[Pancreatic Acinar Cell Carcinoma with Peritoneal Recurrence Treated with Peritonectomy and Intraoperative Hyperthermic Intraperitoneal Chemotherapy-A Case Report].

A 31-year-old man with a big epigastric mass from pancreas body was completely removed by distal pancreatectomy and segmental gastrectomy. Two years after oral administration of S-1 for 4 courses, peritoneal dissemination on the right subdiaphragmatic space was detected. Laparotomy revealed white colored round nodules were found scattered on the peritoneal surface, and the peritoneal cancer index(PCI)was 18. To achieve complete resection of peritoneal nodules, peritonectomy was performed. After complete removal of macroscopic peritoneal metastasis(PM), intraoperative hyperthermic intraoperative peritoneal chemotherapy using 1 gr of gemcitabine and 60 mg of docetaxel was performed for 40 min with thermal dose of 41.5 min. Postoperative course was uneventful. Drug sensitivity test(HDRA method)showed that gemcitabine that gemcitabine showed the highest inhibition rate. The patient was treated with systemic gemcitabine chemotherapy. He is still alive without recurrence 18 months after peritonectomy plus intraoperative HIPEC. Pathological examination showed pancreatic acinar cell carcinoma(PACC)demonstrating positive for chymotrypsin. In conclusion, we present a PACC-case with PM successfully treated by a comprehensive treatment. Intraoperative HIPEC using gemcitabine may be effective for PACC patients with PM in treating residual micrometastasis after peritonectomy.

Rationale of Treatment for Peritoneal Metastasis.

In 1998, the Peritoneal Surface Oncology Group International(PSOGI)proposed a novel treatment referred to as comprehensive treatment(COMPT). COMPT involves the complete removal of macroscopic tumors(cytoreductive surgery: CRS) and eradication of micrometastasis(MM)with neoadjuvant chemotherapy(NAC)plus intraoperative hyperthermic intraperitoneal chemotherapy(HIPEC). This article provides a rationale for curative COMPT. Additionally, based on our experience, the selection criteria for treatment will be clarified. RATIONALE: The residual cancer cell burden is lowest immediately following CRS, and intraoperative HIPEC plays a crucial role in the treatment of patients with peritoneal surface malignancy (PSM). COMPT will fail if the number of the MM remaining after CRS exceeds the limit of complete eradication by intraoperative HIPEC(threshold). However, if the residual number of MM is less than the threshold, patients will respond positively to treatment. PATIENTS AND METHODS: To validate the direct effect of HIPEC, laparoscopic HIPEC(LHIPEC)was performed, and changes in the peritoneal cancer index(PCI)were then evaluated. Complete cytoreduction and HIPEC carried out based on the concept of COMPT was performed in 171 gastric cancer(GC)patients with PCI≤12, 183 colorectal cancer(CRC)with PCI≤21 and 460 pseudomyxoma peritonei(PMP)patients with PCI≤28. The postoperative survivals rates were then analyzed. RESULTS: After 1 cycle of LHIPEC, PCIs in GC and PMP were significantly reduced by 1.85 and 2.7 1 month after LHIPEC. However, PCI of CRC increased. Positive cytology at LHIPEC became negative in 57.6%, 42.9% and 60.9% of patients with GC, CRC and PMP, respectively. Median survival time(MST)for GC and CRC was 21.2 and 71.5 months, respectively MST of PMP was not reached. MST of PMP was not reached. Ten-year survival rates were 12.6%, 21.7% and 81.6%, respectively. Grade 5 complications for each disease were 0.8%, 1.0% and 1.1%, respectively. CONCLUSIONS: Complete cytoreductive surgery combined with intraoperative HIPEC may improve the long-term survival of patients with PSM who have PCIs less than the threshold levels, by keeping the mortality rates after CRS plus intraoperative HIPEC within acceptable levels.

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.

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 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.

Laparoscopic Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosisfrom Gastric Cancer: Its Beneficial Effects on Reduction and Exact Evaluation of the Peritoneal Cancer Index.

We assessed whether the laparoscopic hyperthermic intraperitoneal chemotherapy (L-HIPEC) + neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) could reduce the peritoneal cancer index (PCI; which is defined by Sugerbaker) and improve the possibility to obtain a complete cytoreductive surgery (CRS with peritonectomy; basically according to the Sugerbaker's procedure). After L-HIPEC + NIPS, the PCI score was decreased in 89.5 per cent of patients, and the average score was significantly reduced. The average PCI reduction of improved PCI cases was 10.2 ± 8.4. The hypothetical cut-off was at a PCI score of six with significant higher possibility of CRS completeness. Twelve patients had high-PCI (PCI > 6), and six of them (50.0%) were converted to low-PCI (PCI ≦ 6) and got a complete CRS. There was a significant relationship between post-PCI (PCI after L-HIPEC + NIPS) and CRS completeness; however, pre-PCI (PCI before L-HIPEC + NIPS) value was not a relevant factor. The high-PCI and increased PCI even after L-HIPEC + NIPS (deteriorated-PCI) were suggested as important risk factors for surgical completeness. Neither pre- nor postcytological results had a significant relationship between CRS completeness. However, the deteriorated cytological class was considered as a risk factor for CRS completeness. The second-look laparoscopy would be recommended for the better selection of the patients who can receive benefits by this extensive surgery.

[A Case of Colorectal Cancer with Peritoneal Dissemination and Liver Metastasis That Responded to Comprehensive Treatment by Chemotherapy and CRS plus HIPEC].

We report a case of colorectal cancer with peritoneal dissemination and liver metastasis that achieved R0 resection by preoperative chemotherapy and CRS plus HIPEC. A 33-year-old man presented with a complaint of abdominal bloating. After further examination, he was diagnosed with transverse colon cancer with peritoneal dissemination and liver metastasis. After 9 courses of preoperative XELOX plus cetuximab and 4 courses of preoperative XELIRI plus bevacizumab, he underwent transverse colon resection, peritoneal resection, and HIPEC(MMC 20mg/4,000mL physiological saline, 40mins). There was little histological evidence of peritoneal dissemination around the region of the primary tumor. Moreover, no tumor cells were found in other peritoneal disseminations or in the liver metastasis. As a result, he was able to undergo curative resection. Colorectal cancer with peritoneal dissemination still has a poor prognosis, but combination therapy with chemotherapy and CRS plus HIPEC is expected to improve prognosis.

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.

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.

Cytoreductive surgery under aminolevulinic acid-mediated photodynamic diagnosis plus hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis from ovarian cancer and primary peritoneal carcinoma: results of a phase I trial.

BACKGROUND: We conducted a phase I clinical trial to evaluate the sensitivity, specificity, and safety of cytoreductive surgery (CRS) under aminolevulinic acid-mediated photodynamic diagnosis (ALA-PDD) plus hyperthermic intraperitoneal chemotherapy (HIPEC) on 20 patients with peritoneal carcinomatosis (PC) from ovarian cancer and primary peritoneal carcinoma (PPC). PATIENTS AND METHODS: Patients took 5-aminolevulinic acid (5-ALA) at a dose of 20 mg/kg orally with 50 mL of water 2 h before surgery. During surgery, the abdominal cavity was observed under blue light (wavelength of 440 nm) before and after CRS plus HIPEC. Specimens were excised and submitted for pathological examination to evaluate the specificity of ALA-PDD. Postoperative course was closely monitored and detailed information was recorded. RESULTS: CRS under ALA-PDD plus HIPEC was performed 21 times in 20 patients with PC (16 ovarian cancer, 4 PPC) between June 2011 and October 2013. With the exception of 1 (5 %) patient, strong red fluorescence was detected in 19 patients with ovarian cancer, with a sensitivity of 95 %. All specimens from red fluorescent lesions were invaded by cancer cells, with a specificity of 100 %. No severe adverse events occurred during the perioperative period, with the exception of some abnormal laboratory results and mild complications. All patients were alive until the last follow-up. CONCLUSION: ALA-PDD provided a high sensitivity and specificity in detecting peritoneal metastasis in patients with PC from ovarian serous carcinoma and PPC. CRS under ALA-PDD plus HIPEC was a feasible and safe treatment option for patients with PC from ovarian cancer and PPC.

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.

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.