369

ORIGINAL
How many times can patients tolerate reoperation for the local
recurrence of colorectal cancer in terms of complications?
Koji Komori, Takashi Kinoshita, Yusuke Sato, Akira Ouchi, Seiji Ito, Tetsuya Abe, Kazunari Misawa, Yuichi Ito,
Seiji Natsume, Eiji Higaki, Tomonari Asano, Masataka Okuno, Hironori Fujieda, Satoshi Oki, Tsukasa Aritake,Kakeru Tawada, Satoru Akaza, Hisahumi Saito, Kiyoshi Narita, Hiroki Kawabata, and Yasuhiro Shimizu
Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan

Abstract : The frequency of resection for the recurrence of colorectal cancer has not been investigated in previous studies. Likewise, the related postoperative complications and the limit for indicating surgical resection has
not been reported. Herein, we reported the complications of a highly frequent surgical approach for rectal cancer recurrence, i.e., exceeding three reoperations, based on our clinical experience. We included 15 cases exceeding two operations for the local recurrence of colorectal cancer from 2014 to 2019. We examined the postoperativecomplications classified as Clavien–Dindo IIIb. The positive rates of the complications were 0 (0.0%), 0 (0.0%), 2(13.3%), 3 (37.5%), and 0 (0.0%) for the primary, 1st recurrent, 2nd recurrent, 3rd recurrent, and 4th recurrent operation group (p = 0.027), respectively. It is important to exercise caution in handling cases exceeding two reoperations (exceeding three reoperations including the primary operation). J. Med. Invest. 70 : 369-376, August, 2023
Keywords : reoperation, local recurrence of colorectal cancer, complications

INTRODUCTION
We previously reported that frequent and multiple but resectable peritoneal recurrences can be aggressively treated bysurgical removal to improve the long-term survival of patientswith colorectal cancer (1). Likewise, we aggressively resectedrecurrent rectal cancer in our hospital when possible (2, 3). Additionally, we reported that ensuring adequate surgical margins
prevents the local recurrence of rectal cancer (4).
However, the frequency of resection for recurrent colorectal
cancer has not been investigated in previous studies. Likewise,
related postoperative complications and the limit for indicating
surgical resection has not been reported. Most importantly,
the tolerable number of reoperations for patients with locallyrecurrent colorectal cancer has not been determined in terms ofcomplications.
Herein, we reported the complications of a highly frequent surgical approach for rectal cancer recurrence, i.e., exceeding three
reoperations, based on our clinical experience.

METHODS
Study design

Our inclusion criteria included cases exceeding two reoperations for locally recurrent colorectal cancers, i.e., exceeding three
reoperations including the initial operation, at the Department
of Gastroenterological Surgery, Aichi Cancer Center Hospitalfrom 2014 to 2019. There was no case that we could resect
completely before operation but could not resect recurrent lesion
intraoperatively. But if unresectable distant recurrent lesion isrecognized, we do not select the surgical therapy.
Received for publication January 3, 2023 ; accepted April 20, 2023.
Address correspondence and reprint requests to Koji Komori, Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa, Nagoya, Aichi 464-8681, Japan andFax : +81-52-763-5233. E-mail : kkomori@aichi-cc.jp

This research project was approved by the Ethics Committeeof our institution (2022-0-061) and conformed to the provisionsof the Declaration of Helsinki. Comprehensive informed consent
was obtained from all patients prior to surgery. Fifteen cases
were eligible : six primary operations were performed at our
hospital, and nine primary operations were performed at otherhospitals. All cases underwent either a high or low anterior resection in the primary operation.
Figure 1 shows the eligible 15 cases. We classified five groups,
primary operation group, 1st recurrent operation group, 2ndlocal recurrent operation group, 3rd local recurrent operationgroup, and 4th local recurrent operation group with overlapping.
Seven cases were “2nd recurrent operation group”, i.e., 3 times
operations (primary operation + 1st recurrent operation + 2ndrecurrent operation). Six cases were “3rd recurrent operationgroup”, i.e., 4 times operations (primary operation + 1st recurrent
operation + 2nd recurrent operation + 3rd recurrent operation). Twocases were “4th recurrent operation group”, i.e., 5 times operations (primary operation + 1st recurrent operation + 2nd recurrent
operation + 3rd recurrent operation + 4th recurrent operation). The
number of primary operation group, 1st local recurrent operationgroup, 2nd local recurrent operation group, 3rd local recurrent
operation group, and 4th local recurrent operation group were 15
cases, 15 cases, 15 cases, 8 cases, and 2 cases, respectively.
The surgical procedures included local resection (LR), highanterior resection + low anterior resection (HAR + LAR), abdominoperineal resection (APR), and total pelvic exenteration (TPE).
Clinicopathologic factors, such as age, gender (male / femal),operation place (our hospital / another hospital), surgical procedures (LR / HAR + LAR / APR / TPE / others), operative time(minute), operative bleeding (ml), complication (Clavien–Dindo
IIIb) (present / absent), and hospital mortality (present / absent) were estimated between operations (primary operationgroup / 1st local recurrent operation group / 2nd local recurrent
operation group / 3rd local recurrent operation group / 4th local
recurrent operation group).

Statistical analysis
All data are expressed as the mean ± standard deviation

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K. Komori, et al. How many times can patients tolerate reoperation?

(S.D.). The chi-squared test and non-parametric test were subsequently performed to identify factors that may influence clinicopathologic variables. The level of statistical significance wasset at p < 0.05.

RESULTS
Table 1 shows the detailed outcomes. The total numbers of LR,
HAR + LAR, APR, TPE, and others were 0 (0.0%), 15 (100.0%), 0(0.0%), 0 (0.0%), and 0 (0.0%) for the primary operation group ; 8(53.3%), 3 (20.0%), 2 (13.3%), 1 (6.7%), and 1 (6.7%) for the 1st recurrent operation group ; 8 (53.3%), 1 (6.7%), 0 (0.0%), 5 (33.3%),
and 1 (6.7%) for the 2nd recurrent operation group ; 7 (77.8%),
0 (0.0%), 0 (0.0%), 1 (1.1%), and 1 (1.1%) for the 3rd recurrent
operation group ; and 1 (50.0%), 0 (0.0%), 0 (0.0%), 1 (50.0%),
and 0 (0.0%) for the 4th recurrent operation group (p < 0.001),
respectively. The frequency of TPE was grown in the 2nd and 3rdrecurrent operation group.
Five patients suffered complications once (Complication

Figure 1. We classified five groups, such as primary operation group (Once operation), 1st local recurrent group

operation (Twice operations), 2nd local recurrent group operation (3 times operations), 3rd local recurrent group operation (4times operations), and 4th local recurrent group operation (5 times operations) with overlapping.

Table 1. The detailed outcomes of clinicopathologic factors
Primary
operation group(n = 15)

1st recurrent
operation group(n = 15)

2nd recurrent
operation group(n = 15)

3rd recurrent
operation group(n = 8)

4th recurrent
operation group(n = 2)61.4 ± 7.7

64.7 ± 7.6

66.5 ± 7.6

66.6 ± 7.3

64.0 ± 11.0

male

7 (46.7%)

7 (46.7%)

7 (46.7%)

5 (62.5%)

1 (50.0%)

female8 (53.3%)

8 (53.3%)

8 (53.3%)

3 (37.5%)

1 (50.0%)

Our hospital

6 (40.0%)

14 (93.3%)

15 (100.0%)

8 (100.0%)

2 (100.0%)

Another hospital

9 (60.0%)

1 (6.7%)0 (0.0%)0 (0.0%)0 (0.0%)LR

0 (0.0%)8 (53.3%)

8 (53.3%)

6 (75.0%)

1 (50.0%)

HAR+LAR15 (100.0%)

3 (20.0%)

1 (6.7%)0 (0.0%)0 (0.0%)APR

0 (0.0%)2 (13.3%)

0 (0.0%)0 (0.0%)0 (0.0%)TPE

0 (0.0%)1 (6.7%)5 (33.3%)

1 (12.5%)

1 (50.0%)

othersAge
GenderOperation place

Surgical procedure

p
0.436
0.953
0.455

< 0.00010 (0.0%)1 (6.7%)1 (6.7%)

1 (12.5%)

0 (0.0%)Operative time (min)371.9 ± 98.7

266.4 ± 112.5

401.8 ± 159.6

434.2 ± 172.6

359.5 ± 655.5

0.072

Operative bleeding (ml)1396.4 ± 2111.1

876.8 ± 923.6

2573.7 ± 2951.6

2777.8 ± 2499.9

1000.0 ± 800.00

0.219

Complication
Clavien–Dindo IIIb
Hospital mortality‡‡

present

0 (0.0%)0 (0.0%)2 (13.3%)

3 (37.5%)

0 (0.0%)absent15 (100.0%)

15 (100.0%)

13 (86.7%)

5 (62.5%)

2 (100.0%)

present

0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)absent15 (100.0%)

15 (100.0%)

15 (100.0%)

8 (100.0%)

2 (100.0%)

0.027
–

(mean ± S.D.)
LA : local resection, LAR : low anterior resection of rectum, HAR : high anterior resection of rectum, APR : abdominoperineal resection,
TPE : total pelvic exenteration‡
Small intestinal perforation

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The Journal of Medical Investigation Vol. 70 August 2023
Clavien–Dindo IIIb), but no patient suffered complications twice.
The positive rates of the complications were 0 (0.0%), 0 (0.0%),
2 (13.3%), 3 (37.5%), and 0 (0.0%) for the primary, 1st recurrent,
2nd recurrent, 3rd recurrent, and 4th recurrent operation group(p = 0.027), respectively. A statistically significant difference wasobserved ; the rate of complications increased with the numberof operations.
The operative times of the primary operation group, 1st recurrent operation group, 2 nd recurrent operation group, 3 rdrecurrent operation group, and 4th recurrent operation groupwere 371.9 ± 98.7, 266.4 ± 112.5, 401.8 ± 159.6, 434.2 ± 172.6, and359.5 ± 655.5 minutes (p = 0.072), respectively. The number ofoperations increased with the operative time. However, the 4threcurrent operation had the shortest operative time in 2nd, 3rd,and 4th recurrent operation group.
Operative bleeding from the primary, 1st recurrent operationgroup, 2nd recurrent operation group, 3rd recurrent operationgroup, and 4th recurrent operation group were 1396.4 ± 2111.1
ml, 876.8 ± 923.6 ml, 2573.7 ± 2951.6 ml, 2777.8 ± 2499.9 ml, and1000.0 ± 800.0 ml (p = 0.219), respectively. No statistically significant difference was observed among the primary, 1st recurrent
operation group, 2nd recurrent operation group, 3rd recurrent
operation group, and 4th recurrent operation group. However, the
4th recurrent operation group had the least operative bleeding.

In terms of age and gender, no statistically significant difference
was observed among the primary, 1st recurrent operation group,
2nd recurrent operation group, 3rd recurrent operation group, and4th recurrent operation group.
There was no hospital mortality in all cases.
There was no relation between the present or absent of neoadjuvant therapy and complications (Clavien–Dindo IIIb). And
there was no relation between the laparoscopic surgery or laparotomy of surgical procedure and complications (Clavien–Dindo
IIIb). (Table 2)5-year disease free survival (5y-DFS) from the primary operation was 66.7% and 5-year overall survival rate (5y-OS) from theprimary operation was 79.4% (Fig. 2). And 5-year disease freesurvival (5y-DFS) from the 1st recurrent operation was 33.3%(Fig. 3).
Most complications (Clavien–Dindo IIIb) (5) were rapturesand intestinal leakages due to intestinal thinning caused byorgan detachment. In 2nd recurrent operation group, the rapturesand intestinal leakages occurred on postoperative day (POD) 4
in all cases. In 3rd recurrent operation group, the raptures andintestinal leakages occurred on POD 3 in one case, POD 4 in one
case, and POD 42 in one case (Table 3). The detail description of
the cases are as follows :Table 2. The detailed outcomes of clinicopathologic factors

Neoadjuvant therapy

Primary operation(n = 15)

1st recurrent operation(n = 15)

2nd recurrent operation(n = 15)

3rd recurrent operation(n = 8)

4th recurrent operation(n = 2)

Clavien–Dindo IIIb

Clavien–Dindo IIIb

Clavien–Dindo IIIb

Clavien–Dindo IIIb

Clavien–Dindo IIIb

present

absentpresent

absentpresent

absentpresent

absentpresent

absentpresent

0 (0.0%)0 (0.0%)0 (0.0%)1 (%)

0 (0.0%)2 (13.3%)

0 (0.0%)2 (25.0%)0 (0.0%)0 (0.0%)absent0 (0.0%)15 (100.0%)

0 (0.0%)14 (%)

2 (13.3%)

11 (73.4%)

3 (37.5%)

3 (37.5%)

0 (0.0%)−p
Surgical procedure

Laparoscopic

0 (0.0%)laparotomy

0 (0.0%)−2 (13.3%)

0 (0.0%)13 (87.6%)

0 (0.0%)−p

0.55130 (0.0%)0 (0.0%)15 (100.0%)

0 (0.0%)−0 (0.0%)0 (0.0%)15 (100.0%)

0 (0.0%)−（ ）0 (0.0%)0 (0.0%)8 (100.0%)

0 (0.0%)

−

10

15
（

0
）

Figure 2. The prognosis from the primary operation

Left side : 5-year disease free survival (5y-DFS) from the primary operation was 66.7%.
Right side : -year overall survival rate (5y-OS) from the primary operation was 79.4%.

0 (0.0%)2 (100.0%)
−

（ ）

5

2 (100.0%)−

0.2059

15
（

）

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K. Komori, et al. How many times can patients tolerate reoperation?
Surgical technique）

In April 2019 the patient underwent resection of the sacrum(S3), ileal conduit, and a part of the ileum as the 3rd recurrent
operation (Fig. 4). The ileum was reconstructed by an Albert–
Lembert end-to-end anastomosis.

5

10

15
（Years）

Figure 3. The prognosis from from the 1st recurrent operation
5-year disease free survival (5y-DFS) from the 1st recurrent operation
was 33.3%.

Table 3. The onset of complications (Clavien–Dindo IIIb)
2nd recurrent
operation group(n = 2)

3rd recurrent
operation group(n = 3)POD30 (0.0%)1 (33.3%)

POD4

2 (100.0%)

1 (33.3%)

POD42

0 (0.0%)1 (33.3%)

Case 1

A 63-year-old male with a history of lower abdominal distension and a cancer pathological status of stage I : T1aN0M0 (6)underwent LAR as a primary operation at another hospital in
February 2008. However, the patient had a local recurrence on
the coccyx, with an approximate diameter of 2 cm and lymph
node metastasis in the bifurcation of the common iliac artery.
The patient underwent APR as the 1st recurrent operation at
another hospital in November 2014, as well as postoperative adjuvant chemotherapy with capecitabine (7). The patient had a 2nd
local recurrence on the sacrum without distant recurrence upon
examination at another hospital in December 2015.
The patient was referred to our hospital and underwent TPEwith sacrum (S5) resection as the 2nd recurrent operation in
March 2016. The pathological finding was adenocarcinoma of
the lymph node with no cancer in the surgical margin of the resected sacrum. However, in July 2016, the patient had a 3rd local
recurrence on the residual sacrum without distant recurrence.
Subsequently, radiation therapy (45 Gy / 18 Fr) followed by chemotherapy with eight cycles of intravenous S-1 and oxaliplatin(SOX) (8) were administered. In May 2018, an ileal conduit was
exteriorized to the skin, i.e., cutaneous fistula. Subsequently, abilateral percutaneous nephrostomy tube was placed in the lumbar area, and 40 cycles of intravenous folinic acid plus irinotecan(FOLFIRI) were administered (9). However, in March 2019 thesize of the locally recurrent tumor increased.

Figure 4. Upper and middle side : For the 3rd recurrent operation,

the patient underwent sacrum resection (S3), ileal conduit creation(red circle : the locally recurrent tumor, red thick frame : the resectedarea), and partial ileum resection to remove the locally recurrent
tumor
Lower side : Ileum reconstruction by Albert–Lembert end-to-end
anastomosis (red dotted circle)

Surgical technique for the complication
POD 3, the ileum-to-ileum anastomosis leaked. An emergent
operation was performed : the patient underwent an ileostomy at
the oral side of the leakage and drainage (Fig. 5).
On POD 33, diffuse peritonitis occurred, perforating the ileum
and left ureter. An emergent operation was performed : theThe Journal of Medical Investigation Vol. 70 August 2023
patient underwent a side-to-end anastomosis of the jejunum andtransverse colon and ligation of the left ureter (Fig. 6).
On POD 90, a computed tomography (CT) scan revealed a373

pseudoaneurysm in the right common iliac artery (Fig. 7). Embolization of the right internal iliac artery was performed using
coils (Fig. 8). The postoperative course was uneventful.

Figure 5. Left side : Leakage from the ileum-to-ileum anastomosis (red circle).

Right side : An emergent operation was performed : the patient underwent ileostomy at the oral side of theleakage and drainage (red dotted circle)

Figure 6. Left side : Diffuse peritonitis (red circle) perforating the ileum and left ureter (blue circle)

Right side : An emergent operation was performed : the patient underwent a side-to-end anastomosis of thejejunum and transverse colon (red dotted circle) and left ureter ligation (blue dotted circle)

Figure 7. A CT scan revealed a pseudoaneurysm in the right common
iliac artery (yellow circle)

Figure 8. Embolization of the right internal iliac
artery was performed using coils (yellow arrow)

K. Komori, et al. How many times can patients tolerate reoperation?

374
Case 2

A 61-year-old female with a history of lower abdominal pain
and a cancer pathological status of stage IIIC : T2N3M0 underwent LAR with lateral pelvic lymph node dissection. The
primary operation was performed at our hospital in September
2010. We administered adjuvant chemotherapy with four cycles
of modified intravenous FOLFOX (10). In May 2018, a CT scandetected a single, left lateral lymph node recurrence. For the 1strecurrent operation, the recurrent lymph node was excised in theleft lateral obturator area through an intra and extraperitoneal
approach. The patient rejected the subsequent chemotherapy administration. In February 2019, a positron emission tomography(PET) scan revealed a single, left lateral lymph node recurrence.

the bladder, descending colon, and ileum.
In December 2017, CT and PET scans revealed the 2nd local recurrence. For the 2nd recurrent operation, the patient underwent
excision of the locally recurrent tumor and partial resection of
the bladder and ileum. The operative finding indicated that the
2nd locally recurrent tumor was located between the bladder andileum.
In December 2018, CT and PET scans revealed the 3rd local
recurrence. The patient was preoperatively catheterized withdouble-J stents for palpating the ureters easily during the 3rdrecurrent operation (2). The operative finding indicated that thethree locally recurrent tumors were located between the bladderand ileum.

Surgical technique

Surgical technique

For the 2 recurrent operation, we excised the 2 recurrent
lymph node in the left lateral obturator area by partially resecting the ileum. The maximum diameter of the 2nd locally recurrent tumor was approximately 2 cm.

The patient underwent excision of three locally recurrent
tumors with partial resection of the bladder and ileum. The
maximum diameters of the three locally recurrent tumors wereapproximately 4 cm, 2 cm, and 2 cm.

Surgical technique for the complication

Surgical technique for the complication

On POD 4, the patient remained febrile, and diffuse peritonitis occurred. An emergent operation was performed. The operative findings indicated that intestinal juice flowed out throughthe ileal perforation. The perforation was sutured, and drainage
tubes were placed. The postoperative course was uneventful.

On POD 4, the patient complained of severe abdominal pain
and became febrile. An emergent operation was performed.
The operative finding indicated a leakage in a longitudinal fissure along the ileum, particularly on the anastomotic site. The
diameter of the hole through which the leakage occurred was
extremely small, making closure difficult. The drainage tubes
were placed in the intraperitoneal space. The postoperative
course was uneventful.

ndndCase 3A 48-year-old female with a history of lower abdominal pain
and a cancer pathological status of stage IIIC : T2N3M0 underwent LAR as a primary operation at another hospital in September 2010. Adjuvant chemotherapy (SOX) was also administered.
In February 2015, a single, left lateral lymph node recurrence
was detected, and the patient was referred to our hospital. A
PET scan revealed that the locally recurrent tumor was approximately 2 cm in diameter and was located on the left common iliac
artery. For the 1st recurrent operation, we excised the recurrent
lymph node on the left common iliac artery.

Surgical technique
In July 2015, A CT scan detected the 2nd locally recurrent
tumor on the left ureter. For the 2nd recurrent operation, we performed LAR and left nephrectomy with left ureter resection andcovering ileostomy formation.

Surgical technique for the complication
On POD 4, the patient complained of severe abdominal pain,
and a CT scan revealed a significant amount of free air in theabdomen. An emergent operation was performed. The operative
findings indicated that intestinal juice flowed out through theileal perforation approximately 150 cm from the ileocecal valve.
The perforation was sutured, and drainage tubes were placed.
The postoperative course was uneventful.

Case 4

A 58-year-old male with a cancer pathological status of stage
IIIB : T4aN1M0 underwent HAR as a primary operation at
another hospital in December 2012. The patient was started on
postoperative adjuvant chemotherapy with capecitabine plus oxaliplatin (CapeOX) (11) ; however, the treatment had side effects
and was subsequently discontinued.
In February 2016, CT and PET scans revealed local recurrence. For the 1st recurrent operation, the patient underwent
excision of the locally recurrent tumor and partial resection of
the bladder, descending colon, and ileum. The operative finding
indicated that the locally recurrent tumor was located in among

Case 5

A 74-year-old female with a cancer pathological status of stage
IIa : T3N0M0 underwent LAR as a primary operation in July
2019. Subsequently, an anastomotic stricture and a rectovaginal fistula formed. These were not treated conservatively. The
resection of anastomotic stricture and reanastomosis of the colon-anus were performed on October 2019. The histopathologicaldiagnosis revealed adenocarcinoma in the anastomotic strictureline. The 1st recurrent operation was performed on the 1st locallyrecurrent tumor.
The 2nd locally recurrent tumor was found in the dorsal side of
the anastomosis. An endoscopic ultrasound-guided fine needle
aspiration of the tumor revealed adenocarcinoma. In February
2020, the patient underwent TPE as the 2nd recurrent operation.
The operative finding indicated that the tumor was in two portions of the small intestine. Subsequently, inflammation of thepelvic dead space persisted and was managed conservatively.
The patient consistently rejected chemotherapy.
In May 2020, the 3rd locally recurrent tumor was detected on
the sacrum. It may have invaded the sacrum directly.

Surgical technique
In May 2020, TPE with sacral resection was attempted ; however, the tumor occupied a significant portion of the small
intestine. Additionally, a complete resection entails resecting asignificant portion of the small intestine, resulting in short bowel
syndrome. In this regard, exploratory laparotomy was selected
as the 3rd recurrent operation.

Surgical technique for the complication
On POD 4, intestinal juice flowed through the drainage tube,
suggesting small intestinal perforation. However, the patient
did not become febrile and did not complain of abdominal pain
because the drainage was extremely effective. A conservative
follow up was undertaken for a short period but with no improvement. In July 2020, the patient underwent a side-to-end

The Journal of Medical Investigation Vol. 70 August 2023
anastomosis of the jejunum and transverse colon. The postoperative course was uneventful.

DISCUSSION
The 2019 JSCCR guidelines recommend resection for the local
recurrence of rectal cancer when R0 resection is possible (12).
Many previous studies have reported cases of recurrent lesion
resection and their corresponding prognoses (13), particularlythat of hepatic, para-aortic lymph node, and peritoneal metastases secondary to colorectal cancer (14-16).
In previous years, chemotherapy had little to no effect. Thus,
most cases of colorectal cancer recurrence were aggressively
treated through surgery. However, in recent years, significant
advancements have been made in colorectal cancer chemotherapy, making it an ideal alternative to surgical treatment.
Additionally, reoperation for the local recurrence of colorectal
cancer is difficult due to organ adhesion. As such, most surgeons
do not select this option. Nevertheless, choosing between chemotherapy and surgery for the frequent recurrence of colorectal
cancer remains debatable. If chemotherapy was ineffective, thepatient was unable to receive the treatment, and severe side
effects occurred in relation to the treatment, then surgery could
be the next choice of treatment. The data from this study was invaluable in selecting the treatment method for colorectal cancer
recurrence.
Previous studies have not explored repeated resection for the
local recurrence of colorectal cancer. Further, the 2nd and 3rd recurrence of rectal cancer cannot be determined without distantrecurrence, when R0 resection is possible. Additionally, the tolerable number of reoperations for patients with locally recurrent
colorectal cancer has not been determined in terms of complications. Thus, elucidating complications from frequent reoperation
is highly significant.
In this study, the prognoses were not investigated. Few surgeons aggressively performed frequent reoperation because few
participants were eligible for the operation and the cases were ofvarious stages, making statistical analysis difficult. Thus, analyzing the prognoses may not be possible in the future.
Additionally, no apparent evidence supports the superiorityof either surgery or chemotherapy over the other in the local recurrence of colorectal cancers. Both reoperations and recurrent
cases referred for surgical treatment are very few. Thus, conducting a prospective study to investigate the local recurrence ofcolorectal cancer is difficult.
Complications (Clavien–Dindo IIIb) were more frequent in
the 2nd recurrent operation than in the 1st recurrent operation
because the degree of adhesion was more severe in the 2nd recurrent operation than in the 1st recurrent operation. Similarly,
the complications (Complication Clavien–Dindo IIIb) were more
frequent in the 3rd recurrent operation than in the 2nd recurrent
operation because the degree of adhesion was more severe in the
3rd recurrent operation than in the 2nd recurrent operation.
Likewise, the 2nd recurrent operation had a longer operative
time and more severe operative bleeding than the 1st recurrent
operation, and the 3rd recurrent operation had a longer operative
time and more severe operative bleeding than the 2nd recurrent
operation because the 3rd recurrent operation had the most severe degree of adhesion among all recurrent operations.
In contrast, the 4th recurrent operation had no complications(Clavien–Dindo IIIb). Further, it had a shorter operative timeand milder operative bleeding than the 1st, 2nd, and 3rd recurrent
operations. However, this outcome is expected in cases exceeding
5 resections (6 resections including the primary operation) because the 4th recurrent operation does not usually involve severe375adhesion.
The diverting (covering) ileostomy is prevent leakage of anastomosis, but in the case of frequent operation, the lesion of thediverting (covering) ileostomy will be made on the upper small
intestine, thus we do not intentionally make the diverting (covering) ileostomy.
It is important to exercise caution in handling “2nd recurrent
operation group”, “3rd recurrent operation group”, and “4th recurrent operation group” to prevent complications (Clavien–Dindo
IIIb).

ACKNOWLEDGEMENTS
The authors have no conflicts of interest to disclose and received no financial support for this report.

ETHICAL STATEMENTS
The Ethics Committee of Aichi Cancer Center Hospital approved this manuscript and agreed to submission to The Journalof Medical Investigation. The subject gave informed consent, andpatient anonymity was preserved.

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