Surgical treatment of gallbladder cancer: An eight-year experience in a single center

Table 1 Preoperative evaluation, chemotherapy and/or radiation, and the final stage

Case	Symptomatic (Yes or No)	Preoperative biliary drainage (Yes or No)	PBM (Yes or No)	Preoperative diagnosis (GBC or benign)	Preoperative stage1	Neoadjuvant chemotherapy (Yes or No)	Preoperative radiation (Yes or No)	Conversion to surgery (Yes or No)	The final stage1	Adjuvant chemotherapy (Yes or No)	Chemotherapy for metastases/recurrences (Yes or No)
1	No	No	No	Benign	-	No	No	No	IA	No	No
2	No	No	Yes	Benign	-	No	No	No	IB	No	No
3	No	No	No	GBC	IIIB	No	No	No	IIA	No	No
4	No	No	No	Benign	-	No	No	No	IIA	No	No
5	No	No	No	GBC	IIA	No	No	No	IIA	No	No
6	Yes	No	No	Benign	IIB	No	No	No	IIB	No	No
7	Yes	No	No	Benign	IIB	No	No	No	IIB	No	Yes
8	No	No	No	Benign	IIIA	No	No	No	IIIA	No	No
9	Yes	No	No	GBC	IVB	No	No	No	IIIA	No	No
10	Yes	No	No	GBC	IVA	No	No	Yes	IIIA	No	Yes
11	No	No	No	GBC	IIA	No	No	No	IIIA	Yes	No
12	Yes	No	No	GBC	IIIA	No	No	No	IIIA	No	No
13	No	No	No	GBC	IVA	No	No	No	IIIB	No	No
14	Yes	Yes	No	GBC	IVB	No	No	No	IIIB	No	No
15	No	No	No	GBC	IIA	No	No	No	IIIB	No	No
16	No	No	Yes	GBC	IVB	No	No	No	IIIB	No	No
17	Yes	Yes	No	GBC	IVB	No	No	No	IVA	No	No
18	Yes	No	No	GBC	IIIB	No	No	No	IVB	No	No
19	No	No	No	GBC	IVB	No	No	No	IVB	No	Yes

¹Staging according to the tumor-node-metastasis classification. GBC: Gallbladder cancer; PBM: Pancreaticobiliary maljunction.

Table 2 Operative factors

Case	Surgical approach (Primary or two-stage)	Surgical procedures			Caudate Lobectomy (Yes or No)	Graphic/Surgical R03(Curative resection) (Yes or No)	Postoperative complications
		Resected area1	Intentional LN dissection2 (Yes or No)	EHBD resection (Yes or No)
							POD	Grade4
1	Primary	LC	No	No	No	Yes	-	-
2	Primary	LC	No	No	No	Yes	-	-
3	Primary	Extended cholecystectomy	Yes	Yes	No	Yes	Intraperitoneal abscess (8)	3a
4	Primary	LC	No	No	No	Yes	-	-
5	Primary	Extended cholecystectomy	No	No	No	Yes	-	-
6	Two-stage	Wedge resection	Yes	No	No	Yes	-	-
7	Two-stage	Wedge resection	Yes	Yes	No	Yes	-	-
8	Two-stage	Wedge resection	Yes	No	No	Yes	Intraperitoneal abscess (8)	2
9	Primary	Extended cholecystectomy	No	No	No	No	Intraperitoneal abscess (20)	3a
10	Primary	Extended cholecystectomy	No	No	No	No	-	-
11	Primary	Extended cholecystectomy	Yes	Yes	No	No	-	-
12	Primary	Extended cholecystectomy	No	No	No	Yes	-	-
13	Primary	Extended cholecystectomy + SSpPD	Yes	Yes	No	Yes	Intraperitoneal abscess (14)	2
14	Primary	Extended cholecystectomy + SSpPD + partial resection of the portal vein	Yes	Yes	No	Yes	-	-
15	Primary	LC	No	No	No	Yes	-	-
16	Primary	Extended cholecystectomy + SSpPD	Yes	Yes	No	Yes	Pancreatitis (21)	2
17	Primary	Right hepatectomy + SSpPD	Yes	Yes	Yes	No	Pancreatic fistula (14)	3b
18	Primary	Extended cholecystectomy+partial hepatectomy	Yes	No	No	Yes	-	-
19	Primary	Extended cholecystectomy + SSpPD	Yes	Yes	No	Yes	-	-

¹Extended cholecystectomy was the primary whole-layer resection with partial hepatectomy, and the wedge resection was partial hepatectomy of the gallbladder bed at two-stage surgery.

²Intentional dissection of parabiliary, paraarterial and periportal venous lymph nodes.

³R0 means no remnant of gallbladder cancer by curative resection, according to the Japanese guideline (General rules for clinical and pathological studies on cancer of the biliary tract).

⁴Grading according to the Clavien-Dindo classification. EHBD: Extrahepatic bile duct; LC: Laparoscopic cholecystectomy; LN: Lymph node; POD: Postoperative day; SSpPD: Subtotal stomach-preserving pancreaticoduodenectomy.

Table 3 Pathological findings

Case	Tumor occupation1		Depth2 (invaded organ)	Invasions into the neck and/or cystic duct (Yes or No)	Invasions			Positive margin at the cut end (Yes or No)	Metastatic LNs (Positive LNs/total LNs)	Metastatic LN #12c3 (The LN around the cystic duct) (Positive LNs/sampling LNs)
					Lymphoid duct (Yes or No)	Vessels (Yes or No)	Nerve plexus (Yes or No)
		Ventral or liver side
1	Gb	Ventral side	m	No	No	No	No	No	-	-
2	Gf	Ventral side	mp	No	No	No	No	No	0 / 1	0 / 1
3	Gf	Ventral side	ss	No	No	No	No	No	0 / 13	-
4	Gf	Ventral side	ss	No	No	No	No	No	-	-
5	Gf	Ventral side	ss	No	No	Yes	No	No	-	-
6	Gfbn	Liver side	ss	Yes	No	No	No	No	0 / 20	-
7	Gfbn	Liver side	ss	Yes	No	No	No	No	0 / 19	0 / 1
8	Gfb	Liver side	ss	No	No	Yes	No	No	0 / 16	-
9	Gfbn	Liver side	si (liver)	Yes	No	Yes	No	Yes	-	-
10	Gfb	Liver side	ss	No	No	No	No	No	-	-
11	Gfbn	Ventral side	si (liver)	Yes	Yes	Yes	Yes	Yes	0 / 6	-
12	Gfbn	Liver side	si (liver, EHBD)	Yes	Yes	No	No	Yes	-	-
13	Gfb	Liver side	si (liver)	No	Yes	Yes	Yes	No	2 / 35	-
14	Gnb	Liver side	si (liver, EHBD)	Yes	No	Yes	Yes	No	3 / 13	-
15	Gf	Ventral side	ss	No	No	No	No	No	1 / 1	1 / 1
16	Gfbn	Ventral side	ss	Yes	Yes	Yes	No	No	2 / 6	1 / 1
17	Gfbn	Ventral side	si (EHBD)	Yes	Yes	Yes	Yes	Yes	0 / 4	-
18	Gfbn	Liver side	si (liver)	Yes	No	Yes	No	No	0 / 4	-
19	Gfbn (b)	Liver side	si (liver)	No	Yes	Yes	Yes	No	18 / 29	-

¹Tumor location according to the Japanese guideline (General rules for clinical and pathological studies on cancer of the biliary tract).

²Tumor depth according to the Japanese guideline (General rules for clinical and pathological studies on cancer of the biliary tract).

³The lymph node around the cystic duct, according to the Japanese guideline (General rules for clinical and pathological studies on cancer of the biliary tract). Gf: Fundus; Gb: Body; Gn: Neck. EHBD: Extrahepatic bile duct; LN: Lymph node.

Table 4 Metastases, recurrences and outcome

Case	Metastasis and/or recurrence (Yes or No)	The target sites of metastases/recurrences1	Postoperative liver metastases (Right and/or left side)	Disease-free survival (yr)	Overallsurvival(yr)	Follow-up term (yr)	Prognosis (Dead or alive)
1	No	-	-	2.4	2.4	2.4	Alive
2	No	-	-	2.3	5.0	5.0	Alive
3	No	-	-	3.6	3.6	3.6	Alive
4	No	-	-	3.6	3.6	3.6	Alive
5	Yes	Liver	Right side	0.4	0.8	0.8	Alive
6	No	-	-	8.0	8.0	8.0	Alive
7	Yes	Peritoneal cavity	-	2.0	2.8	2.8	Dead
8	Yes	Liver	Right side	1.4	2.0	2.0	Dead
9	Yes	Peritoneal cavity	-	0.1	0.2	0.2	Dead
10	Yes	Local site, hepatic hilum	-	1.2	2.6	2.6	Dead
11	Yes	Perineal cavity	-	0.8	1.0	1.0	Dead
12	Yes	Local site, liver	Left side	0.1	0.2	0.2	Dead
13	Yes	Peritoneal cavity, paraaortic LN	-	0.4	1.7	1.7	Dead
14	Yes	Local site	-	0.9	3.4	3.4	Dead
15	Yes	Paraaortic LN	-	4.0	5.4	5.4	Alive
16	Yes	Bone, paraaortic LN	-	2.0	7.5	7.5	Alive
17	Yes	Liver remnant	Left side	0.6	0.7	0.7	Dead
18	Yes	Liver	Right and left sides	0.2	0.3	0.3	Dead
19	Yes	Liver, local site, paraaortic LN	Left side	0.6	1.0	1.0	Dead

¹Perineal cavity involved dissemination and carcinomatosis. LN: Lymph node.

Table 5 Important literature and guidelines

Ref.	Country	Year	Remarks	Comments in each guideline
[43]	Germany	2013	Prognosis of incidental GBC was not influenced by the primary access technique.	Conventional open surgery is recommended for suspicious GBCs.
[44]	Japan	2003	Preoperative information indicated strategies for surgical treatment of GBCs.	Conventional open surgery is recommended for suspicious GBCs.
[45]	Japan	1996	Outcome of radical surgery for GBCs was evaluated according to the TNM classification.	Intentional LN dissection and prophylactic EHBD resection are considered for potential pathological invasions.
[46]	Japan	2004	Strong consideration should be given to intentional LN dissection and EHBD resection.	Intentional LN dissection and prophylactic EHBD resection are considered for potential pathological invasions.
[47]	Japan	2013	Hepatectomy of segments 4a and 5 was not superior to extended cholecystectomy in patients with pathological T2.	The EHBD resection does not improve the prognosis in patients with T2N0.
[48]	Korea	2013	Radical resection (R0 surgery) including EHBD resection should be considered in patients with T2 and T3 (A single-centre retrospective study).	The EHBD resection does not improve the prognosis in patients with T2N0.
[49]	Japan	2014	Surgery might not be indicated for patients with advanced invasion to the EHBD and visible paraaortic LN metastasis (A single-centre retrospective study).	The EHBD resection does not improve the prognosis in patients with T2N0.
[50]	Korea	2015	Two-stage surgery was highly recommended for patients with pathological T2 (A single-centre retrospective study).	The EHBD resection does not improve the prognosis in patients with T2N0.
[51]	Japan	2015	Combined treatment of intentional LN dissection and prophylactic EHBD resection had no survival impact for patients without the EHBD invasion (A single-centre retrospective study).	The EHBD resection does not improve the prognosis in patients with T2N0.
[52]	Japan	2012	Hepatectomy procedures (e.g., systematic, segmental and partial resections) did not significantly affect surgical outcomes	Radical resection (R0 surgery) is the most important prognostic factor
[53]	United States	2008	GBC was commonly diagnosed incidentally, and two-stage surgery revealed a high incidence of residual disease.	Overall prognosis is poor.
[54]	United States	2004	Surgeries were not routinely indicated for advanced GBCs with jaundice.	Jaundice is common in patients with advanced GBC.
[55]	France	2011	EHBD resection increased postoperative morbidity but did not improve survival.	Partial hepatectomy without EHBD resection indicates incidental GBC.
[56]	Korea	2011	Extended cholecystectomy was not advantageous over simple cholecystectomy for patients with T1b.	Simple cholecystectomy is adequate therapy for patients with T1a.
[57]	United States	2007	Radical resection for patients with T2 and T3 resulted in a significant survival advantage compared with simple cholecystectomy.	Advantages of radical resection including extended hepatectomy for incidental GBC and patients with T1b are controversial.
[58]	Canada	2008	Intentional LN dissection and EHBD resection may have stage-specific effects on survival.	Radical resection improves survivals in patients with T1b and T2 (not in patients with T3).
[59]	Korea	2008	Cholecystectomy with intentional LN dissection without EHBD resection was recommended for patients with T1b.	Advantages of radical resection including extended hepatectomy for incidental GBC and patients with T3b are controversial.
[60]	United States	2009	Radical resection had survival advantage for patients with T1b and T2.	Radical resection improves survival in patients with T1b and T2 (not in patients with T3).
[61]	United States	2011	Extended surgery including intentional LN dissection improved survival for incidental GBC	Aggressive surgeries including hepatectomy, LN dissection and EHBD resection are indicated for patients with T3, localized hepatic invasion and regional LN metastases.
[62]	Japan	2012	Extended cholecystectomy was adequate for patients with T2, and more aggressive surgeries were indicated for patients with T3, localized hepatic invasion and regional LN metastases.	Aggressive surgeries including hepatectomy, LN dissection and EHBD resection are indicated for patients with T3, localized hepatic invasion and regional LN metastases.
[63]	United States	2009	Major hepatectomy and EHBD resection were significantly associated with perioperative morbidity, and were not mandatory in all cases.	Independent prognostic factors associated with survival are T factor, N factor, pathological poor differentiation and EHBD involvement.
[64]	United States	2007	EHBD resection did not yield a greater count of LNs. Over one-third had residual disease in the EHBD at two-stage surgery.	During two-stage surgery, EHBD resection is indicated for negative cystic duct margins.
[65]	United States	2000	Radical resection can provide long-term survival, even for large tumors with extensive liver invasion.	Aggressive surgeries including hepatectomy, LN dissection and EHBD resection are indicated for patients with T3, localized hepatic invasion and regional LN metastases.
[66]	United States	2007	Incidental GBCs during laparoscopic cholecystectomy did not indicate immediate conversion to open surgery, and these patients should be referred to a tertiary care center for further surgery.	There was no difference in surgical deficit between immediate resection at the initial hospital and delayed resection at tertiary care center.
[67]	France	2011	Jaundice was a poor prognostic factor, but radical resection had survival benefit especially in highly selected patients with N0.	Radical resection improves survival in patients with N0.
[20]	Japan	2011	Patients with advanced GBCs were candidates for EHBD resection, if radical resection (R0) was achievable.	Radical resection improves survival in patients with EHBD invasion.
[68]	India	2016	Chemoradiotherapy in unresectable GBCs resulted in the resectability, and subsequent radical surgery (R0) had survival benefit. LN regression could serve as a predictor of response to radiochemotherapy.	Chemoradiotherapy in unresectable GBCs may result in the resectability, and conversion surgery (R0) has survival benefit.
[69]	United States	2017	Radical surgeries after favorable responses to neoadjuvant chemotherapies were associated with long-term survival in selected patients.	Chemoradiotherapy in unresectable GBCs may result in the resectability, and conversion surgery (R0) has survival benefit.
[70]	United States	2011	Pathological assessment of at least 6 LNs was important.	Patients with incidental GBC and T2 associated with residual tumor, and should undergo surgery to reflect the adverse outcome.
[71]	Canada	2012	Adjuvant radiochemotherapy had the greatest benefit in patients with positive LNs and R1 disease.	Adjuvant radiochemotherapy is beneficial.

EHBD: Extrahepatic bile duct; GBC: Gallbladder cancer; LN: Lymph node.