Effects of Neoadjuvant Intraperitoneal/Systemic Chemotherapy (Bidirectional Chemotherapy) for the Treatment of Patients with Peritoneal Metastasis from Gastric Cancer

Novel multidisciplinary treatment combined with neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS) and peritonectomy was developed. Ninety-six patients were enrolled. Peritoneal wash cytology was performed before and after NIPS through a port system. Patients were treated with 60 mg/m(2) of oral S-1 for 21 days, followed by a 1-week rest. On days 1, 8, and 15, 30 mg/m(2) of Taxotere and 30 mg/m(2) of cisplatin with 500 mL of saline were introduced through the port. NIPS is done 2 cycles before surgery. Three weeks after NIPS, 82 patients were eligible to intend cytoreductive surgery (CRS) by gastrectomy + D2 dissection + periotnectomy to achieve complete cytoreduction. Sixty-eight patients showed positice cytology before NIPS, and the positive cytology results became negative in 47 (69%) patients after NIPS. Complete pathologic response on PC after NIPS was experienced in 30 (36.8%) patients. Stage migration was experienced in 12 patients (14.6%). Complete cytoreduction was achieved in 58 patients (70.7%). By the multivariate analysis, complete cytoreduction and pathologic response became a significantly good survival. However the high morbidity and mortality, stringent patient selection is important. The best indications of the therapy are patients with good pathologic response and PCI ≤ 6, which are supposed to be removed completely by peritonectomy

Laparoscopic Diagnosis and Laparoscopic Hyperthermic Intraoperative Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei Detected by CT Examination

Background. Patients with early stage of pseudomyxoma peritonei (PMP) are sometimes difficult to diagnose the primary sites and intraperitoneal spread of tumor and to perform a cytological study. Methods. Patients without a definitive diagnosis and with unknown extent of peritoneal spread of tumor underwent laparoscopy. Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) was administered as part of the same intervention. The results of treatment were evaluated at the time of second-look laparotomy (SLL) as a subsequent intervention. Results. Eleven patients were managed by diagnostic laparoscopy followed by laparoscopic HIPEC (LHIPEC). The operation time of laparoscopic examination and LHIPEC was 177 ± 26 min (range 124–261 min). No intraoperative complication was experienced. The peritoneal carcinomatosis index (PCI) score by laparoscopic observation was 16.5 ± 6.4 (range 0–30). One patient with localized pseudomyxoma peritonei (PMP) mucocele did not received LHIPEC; the other 10 patients with peritoneal metastases (PM) were treated with LHIPEC. After LHIPEC, ascites disappeared in 2 cases and decreased in the amount in the other 8 cases. Nine patients underwent SLL and cytoreductive surgery (CRS) combined with HIPEC. The duration between LHIPEC and SLL ranged from 40 to 207 days (97 ± 40 days). The PCI at the SLL ranged from 4 to 27 (12.9 ± 7.1). The PCI at the time of SLL decreased as compared to PCI at the time of diagnostic laparotomy in 7 of 9 patients. Median follow-up period is 22 months (range 7–35). All 11 patients are alive. Conclusion. The early results suggest that laparoscopic diagnosis combined with LHIPEC is useful to determine the surgical treatment plan and reduce the tumor burden before definitive CRS at SLL

Indications for cytoreductive surgery plus HIPEC in patients with colorectal cancer and peritoneal metastasis.

AbstractComprehensive treatment (COMPT) consisting of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in selected patients with peritoneal metastasis (PM) from colorectal cancer (CRC). The aim of the present study was to clarify clinicopathologic parameters that are indications to perform COMPT in CRC-patients with CRC-PM.Between 2006 and 2021, 447 patients were selected as eligible for COMPT among 906 CRC-patients with PM. Clinicopathologic parameters contributing to long-term survival and cure were analyzed.Results: A log-rank test showed a significant survival difference for peritoneal cancer index (PCI) (≤12 vs. ≥13), completeness of cytoreduction (CCR) score (CCR-0 vs. CCR-1), small bowel (SB)-PCI (≤2 vs. ≥3), liver/lung metastasis (LLM) (negative vs. positive), histologic type (differentiated type vs. signet ring cell (SRC) subtype), number of involved peritoneal sectors (≤6 vs. ≥7), HIPEC (done vs. not done) and postoperative complication (grade 0, 1, or 2 vs. grade 3, 4, or 5). Muti-variate analyses revealed that CCR score (CCR-0 vs. CCR-1), SB-PCI score (≤2 vs. ≥3), LLM (negative vs. positive), and HIPEC (performed vs. not done) were independent prognostic factors. The incidence of postoperative grade 3, 4 or 5 complication was 19.0% (85/447) and the mortality rate was 2.0% (9/447). One hundred and seventy patients fulfilled the following clinicopathologic factors,PCI ≤12, SB-PCI ≤2, number of involved peritoneal sectors ≤6, no LLM, differentiated histologic type and CCR-0. The MST of these patients was 5.5 years, and 5- and 10-year survival rates were 57.8% and 24.6%, respectively. Postoperative grade 3, 4, and 5 complications in these 170 patients occurred in 9 (5.3%), 15 (8.8%) and 1 (0.6%), respectively. Cured patients were defined as those alive without recurrence more than 5 years after CRS. All of the cured patients underwent CCR-0 resection. The PCI and SB-PCI of these 23 patients were ≤12 and ≤2, respectively

アクセイ フクマク チュウヒシュ ニ タイスル cytoreductive surgery

海外では悪性腹膜中皮腫に対してcytoreductive surgery (CRS)と腹腔内温熱化学療法を含めた周術期化学療法が普及しているものの、本邦では悪性腹膜中皮腫に対する外科的治療の報告は乏しい。今回我々は当院でのCRSと周術期化学療法による悪性腹膜中皮腫に対する治療成績を報告する。2013年2月から2022年4月までの期間において、15例の悪性腹膜中皮腫に対してCRSを施行した。患者年齢の中央値は58歳(42-67)で、男性5例と女性10例であった。CRSは病変の存在する壁側腹膜と臓器切除を組み合わせて施行した。10例に対して術前化学療法を施行し、12例に対して術後化学療法を施行した。腹腔内温熱化学療法を8例に対して施行した。全生存期間の中央値は41か月であった。3年生存率57.7%で、5年生存率は34.6%であった。上皮型でperitoneal cancer index≦22であった6例については全例生存中であり、今後の長期生存が期待される結果であった。2.5cmより大きな腫瘍が遺残した場合でも術後化学療法の奏功により3年以上の生存が得られる症例も存在していた。単変量解析をおこなうも、生存に関する統計学的に有意な因子は認めなかった。手術合併症（Clavien-Dindo分類3以上）はGrade 3aが2例、Grade 3bが1例、Grade 4aが2例であった。悪性腹膜中皮腫に対して、これまで日本で施行されてきた化学療法単独療法では予後不良であることが知られている。一方、今回の我々が施行したCRSと周術期化学療法の治療成績は比較的予後良好であり、合併症も許容範囲内であると考えられた。悪性腹膜中皮腫に対する海外におけるCRSと化学療法による良好な治療成績の報告があることからも、本邦でのCRSと周術期化学療法の継続と症例の集積により、体系的な治療法確立と治療成績向上が期待できるであろう。Cytoreductive surgery and perioperative chemotherapy, including hyperthermic intraperitoneal chemotherapy, the standard treatments for malignant peritoneal mesothelioma worldwide are not yet widespread in Japan. We report the surgical outcomes of cytoreductive surgery with perioperative chemotherapy for patients with malignant peritoneal mesothelioma at our institution. We encountered 15 patients who required cytoreductive surgery from February 2013 to April 2022. Their median age was 58 (range 42–67) years, and there were 5 men and 10 women. Cytoreductive surgery was performed by combining extensive peritoneal resection and the resection of various organs. Ten patients underwent neoadjuvant chemotherapy. Hyperthermic intraperitoneal chemotherapy was performed in 8 patients, and 12 patients received postoperative systemic chemotherapy. The median overall survival period was 41 months for all patients. After the cytoreductive surgery, the 3- and 5-year survival rates were 57.7% and 34.6%, respectively. All six patients with epithelial-type peritoneal mesothelioma with a peritoneal cancer index of ≤22 are alive, with expected long-term survival. Furthermore, among patients with a cytoreduction completeness of 3, which indicates residual tumors of >2.5 cm in diameter, long-term survival was achieved in those who responded to chemotherapy. In the univariate analysis, no significant factor was identified for overall survival. For malignant peritoneal mesothelioma, the treatment outcome of chemotherapy alone, which is the standard treatment in Japan, is known to be poor. This study demonstrated that cytoreductive surgery with chemotherapy achieved better outcomes than known reports in Japan. The results of cytoreductive surgery with chemotherapy from across the world may improve treatment outcomes in Japan

Effects of Neoadjuvant Intraperitoneal/Systemic Chemotherapy (Bidirectional Chemotherapy) for the Treatment of Patients with Peritoneal Metastasis from Gastric Cancer

Novel multidisciplinary treatment combined with neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS) and peritonectomy was developed. Ninety-six patients were enrolled. Peritoneal wash cytology was performed before and after NIPS through a port system. Patients were treated with 60 mg/m2 of oral S-1 for 21 days, followed by a 1-week rest. On days 1, 8, and 15, 30 mg/m2 of Taxotere and 30 mg/m2 of cisplatin with 500 mL of saline were introduced through the port. NIPS is done 2 cycles before surgery. Three weeks after NIPS, 82 patients were eligible to intend cytoreductive surgery (CRS) by gastrectomy + D2 dissection + periotnectomy to achieve complete cytoreduction. Sixty-eight patients showed positice cytology before NIPS, and the positive cytology results became negative in 47 (69%) patients after NIPS. Complete pathologic response on PC after NIPS was experienced in 30 (36.8%) patients. Stage migration was experienced in 12 patients (14.6%). Complete cytoreduction was achieved in 58 patients (70.7%). By the multivariate analysis, complete cytoreduction and pathologic response became a significantly good survival. However the high morbidity and mortality, stringent patient selection is important. The best indications of the therapy are patients with good pathologic response and PCI≤6, which are supposed to be removed completely by peritonectomy

Morbidity and Mortality Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy at a Single Institution in Japan

Background. Even though cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are associated with a high morbidity and mortality rates, it has been reported that CRS and HIPEC improved survival of selected patients with peritoneal carcinomatosis. We aimed to report morbidity and mortality results of CRS and HIPEC from a single institution in Japan. Methods and Results. Total of 284 procedures of CRS were performed on patients with pseudomyxoma peritonei, peritoneal carcinomatosis (PC) from colon cancer and gastric cancer between 2007 and 2011 in our institution. The morbidity rate was 49% of all procedure, and grades I/II and grades III/IV complications were 28% and 17%, respectively. Most frequent complication was surgical site infections including intraabdominal abscess. The mortality rate was 3.5%, and reoperation was needed in 11% of all procedures. Univariate and multivariate analysis showed peritoneal carcinomatosis index (PCI) greater than 20 was the only significant factor for occurrence of postoperative complications (P<0.01). In contrast, HIPEC significantly reduced postoperative complications (P<0.05). Conclusions. The morbidity and mortality rates of our institution are comparable with previous reports that are in acceptable rates. Optimal patient selection such as patients with PCI less than 20 seems to be of paramount importance to CRS and HIPEC

Cytoreductive surgery for synchronous and metachronous colorectal peritoneal dissemination: Japanese P classification and peritoneal cancer index

Abstract Aim The outcomes of cytoreductive surgery (CRS) for synchronous and metachronous colorectal peritoneal dissemination were investigated using the Japanese P classification and peritoneal cancer index (PCI). Methods CRS was performed in 111 cases of synchronous peritoneal dissemination and 115 cases of metachronous peritoneal dissemination. The P classification and PCI were determined at the time of laparotomy. Results In the synchronous dissemination group, the 5‐year overall survival rates after CRS in P1/P2 and P3 cases were 51% and 13%, respectively. Even for P3, 51% of the patients achieved macroscopic cytoreductive complete resection (CC‐0), with a 5‐year survival rate of 40%. When P3 cases were classified into PCI 0–9, 10–19, 20–29, and 30–39, CC‐0 was achieved in 93%, 70%, 6%, and 0% of the cases, respectively, and the 5‐year survival rate of PCI 0–9 was 41%. In the metachronous dissemination group, the 5‐year survival rates were 62% for PCI 0–9 and 22% for PCI 10–19; 5‐year survival was not observed in patients with a PCI ≥ 20. CC‐0 was significantly associated with the postoperative prognosis in both synchronous and metachronous peritoneal dissemination. Conclusion In cases of synchronous dissemination, CRS must be performed for P1 and P2 cases or those with a PCI < 10, while detailed examination using PCI is required for P3 cases. In cases of metachronous dissemination, CRS should be considered when the PCI score is <20

Multidisciplinary therapy for treatment of patients with peritoneal carcinomatosis from gastric cancer

There is no standard treatment for peritoneal carcinomatosis (PC) from gastric cancer. A novel multidisciplinary treatment combining bidirectional chemotherapy [neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)], peritonectomy, hyperthermic intraperitoneal chemoperfusion (HIPEC) and early postoperative intraperitoneal chemotherapy has been developed. In this article, we assess the indications, safety and efficacy of this treatment, review the relevant studies and introduce our experiences. The aims of NIPS are stage reduction, the eradication of peritoneal free cancer cells, and an increased incidence of complete cytoreduction (CC-0) for PC. A complete response after NIPS was obtained in 15 (50%) out of 30 patients with PC. Thus, a significantly high incidence of CC-0 can be obtained in patients with a peritoneal cancer index (PCI) ≤ 6. Using a multivariate analysis to examine the survival benefit, CC-0 and NIPS are identified as significant indicators of a good outcome. However, the high morbidity and mortality rates associated with peritonectomy and perioperative chemotherapy make stringent patient selection important. The best indications for multidisciplinary therapy are localized PC (PCI ≤ 6) from resectable gastric cancer that can be completely removed during a peritonectomy. NIPS and complete cytoreduction are essential treatment modalities for improving the survival of patients with PC from gastric cancer

Long Term Survival after Cytoreductive Surgery Combined with Perioperative Chemotherapy in Gastric Cancer Patients with Peritoneal Metastasis

The present study demonstrated prognostic factors for long-term survival in patients after a comprehensive treatment (CHT) for peritoneal metastasis (PM) from gastric cancer (GC). Materials and Methods: Among 419 patients treated with neoadjuvant intraperitoneal/systemic chemotherapy (NIPS), 266 (63.5%) patients received complete resection (CC-0) of the macroscopic tumors. In total, 184 (43.9%) patients were treated with postoperative systemic chemotherapy. Results: All patients treated who received incomplete cytoreduction (CC-1) died of GC within 6 years. In contrast, 10- year survival rates (-YSR) of CC-0 resection were 8.3% with median survival time (MST) of 20.5 months. Post-NIPS peritoneal cancer index (PCI) &le;11, and pre-NIPS PCI &le;13 were the significant favorable prognostic factors. Patients with numbers of involved peritoneal sectors &le;5 survived significant longer than those with &ge;6. Both negative pre- and post-NIPS cytology was associated with significant favorable prognosis. Multivariate analyses identified pre-PCI (&le;13 vs. &ge;14), and cytology after NIPS (negative cytology vs. positive cytology) as independent prognostic factors. Ten year-survivors were found in patients with involvement of the greater omentum (9%), pelvic peritoneum (3%), para-colic gutter (13.9%), upper jejunum (5.6%), lower jejunum (5.5%), spermatic cord (21.9%), rectum (9.5%), ureter (6.3%), ovary (6.7%), and diaphragm (7.0%) at the time of cytoreduction. Twenty-one patients survived longer than 5 years, and 17 patients are still alive without recurrence. Conclusions: GC-PM should be removed aggressively, in patients with PCI after NIPS &le;11, PCI before NIPS &le;13, mall bowel PCI &le;2, and complete cytoreduction should be performed for metastasis in &le;5 peritoneal sectors

Retrospective Analysis of Patients with Signet Ring Subtype of Colorectal Cancer with Peritoneal Metastasis Treated with CRS &amp; HIPEC

Signet ring cell subtype (SRC) of colorectal cancer (CRC) is a rare subtype and occurs in approximately 1% of all patients with CRC. Patients with peritoneal metastasis (PM) of SRC have a poor prognosis, and this subtype is frequently considered as a contra-indication for extensive surgical treatment. This retrospective study from two dedicated peritoneal surface malignancy centers in Japan included all patients treated with CRS &plusmn; hyperthermic intraperitoneal chemotherapy (HIPEC) between July 1994 and December 2017 from a prospectively maintained database. Preoperative, operative, and postoperative parameters were recorded, including complication rates and follow-up. Sixty of the 320 patients treated with CRS due to CRC were diagnosed with SRC subtype. The mean age of the patients was 51.4 years, and the mean peritoneal carcinomatosis index (PCI) was 13.1. Complete cytoreduction was achieved in 61.7% of cases. The postoperative morbidity rate was 25% and the mortality rate was 1.7%. The median overall survival (OS) was 14.4 months. Cox regression analysis revealed small bowel PCI &gt; 2 (hazard ratio (HR) 6.5; p = 0.008) as the most important factor for OS. With accurate patient selection (e.g., PCI &le; 12 or small bowel PCI &le; 2), even patients with PM of CRC with SRC subtype may benefit from CRS and HIPEC, with median OS from 17.8 to 20.8 months and 5-year OS of 11.6%