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.

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.

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.

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.

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.

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.

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.

[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.

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.

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.

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.

The hypothalamic arcuate nucleus: a key site for mediating leptin's effects on glucose homeostasis and locomotor activity.

Leptin is required for normal energy and glucose homeostasis. The hypothalamic arcuate nucleus (ARH) has been proposed as an important site of leptin action. To assess the physiological significance of leptin signaling in the ARH, we used mice homozygous for a FLPe-reactivatable, leptin receptor null allele (Lepr(neo/neo) mice). Similar to Lepr(db/db) mice, these mice are obese, hyperglycemic, hyperinsulinemic, infertile, and hypoactive. To selectively restore leptin signaling in the ARH, we generated an adeno-associated virus expressing FLPe-recombinase, which was delivered unilaterally into the hypothalamus using stereotaxic injections. We found that unilateral restoration of leptin signaling in the ARH of Lepr(neo/neo) mice leads to a modest decrease in body weight and food intake. In contrast, unilateral reactivation markedly improved hyperinsulinemia and normalized blood glucose levels and locomotor activity. These data demonstrate that leptin signaling in the ARH is sufficient for mediating leptin's effects on glucose homeostasis and locomotor activity.

Indication of peritonectomy for peritoneal dissemination.

A total of 521 patients with peritoneal carcinomatosis (PC) were treated by peritonectomy and perioperative chemotherapy. Each of the 95, 58, 316, 31, 10 and 11 patients were from gastric, colorectal, appendiceal, ovarian, small bowel cancer and mesothelioma, respectively. The distribution and volume of PC are recorded by the Sugarbaker peritoneal carcinomatosis index (PCI). Peritonectomy was performed with a radical resection of the primary tumor and all gross PC with involved organs, peritoneum, or tissue that was deemed technically feasible and safe for the patient. The postoperative major complication of grade 3 was found in 14%, and total 30-day mortality was 2.7%. The survival of gastric cancer patients with a PCI score ≤ 6 was significantly better than those with a PCI score ≥ 7. In appendiceal neoplasm, patients with PCI score less than 28 showed significantly better survival than those with PCI score greater than 29. The survival of colorectal cancer patients with a PCI score ≥ 11 was significantly poorer than those with a PCI score ≤ 10. Among the various prognostic factors in appendiceal neoplasm and gastric cancer patients, CC-0 complete cytoreduction was the most important independent prognostic factor. Peritonectomy is done to remove macroscopic disease and perioperative intraperitoneal chemotherapy to eradicate microscopic residual disease aiming to remove disease completely with a single procedure. Peritonectomy combined with perioperative chemotherapy may achieve long-term survival in a selected group of patients with PC. The higher mortality rate underlines this necessarily strict selection that should be reserved to experienced institutions.

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.