INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

2022.05.17
高雄榮民總醫院 一般外科
PGY 潘喬云
指導醫師 : 周楠華主任
INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

常見惡性腫瘤 No. 5
INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

腫瘤死亡原因 No. 4
INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS
 INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

胃癌 Peritoneal recurrence
HIPEC
50 個月 腹膜復發 腹腔溫熱灌注化療
佔治療失敗原因 70% Hyperthermic intraperitoneal chemotherapy
Median survival
Curative treatment 平均餘命 4 個月  標準治療
( 直腸癌、偽粘液瘤、間皮瘤、胃癌腹膜轉移
Chemotherapy Palliative chemotherapy )
Gastrectomy
腹膜滲透性較差  預防性治療 (Adjuvant therapy)
( 腹膜復發高風險患者 )
 INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

胃癌 Peritoneal recurrence
HIPEC
50 個月 腹膜復發 腹腔溫熱灌注化療
佔治療失敗原因 70% Hyperthermic intraperitoneal chemotherapy
Median survival
Curative treatment 平均餘命 4 個月  標準治療
( 直腸癌、偽粘液瘤、間皮瘤、胃癌腹膜轉移
Chemotherapy Palliative chemotherapy )
Gastrectomy
腹膜滲透性較差  預防性治療 (Adjuvant therapy)
( 腹膜復發高風險患者 )
 INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

胃癌 Peritoneal recurrence
HIPEC
50 個月 腹膜復發 腹腔溫熱灌注化療
佔治療失敗原因 70% Hyperthermic intraperitoneal chemotherapy
Median survival
Curative treatment 平均餘命 4 個月  標準治療
( 直腸癌、偽粘液瘤、間皮瘤、胃癌腹膜轉移
Chemotherapy Palliative chemotherapy )
Gastrectomy
腹膜滲透性較差  預防性治療 (Adjuvant therapy)
( 腹膜復發高風險患者 )
02
METHODS
INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

文獻搜尋  文章類型 : Comparative studies.

 搜尋年限 : 1980.01→2019.06
 撰寫語言 : English or Dutch

搜尋資料庫
• PubMed,
• Embase,
• Cochrane Database of Systematic Reviews,
• Cochrane Central Register of Controlled Trials,
• American Society of Clinical Oncology (ASCO) meeting library

搜尋關鍵字
「 prophylactic 」
「 hyperthermic 」
「 intraperitoneal
」
「 chemotherapy
」
INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

 Primary cancer of the stomach.

 Underwent radical resection.
P Participants
Peritoneal or distant metastases
Peritoneal cytology positive (metastatic disease in TNM-7)
I Intervention Radical surgery in combination with prophylactic HIPEC

C Comparison Surgery alone (SA)

No selection was made based on the lymphadenectomy performed.
Primary endpoint: Overall survival.
Secondary endpoints:
• 5-year survival
O Outcomes • Disease-free survival
• Peritoneal recurrence
• Post-operative morbidity and mortality
• Quality of life.
03
RESULTS
INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

文
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搜
尋

Quality of life was not measured

in any of the studies.
INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

文
獻
搜
尋

RCT
INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

文
獻
搜
尋

Non-RCT
INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

誤
差
風
險

Randomized controlled trials, the Risk of Bias Tool 2.0 provided by Cochrane.
Non-randomized comparative studies : ROBINS-I by Cochrane.
INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

• Most of the studies were conducted in Asia

with only one study having been performed in
Europe.
• There were 10 studies that performed HIPEC
for T3-4 tumors: seven of these studies
included patients with clinically diagnosed T3-
4 tumors, and three included pathologically
confirmed T3-4 tumors.
• Mitomycin C was used in the therapy
regimen in 10 studies, whether alone, in
combination with cisplatin, etoposide, both
cisplatin and etoposide or cisplatin with 5-FU.
In one study, only cisplatin in combination with
paclitaxel was used.
• Temperature during HIPEC ranged from 40 to
45 degrees, and the duration of the
procedure ranged from 30 to 120 min.
• Studies performed either a D1 or D2
lymphadenectomy during gastrectomy, which
did not differ between treatment arms.
 INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

併發症
- HIPEC 16.7-60%
- SA 25-42.5%
呼吸衰竭 (P<0.0001)
- HIPEC 73%
- SA 19%
吻合滲漏
- HIPEC 2-20%
- SA 3-15%
腸道阻塞
- HIPEC 2-4%
- SA 4-7.1%
胰臟瘻管
- HIPEC 20-39%
- SA 7.5-46%
腸道瘻管
- HIPEC once (2.1%)
- SA
腎臟衰竭、腹內膿瘍
肝臟受損、大量出血
膽道瘻管
 INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

死亡率
- HIPEC 0-15.6%
- SA 0-9.8%
(no significant
differences)
 INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

Overall survival
- HIPEC 32-34.6 month
- SA 22-28.2 month

significant

The median follow up of

the studies ranged from
14.6 months to 5 years.
 INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

5-year survival
- HIPEC 39.1-86.8%
- SA 17.3-61%
no statistical significance

significantly higher

significantly higher

significantly higher

The median follow up of

the studies ranged from no statistical significance
14.6 months to 5 years.
 INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

Disease-free
survival (No P value)
- HIPEC 34.5month
- SA 24.7 month

腹膜復發率
- HIPEC 6.8.-26.7 %
- SA 14.1-45%

significant
04
DISCUSSION
 INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

對於沒有遠端轉移或細胞學陽性的 T3-4 腫瘤患者，預防性 HIPEC 可以延長生存期並預防腹膜復

本篇結論 發。
在胃切除手術期間進行了預防性
PAPER HIPEC ，並不會顯著提高併發症發生率或死亡率。
相似結論 矛盾結論 ( 除了呼吸衰
竭 )Surgery combined with intraoperative hyperthermic
• 預防性 HIPEC 與更高的骨
intraperitoneal chemotherapy (IHIC) for gastric cancer:
24 A systematic review and meta-analysis of randomised 髓抑制、吻合口漏、腸梗阻
controlled trials. Int. J. Hyperth. 2013, 29, 156–167 或腸穿孔風險無關
Benefits of hyperthermic intraperitoneal chemotherapy • HIPEC 組的總生存期顯著改
for patients with serosal invasion in gastric cancer: a
25 meta-analysis of the randomized controlled trials. BMC 善（ RR 0.73 ）
Cancer 2012, 12, 526. • 預防性 HIPEC 可降低復發
率 (RR 0.45)

過 26
Comparison Different Methods of Intraoperative and
Intraperitoneal Chemotherapy for Patients with Gastric
Cancer: A Meta-analysis. Asian Pac.J. Cancer Prev. 2012,
13, 4379–4385.
• 腹腔內化療的應用會增加骨
髓抑制 (OR = 5.74) 、發燒
(OR = 3.67) 和腹腔內膿瘍

去 27
A Systematic Review and Meta-analysis of the
Randomized Controlled Trials on Adjuvant
Intraperitoneal Chemotherapy for Resectable Gastric
• HIPEC 組的總生存期顯著改
善（ HR 0.60 ）
(OR = 3.57) 的風險 。

文
Cancer. Ann. Surg. Oncol. 2007, 14, 2702–2713

Meta-analysis of intraperitoneal chemotherapy for gastric

cancerXu DZ, Zhan YQ, Sun XW, Cao SM, Geng QR. Meta-
28
獻
analysis of intraperitoneal chemotherapy for gastric
cancer. World J. Gastroenterol. 2004, 10, 2727–2730
 INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

Limitation
The total number of patients included in this paper is small, and the information is often extracted from subgroup
樣本數少 data.

誤差風險 The majority of the studies have a high risk of bias.

年代久遠 Most of the studies were published more than 10 years ago.

Recently, the FLOT4 study established FLOT as the chemotherapy regimen of choice. However, most of the included
化療更新 studies did not administer perioperative chemotherapy, which may have resulted in lower efficacy.

New techniques as positron emission tomography (PET) and diagnostic laparoscopy have improved staging
檢查更新 and therefore may have led to better patient selection.
Gastric cancer care in general has changed including the shift from laparotomy to minimally invasive techniques,
手術更新 and techniques of HIPEC have changed as well. ( 重建前 / 重建後 / 手術後數周 )
Patient and tumor characteristics differed between the studies.
異質性大 The technique, temperature, time and chemotherapeutic agent of HIPEC varied.

限亞洲人 The results gathered in Asian studies cannot be fully applied to Western populations.
INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

研 GASTRICHIP-trial
究 In 2014, GASTRICHIP-trial was commenced, a prospective randomised phase III study
conducted in France to evaluate the effects of prophylactic HIPEC on patients with gastric cancer
involving the serosa and/or lymph node involvement and/or with positive cytology [34].

方 This currently on-going study is one of the first phase III trials conducted in a Western country
that evaluates the effect of prophylactic HIPEC on gastric cancer. This study also includes
translational research, which will be valuable for future studies.
向
QoL
• In a study monitoring quality of life (QoL) before and after HIPEC for peritoneal metastases
from various origins, a reduction in QoL was seen that recovered in six months after the
intervention [35].
• Considering the relatively low life expectancy of patients diagnosed with gastric cancer, QoL
must be investigated in the future studies along with efficacy and morbidity.
02
CONCLUSIONS
INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS

Prophylactic HIPEC for gastric cancer can be performed safely, and may prevent
peritoneal recurrence, and may prolong survival of patients with neither clinically
evident metastases nor positive peritoneal cytology.

However, the heterogeneity and age of the studies in this review show the need for well-
designed trials conducted according to current standards.