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

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

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

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

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

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

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

Phase II Study of a Comprehensive Treatment Using Perioperative Chemotherapy Combined with Cytoreductive Surgery for Curatively Resected Gastric Cancer Patients with Positive Peritoneal Wash Cytology

Patients with curatively resected gastric cancer patients with positive peritoneal wash cytology are called P0/Cy1 status. The aim of the present study is to verify the survival benefit of the comprehensive treatment for patients with P0/Cy1 status.Twenty gastric cancer patients were diagnosed as P0/Cy1 by laparoscopy or laparotomy, and were treated with a comprehensive treatment consisting of neoadjuvant intraperitoneal/systemic chemotherapy (NIPS), cytoreductive surgery (CRS) consisting of gastrectomy with lymph node dissection and peritonectomy, intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and postoperative systemic chemotherapy. At the second look laparotomy, the peritoneal wash cytology became negative in 15 patients. No grade 3, 4, 5 complications were experienced after second look operations for CRS. Median follow-up time is 3.7 years. Eight patients died of recurrence, but the other 21 patients are alive without recurrence. Five-year survival rate was 42%.The present study demonstrated the efficacy and safety of the comprehensive treatment on the gastric cancer patients in P0/Cy1 status. Â

Observations of the Matsushiro Earthquake Swarm at Five Temporary Stations : Part 1

1. In November, 1965, observations of the Matsushiro earthquake swarm were carried out at five temporary observation sites northeast of the swarm area. These five stations are on a line as shown in Fig. 1, the relative distances being about 10km as given in Table 1. The range of epicentral distances of these sites from each shock is roughly between 15 and 55km. Observation schedule was usually from 22h 00m to 4h 00m of the next day, that is, six hours during the night. A magnetic tape recording system was used together with six vertical and two horizontal moving coil type seismometers with natural period 1 sec. The total system of recording has a flat frequency characteristic in the range 1～100c/s

The hypothalamic arcuate nucleus: A key site for mediating leptin’s effects on glucose homeostasis and locomotor activity

SummaryLeptin 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 (Leprneo/neo mice). Similar to Leprdb/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 Leprneo/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

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