Haruo Ohkubo

Improved mortality rate of gastric carcinoma patients with peritoneal carcinomatosis treated with intraperitoneal hyperthermic chemoperfusion combined with surgery

Peritoneal carcinomatosis from gastric carcinoma has a very poor prognosis. The purpose of this study was to evaluate the efficacy of intraperitoneal hyperthermic chemoperfusion (IHCP) in advanced gastric carcinoma patients with peritoneal carcinomatosis.

Cytohistologic assessment of antitumor effects of intraperitoneal hyperthermic perfusion with mitomycin C for patients with gastric cancer with peritoneal metastasis

For 15 patients with refractory gastric cancer and peritoneal metastasis, intraperitoneal hyperthermic perfusion (IPHP) using mitomycin C combined with extensive surgery was prescribed. The antitumor effects were assessed cytohistologically in pre‐IPHP and post‐IPHP specimens of the abdominal effusion and peritoneal tissue. Gastric cancer cells in the abdominal effusion and/or lavage vanished from post‐IPHP peritoneal exudate obtained from the pouch of Douglas. Peritoneal tissues from nine patients were harvested just after the IPHP treatment. All the nuclei of cancer cells were pyknotic in three of nine patients, and two of these three patients are alive with no local recurrence; one patient died of hepatic metastasis. In the remaining six patients, four with preoperative ascitic effusion and positive post‐IPHP histologic findings died of peritoneal, intraabdominal, and pericardial metastases. The other two had some residual microscopic foci in the subperitoneal deep layer; one patient died of pleural recurrence, and the other is alive with no evidence of recurrence 42 months after the IPHP. Among the other six patients, whose post‐IPHP peritoneal tissues were not available because of disappearance of disseminating foci as a result of the IPHP, two are living with no recurrence and, of the remaining four patients, three died of hepatic and intraabdominal metastases and the other one died of other causes. The histologic findings are suggestive of the following: (1) uniform heat and drug distribution in the abdominal cavity with IPHP treatment, except for an area adjacent to the inflow point of the perfusate; and (2) limited penetration of heat and drug through the subperitoneal layer. Thus, IPHP treatment results in complete destruction of cancer cells in the abdominal effusion and on and just beneath the peritoneum.

Combined treatment of pelvic exenterative surgery and intra-operative pelvic hyperthermochemotherapy for locally advanced rectosigmoid cancer: Report of a case

A huge rectosigmoidal cancer which extended into the urinary bladder in a 64-year-old man is herein described. The tumor occupied the pelvic and lower abdominal cavities, while the rectosigmoid was totally obstructed. No hepatic or pulmonary metastasis was evident. The ventral and flank sides of the peritoneum in the right lower abdomen, right common iliac vessels, bilateral ureters, terminal ileum, cecum, ascending colon, and urinary bladder were all directly invaded by the tumor, but the aorta, sacrum, and lower rectum were free of cancer. Consequently, an anterior pelvic exenteration was carried out along with an ileal conduit and a right hemicolectomy. Immediately after the exenteration, intra-pelvic hyperthermochemotherapy was performed using a 46–47°C perfusate containing 40 μg/ml of mitomycin C (MMC) and 200 μg/ml of cisplatin (CDDP), for 90 min, in an attempt to prevent any further local recurrence. A right hemicolectomy and a permanent colostomy were done simultaneously with the hyperthermia treatment. After an uneventful postoperative course, the patient was prescribed adjuvant chemotherapy, i.e., two administrations of 17 mg/m2 and 21 mg/m2 of MMC, and ten doses of 710 mg/m2 of 5-fluorouracil (5-FU) followed by five doses of 535 mg/m2 of 5-FU. At the time of this writing, the patient is still alive without recurrence at 21 months after surgery.

Heated intraperitoneal mitomycin C infusion treatment for patients with gastric cancer and peritoneal metastasis

The vast majority of peritoneal carcinomatosis occurs in the form of a secondary metastatic lesion. In Japan, the stomach is the most frequent origin of metastatic cancer in the abdominal cavity, while in Western countries the ovary is usually affected. The bile duct, large intestine, and breast are other primary sites. With cancerous invasion of the peritoneoserosal membrane, ascitic fluid frequently accumulates in the abdominal cavity and a terminal state can be thus identified.

Survival time and prevention of side effects of intraperitoneal hyperthermic perfusion with mitomycin C combined with surgery for patients with advanced gastric cancer

In an attempt to prevent postoperative intraperitoneal recurrence in patients with advanced gastric cancer and consequently to improve survival time, we treated patients with intraperitoneal hyperthermic perfusion (IPHP) using mitomycin C (MMC) combined with surgery. There were 60 patients with advanced gastric cancer who were treated with IPHP (long-term study) group, and the survival of this group was compared with the outcome in 52 patients with advanced gastric cancer treated with surgery alone (control group). To avoid or diminish side effects derived from scald injury of the peritoneal surface due to IPHP, 50 mg/kg of cimetidine was given intravenously just before administration of IPHP. For prophylaxis of anastomotic leakage, duodenostomy using a Foley catheter was performed. The 60 patients who were treated with IPHP lived longer than the 52 patients in the control group (p = 0.000610). The 3 year survival rate was 45 percent for the former compared with 16 percent for the latter. The intravenous administration of cimetidine just prior to IPHP protected the peritoneoserosal surface from scald injury, even though the heated perfusate exposure was at 44.3-46.3 degrees C for 2 hours. Because the intraabdominal pressure within the duodenum and jejunum was decompressed postoperatively through catheter duodenostomy and the peritoneoserosal surface was protected from scald injury caused by IPHP, anastomotic leakage in the study group was nil. Therefore, IPHP treatment plus aggressive surgery combined with pre-IPHP cimetidine administration are indicated for patients with advanced gastric cancer. The side effects of IPHP and postoperative morbidity can thus be reduced and a favorable outcome obtained.

Prognostic impact of platelet-derived growth factor in breast carcinoma patients with hematogenous metastasis

AbstractBackground. Many recent studies have found that several angiogenic factors play an important role in primary and metastatic tumor growth. Platelet-derived growth factor (PDGF) is known to induce angiogenesis. In this study, we investigated whether tumor PDGF can reliably predict metastatic potential and survival benefit in patients with breast cancer. Methods. Histoimmunological analysis with two isoforms of PDGF, PDGF-AA and PDGF-BB, was performed on formalin-fixed, paraffin-embedded tissue. This analysis was performed in 83 patients with breast cancer; 30 with hematogenous recurrence, 13 with locoregional recurrence, and 40 surviving without recurrence. Results. Of the 30 patients with hematogenous recurrence, 13 (43.3%) showed PDGF-AA expression [PDGF-AA(+) group] and the remaining 17 (56.7%) showed no expres-sion of tumor PDGF-AA [PDGF-AA(−) group]. In the locoregional recurrence group, 1 patient (7.7%) showed PDGF-AA expression, and 2 of the 40 patients surviving without recurrence (5%) showed PDGF-AA expression in the primary tumor tissue. In contrast, PDGF-BB expression was observed in all 43 patients with recurrence and in 37 of the 40 patients surviving without recurrence. The PDGF-AA(+) and locoregional recurrence groups had almost the same period to recurrence after surgery (25.2 ± 18.5 months and 24.0 ± 11.3 months, respectively), whereas this period in the PDGF-AA(−) group was significantly longer (P < 0.0489 and P < 0.0400, respectively) than that of these other two groups. The 2-, 5-, and 8-year survival rates for the PDGF-AA(−) group were 70.6%, 47.1%, and 35.3%, respectively, whereas those for the PDGF-AA(+) group were 61.5%, 23.1%, and 15.4%, respectively; those for the locoregional recurrence group were 76.9%, 23.1%, and 7.7%, respectively. The survival rate for the PDGF-AA(−) group tended to be better (P = 0.0907) than that for the PDGF-AA(+) group, and showed no difference (P = 0.148) from that of the locoregional recurrence group. Conclusion. The data on PDGF-BB expression indicate that PDGF-BB is largely concerned with primary tumor growth and is not related to hematogenous metastasis. In contrast, PDGF-AA expression seems to be linked with hematogenous metastasis.

Intracavitary hyperthermic chemoperfusion in patients with far-advanced gastric cancer or rectal cancer

SummaryBackgroundLocal recurrence after surgery for patients with advanced gastric cancer and rectal cancer is often fatal. In an attempt to prevent local recurrences, we carried out intracavitary hyperthermic chemoperfusion (IHCP) combined with surgery.Methods60 patients with advanced gastric cancer and 27 patients with advanced rectal cancer were treated with IHCP plus surgery and, 52 and 35 patients with advanced gastric and rectal cancer, respectively, were treated by surgery alone.ResultsIn case of rectal cancer, the incidence of local recurrence in the IHCP group is 3/27 patients (11.1%) and that in the control group is 13/35 patients (37.1%), thus differences between the groups are significant at p=0.043. With regard to gastric cancer, 13/60 patients (21.7%) in the IHCP group had a peritoneal recurrence and in the control group 40/52 patients (76.9%) had a recurrence; the statistical difference between the groups being significant (p=6.43 × 10−9).ConclusionsIHCP treatment can diminish the incidence of local recurrence after surgical treatment for patients with advanced gastric or rectal cancer.ZusammenfassungGrundlagenLokale Rezidive nach Operation bei Patienten mit weit fortgeschrittenem Magen-oder Rektumkrebs sind meistens fatal. In einem Versuch, lokale Rezidive zu verhindern, haben wir in Verbindung mit Operationen eine intrakavitäre, hyperthemische Chemoperfusion (IHCP) durchgeführt.Methodik60 Patienten mit fortgeschrittenem Magenkrebs und 27 Patienten mit fortgeschrittenem Rektumkrebs wurden sowohl mit IHCP als auch operativ behandelt. Außerdem wurden jeweils 52 und 35 Patienten mit fortgeschrittenem Magen- und Rektumkrebs ausschließlich operativ behandelt.ErgebnisseBei Rektumkrebs betrug die Häufigkeit lokaler Rezidive in der IHCP-Gruppe 3 von 27 Patienten (11,1%) und in der Kontrollgruppe 13 der 35 Patienten (37,1%). Der Unterschied zwischen den beiden Gruppen ist somit signifikant (p=0,043). In der Gruppe der Patienten mit Magenkrebs fanden sich bei 13 der 60 Patienten (21,7%) der IHCP-Gruppe peritoneale Rezidive, während in der Kontrollgruppe bei 40 der 52 Patiente (76,9%) auftraten. Die statische Differenz zwischen den beiden Gruppen war somit signifikant (p=6.43×10−9).SchlußfolgerungenDie IHCP-Behandlung kann die Häufigkeit lokaler Rezidive nach operativer Behandlung bei Patienten mit fortgeschrittenem Magen- oder Rektumkrebs herabsetzen.