International Journal ofEnvironmental Researchand Public Health
ArticleEffects of In-Hospital Physical Therapy on
Activities of Daily Living in Patients with
Hepatocellular Carcinoma
Hayato Narao 1 , Keisuke Hirota 2 , Shunji Koya 2 , Manabu Tomita 3 , Yuta Manako 1 ,Satosi Ogawa 4 , Naomi Nakao 4 , Tsubasa Tsutsumi 5 , Dan Nakano 5 , Ryuki Hashida 2,6 ,Takumi Kawaguchi 5, * , Hiroo Matsuse 2,6 , Hiroaki Nagamatu 7 and Takuji Torimura 5
1
2

3
4
5

6
7

*

Department of Rehabilitation, Yame General Hospital, Yame 834-0034, Japan;
hayatonarao198071@gmail.com (H.N.); ymhp1892@yamehp.jp (Y.M.)
Division of Rehabilitation, Kurume University Hospital, Kurume 830-0011, Japan;
hirota_keisuke@kurume-u.ac.jp (K.H.); kouya_shunji@kurume-u.ac.jp (S.K.);
hashida_ryuuki@med.kurume-u.ac.jp (R.H.); matsuse_hiroh@kurume-u.ac.jp (H.M.)
Department of Rehabilitation, Saga Central Hospital, Saga 849-8522, Japan; sp4u7m99@ray.ocn.ne.jp
Department of Nursing, Yame General Hospital, Yame 834-0034, Japan; ymhp0311@yamehp.jp (S.O.);
ymhp1430@yamehp.jp (N.N.)
Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine,
Kurume 830-0011, Japan; tsutsumi_tsubasa@med.kurume-u.ac.jp (T.T.);nakano_dan@med.kurume-u.ac.jp (D.N.); tori@med.kurume-u.ac.jp (T.T.)
Department of Orthopedics, Kurume University School of Medicine, Kurume 830-0011, Japan
Department of Gastroenterology, Juntendo University, Tokyo 113-8421, Japan; angio0112tiger@gmail.com
Correspondence: takumi@med.kurume-u.ac.jp; Tel.: +81-942-35-3311; Fax: +81-942-34-2623

Received: 11 October 2020; Accepted: 5 December 2020; Published: 6 December 2020


Abstract: Activities of daily living (ADL) are frequently impaired in patients with hepatocellular
carcinoma (HCC). In this retrospective study, we aimed to investigate the effects of physical therapy
on ADLs in patients with HCC during hospitalization for cancer treatment. Nineteen patientswith HCC were enrolled. During hospitalization, patients performed a combination of resistancetraining, stretching, and aerobic exercise (20–60 min/day). ADLs were assessed using the functional
independence measure (FIM). Changes in FIM were evaluated by before–after analysis. No significant
difference was seen in Child–Pugh class before and after physical therapy. The bilateral knee extension
strength and chair stand test were significantly increased after physical therapy compared with
before physical therapy (p = 0.001 and p = 0.008, respectively). The total FIM score was significantly
increased after physical therapy compared with that before physical therapy (p = 0.0156). Among the
18 indexes of FIM, the stairs index was significantly improved after physical therapy comparedwith that before physical therapy (5.9 vs. 6.4 points, p = 0.0241). We demonstrated that physicaltherapy improved muscle strength without worsening liver function. Furthermore, physical therapy
improved FIM, especially in the stairs index, in patients with HCC. Thus, physical therapy may bebeneficial in patients with HCC during cancer treatment.
Keywords: supervised physiotherapy; functional independence measure; hepatoma; liver;
hospitalization

1. Introduction
Activities of daily living (ADLs) are frequently impaired in patients with cancer [1]. Impairmentof ADLs is associated with a poor response to cancer treatment, mortality, and quality of life [1].

Int. J. Environ. Res. Public Health 2020, 17, 9098; doi:10.3390/ijerph17239098

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ADLs can be impaired by muscle atrophy and physical dysfunction [2]. In patients with hepatocellular
carcinoma (HCC), sarcopenia is frequently seen. The muscle mass significantly decreases, and ADLs
are impaired during hospitalization in patients with HCC [1,3,4]. One of the causative factors is thatpatients with HCC are generally instructed to be on bed rest during hospitalization [5].
The functional independence measure (FIM), reported by Granger et al. in 1983 [6], explores anindividual’s physical, psychological, and social function, thus evaluating ADLs [7]. FIM consists of
18 physical/cognitive items, which are graded on a scale of 1–7 based on the level of independence [7];a higher FIM score indicates more independence with ADLs [8]. The FIM is also used to evaluate thefunctional outcomes of medical rehabilitation [9]. FIM has been used to evaluate ADLs in patients withvarious cancers, including colorectal cancer [10]. FIM is associated with cognitive function, mortality,and quality of life in patients with various cancers [11–13].
Rehabilitation is effective at maintaining muscle mass, physical function, and cognitive function,
resulting in an improvement of ADLs [13,14]. We developed a physical therapy program for patientswith HCC, which is a combination of stretching, strength training, balance practice, and endurance
training [15]. This physical therapy does not worsen liver function in patients with HCC [15].
In addition, physical therapy increased skeletal muscle mass in patients with HCC, even if they werereceiving chemotherapy [14,16]. Physical therapy also improves cardiopulmonary function and muscle
cramps during hospitalization for HCC treatment [15]. However, it remains unclear if physical therapy
improves FIM scores in patients with HCC during hospitalization for cancer treatment.
In this study, we aimed to examine the impact of in-hospital physical therapy on FIM scores inpatients with HCC.
2. Materials and Methods
2.1. Study Design
This is a retrospective chart review study to evaluate the impact of physical therapy on ADLs inpatients with HCC during hospitalization for cancer treatment.
2.2. Ethics
The study protocol conformed to the ethical guidelines of the Declaration of Helsinki and wasapproved by the institutional review board of Public Yame General Hospital (approval #16-001).
Informed consent from patients was obtained through an opt-out approach. Personal information wasprotected throughout the study. None of the patients were institutionalized.
Physical therapy for in-hospital patients with cancer is an approved healthcare service coveredby the Ministry of Health, Labor, and Welfare of Japan’s health insurance. Therefore, a randomized
controlled trial with an intentional setting of a non-physical therapy group is contrary to medical ethics.
2.3. Subjects
We enrolled 19 consecutive patients with HCC from January 2017 to September 2017. Inclusion
criteria were hospitalized patients with HCC who (1) were 20 years of age or older, (2) had a performancestatus of grade 0 to 1 as defined by the Eastern Cooperative Oncology Group [17], (3) were hospitalized
for more than 1 week and had more than 4 days of physical therapy, and (4) agreed to exercise.
Exclusion criteria were as follows: (1) risk of HCC rupture, (2) grade 2–4 hepatic encephalopathy
according to the West Haven Criteria [18], (3) risk of esophageal varices rupture, (4) heart failure,(5) respiratory failure, (6) fever of ≥38 ◦ C, (7) leg vein thrombus, and (8) orthopedic disease within thepast year resulting in the patient being unable to walk.
2.4. Protocol for Physical Therapy
This physical therapy for patients with HCC has not been used before in our facility. Duringhospitalization for HCC treatment, patients were treated with exercise (20–60 min/day), as instructed

Int. J. Environ. Res. Public Health 2020, 17, 9098

3 of 13by physical therapists who were certified in the rehabilitation of patients with cancer. The exercise
consisted of three types of training according to the guidelines of the American College of Sports
Medicine (Table 1) [19]. The exercise was initiated the day after HCC treatment, as previously
described [15]. Patients were instructed to continue the exercises after discharge. In our study, patients
received only physical therapy, but not occupational therapy and speech–language–hearing therapy.
Table 1. A protocol of physical therapy for patients with hepatocellular carcinoma (HCC).
Type of Exercise

1. Resistance training

2. Stretching
3. Aerobic exercise

Physical Therapy
Knee extension(Used Combit CB-1)
Standing stepping
Calf raise
Half squat
Lower limb stretching
Walking

Exercise Intensity

Frequency

60% of MVC

2–3 days/week

Bodyweight
Bodyweight
Bodyweight
Painless strength
Borg scale 11–13(Fairly light to somewhat hard)

5 days/week
5 days/week
5 days/week
3 days/week
Every day

2.4.1. Resistance Training
Patients underwent strength training for 10–20 min, targeting the bilateral quadriceps femorismuscles, gastrocnemius, and iliopsoas muscle. Bilateral quadriceps femoris muscle strength training
was performed at 60% of the maximum voluntary contraction (MVC; moderate to high intensity) usinga Combit CB-1 (Minato Medical Science Co., Ltd., Osaka, Japan) [20]. The quadriceps, gastrocnemius,
and iliopsoas muscles were trained using the patient’s weight. One set consisted of 10 repetitions,and a maximum of four sets were performed [15,19].
2.4.2. Stretching
Patients performed stretches for 3–5 min, targeting the quadriceps femoris muscles, the iliopsoas
muscle, hip adductor muscles, and gastrocnemius muscles. Stretches were statically held for 20 s at the
point of feeling tightness or slight discomfort [15,19].
2.4.3. Aerobic Exercise
Patients practiced voluntary walking with a goal of 10–30 min, depending on their motor
skills. The intensity of exercise was adjusted to maintain a subjective rating of perceived exertion of
11–13 points on the Borg scale [15,19].
2.5. Diagnosis, Tumor Node Metastasis (TNM) Staging, and Treatment of HCC
HCC was diagnosed using a tumor biopsy or a combination of tests for serum tumor markers
and imaging procedures, such as ultrasonography, computed tomography (CT), magnetic resonanceimaging, and/or angiography. The clinical stage of HCC was evaluated by TNM staging based on
the Liver Cancer Study Group of Japan criteria [21]. Treatment for HCC was selected based on theevidence-based clinical practice guidelines for HCC of The Japan Society of Hepatology [22].
2.6. Measurement of Psoas Muscle Index (PMI) and Skeletal Muscle Index (SMI)
PMI and SMI were evaluated using CT images obtained before and after physical therapy. The CT
images were taken for the assessment of HCC in the outpatient department. A standard landmark formeasuring the psoas muscle mass and skeletal muscle mass was the lower border of the third lumbar
vertebra (L3). We measured the psoas muscle mass and skeletal muscle mass by manual tracings on
CT images using Image-J software (National Institutes of Health, Bethesda, Maryland, USA, version
Windows 10), and their sum was calculated [23]. Skeletal muscle mass and psoas muscle mass werenormalized by the square of the height, and the data were expressed as PMI and SMI [24].

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4 of 132.7. Measurement of Muscle Strength
2.7.1. Maximum Muscle Strength Assessment of Knee Extension Strength
The maximum knee extension strength was measured during isometric contraction using Combit
CB-1 according to the manufacturer’s instructions. To prevent injury, several knee extension exercises
were performed before the measurement. The measurement angle was set at 90◦ of the knee joint
flexion. The measurement posture was set to start with the trunk and both thighs secured with a belt
while sitting on the seat of Combit CB-1, and the lower leg of the measurement side was secured to theattachment. During the measurement of maximum knee extension strength, a mechanical voice played
from the Combit CB-1 asking the patient to apply force in the direction of knee extension. In addition,
the measurer also asked the patient to put more force in the direction of knee extension. Each side of
the knee extension strength was measured once. The measured value was displayed as the maximum
knee extension strength on the Combit CB-1 monitor.
2.7.2. Grip Strength
An analog grip strength meter (Takei Machine Industry, Niigata, Japan) was used to measuregrip strength. Left and right grip strength were measured in a standing position with the upper limbs
hanging down to the side of the body. The test was completed twice each in both the left and rightarms. A resting interval of at least 30 s was allowed between each measurement. The grip strength
was defined as the average value of the higher grip strength of the left and right arms. [25,26].
2.7.3. 30-Second Chair–Stand Test (CS-30)
We employed the CS-30 to evaluate lower extremity muscle strength with a high retest
reliability [27]. CS-30 was measured according to previous reports [28]. The patients were asked to sit
on a chair that was 40 cm high. They were asked to position their legs shoulder width apart and to
cross their arms in front of their chest as the starting posture. A single attempt was given before themeasurement of CS-30. The test lasted 30 s. The subject was instructed to repeatedly stand and sit as
many times as possible with their arms crossed.
2.8. Measurement of Walking Speed
Walking speed in meters per second (m/s) was measured by a 10-m walking test (10MWT).
The 10MWT was modified from a previous report [29]. A stopwatch was used to measure thesteady-state walking speed. To record the steady state walking speed during the 10MWT, 3 m
acceleration and deceleration zones were added at the beginning and end of the course. Thus, the total
walking distance was 16 m. The watch was started and stopped when the patient’s toe passed over thelines marking the start and end of the 10-m course, respectively [26]. We conducted the 10MWT twice,
and the average walking speed was used for the analysis. Two subjects used walking aids.
2.9. Measurement of FIM
FIM is an assessment tool comprising 18 items, including eating, grooming, bathing, dressing
the upper body, dressing the lower body, toileting, bladder management, bowel management,
bed/chair/wheelchair, toilet, tub/shower, walk/wheelchair, stairs, comprehension, expression, social
interaction, problem solving, and memory. Thirteen items belong to the motor subscale, and five items
belong to the cognitive subscale, including comprehension, expression, social interaction, problem
solving, and memory [7]. All of the items were scored as follows: 1 (total assist), 2 (maximal assist),
3 (moderate assist), 4 (minimal assist), 5 (supervision), 6 (modified independence), and 7 (complete
independence). The FIM item scores were added together for a total score ranging between 18 and 126,
or a total motor score ranging between 13 and 91 and a total cognitive score ranging between 5 andInt. J. Environ. Res. Public Health 2020, 17, 9098

5 of 1335 [30]. These assessments were evaluated by physical therapists qualified in cancer rehabilitation
with more than 13 years of experience.
2.10. Biochemical Tests
The following blood biochemical tests were performed: serum levels of aminotransferase(AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), alkaline phosphatase (ALP),
gamma-glutamyl transpeptidase (GGT), albumin, total bilirubin, blood urea nitrogen (BUN), creatinine,estimated glomerular filtration rate (eGFR), sodium, and potassium, which were measured usinga BM-6070 (JEOL Ltd., Tokyo, Japan). Hemoglobin A1c (HbA1c) was measured using HA8181(ARKRAY Inc. Kyoto, Japan). The prothrombin activity was measured using a CS2100 (Sysmex, Kobe,
Japan). Alpha-fetoprotein and des-γ-carboxy prothrombin were measured using the Lumipulse G1200(Fujirevio, Tokyo, Japan). The platelet count was measured using a Sysmex XE-5000. Ammonia wasmeasured using Pocket Chem BA (ARKRAY Inc).
2.11. Statistical Analysis
Data are expressed as median (interquartile range (IQR)), range, or number. Changes in variables
between before and after physical therapy were evaluated using Wilcoxon signed-rank tests. The
level of statistical significance was set at p < 0.05. These analyses were performed using JMP Pro® 14(SAS Institute Inc., Cary, NC, USA).
3. Results
3.1. Patient Characteristics
The patient characteristics are summarized in Table 2. The median age of the patients was 78 years,
and 31.6% were women. The median BMI was 21.2 kg/m2 . All of the patients had a performance statusof grade 0 or 1, and the median FIM score was 126 points.
Table 2. Patient characteristics.

N
Age (years)
Sex (female/male)
Body mass index (kg/m2 )Reference ValueMedian (IQR)

N/A
N/A
N/A
18.5–24.9

1978.0 (73.0–82.0)
6/13
21.2 (20.7–26.5)
73.7%/26.3%/0%/0%/0%(14/5/0/0/0)
126 (123–126)
10.5%/89.5%(2/17)
5.3%/84.1%/5.3%/5.3%(1/16/1/1)
78.9%/15.8%/5.3%(15/3/1)
10.0 (10.0–13.0)
5.0 (5.0–6.0)
66.7 (51.8–77.5)
66.7 (51.8–77.5)
66.7 (51.8–77.5)
66.7 (51.8–77.5)
66.7 (51.8–77.5)
75.0 (56.0–90.0)

Performance status (0/1/2/3/4)

N/A

FIM score (points)

N/A

Walking assistance devise (yes/no)

N/A

HCC stage (I/II/III/IV)

N/A

HCV/HBV/others

N/A

Hospitalization (days)
Physical therapy (days)
Implementation rate of knee extension (%)
Implementation rate of standing stepping (%)
Implementation rate of calf raise (%)
Implementation rate of half squat (%)
Implementation rate of stretching (%)
Implementation rate of aerobic exercise (%)

N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A

Range
(Min–Max)
N/A
60–86
N/A
16.8–31.5
N/A
92–126
N/A
N/A
N/A
7.0–28.0
4.0–15.0
33.0–100.0
33.0–100.0
33.0–100.0
33.0–100.0
33.0–100.0
0.0–100.0

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Table 2. Cont.
Reference Value
Hepatic encephalopathy (Yes/No)

N/A

Ascites (Yes/No)

N/A

Walking speed (m/sec)
Six-minute walk test (m)

N/A
N/A

Grip strength (women/men) (kg)

N/A

Grip strength (low/normal)
Right knee extension strength (kgf)
Left knee extension strength (kgf)

N/A
N/A
N/A

SMI (women/men) (cm2 /m2 )N/A

SMI (muscle atrophy/non-muscle atrophy)

N/A

PMI (women/men) (cm2 /m2 )N/APresence of sarcopenia (Yes/No)
CS-30 (times/30 s)
Child-Pugh score (points)

N/A
N/A
N/A

Child-Pugh class (A/B/C)

N/A

Anti-diabetic medication (Yes/No)

N/A

BCAA supplementation (Yes/No)

N/A

Median (IQR)
10.5%/89.5%(2/17)
10.5%/89.5%(2/17)
1.1 (0.9–1.3)
300 (262–340)
17.1 (13.8–21.7)/28.0 (24.3–31.3)
42.1%/57.9% (8/11)
25.2 (17.0–36.3)
24.2 (16.5–36.9)
39.9 (35.8–42.7)/41.1 (39.3–42.2)
26.3%/73.7% (5/14)
3.6 (3.4–4.6)/5.0 (4.9–5.6)
31.6%/68.4% (6/13)
10.0 (8.0–12.0)
5 (5–6)78.9%/15.8%/5.3%(15/3/1)
26.3%/73.7%(5/14)
31.6%/68.4%
6/13

Range
(Min–Max)
N/A
N/A
0.6–1.6
150.5–465.0
12.0–22.3/21.0–44.8
N/A
10.5–53.0
14.3–62.3
26.9–50.2/27.4–50.2
N/A
3.25–6.11/3.48–6.07
N/A
7–22
5–12
N/A
N/A
N/A

Biochemical examinations
Platelet count (× 104 /µL)
AST (U/L)
ALT (U/L)
Lactate dehydrogenase (U/L)
ALP (U/L)GGT (U/L)
Albumin (g/dL)
Prothrombin activity (%)
Total bilirubin (mg/dL)
AFP (ng/mL)
des-γ-carboxy prothrombin (mAU/mL)
BUN (mg/dL)
Creatinine (mg/dL)
eGFR (mL/min/1.73 m2 )Sodium (mmol/L)
Potassium (mmol/L)
HbA1c (%)
Ammonia (µg/dL)

13.3–36.9
10–40
5–40
115–245
115–359
0–30
4.0–5.0
70–1300.30–1.20
0–10
0–39
8.0–22.0
0.61–1.04>90.0
138–145
3.6–4.8
4.3–5.8
13–86

11.0 (7.4–17.6)
33.0 (29.0–52.0)
26.0 (18.0–43.0)
213.0 (186.0–255.0)
377.0 (276.0–522.0)
37.0 (23.0–69.0)
3.7 (3.0–4.1)
79.2 (67.1–86.8)
0.8 (0.6–0.9)
13.3 (5.8–40.2)
107 (21.0–352.0)
15.5 (13.5–17.8)
0.8 (0.6–1.0)
65.1 (55.0–82.9)
139 (138.0–141.0)
4.0 (3.7–4.2)
5.6 (5.4–6.8)
79.0 (52.7–134.2)

4.8–26.7
16.0–79.0
13.0–70.0
166.0–355.0
192.0–870.0
15.0–187.0
2.6–4.6
55.0–102.0
0.3–3.1
3.5–1216.7
15–618
6.4–28.1
0.5–1.36
39.1–90.0
134–142
2.9–5.2
4.5–7.8
40.0–156.0

Note: Data are expressed as median (IQR), range, or number.
IQR—interquartile range; N/A—not
applicable; FIM—functional independence measure; HCC—hepatocellular carcinoma; HCV—hepatitis C virus;
HBV—hepatitis B virus; SMI—skeletal muscle index; PMI—psoas muscle index; CS-30, 30-s chair–stand
test; ALBI—albumin–bilirubin; BCAA, branched chain amino acids; AST—aspartate aminotransferase;U/L—unit/litter; ALT—alanine aminotransferase; ALP—alkaline phosphatase; GGT—gamma-glutamyltranspeptidase; AFP—alpha-fetoprotein; BUN—blood urea nitrogen; eGFR—estimated glomerular filtration
rate; HbA1c—hemoglobin A1c.

More than 80% of patients had stage II HCC. The median Child–Pugh score was 5, and 78.9% of
patients were Child–Pugh class A. The prevalence of sarcopenia was 31.6%. The median hospitalization
time was 10 days, and the median duration of exercise therapy was 5 days. The median rightknee extension strength and left knee extension strength were 25.2 kgf and 24.2 kgf, respectively.
The implementation rate was 66.7% for resistance training, stretching, standing stepping, calf raise,and half squat. The implementation rate for aerobic exercise was 75% (Table 2).

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7 of 133.2. Changes in Liver and Renal Function after Physical Therapy
No significant differences were observed in the serum levels of AST, ALT, LD, ALP, and GGT(Table 3). There was no significant difference in the Child–Pugh score and Child–Pugh class before andafter physical therapy (Table 3). No significant difference was seen in eGFR (Table 3).
Table 3. Changes in liver and renal functions after physical therapy.
BeforeMedian (IQR)
Child-Pugh score (point)
Child-Pugh class (A/B/C)
AST (U/L)
ALT (U/L)
Lactate dehydrogenase (U/L)
ALP (U/L)GGT (U/L)eGFR (mL/min/1.73 m2 )5 (5–6)78.9%/15.8%/5.3%(15/3/1)
33.0 (29.0–52.0)
26.0 (18.0–43.0)
213.0 (186.0–255.0)
377.0 (276.0–522.0)
37.0 (23.0–69.0)
65.1 (52.8–84.3)

After
Range
(Min–Max)
5–12
N/A
16.0–79.0
13.0–70.0
166.0–355.0
192.0–870.0
15.0–187.0
39.1–90.0

Median (IQR)
6 (6–7)63.1%/31.6%/5.3%(12/6/1)
37.0 (28.0–49.0)
37.0 (23.0–56.0)
198.0 (171.0–246.0)
382.0 (305.0–479.0)
53.0 (29.0–82.0)
65.8 (57.9–84.6)

Range(Min–Max)

p

5–10

0.112

N/A

0.180

21.0–114.0
15.0–99.0
148.0–392.0
158.0–511.0
14.0–203.0
34.0–99.9

0.72100.25790.32250.17030.42470.2293

Note: Data are expressed as median (IQR), range, or number. IQR—interquartile range; N/A—not applicable;
AST—aspartate aminotransferase; U/L—unit/litter; ALT—alanine aminotransferase; ALP—alkaline phosphatase;
GGT—gamma-glutamyl transpeptidase; eGFR—estimated glomerular filtration rate.

3.2.1. Changes in Skeletal Muscle Mass after Physical Therapy
There was no significant decrease in PMI or SMI after physical therapy compared with before
physicaltherapy(FigureInt. J. Environ.
Res. Public
Health 1A,B).
2020, 17, x FOR PEER REVIEW
8 of 13

Figure 1.
1. Changes
Changes inin skeletalskeletal muscle
muscle mass
mass after
after physicalphysical therapy:
therapy: (A)(A) psoas
psoas muscle
muscle index
index (PMI)(PMI) and
and
Figure(B) skeletalskeletal muscle
muscle index
index (SMI).
(SMI). N.S.—not
N.S.—not significant.
significant.
(B)

3.2.2. Changes in Walking Speed and Muscle Strength after Physical Therapy
3.2.2. Changes in Walking Speed and Muscle Strength after Physical Therapy
No significant difference was seen in walking speed before and after physical therapy (Figure 2A).
No significant difference was seen in walking speed before and after physical therapy (Figure
There was no significant difference in grip strength before and after physical therapy (Figure 2B).
2A). There was no significant difference in grip strength before and after physical therapy (Figure
There was a significant increase in right and left knee extension strength after physical therapy2B). There was a significant increase in right and left knee extension strength after physical therapy
compared with before physical therapy (Figure 2C,D). CS-30 was significantly improved after physicalcompared with before physical therapy (Figure 2C,D). CS-30 was significantly improved after
therapy compared with that before physical therapy (Figure 2E).
physical therapy compared with that before physical therapy (Figure 2E).

3.2.2. Changes in Walking Speed and Muscle Strength after Physical Therapy
No significant difference was seen in walking speed before and after physical therapy (Figure2A). There was no significant difference in grip strength before and after physical therapy (Figure2B). There was a significant increase in right and left knee extension strength after physical therapy
Int. J. Environ.with
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compared
beforephysicaltherapy (Figure 2C,D). CS-30 was significantly improved 8after
physical therapy compared with that before physical therapy (Figure 2E).

Figure 2.
2. Changes
Changes inin walking
walking speed
speed andand muscle
muscle strength
strengthafter
afterphysicalphysicaltherapy.
therapy. (A)(A)Walking
Walking speed,
speed,
Figure(B)
gripstrength,
(C)
right
knee
extension
strength,
(D)
left
knee
extension
strength,and(E)
CS-30.
(B) grip strength, (C) right knee extension strength, (D) left knee extension strength, and (E) CS-30.
Abbreviations:
N.S.—notsignificant;CS-30—30-s
chair–stand
test.
Abbreviations: N.S.—not significant; CS-30—30-s chair–stand test.

3.2.3. Changes in FIM Score and All Items of FIM after Physical Therapy
3.2.3. Changes in FIM Score and All Items of FIM after Physical Therapy
The total FIM score was significantly increased after physical therapy compared with before
Int. J. The
Environ.
Res.FIM
Publicscore
Health was
2020, significantly
17, x FOR PEER REVIEW
9 of 13
total
increased after physical therapy compared with before
physical therapy (Figure 3). The stairs index is a motor index of FIM, and was the only item that was
physical therapy (Figure 3). The stairs index is a motor index of FIM, and was the only item that wassignificantly
There weresignificantly improved
improved after
after physicalphysical therapy
therapy (Figure(Figure 4).
4). There
were nono significant
significant changes
changes inin thethescores
of
the
other
motor
and
cognitiveindexes
between
beforeandafter
physicaltherapy(Figure4).
scores of the other motor and cognitive indexes between before and after physical therapy (Figure 4).

Figure3. Changes
in functional
independence
measure(FIM)(FIM)
scorescoreafter after
physicaltherapy.
Figure3. Changes
in functional
independence
measurephysicaltherapy.

Int. J. Environ. Res. Public Health 2020, 17, 9098

Figure 3. Changes in functional independence measure (FIM) score after physical therapy.

9 of 13

Figure 4. Changes in all items of FIM after physical therapy *, p < 0.01.
Figure 4. Changes in all items of FIM after physical therapy *, p < 0.01.

4. Discussion
4. Discussion
We demonstrated the safety and beneficial effects of in-hospital physical therapy, including
We demonstrated
the safety
andHCC.
beneficial
effectsof in-hospitalphysicaltherapy,
resistance
exercise, for patientswith
Liver and
renal
function did
not worsen
afterincluding
physicalresistance
exercise,for patientswith HCC. intensity
Liver andimproved
renal function
not worsen
physicaltherapy.
Physicaltherapywith personalizedmuscledid
strengthwith noafter
reductionintherapy.
Physicaltherapywithpersonalized
intensity
improvedmusclestrengthwith
noreductionmuscle mass during hospitalization for HCC treatment. In addition, physical therapy improved FIM,
in muscle inmass
hospitalization
HCC
treatment.
In addition, physicaltherapy
improved
especiallythe during
stairs index,
in patients forwith
HCC
during hospitalization
for cancer
treatment.
FIM,Inespeciallyinliverthe stairs
index,
in patients
HCC duringforOncancertreatment.
our study,
and renal
function
werewith
not worsenedby hospitalization
physical therapy.
the otherhand,
García-Pagàn et al. reported that moderate exercise increased the risk of variceal bleeding in patientswith esophageal varices [31]. Saló et al. reported that moderate physical exercise may cause marked
impairment in renal function in patients with liver cirrhosis [32]. Although it remains unclear why theliver function did not worsen with physical therapy, a possible reason is a difference in the type of
exercises used in our study compared with that of previous studies. In our study, we mainly employedresistance training. However, previous studies employed aerobic exercise such as cycloergometric
exercise [31,32]. The intensity of aerobic exercise is generally higher than that of resistance exercise [33],and cardiopulmonary function is known to be impaired in patients with HCC [34]. Therefore, aerobic
exercise is a cardiopulmonary burden in patients with HCC. Our results may indicate that resistance
exercise is more suitable than aerobic exercise for patients with HCC.
In this study, our physical therapy program was able to maintain muscle mass in patients with
HCC. Our results were in good agreement with a previous report of HCC patients [14]. In addition,
we demonstrated that our physical therapy program improved the muscle strength of the lower limbs.
Although the reason the physical therapy program improved the muscle strength of the lower limbs

Int. J. Environ. Res. Public Health 2020, 17, 9098

10 of 13remains unclear, it may be because resistance exercises were performed at a personalized intensity
using a machine such as COMBIT CB-1. COMBIT CB-1 is able to precisely assess the maximal muscle
strength of the lower limbs and allows the operator to set the appropriate intensity of exercise [20],which may result in increased muscle strength in the lower limbs. In fact, Nadia Schott et al. reported
that exercise using machine training significantly increased the muscle strength of the lower limbs [35].
We first demonstrated that physical therapy increased the FIM score in patients with HCC.
In previous studies, physical therapy has been reported to increase the FIM score in patients withvarious cancers, including colorectal cancer [10] and pancreatic cancer [36]. Thus, our results are ingood agreement with these previous reports. Saotome et al. reported that an increase in FIM score bycancer rehabilitation was associated with prolonged survival in patients with cancer [37]. Moreover,an increase in FIM score through physical therapy has been reported to improve cognitive function inpatients with cancer [13,38]. Furthermore, an increase in FIM score has been reported to be associatedwith an improved quality of life in patients with cancer. Therefore, evaluation of FIM seems to beimportant for the management of patients with HCC.
In this study, our physical therapy program increased the FIM score in patients with HCC.
A possible reason for an increase in the FIM score is that we performed machine training withappropriate exercise intensity using COMBIT CB-1. Furthermore, a feature of our physical therapy
program was that we mainly focused on exercising the lower-limb muscles, which is associated withphysical performance [39]. As a result, physical therapy improved CS-30, an index for the strength oflower limb muscles in this study. In fact, among all 18 factors consisting of the FIM score, the ability toclimb stairs was the only factor that was improved by physical therapy in this study. Matsufuji et al.
also reported that chair stand exercises improved ADLs in patients on hemodialysis aged >60 years
in a randomized controlled trial [40]. Yoshimura et al. also reported that an in-hospital chair–standexercise was independently associated with an improvement in FIM-motor scores [41]. These findings
indicate that physical therapy improved lower limb strength and subsequently the ability to climb
stairs, leading to an increase in FIM score in this study.
This study has several limitations. First, this was a single-center study with a small sample size.
Second, this was a retrospective chart review with no control group, which cannot prove the efficacyof physical therapy. Third, ADLs were assessed using only the FIM score and not by other methods
such as the cancer functional assessment set [42]. Fourth, we could not perform a multivariate analysis
because of the small sample size, and it remains unclear what type of physical therapy was associatedwith an improvement of FIM. Thus, the usefulness of physical therapy should be evaluated by amulti-center prospective study with a large sample size by using multiple assessments for ADLs. Fifth,
Saotome et al. have reported that survival was significantly improved in patients with a total FIM score≥80 after cancer rehabilitation [37]. In our study, all patients showed a total FIM score ≥ 80, even at theadmission of the hospital. Therefore, it remains unclear if physical therapy had an impact on prognosis
in our study. It also remains unclear which subscale of the FIM is important for survival. Thus, further
studies should be focused on an association between an increase in FIM scores/the subscale of the FIM
and an improvement in survival.
5. Conclusions
In this study, we performed in-hospital physical therapy, including resistance exercises, at apersonalized intensity for patients with HCC. We demonstrated that in-hospital physical therapy
did not worsen hepatic function. We also showed that exercise improved muscle strength with no
reduction in muscle mass. Furthermore, we also showed that exercise improved the stair index of FIM
in patients with HCC. Thus, in-hospital physical therapy may improve the ability to climb stairs inpatients with HCC. Future research is needed to more clearly assess the benefits of physical therapy for
ADL performance.

Int. J. Environ. Res. Public Health 2020, 17, 9098

11 of 13

Author Contributions: Conceptualization, H.N. (Hayato Narao), K.H., S.K., M.T., T.K., and H.N.
(Hiroaki Nagamatu); methodology, H.N. (Hayato Narao), K.H., and S.K.; validation, M.T., T.K., and H.N.
(Hiroaki Nagamatu); formal analysis, D.N. and R.H.; investigation, Y.M., S.O., N.N., T.T. (Tsubasa Tsutsumi),
and R.H.; resources, H.N. (Hayato Narao); data curation, Y.M., S.O., and N.N.; writing—original draft preparation,
H.N. (Hayato Narao), K.H., S.K., M.T., and T.K.; writing—review and editing, H.M. and T.T. (Takuji Torimura);
visualization, H.N. (Hayato Narao) and K.H.; supervision, H.M. and T.T. (Takuji Torimura); project administration,
H.N. (Hayato Narao); funding acquisition, T.K. All authors have read and agreed to the published version of
the manuscript.
Funding: This research was funded by the Research Program on Hepatitis from the Japan Agency for Medical
Research and Development, AMED under JP20fk0210045.
Conflicts of Interest: Takumi Kawaguchi received lecture fees from Mitsubishi Tanabe Pharma Corporation andOtsuka Pharmaceutical Co., Ltd. The other authors declare no conflict of interest. The funders had no role in thedesign of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in thedecision to publish the results.

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