Thirty-three long-term survivors after cytoreductive surgery in patients with peritoneal metastases from colorectal cancer: a retrospective descriptive study.

BACKGROUND: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in selected patients with peritoneal metastasis (PM) from colorectal cancer (CRC). However, little has been reported on characteristics and clinical course of long-term survivors with CRC-PM beyond 5 years. The objective of this study was to identify the clinical and oncological features affecting long-term survival of CRC-PM after comprehensive treatment. METHODS: Between January 1990 and April 2015, CRC-PM patients who underwent CRS with or without HIPEC in two Japanese tertiary hospitals were analyzed. Clinicopathological parameters and therapeutic details for long-term survivors (patients surviving ≥ 5 years after CRS) were described and compared with those for non-survivors (patients surviving < 5 years). RESULTS: The study identified 236 patients with CRC-PM who underwent CRS, with a median follow-up period of 2.5 years. Thirty-three patients (14.0%) were considered as long-term survivors. Compared with non-survivors, long-term survivors had a lower median peritoneal cancer index (PCI) [4 (1-27) vs 9 (0-39), p < 0.001]. Complete cytoreduction (CCR-0) was achieved in all long-term survivors, with a significantly higher rate [33/33 (100%) vs 141/203 (69.8%), p < 0.001]. Metachronous onsets of PM were more frequently observed in the long-term survivor group [26/33 (78.8%) vs 103/203 (50.3%), p = 0.018]. Regarding histopathology, long-term survivors more frequently had mucinous adenocarcinoma than non-survivors [8/33 (24.2%) vs 27/203 (13.3%)] and less likely exhibited poorly differentiated or signet ring cell carcinoma [2/33 (6.1%) vs 48/203 (23.7%)] (p < 0.001). CONCLUSIONS: One in seven patients with CRC-PM achieved the long-term milestone after CRS. A long-term survival was associated with the presence of low PCI, CCR-0, metachronous onset, and mucinous histology.

Retrospective Analysis of Patients with Signet Ring Subtype of Colorectal Cancer with Peritoneal Metastasis Treated with CRS & 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 ± 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 > 2 (hazard ratio (HR) 6.5; p = 0.008) as the most important factor for OS. With accurate patient selection (e.g., PCI ≤ 12 or small bowel PCI ≤ 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%.

Neoadjuvant Intraperitoneal Chemotherapy in Patients with Pseudomyxoma Peritonei-A Novel Treatment Approach.

Neoadjuvant intravenous chemotherapy in patients with pseudomyxoma peritonei (PMP) has not shown convincing results. The effectiveness of neoadjuvant intraperitoneal (IP) chemotherapy has never been reported. This prospective, non-randomized phase II study included patients with PMP treated between May 2017 and December 2018, who were not considered suitable for primary cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The majority of patients were treated with laparoscopic HIPEC (oxaliplatin 200 mg/m2, 60 min, 43 °C). IP chemotherapy was started 2 weeks after docetaxel 40 mg/m2 + cisplatin 40 mg/m2, accompanied by oral S1 (tegafur, gimeracil, and oteracil) (50 mg/m2) for 14 days, followed by one week rest. Clinical parameters and complications were recorded. In total, 22/27 patients qualified for CRS and HIPEC after neoadjuvant treatment. A complete cytoreduction (Completeness of cytoreduction Score 0/1) could be achieved in 54.5%. The postoperative morbidity rate was 13.6% and mortality was rate 4.5%. In total, 20/22 patients had major pathological tumor responses. The mean drop in CEA was 28.2% and in the peritoneal carcinomatosis index (PCI) was 2.6. Positive or suspicious cytology turned negative in 69.2% of patients. Thus, for PMP patients who were not amenable for primary surgery, the majority received complete cytoreduction after treatment with neoadjuvant IP chemotherapy, with satisfying tumor regression and with low complication rates. The oncological benefit in terms of survival with this new treatment regimen needs to be proven.

Advances with pharmacotherapy for peritoneal metastasis.

INTRODUCTION: A new treatment strategy involving cytoreductive surgery (CRS) combined with perioperative intraperitoneal (IP) chemotherapy was proposed in 1999 by the Peritoneal Surface Oncology Group International, and the strategy is now justified as a state-of-the-art treatment to improve the long-term survival of patients with peritoneal metastasis (PM). To achieve cure in the patients with PM, complete removal of macroscopic tumors and eradication of micrometastasis on the peritoneum, left after CRS are essential. Systemic chemotherapy is not indicated for the treatment of PM. In contrast, intraperitoneal (IP) chemotherapy brings about significantly higher locoregional dose intensity in the peritoneal cavity and subperitoneal tissues. In combination with anticancer drugs, hyperthermia enhances cytotoxicity against cancer cells. AREA COVERED: This article provides a systematic overview of PM from various cancers including gastric, colorectal, small bowel, appendiceal cancer, and mesothelioma. It also includes all the essential aspects of therapy. EXPERT OPINION: CRS plus perioperative intraperitoneal chemotherapy is safe with acceptable morbidity and mortality. It is justified as a standard treatment to improve the long-term survival of patients with PM and is now performed with curative intent for PM from various malignancies.

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) ≤11, and pre-NIPS PCI ≤13 were the significant favorable prognostic factors. Patients with numbers of involved peritoneal sectors ≤5 survived significant longer than those with ≥6. Both negative pre- and post-NIPS cytology was associated with significant favorable prognosis. Multivariate analyses identified pre-PCI (≤13 vs. ≥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 ≤11, PCI before NIPS ≤13, mall bowel PCI ≤2, and complete cytoreduction should be performed for metastasis in ≤5 peritoneal sectors.

History of Peritoneal Surface Malignancy Treatment in Japan.

In this review, Japanese experience of cytoreductive surgery and perioperative chemotherapy is described. The new concept of peritoneal metastasis (PM) type, i.e., trans-mesothelial, trans-lymphatic, and superficial growing metastasis type was proposed in 2012. Surgeons should perform peritonectomy according to the type of PM. Since 1980, Japanese surgical oncologists have been spearheading the use of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemoperfusion (HIPEC) as treatment for PM from gastric cancer. Two RCTs were conducted to verify the effect of HIPEC for the prophylaxis of peritoneal recurrence after curative resection of advanced gastric cancer. These two studies indicated that HIPEC is effective in preventing peritoneal recurrence of gastric cancer with serosal invasion. In 2002, intraperitoneal chemotherapy using taxans was developed for the treatment of PM from gastric cancer and led to the development of neoadjuvant intraperitoneal/systemic chemotherapy (NIPS), which was reported in 2006. In 2009, extensive intra-operative peritoneal lavage (EIPL) was developed, and contributed to the remarkable improvement in survival of patients with positive lavage cytology as demonstrated by prospective randomized clinical trials. In 2017, the Peritoneal Surface Oncology Group International proposed the value of complete cytoreduction and peritoneal cancer index cut-off as independent prognostic factors after CRS for gastric cancer with PM. Founded in 2016, the Japanese/Asian School of Peritoneal Surface Oncology (JASPSO) trains beginners to perform CRS and HIPEC safely. Sixteen students have already graduated from JASPSO and started to perform the treatment in their home countries.

Prognostic Factors of Malignant Peritoneal Mesothelioma Experienced in Japanese Peritoneal Metastasis Center.

BACKGROUND AND OBJECTIVES: The current standard of treatment for malignant peritoneal mesothelioma(MPM)is cytoreductive surgery(CRS)plus perioperative intraperitoneal or systemic chemotherapy(comprehensive treatment), The present study was performed to clarify the prognostic factors of PMP after comprehensive treatment. METHODS: Among 63 patients with MPM, male and female patients were 34 and 29. CRSwas performed in 47 patients and complete cytoreduction(CC-0) was performed in 14(22%)patients. Mean numbers of resected peritoneal sectors and organs were 5.2(1-13), and 2.9(0- 9), respectively. Hyperthermic intraperitoneal chemoperfusion(HIPEC)was performed in 27 patients. Grade 1/2, Grade 3, and Grade 4 complications were experienced in 5, 6, and 3 patients, respectively. One patient died of sepsis, and the mortality rate was 2.3%. Independent prognostic factors for favorable prognosis were performance of HIPEC, peritoneal cancer index (PCI)score C12, no distant metastasis and histologic epithelial type. Relative risk of no HIPEC, PCI score B13, presence of distant metastasis and non epithelial type were 7.69, 22.1, 3.6 and 3.9, respectively. CONCLUSIONS: Risk factors for death after comprehensive treatment were no HIPEC, PCI score B13, and non epithelial type. However, only 11(17%)patients showed PCI score C12. Accordingly, PCI score should be reducedC12 before CRSby neoadjuvant chemotherapy.

Analysis of Treatment Failure after Complete Cytoreductive Surgery for Peritoneal Metastasis from Appendiceal Mucinous Neoplasm at a Japanese High Volume Center for Peritoneal Surface Malignancy.

BACKGROUND AND OBJECTIVES: Treatment failure after complete cytoreduction for appendiceal mucinous carcinoma peritonei (AMCP)has not been fully investigated. The present study was performed to clarify the risk factor for recurrence after complete cytoreduction for AMCP. METHODS: A total of 400 patients with AMCP who underwent complete cytoreductive surgery combined with perioperative chemotherapy were investigated. RESULTS: Documented recurrence was developed in 135 (33.8%)patients. The 5- and 10-year progression-free survival was 51% and 49%, respectively. By multivariate analysis, histological subtype of peritoneal disease(high-grade AMCP[AMCP-H]and AMCP-H with signet ring cells), serum CA19- 9 level, and PCIB20 were significantly associated with reduced progression-free survival. In contrast, histologic subtype of mucin without epithelial cells(MWEC)showed the lowest risk for recurrence. Eighty-six patients had localized intra-abdominal recurrence, and 42 patients had diffuse peritoneal recurrence. Recurrence was found in the various peritoneal sectors. Eighty-one patients underwent complete cytoreduction for the recurrence, and the overall survival 5-year survival rate after secondary cytoreduction was 49%. CONCLUSIONS: Risk factors for recurrence were histologic subtype, PCI cutoff level, and serum CA19-9 levels. Aggressive second attempt of cytoreduction in patients with localized recurrence improved the survival.

Effects of Cytoreductive Surgery Combined with Perioperative Chemotherapy on Long-Term Survivals of Colorectal Cancer Patients with Peritoneal Metastasis, with Special Reference to the Involved Peritoneal Sectors and Organs.

Peritoneal Surface Oncology Group International(PSOGI)proposed a novel treatment, named comprehensive treatment for peritoneal metastasis(PM)from colorectal cancer(CRC). The present study demonstrated the efficacies of the treatment regarding the peritoneal sectors and organs involved with PM from CRC. MATERIALS AND METHODS: Among 365 patients received laparotomy, 278 CRC patients with PM underwent complete cytoreductive surgery(CC-0). RESULTS: After CC-0 resection Grade 3, Grade 4, and Grade 5 postoperative complication were found in 20(7.2%), 26(9.3%), and 6(2.2%). Five- and 10-year survival rate(YSR)of CC-0 resection were 24.5%, and 11.6% with median survival time(MST)of 42.0 months. Regarding the peritoneal cancer index(PCI)of small bowel(SB-PCI), all patients of PCI B3 died of the disease. In contrast, 10-YSR of patients with SB-PCI of 0, 1, and 2 were 26.1%, 19.5%, and 6.2%, respectively. Ten-YSR of patients with the number of involved peritoneal sectors C9 ranged from 6.9% to 29.8%. MST of patients with PM in each peritoneal sector(sector 0 to sector 8)ranged from 26.4 months to 49.2 months, and 10-YSR ranged from 4.2%to 17.2%. Ten-YSR of patients with involvement of rectum, stomach, liver capsule, seminal vesicle, ureter, uterus, or ovary ranged from 0% to 16.9%. CONCLUSIONS: From the present data, PM should be removed aggressively to achieve complete cytoreduction, when the patients with PCIC26, involved peritoneal sectorsC9 and SB-PCIC2 are supposed to receive complete cytoreduction of PM.

Photodynamic Detection of Peritoneal Metastases Using 5-Aminolevulinic Acid (ALA).

In the past, peritoneal metastasis (PM) was considered as a terminal stage of cancer. From the early 1990s, however, a new comprehensive treatment consisting of cytoreductive surgery and perioperative chemotherapy has been established to improve long-term survival for selected patients with PM. Among prognostic indicators after the treatment, completeness of cytoreduction is the most independent predictors of survival. However, peritoneal recurrence is a main cause of recurrence, even after complete cytoreduction. As a cause of peritoneal recurrence, small PM may be overlooked at the time of cytoreductive surgery (CRS), therefore, development of a new method to detect small PM is desired. Recently, photodynamic diagnosis (PDD) was developed for detection of PM. The objectives of this review were to evaluate whether PDD using 5-aminolevulinic acid (ALA) could improve detection of small PM.

A case of ovarian growing teratoma syndrome treated by cytoreductive surgery.

Ovarian growing teratoma syndrome (GTS) is a rare disease characterized by growth of a benign tumor during or after chemotherapy, following the removal of germ cell gonadal cancers. Although benign, GTS tumors grow gradually and may compress surrounding organs. In addition, up to 3% of GTS cases can undergo malignant transformation. It is, therefore, needed to treat GTS. No standardized management protocol has been established to treat GTS; however, surgical resection is likely the only effective treatment because tumors in GTS are resistant to chemotherapy and radiation therapy. However, complete resection with conventional procedures is sometimes difficult when peritoneal metastasis is widespread. We report a rare case of ovarian GTS with widespread peritoneal metastases, which was totally resected by peritonectomy procedures. A 45-year-old Japanese woman was initially diagnosed with an immature teratoma grade 3, which was treated by hysterectomy and bilateral salpingo-oophorectomy. Adjuvant chemotherapy was performed after surgery with bleomycin, etoposide, cisplatin, and other chemotherapies. Due to recurrence of a chemoresistant tumor and normalization of tumor markers, GTS was suspected. She was referred to our institute, and complete cytoreductive surgery was performed using peritonectomy procedures, including parietal peritoneal resection, greater omentectomy, lesser omentectomy, rectosigmoid colectomy, diaphragm dissection, and cholecystectomy. A complete cytoreduction with no visible residual tumor tissue was achieved.

Comprehensive Treatment Using Cytoreductive Surgery Combined with Perioperative Chemotherapy Improved Outcome of Colorectal Cancer Patients with Metachronous Peritoneal Metastasis.

To analyze the role of cytoreductive surgery(CRS)plus perioperative chemotherapy on the survival of colorectal cancer(CRC)patients with metachronous peritoneal metastasis(PM). A comprehensive treatment consisting of neoadjuvant chemotherapy plus CRS was performed in 291 CRC patients. Among the 291, 142 and 149 patients had synchronous and metachronous PM, respectively. The results showed no survival difference between the 2 groups. Median survival time(MST)of patients with metachronous PM with complete cytoreduction(CCR-0), small bowel(SB)-PCIC2, PCIC14 and differentiated histologic type ranged from 3.1 to 4.1 years. Five-year survival rates of metachronous group of the CCR-0, SB-PCIC2, PCI C14 and differentiated histologic type ranged from 25.8 to 38.9%. However, the 5-year survival rates of the incomplete cytoreduction(CCR-1), SB-PCIB3, PCIB15 and poorly differentiated type were significantly lower than those of the CCR-0, SB-PCIC2, PCIC14 and differentiated histologic type. Postoperative Grade 3, and Grade 4 morbidity were experienced in 11(5.8%)and 16(10.7%)in metachronous group. Mortalities of metachronous group were 1.3%(2/149). The comprehensive treatment can be performed safely and improves the survival of CRC patients with metachronous PM. After NAC, patients with SB-PCIC2, PCIC14 and differentiated type of histology are candidates for CRS, and CCR-0 resection combined with HIPEC is recommended.

Effects of Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy and Neoadjuvant Intraperitoneal/Systemic Chemotherapy on Peritoneal Metastases from Gastric Cancer.

BACKGROUND: The Peritoneal Cancer Index (PCI) is the most important prognostic factor following comprehensive treatment for peritoneal metastasis (PM) from gastric cancer (GCPM); however, 70 % of patients with GCPM showed a PCI score above the cut-off level at the time of diagnosis. Furthermore, neoadjuvant chemotherapy may reduce the PCI score to lower than the cut-off levels. In this study, the effects of neoadjuvant laparoscopic hyperthermic intraperitoneal chemoperfusion (NLHIPEC) and neoadjuvant intraperitoneal/systemic chemotherapy (NIPS) were investigated. MATERIALS AND METHODS: In group A, NLHIPEC was performed twice in 53 patients with GCPM, separated by a 1-month rest interval. Changes in the PCI were studied at the time of first and second laparoscopy. In group B, after NLHIPEC, a series of 3-week cycles of NIPS were performed over three courses in 52 patients. A laparotomy for cytoreductive surgery (CRS) was then carried out and the PCI changes were studied. RESULTS: In group A, the PCI score at the time of the second session (11.8 ± 11.0) was significantly lower than at the time of the first session (14.2 ± 10.7), while in group B, the PCI at the time of laparotomy (9.9 ± 11.3) was significantly lower than at the time of NLHIPEC (14.8 ± 11.4). After NLHIPEC plus NIPS, complete cytoreduction was achieved in 30 (57.6 %) patients. CONCLUSIONS: NLHIPEC and NIPS are effective methods of reducing PCI levels before CRS.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Dissemination from Small Bowel Malignancy: Results from a Single Specialized Center.

BACKGROUND: Peritoneal dissemination is a frequent pattern of recurrence and metastasis of small bowel malignancy (SBM). However, the survival of patients with peritoneal dissemination from SBM is not clear, and there is no consensus on the treatment for it. PATIENTS AND METHODS: A total of 31 selected patients with peritoneal dissemination from SBM were treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) between January 2006 and January 2014. The major focus of this study was overall survival, as well as morbidity and mortality. RESULTS: Twenty-five patients had small bowel adenocarcinoma (SBA), and six patients had non-adenocarcinoma SBM. HIPEC was performed on 21 patients, and 21 patients received complete cytoreduction. There was no treatment-related mortality, and eight (25.8 %) patients had grade 3-4 complications. Until the latest follow-up, the median survival of 31 patients after CRS and HIPEC was 36 months (range 5-95 months), and the median survival after diagnosis was 51 months (range 18-101 months). For 25 patients with peritoneal carcinomatosis from SBA, the median survival after CRS and HIPEC was 36 months (range 6-95 months), and the median survival after diagnosis was 50 months (range 18-101 months). Multivariate analysis revealed that peritoneal cancer index <15 (p = 0.009) and HIPEC (p < 0.001) were independent predictors of better survival in patients with peritoneal dissemination from SBM treated by CRS and HIPEC. CONCLUSIONS: Until more data become available, a reasonable strategy for the treatment of SBM is CRS and HIPEC. It can be applied with acceptable safety in selected patients with peritoneal dissemination from SBM.

Treatment Failure Following Complete Cytoreductive Surgery for Peritoneal Metastasis from Colorectal Cancer.

Treatment failure after complete cytoreduction for peritoneal metastasis(PM)from colorectal cancer(CRC)has not been fully investigated. The present study was performed to clarify the risk factors for recurrence after complete cytoreduction for CRC with PM and the role of repeat surgery for recurrence. MATERIALS AND METHODS: A total of 205 patients with CRC who underwent complete cytoreductive surgery combined with perioperative chemotherapy were investigated. RESULTS: Recurrence occurred in 149(73%)patients. The 5-year overall and progression-free survival rates were 26%and 7%, respectively. By multivariate analysis, positive cytology, serum CEA level higher than normal range, and small bowel peritoneal cancer index B3 were significantly associated with reduced progression-free survival. Blood-borne recurrence was found in 62 (44%)of 149 patients. Repeat surgery was performed in 44(30%), and complete removal was performed in 28(64%) patients. Long-term survival after repeat surgery was experienced in patients with localized peritoneal recurrence and/or liver recurrence. CONCLUSIONS: This study showed that a second attempt at cytoreduction in patients with localized intra-abdominal and liver recurrence is of benefit. Blood-borne recurrence was found in 44% of recurrent patients. The prophylaxis of recurrence should therefore be performed using systemic chemotherapy after CRS plus HIPEC.

Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei Arising from Urachus.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare locoregional disease characterized by disseminated intraperitoneal mucinous tumors. However, little is known about PMP from urachal neoplasm as a result of its rarity. METHODS: A total of 9 patients with PMP of urachal origin were treated by cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in our institution. All specimens of surgeries were submitted for pathologic examination. Representative slides of tumors and normal urachus were submitted for immunohistochemical staining. RESULTS: Four patients were men; the median age was 48 years (range 27-65 years). Initial radiologic examination of all patients showed a cystic tumor located between posterior aspect of umbilicus and the dome of urinary bladder, with or without leaking mucin. Complete CRS and HIPEC were performed in all patients. Until the latest follow-up, local recurrence occurred in 1 patient. Other 8 patients had a median disease-free survival of 27.5 months. Primary urachal tumors of 9 cases were all mucinous adenocarcinoma. Six patients had low-grade mucinous carcinoma peritonei, and 3 patients had high-grade mucinous carcinoma peritonei. Signet ring cells were noted in 4 patients. All tumor specimens of 9 patients were diffuse positive for CK-20, CDX-2, MUC-2, and MUC-5AC, and were variant positive for CK-7. CONCLUSIONS: PMP arising from urachus comes from neoplastic cells with development of intestinal-type mucinous neoplasm. It shares a similar pathophysiology as PMP from appendix. CRS including total urethrectomy, partial cystectomy, and peritonectomy plus HIPEC can be considered as a new option of treatment for PMP originating from urachus.

[A case of gastric adenosquamous carcinoma with peritoneal dissemination in which treatment with S-1 plus paclitaxel therapy resulted in improved long-term survival].

Gastric adenosquamous carcinoma is a rare malignancy with a poor prognosis. We recently performed palliative gastrectomy for a gastric adenosquamous carcinoma with peritoneal dissemination and provided a course of systemic chemotherapy with S-1 plus paclitaxel(PTX)after the surgery. No serious adverse events were observed, and treatment with S-1 plus PTX was continued for 1 year before being switched to adjuvant chemotherapy with S-1 alone for another year. The tumor maker levels normalized within 2 months of the initial treatment, and the peritoneal dissemination could no longer be detected by abdominal computed tomography(CT). The patient remained in clinical remission and maintained long-term survival of over 8 years.

Peritoneal cancer treatment.

INTRODUCTION: In the past, peritoneal surface malignancy (PSM) was considered as a final stage of cancer, and patients were offered the best supportive care. Recently, a new therapeutic alternative approach based on the combination of surgery with chemotherapy was developed. In this curative intent, the macroscopic disease was treated with cytoreductive surgery (CRS) combined with perioperative chemotherapy, including neoadjuvant chemotherapy, hyperthermic intraoperative intraperitoneal chemotherapy, extensive intraoperative peritoneal lavage and early postoperative intraperitoneal chemotherapy AREAS COVERED: This article reviews the mechanisms of the formation of PSM, quantitative estimation of PSM and residual disease, multimodal treatment, value of laparoscopy, prognostic factors and patients' selection for the multimodal therapy. EXPERT OPINION: Recent studies show that CRS plus intraperitoneal chemotherapy applications confer prolonged survival in patients with PSM from colorectal, gastric, ovarian, appendiceal mucinous carcinoma and diffuse malignant peritoneal mesothelioma. The comprehensive treatment is now justified as state-of-the-art for patients with peritoneal metastasis.

Pharmacokinetics of docetaxel during hyperthermic intraperitoneal chemotherapy for peritoneal metastasis.

UNLABELLED: The purpose of this manuscript is to report the pharmacokinetics of docetaxel during hyperthermic intraperitoneal chemotherapy (HIPEC) after peritonectomy. MATERIALS AND METHODS: Eleven patients with peritoneal metastasis (PM) underwent peritonectomies combined with 40 min of HIPEC with 40 mg/body of docetaxel. The pharmacokinetics of docetaxel were studied by using high-performance liquid chromatography. RESULTS: The docetaxel concentration at the start of HIPEC (0 min) was 9.084 ± 0.972 mg/L. The concentration gradually decreased to 5.599 ± 0.458 mg/L 40 min after HIPEC. In contrast, serum docetaxel levels increased during HIPEC, reaching a maximum level of 0.1334 ± 0.0726 mg/L at 40 min. The clearance (CLp) was 3.164 ± 1.383 L/hr, and the area under the curve (AUC) ratio was 95.12 ± 87.32. The AUC ratio of less-extensive peritonectomies was significantly higher than that of extended peritonectomies. The docetaxel concentration in the tumor tissue increased at 40 min (4.45 mg/gr). The apparent permeability (Papp, 40 min) was 1.47 ± 0.67 mm/40 min. No severe adverse effects were observed after HIPEC. CONCLUSION: From these results, 40 mg is a safe dose for docetaxel combined with HIPEC, and the locoregional intensity of docetaxel is enough to control PM less than 1.47 mm in diameter.