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.

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.

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.

Photodynamic detection and management of intraperitoneal spreading of primary peritoneal papillary serous carcinoma in a man: report of a case.

As a peritoneal surface malignancy, primary peritoneal papillary serous carcinoma (PPPSC) almost always occurs in women. Our search of the literature found only two previous case reports of men with PPPSC, both with very short survival. We report the case of a 63-year-old man with PPPSC, treated effectively with cytoreductive surgery and docetaxel-based hyperthermic intraperitoneal chemotherapy following six cycles of docetaxel-based laparoscopic neoadjuvant intraperitoneal and cisplatin-based systemic chemotherapy. Furthermore, we detected intraoperative intraperitoneal spreading of the tumor after the oral administration of 5-amino levulinic acid (5-ALA). The patient remains in good health without ascites 18 months after his diagnosis. Thus, primary peritoneal papillary serous carcinoma should be managed by intraperitoneal chemotherapy combined with peritonectomy procedures. Moreover, the intraoperative detection of the intraperitoneal spreading of the tumor after administering oral 5-ALA shows that this is an exciting and promising diagnostic technique, which needs to be confirmed by further studies.

Outcome data of patients with peritoneal carcinomatosis from gastric origin treated by a strategy of bidirectional chemotherapy prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a single specialized center in Japan.

BACKGROUND: Management of peritoneal disseminated gastric cancer (GC) remains a challenging problem. The purpose of our study was to evaluate the outcome of bidirectional induction chemotherapy [bidirectional intraperitoneal and systemic induction chemotherapy (BIPSC)] in patients with peritoneal carcinomatosis (PC) arising from GC who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: Overall, 194 patients with PC arising from GC were treated with BIPSC comprising intraperitoneal docetaxel at a dose of 20 mg/m(2) and cisplatin at a dose of 30 mg/m(2) followed by four cycles of oral S-1 at a dose of 60 mg/m(2). CRS and HIPEC were performed in responders to BIPSC. RESULTS: Of these 194 patients, 152 (78.3 %) underwent CRS and HIPEC between January 2005 and December 2012. Treatment-related mortality was 3.9 %, and major complications occurred in 23.6 % of patients. The median survival rate was 15.8 months, with 1-, 2-, and 5-year survival rates of 66, 32 and 10.7 %, respectively, in the patients treated with combined treatment. Multivariate analysis identified pathologic response to BIPSC (p = 0.001), low tumor burden [peritoneal cancer index (PCI) ≤ 6] (p = 0.001), and completeness of CRS (CC-0, CC-1) (p = 0.001) as independent predictors for a better prognosis. CONCLUSION: As a viable option, BIPSC with CRS and HIPEC for patients with PC arising from GC may be performed safely, with acceptable morbidity and mortality, in a specialized unit. Response to BIPSC, optimal CRS and limited peritoneal dissemination seem to be essential to achieve the best outcomes in these patients.

Preoperative carcinoembryonic antigen level predicts prognosis in patients with pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Even though management of pseudomyxoma peritonei (PMP) was improved with cytoreductive surgery (CRS) and hyperthermic chemotherapy (HIPEC), several aspects of PMP still need to be optimized, including patient selection for surgery and prognostic factors. We assessed the role of preoperative carcinoembryonic antigen (CEA) levels in PMP patients treated with CRS and HIPEC. METHODS: A total of 449 PMP patients with documented preoperative CEA levels referred to our center between 2005 and 2011 underwent CRS and HIPEC. The association between CEA levels and characteristics of patients with PMP was assessed with χ (2) test, linear correlation, and logistic regression analyses. Survival analysis was performed with Cox proportional hazard model. RESULTS: Median age was 55 (range 19-84) years. There were 245 (54.5 %) females and 204 (45.5 %) males. Preoperative CEA levels were elevated in 328 (73 %, sensitivity) patients with PMP. Preoperative CEA levels were also related to peritoneal cancer index (P < 0.0001), cytoreductive surgery scores (P < 0.0001), progress free survival (P < 0.001) and overall survival (P < 0.001) in patients with PMP. CONCLUSIONS: Our results indicated that preoperative CEA levels are useful in predicting the extent of disease and surgical success as well as progress-free and overall survival in patients with PMP treated with cytoreductive surgery and HIPEC.

Treatment results of diffuse malignant peritoneal mesothelioma.

During the last 7 years, 21 patients with DMPM were treated. Histologic types were epitheloid type in 18 patients, biphasic type in 2 patients and sarcomatoid type in 1 patient. Preoperative systemic chemotherapy, hyperthermic intraperitoneal chemotherapy(HIPEC) by laparoscopy(LHIPEC), and intraperitoneal(IP) chemotherapy were done in 14, 3 and 1 patients, respectively. Cytoreductive surgery(CRS) was done in 13 patients. Ten patients received HIPEC after CRS. Partial responses were experienced in 4 of 13 patients treated with preoperative systemic chemotherapy. One of three patients treated by LHIPEC showed complete response. Among 13 patients received laparotomy, complete removal of PC was done in 4(31%) patients. The other 9 patients who received incomplete cytoreduction had diffuse involvement on the small bowel and its mesentery. All over 5-year survival was 17%. Patients treated with HIPEC survived significantly longer than non-HIPEC group. Neoadjuvant laparoscopic HIPEC may have a great role in the preoperative control of small PC on the surface of small bowel.

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.

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.

Treatment results of peritonectomy combined with perioperative chemotherapy for colorectal cancer-patients with peritoneal carcinomatosis.

Operation results of 81 colorecatal cancer-patients with peritoneal carcinomatosis (PC) treated with peritonectomy plus perioperative chemotherapy are reported. The patients who had the following evidences are considered to be eligible for peritonectomy: 1) No evidence of N3 lymph node involvement, 2) No evidence of hematogenous metastasis, 3) No progressive disease after preoperative chemotherapy, 4) No severe co-morbidities or no poor general condition. Complete cytoreduction resection is aimed for removing all macroscopic tumors by peritonectomy using electrosurgical techniques. The completeness of cytoreduction (CC scores) after peritonectomy is classified into the following 4 criteria: CC-0-no peritoneal seeding was exposed during the complete exploration, CC-1-residual tumor nodules are less than 2.5 mm in diameter, CC-2-nodules are between 2 .5 mm and 25 mm in diameter, CC-3-nodules are greater than 25 mm in diameter, CC-2 and CC-3 are regarded as incomplete cytoreduction. Operation time and blood loss were 237 ± 124 min. (799-90 min) and 1,598 ± 1,411 mL (6,500-20 mL), respectively. Postoperative complications developed in 37( 46%) patients. The patients received CC-0/ -1 resection survived significantly longer than those of CC-2/ -3 group. The patients with PCI ≤ 10 survived significantly longer than those with PCI≥ 11. CC and PCI scores are the independent prognostic factors. The relative risk for death of CC-2/-3 group was 4.6-fold higher than that of CC-0/ -1 group. Accordingly, peritonectomy is indicated for patients with PCI score≤ 10.