradually increasing physical activity [15]. Low-mineralization drinking mineral waters stimulate patients to increase functional reserves of both stress-mobilizing and stress-limiting systems, which is particularly important in the postoperative period [11, 16]. Furthermore, course treatment with oral mineral water consumption exerts colon-stimulating and colon-modulating therapeutic effects [16, 17].

In recent years, percutaneous electrical nerve stimulation (PENS) has been widely used in medical rehabilitation, demonstrating effectiveness in alleviating pain syndrome, improving metabolic processes, microcirculation, peripheral nerve conductivity, and other therapeutic benefits in patients [11, 18, 19]. The well-documented myorelaxant, spasmolytic, trophic, and vegetocorrective effects (when applied to sympathetic ganglia) of PENS significantly expand its clinical applications. For instance, studies by Al-Zahmil et al. [16] have shown that PENS contributes to motor deficit regression and reduced muscle atrophy severity in patients with syringomyelia-associated amyotrophic lateral sclerosis. Research of Kaisinova et al. [18] has demonstrated that low-frequency pulsed electrical nerve stimulation in health-resort treatment of chronic pancreatitis demonstrated analgesic, anti-inflammatory, and spasmolytic therapeutic effects. Studies by Law et al. [19] of PENS for joint pathology reported not only pain relief but also substantial improvement in joint function.

It is hypothesized that incorporating physical therapeutic factors into outpatient rehabilitation programs for patients after surgical intervention for colorectal cancer will have a positive impact on improving the motor-evacuatory function of the large intestine, reducing the severity of anxiety-depressive disorders, and restoring quality of life (QoL).

The study aimed to evaluate the effectiveness of an outpatient medical rehabilitation program for patients after colorectal cancer surgery using therapeutic physical factors.

METHODS

Study Design

This was a prospective randomized controlled clinical study.

Eligibility Criteria

Inclusion criteria: status after left-/right-sided hemicolectomy (or sigmoid colon resection) for colorectal cancer without regional lymph node involvement or metastasis (T₁-T₃N₀M₀); 3–6 months post-surgery; patient condition assessment score of 3 points on the rehabilitation routing scale; informed voluntary consent.

Non-inclusion criteria: stage IV–V colon cancer; acute-phase and/or decompensated somatic diseases; general contraindications to physical therapy; general contraindications to therapeutic exercise.

Exclusion criteria: sudden deterioration of the patient’s general health; patient’s refusal to participate in the study.

Study Setting

The study was conducted in outpatient clinics of the Karachay-Cherkess Republic in accordance with ethical principles (Helsinki Declaration, Brazil 2013).

Study Duration

The study was conducted from January 2021 to June 2024.

Intervention

The study participants (n = 126) were divided into three groups comparable in sex, age, disease stage, and severity. In comparison group 1 (n = 40), patients received rehabilitation according to Russian clinical guidelines: diet therapy (a standard mechanically and chemically sparing diet); individual physical therapy sessions lasting 25 minutes (10 sessions per treatment course); small-group psychotherapy sessions lasting 30 minutes daily (8 sessions per treatment course); and the spasmolytic agent pinaverium bromide (France) at 10 mg (1 tablet 3 times daily 30 minutes before meals for 1 month).

In comparison group 2 (n = 43), patients received additional rehabilitation beyond those in group 1: Psyzh chloride-sulfate sodium-magnesium mineral water (Karachay-Cherkess Republic) with low mineralization (2.4 g/dm³), taken at 3.0 mL/kg body weight 3 times daily 30 minutes before meals in warm form for 21 days.

In the main group (n = 43), in addition to the rehabilitation program of the second comparison group, patients received transcutaneous electrical nerve stimulation (TENS) over the cervical sympathetic ganglia using the Simpatokor-01 device (Russia; medical device registration certificate FSR No. 2007/00757) according to the following protocol: with the patient in a seated position, special straps with embedded conductive elements (6 cathodes arranged around a central anode) were placed on the neck skin (pre-treated with a special gel) and secured to position the anodes over the projection of the cervical ganglia. Current was applied using sequential clockwise circuit closure between the anode of one strap and the 6 cathodes of the opposite strap. The stimulation parameters included a unipolar rectangular pulsed current with a pulse duration of 40 μs and frequency of 40 Hz. Current amplitude was individually adjusted for each patient (increased until mild tingling or vibration was perceived (2–3 V) in cases of vagotonia, and until ear lobe numbness was reported (4–5 V) in cases of sympathicotonia). Each 15-minute session consisted of 5 minutes of opposite strap circuit closure, 5 minutes of functional rest, and 5 minutes of stimulation with reversed current direction. The treatment course included 10 daily procedures.

Outcomes Registration

Clinical symptoms were assessed using the Edmonton Symptom Assessment System (ESAS) in all patients before and after rehabilitation [20]. This questionnaire evaluates the intensity of 9 common symptoms experienced by cancer patients: pain, tiredness, drowsiness, nausea, appetite, depression, anxiety, well-being, and bowel irregularities, where 0 indicates absence of the symptom and 10 represents maximal symptom severity.

Patients’ quality of life (QoL) was also studied using the European Quality of Life Questionnaire EQ-5D [21]. The questionnaire comprises two sections: the first describes 5 QoL components (Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression), each rated as “no problems,” “moderate problems,” or “severe problems”; the second section assesses QoL using a visual analog scale (0 = worst health state, 100 = best health state).

Ethics Approval

This research was approved by the Ethics Committee of the Pyatigorsk Research Institute of Balneology, a branch of the North Caucasus Federal Scientific and Clinical Center of the Federal Medical-Biological Agency (Protocol No. 1 dated January 28, 2022).

Statistical Analysis

Statistical analysis was performed using STATISTICA 13.0 software. The reliability of differences was assessed by calculating mean values (M) and standard deviation (SD), presented as M ± SD. The strength of correlations was evaluated using Spearman’s rank correlation coefficient (r). The level of p < 0.05 was considered statistically significant.

RESULTS

Participants

The study included 126 patients who underwent surgery for colorectal cancer at the age of 18 to 65 years. All patients were under oncologist follow-up.

Primary Results

Prior to rehabilitation, all patients who underwent surgery for colorectal cancer were assessed using the ESAS scale. The assessment revealed that the average severity of the most common symptoms was rated as moderate, scoring 5.1 ± 1.2 points (see Table 1). Patients most frequently reported increased tiredness, anxiety-depressive manifestations, and bowel disorders, with obstipation syndrome (less than 3 bowel movements per week) predominating in the majority of cases. Significant differences from population norms were observed [21, 22].

 

Table 1. Monitoring of symptom severity by Edmonton ESAS (Score)

Parameters	Rehabilitation period	Group
		Comparison 1 n=40	Comparison 2 n=43	Main n=43
		M±SD
Pain	Before	3.8±1.5	3.9±1.7	3.8±1.4
	After	2.4±1.0**	1.8±1.2**	1.5±1.0**′
Fatigue	Before	5.3±1.6	5.5±1.4	5.4±1.7
	After	2.8±1.1**	2.2±1.2**	2.0±1.0**′
Somnolence	Before	4.2±1.3	4.4±1.6	4.4±1.5
	After	2.8±1.5**	2.0±1.2**	1.6±1.3**′
Nausea	Before	5.8±1.4	6.1±1.3	5.9±1.6
	After	3.7±1.5**	2.4±1.3**	2.2±1.6**′
Appetite	Before	4.9±1.4	4.8±1.6	4.8±1.2
	After	3.5±1.3**	2.4±1.7**	2.1±1.4**′
Depression	Before	5.1±1.6	5.4±1.5	5.3±1.3
	After	4.0±1.7*	3.6±1.4**	1.8±1.3**′
Anxiety	Before	5.3±1.5	5.3±1.3	5.4±1.6
	After	4.2±1.8*	3.1±1.4**	1.9±1.6**′
Dyspnea	Before	2.6±1.0	2.8±1.2	2.5±1.0
	After	1.3±0.8**	1.0±0.7**	0.8±0.5**′
Well-being	Before	5.3±1.5	5.6±1.3	5.5±1.6
	After	3.5±1.4**	3.4±1.5**	2.5±1.8**′
Stool disorders	Before	6.2±1.4	6.1±1.6	6.2±1.5
	After	4.9±1.7**	3.6±1.8**	3.2±1.4**′

Note. Validity of differences (р) before and after rehabilitation: * ― <0.05; ** ― <0.01; ^# ― validity of differences with the control group by Pearson chi-square test.

 

QoL assessment using the EQ-5D questionnaire showed that 73.9% of patients had moderate impairments, primarily in the domains of Mobility, Pain/Discomfort, and Anxiety/Depression, which aligns with Russian population norms [23].

The assessment of the effectiveness of outpatient rehabilitation using therapeutic physical factors demonstrated the feasibility of our developed rehabilitation program for patients after surgical intervention for colorectal cancer. The severity of ESAS symptoms in the main group decreased by an average of 2.6-fold compared to baseline values (p < 0.01), assessed as mild symptoms, most notably in the Pain, Depression, Nausea, and Bowel Dysfunction scales. Comparative analysis revealed intergroup differences across all scales in final outcomes, with similar data in the comparison group 1 where ESAS symptoms regressed by an average of 1.4-fold (p < 0.05). In comparison group 2, ESAS symptoms decreased by an average of 1.9-fold (p < 0.05), with a statistically significant advantage over final outcomes in the main group for the Depression, Anxiety, and Well-Being scales.

Similarly significant positive changes over time were observed in QoL parameters via the EQ-5D questionnaire: by the end of outpatient rehabilitation, 41.8% of patients in the main group reported no mobility issues, 44.2% no self-care difficulties, and 51.1% no limitations in daily activities. Pain syndrome regression was noted in 46.6% of cases, and anxiety-depressive syndrome in 53.5%, with intergroup differences identified compared to the comparison group 1. In comparison group 2, no issues was recorded in 32.5% of patients for mobility, 37.2% for self-care, 39.5% for usual activities, 32.5% for pain/discomfort, and 39.6% for anxiety/depression.

The most significant indicator demonstrating the advantage of our developed outpatient rehabilitation program for patients after surgical intervention for colorectal cancer was the health status assessment using the visual analog scale: patients in the main group showed QoL recovery compared to baseline values by 1.7 times (p < 0.01) and in comparison group 2 by 1.5 times (p < 0.05), while comparison group 1 only demonstrated a trend toward improvement in this parameter. Monitoring of QoL parameter intensity using the EQ-5D questionnaire is presented in Table 2.

 

Table 2. Monitoring of symptom quality of life by EQ-5D questionnaire

Parameters	Rehabilitation period	Group
		Comparison 1 n = 40	Comparison 2 n = 43	Main n = 43
QoL domains, abs. (%)
Mobility, score No problems Moderate problems Severe problems	Before	2 (5) 34 (85) 4 (10)	2 (4.7) 36 (83.7) 5 (11.6)	2 (4.7) 36 (83.7) 5 (11.6)
No problems Moderate problems Severe problems	After	8 (20) 29 (72.5) 3 (7.5)	14 (32.5) 27 (62.8) 2 (4.7)	18 (41.8) 23 (53.5) 2 (4.7)
Self-care, score No problems Moderate problems Severe problems	Before	8 (20) 26 (65) 6 (15)	9 (20.9) 27 (62.8) 7 (16.3)	8 (18.6) 27 (62.8) 8 (18.6)
No problems Moderate problems Severe problems	After	14 (35) 22 (55) 4 (10)	16 (37.2) 24 (55.9) 3 (6.9)	19 (44.2) 22 (51.1) 2 (4.7)
Ususal activities, score No problems Moderate problems Severe problems	Before	6 (15) 30 (75) 4 (10)	7 (16.3) 33 (76.8) 3 (6.9)	7 (16.3) 32 (74.4) 4 (9.3)
No problems Moderate problems Severe problems	After	13 (32.5) 25 (62.5) 2 (5)	17 (39.5) 25 (58.2) 1 (2.3)	22 (51.1) 21 (48.9) -
Pain/discomfort No problems Moderate problems Severe problems	Before	2 (5) 30 (75) 8 (20)	2 (4.7) 32 (74.4) 9 (20.9)	2 (4.7) 32 (74.4) 9 (20.9)
No problems Moderate problems Severe problems	After	7 (17.5) 28 (70) 5 (12.5)	14 (32.5) 26 (60.6) 3 (6.9)	20 (46.6) 22 (51.1) 1 (2.3)
Anxiety/depression No problems Moderate problems Severe problems	Before	2 (5) 28 (75) 10 (25)	2 (4.7) 30 (69.7) 11 (25.6)	2 (4.7) 30 (69.7) 11 (25.6)
No problems Moderate problems Severe problems	After	8 (20) 27 (67.5) 5 (12.5)	17 (39.6) 22 (51.1) 4 (9.3)	23 (53.5) 19 (44.2) 1 (2.3)
Health state on VAS, M±SD
QoL assessment	Before	51.3±8.2	50.7±8.5	49.2±9.1
	After	61.4±8.6*	76.2±9.8**	84.4±10.3**′

Note. Validity of differences (р) before and after rehabilitation * ― <0.05; ** ― <0.01; ^# ― with the control group by Pearson chi-square test.

 

DISCUSSION

Direct criteria for evaluating the effectiveness of therapeutic interventions include assessment of patients’ QoL, as it compares treatment programs at the group level [21–23]. It should be noted that our developed outpatient medical rehabilitation program for post-operative colorectal cancer patients incorporating physical therapy modalities demonstrated significant advantages in QoL parameters measured by ESAS and EQ-5D questionnaires. Specifically, the intake of mineral water included in the treatment programs of the main study group and comparison group 2 helped alleviate nausea and improve appetite through normalization of motor-secretory functions in the gastrointestinal tract. This therapeutic effect can be attributed to the beneficial impact on gastroentero-pancreatic system activity mediated by bicarbonates and sodium, which leads to neutralization of excess gastric hydrochloric acid secretion, restoration of metabolism and microcirculation processes, and improvement of gastroduodenal mucosal trophism [11, 15, 16]. The sanogenetic potential of mineral waters is demonstrated in the study by Kotenko et al. [23] during rehabilitation of patients with post-COVID syndrome.

The decision to include percutaneous electrical neurostimulation in the rehabilitation program for patients after surgical intervention for colorectal cancer was based on the well-established analgesic, anti-inflammatory, and spasmolytic therapeutic effects of the procedure [17, 18, 20]. As evidenced by multiple studies, this technique aims to provide symptomatic pain relief through the activation of sensory nerve fibers [11, 17, 20]. The effects of electrical neurostimulation are mediated by various neurotransmitters, including serotonin, whose receptors are present in multiple organs, including the intestines: on one hand, serotonin regulates negative emotions, leading to the regression of anxiety-depressive disorders; on the other hand, it participates in the modulation of intestinal motor function [24, 25]. This dual mechanism explains the significant advantage in alleviating anxiety-depressive manifestations observed in the main patient group compared to both comparison groups.

The combined application of rational pharmacotherapy and therapeutic physical factors in patients with colorectal cancer during the outpatient phase significantly enhances rehabilitation outcomes. This is achieved through the synergistic action of the employed therapeutic factors and pharmacological agents, specifically pharmacological effects of medications; acid-regulating, reparative-regenerative, colon-modulating, and other effects of the Psyzh low-mineralized chloride-sulfate sodium-magnesium mineral water; and myorelaxant, spasmolytic, trophic, and vegetocorrective effects of percutaneous electrical neurostimulation.

CONCLUSION

The inclusion of therapeutic physical factors in outpatient medical rehabilitation programs for patients after colorectal cancer surgery leads to a significant improvement in quality of life.

ADDITIONAL INFORMATION

Funding source. This work was not supported by any external sources of funding.

Competing interests. The author declare that she has no competing interests.

Authors’ contribution. All authors made a substantial contribution to the conception of the work, acquisition, analysis, interpretation of data for the work, drafting and revising the work, final approval of the version to be published and agree to be accountable for all aspects of the work. A.S. Kaisinova ― conception and design of the study, writing and editing the text of the manuscript; M.B. Uzdenov ― conception and design of the study, analysis and interpretation of data, scientific revision of the manuscript text, selection and examination of patients; A.A. Dzhanibekova ― review of publications on the topic of the article, selection and examination of patients; D.K. Badakhova ― review of publications on the topic of the article, selection and examination of patients, writing and editing of the text of the manuscript; F.M. Khapaeva ― review of publications on the topic of the article, selection and examination of patients, writing and editing of the text of the manuscript; R.M. Gusov ― review of publications on the topic of the article, selection and examination of patients, writing and editing of the text of the manuscript.

ДОПОЛНИТЕЛЬНАЯ ИНФОРМАЦИЯ

Источник финансирования. Авторы заявляют об отсутствии внешнего финансирования при подготовке статьи.

Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи.

Вклад авторов. Все авторы подтверждают соответствие своего авторства международным критериям ICMJE (все авторы внесли существенный вклад в разработку концепции, проведение исследования и подготовку статьи, прочли и одобрили финальную версию перед публикацией). Наибольший вклад распределён следующим образом: А.С. Кайсинова ― формирование концепции и разработка дизайна исследования, написание и редактирование текста рукописи; М.Б. Узденов ― формирование концепции и разработка дизайна исследования, анализ и интерпретация данных, научная редакция текста рукописи, отбор и обследование пациентов; А.А. Джанибекова ― обзор публикаций по теме статьи, отбор и обследование пациентов; Д.К. Бадахова ― обзор публикаций по теме статьи, отбор и обследование пациентов, написание и редактирование текста рукописи; Ф.М. Хапаева ― обзор публикаций по теме статьи, отбор и обследование пациентов, анализ и интерпретация данных; Р.М. Гусов ― обзор публикаций по теме статьи, отбор и обследование пациентов, анализ и интерпретация данных.

About the authors

Agnessa S. Kaisinova

North Caucasian Federal Scientific and Clinical Centre; Pyatigorsk Medical and Pharmaceutical Institute ― a branch of Volgograd State Medical University; North Caucasian State Academy

Author for correspondence.
Email: zamoms@skfmba.ru
ORCID iD: 0000-0003-1199-3303
SPIN-code: 6552-9684

MD, Dr. Sci. (Medicine); Professor

Russian Federation, 39 Cossack st, Yessentuki, 357600; Pyatigorsk, 357500; Cherkessk, 369000

Marat B. Uzdenov

North Caucasian State Academy

Email: uzdenov1@rambler.ru
ORCID iD: 0000-0002-0077-9013
SPIN-code: 7692-5669

MD, Cand. Sci. (Medicine)

Russian Federation, Cherkessk, 369000

Alina A. Dzhanibekova

North Caucasian State Academy

Email: mardjan2011@yandex.ru
ORCID iD: 0009-0003-7911-7892
SPIN-code: 7875-1770
Russian Federation, Cherkessk, 369000

Dinara K. Badakhova

North Caucasian State Academy

Email: dinna9400@mail.ru
ORCID iD: 0000-0001-9000-3333
Russian Federation, Cherkessk, 369000

Fatima M. Khapaeva

North Caucasian State Academy

Email: fatikhapaeva3888@gmail.com
ORCID iD: 0000-0001-9668-2402
SPIN-code: 6455-5420

MD, Cand. Sci. (Medicine)

Russian Federation, Cherkessk, 369000

Ruslan M. Gusov

Pyatigorsk Medical and Pharmaceutical Institute ― a branch of Volgograd State Medical University

Email: 61312@mail.ru
ORCID iD: 0000-0002-1582-0138
SPIN-code: 1984-9700

Cand. Sci. (Pharmacy), Associate Professor

Russian Federation, Pyatigorsk, 357500

References

Supplementary files