Chang-Yun Lu, Mao-Chih Hsieh Prophylactic hyperthermic intra-peritoneal chemotherapy(HIPEC) in high risk patients for peritoneal carcinomatosis 腹腔溫熱化療對惡性腫瘤腹腔轉移之預防 Chang-Yun Lu, Mao-Chih Hsieh 呂 長運 謝 茂志 Department of Surgery, Division of General Surgery, Taipei medical university affiliated Wanfang Hospital 台北醫學大學 - 萬芳醫院 一般外科

Peritoneal carcinomatosis (PC) Recurrence is frequent after surgery Systemic chemotherapy is less effective for PC Poor prognosis (median survival 7-12M)

Principle of CRS/HIPEC Aggressive cytoreductive surgery (CRS) and visceral organ resection to remove gross peritoneal tumor. Complete cytoreduction: residual tumor<2.5mm Hyperthermic intraperitoneal chemotherapy (HIPEC) to eradicate microscopic residual cancer cell Chemo-solution tissue penetrating depth: 2-3mm

Aggressive CRS combined HIPEC for peritoneal carcinomatosis treatment Better survival compared with traditional treatment (Debulking surgery + systemic chemotherapy) Debulking surgery + systemic chemotherapy CRS/HIPEC Gastric Median survival:7-10M 5y survival: 20% Colon Median survival: 12M 5y survival: 40% Mesothelioma 5y survival: 40-50% Appendix 10y survival: 20-30% 10y survival: 80%

Limitation of CRS/HIPEC

The most two important prognostic factors of CRS/HIPEC treatment Peritoneal cancer index (PCI)

The most two important prognostic factors of CRS/HIPEC treatment Completeness of CRS (CC) score CC-0 no residual tumor Complete CRS CC-1 residual tumor <2.5mm CC-2 residual tumor 2.5-25mm Incomplete CRS CC-3 residual tumor >25mm

Aggressive cytoreductive surgery(CRS) combined HIPEC for peritoneal carcinomatosis treatment Better survival compared with traditional treatment (Debulking surgery + systemic chemotherapy) Debulking surgery + C/T CRS/HIPEC Gastric Median survival:7-10M 5y survival: 20% Colon Median survival: 12M 5y survival: 40% Mesothelioma 5y survival: 40-50% Appendix 10y survival: 20-30% 10y survival: 80% Only for CC 0-1 group patients

Wanfang data (2000-2016 May) CC 0-1 CC 2-3 PCI<20 119 (81%) 27 (19% 146 PCI>=20 26 (23%) 87 (77%) 113

Limitation of CRS/HIPEC -Difficulty in complete tumor resection

Limitation of CRS/HIPEC -Difficulty in complete tumor resection -High morbidity and mortality rate Morbidity Gr 3-4: 20-40% Morbidity 0-18% -Wanfang data: Morbidity Gr 3-4:11% Mortality:3%

Limitation of CRS/HIPEC -Difficulty in complete tumor resection -High morbidity and mortality rate -Experienced surgical team Long operation time Multiple intra-abd organs involvement

Is there a better way to block peritoneal recurrence ?

Gastric cancer Peritoneal recurrence develops in 60% of p’t with T4 tumor Up to 40% of resectable gastric cancer p’t die as a direct result of peritoneal carcinomatosis

Colon cancer 17-50% T4 tumor => peritoneal recurrence 14-58% perforated tumor => peritoneal recurrence 40% to 80% of patients who died from peritoneal recurrence

Appendix 90% appendiceal tumor is mucinous type Mucinous tumor rupture causing pseudomyxoma peritonei development

High risk of peritoneal recurrence T4 tumor Tumor perforation or rupture Positive ascites cytology (free cancer cell in ascites)

Prophylactic HIPEC HIPEC as adjuvant therapy to eradicate free cancer cell in ascites, before development of peritoneal carcinomatosis

Prophylactic HIPEC in Wanfang hospital 2004-2016 Serosa exposure was noted during operation (sT4), or proved by pathologic exam Positive ascites cytologic finding before operation Tumor rupture or perforation were noted during operation or proved by pathologic examination There is no evidence of peritoneal seeding, no distant metastasis at the time of treatment Patient underwent HIPEC at initial OP or interval OP, with laparotomy or laparoscopic approach

Gastric cancer Serosal involvement was suspected during operation (sT4) One patient died 56 months after HIPEC due to distant metastasis (skin) One patient died 15 months after HIPEC from liver metastases The other 6 patients are disease free FU time: 48M (12-151) Pathologic stage IIA IIIA IIIB IIIC No 1 2 4

Colon cancer Serosal involvement was suspected during operation (sT4), or proved by pathologic exam One patient with stage IIIB underwent 1st OP at other hospital He was aware of high risk of peritoneal recurrence and came to Wanfang hospital for laparoscopic prophylactic HIPEC 1 month after 1st OP All 3 patients are disease free, FU time: 62M (24-138) Pathologic stage IIIB IIIC No 2 1

Appendix Three patients presented as ruptured appendicitis and underwent appendectomy Tumor rupture is proved by pathologic exam No peritoneal recurrence FU time: 36M (30-50) P’t Clinical presentation FU 1 Mucinous neoplasm s/p laparoscopic HIPEC 30 M 2 3 Adenocarcinoma s/p right hemicolectomy/ HIPEC 50 M

Hepatoma Four patients of ruptured HCC (stage IIIC) s/p Liver tumor resection + HIPEC No peritoneal recurrence patients Clinical presentation FU 44/M Lung meta and IVC thrombosis in 4 months Death 9M after treatment 59/F No recurrence 104 M 65/F 70 M 50/F 84 M

Gallbladder 68 y male presented of gallbladder stone and cholecystitis, who underwent laparoscopic cholecsytectomy Gallbladder rupture was observed during OP Pathologic exam: adenocarcinoma (stage II) After 20 days, patient underwent Laparoscopic HIPEC FU time: 15 months

Prophylactic HIPEC in Wanfang hospital 2004-2016 Patient number FU time (M) Gastric 8 48(12-151) Colon 3 52(24-138) Appendix 36(30-50) Hepatoma 4 86(70-104) Gallbladder 1 15 19 No peritoneal recurrence in all patients

Complication Two adverse effect (G2): 12.5% No surgical mortality One pneumonia and one minor pancreatic leakage No surgical mortality

Conclusion

Peritoneal carcinomatosis CRS/HIPEC provide better prognosis CRS/HIPEC is limited in advanced disease CRS/HIPEC is combined with higher morbidity and mortality rate

High risk of peritoneal recurrence in patients with following characteristics T3/T4 tumor Tumor perforation or rupture Positive ascites cytology (free cancer cell in ascites)

Prophylactic HIPEC for patients with high risk of peritoneal recurrence 減少腹腔腫瘤復發的風險 並不增加併發症率與死亡率 相對簡單的技術

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