Effective therapy for peritoneal dissemination in gastric cancer

Peritoneal dissemination is the most frequent cause of death from gastric cancer, accounting for death in 20% to 40% of patients. Preoperative intraperitoneal chemotherapy, peritonectomy, intraoperative chemohyperthermic perfusion, and early postoperative intraperitoneal chemotherapy are treatment modalities specifically designed to eliminate peritoneal dissemination and progression. Preoperative intraperitoneal chemotherapy is for containment of peritoneal free cancer cells, and also may facilitate complete eradication of visible peritoneal dissemination by peritonectomy. Further, complete cytoreduction can be achieved more often when peritonectomy is included in the surgical treatment of gastric cancer with peritoneal dissemination. Phase III data shows prolonged survival attributed to complete cytoreduction. Aggressive cytoreduction of peritoneal dissemination by peritonectomy can reduce residual tumor burden to micrometastases on the peritoneal surface that can be treated by intraoperative intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy. Among all these modalities, surgical cytoreduction is probably the most important for survival benefit. If the surgical cytoreduction is visibly incomplete, prolonged survival cannot be expected, despite subsequent treatment. The surgeon's goal is to reduce the cancer cell burden to a microscopic level. Continued refinement of phase II studies is needed for maximal benefit and to standardize the technical and chemotherapeutic options of each modality.     

Recent advances in the treatment of peritoneal dissemination of gastrointestinal cancers by nucleoside antimetabolites

Peritoneal dissemination is the most common cause of metastasis from malignancies in the abdominal cavity. There are no standard treatments for peritoneal dissemination and the results are poor. The reasons for this are as follows: (1) no effective chemotherapeutic agents have been identified or developed; (2) surgical cytoreduction has little effect on survival improvement; and (3) the molecular mechanisms of peritoneal dissemination have not been clarified and no therapy against the target molecules has been developed. However, studies on the molecular mechanisms of peritoneal dissemination have elucidated some of the target molecules and the development of new multimodal therapies has also improved survival. Early postoperative intraperitoneal chemotherapy, hyperthermic intraperitoneal perfusion chemotherapy and neoadjuvant intraperitoneal-systemic chemotherapy have been newly developed, and a novel surgical therapy named peritonectomy has been proposed to perform complete cytoreduction of peritoneal dissemination. At present, these approaches appear to be effective therapeutic modalities for peritoneal dissemination. However, TS-1 and capecitabine have shown worthwhile results in recent clinical trials for patients with advanced gastric cancer. We recently found that newly developed antitumor cytosine nucleoside analogs show a survival advantage in peritoneal dissemination models using human cancer cells. These non-fluoropyrimidine nucleosides may potentially help to improve the poor prognosis observed in patients with advanced cancers involving peritoneal dissemination.     

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.     

Clinical pathway for the management of resectable gastric cancer with peritoneal seeding: best palliation with a ray of hope for cure

Peritoneal seeding from primary gastric cancer occurs in 10-20% of patients. The diagnosis of this advanced disease is usually not provided by clinical studies prior to abdominal exploration. From the data available in the literature, the surgeon is forced to make an intraoperative judgement concerning the risks and benefits of an aggressive management plan versus supportive care. A strategy has evolved that utilizes peritonectomy and extended gastrectomy to maximally cytoreduce tumor combined with perioperative intraperitoneal chemotherapy. In the current state of the art, the perioperative intraperitoneal chemotherapy is heated and manually distributed to provide uniform treatment to all peritoneal surfaces and the resection site. The pharmacologic parameters have been established and the results of phase II studies are reported. Five-year survival of patients in whom a complete cytoreduction was possible is approximately 10% with a median survival of 12 months. Gastrectomy with peritonectomy to eliminate all visible implants combined with perioperative intraperitoneal chemotherapy should be used in selected patients with primary gastric cancer and carcinomatosis.     

Treatment results of peritoneal dissemination from gastric cancer by neoadjuvant intraperitoneal-systemic chemotherapy

No standard treatment exists for peritoneal dissemination from gastric cancer. We reviewed our experience using a novel treatment consisting of peritonectomy and intraoperative chemo-hyperthermic peritoneal perfusion (CHPP). Records of all patients who underwent CHPP and cytoreductive surgery from 1992 to 2001 were reviewed. RESULTS: Data from 107 patients (average age, 52 years) were available. P3 dissemination was found in 72 patients, and 8 and 27 patients showed P1 or P2 dissemination, respectively. Peritoneal metastasis was synchronous in 75 and metachronous in 32 patients. All patients received CHPP after cytoreductive surgery. Peritonectomy was performed in 42 patients. Complete cytoreduction (CC-0) was achieved in 47 patients (44%). Peritonectomy, resulted in CC-0 in 69% (29/42), but CC-0 was achieved in 18 of 65 (28%) patients by ordinary surgical techniques. There were 23 postoperative complications (21%) after operation. The overall operative mortality was 2.8% (3/107). Median follow-up for the entire study group was 46 months. Seventeen patients (15%) were disease-free, and 90 patients were dead at the time of analysis. Eighty-seven deaths were related to progression of disease. The median survival of all patients was 16.2 months, with an actual 5-year survival of 6%. Median survival of CHPP plus ordinary cyoreduction was 12.0 months and that after CHPP and peritonectomy was 22.8 months. Completeness of cytoreduction and peritonectomy were significant prognostic factors on univariate analysis and 5-year survival rate was 27%. Lymph node status, grade of peritoneal dissemination (P1-2 vs P3), age (>60 years vs <60 years), tumor volume of dissemination (>2.5 cm vs <2.5 cm in diameter), and histologic type (differentiated vs. poorly differentiated type) did not affect survival. The cox proportional model demonstrated that completeness of cytoreduction was the strongest prognostic factor. Patients who had an incomplete resection had 2.8-fold higher risk of dying from disease than patients who underwent complete cytoreduction. The 5-year survival after complete cytoreduction was 12%, compared with 2% for incomplete resection. Four patients lived more than 5 years. Cytoreduction was incomplete in one 5-year survivor who showed complete response to CHPP. CONCLUSION: Complete cytoreduction using peritonectomy and CHPP may improve survival of patients with peritoneal dissemination from gastric cancer. This procedure is most appropriate for highly motivated patients who are committed to survive as long as possible.     

Effectiveness of intraperitoneal chemotherapy using new-aged drugs for the peritoneal dissemination of gastric cancer

We evaluated the effectiveness of intraperitoneal chemotherapy for peritoneal dissemination of gastric cancer. A total of 104 patients with primary gastric cancer with peritoneal dissemination were enrolled in this study. In 72 of the 104 patients with gastrectomy performed, 5 patients underwent CDDP-ip (50-100 mg/100-200 ml), 16 patients underwent CHPP (CDDP 300 mg, MMC 30 mg, ETP 150 mg/8 l/42-43 degrees C/60 min), and 17 patients underwent CMV-ip (CDDP 150 mg, MMC 20 mg, ETP 100 mg/1 l/60 min). The prognosis of patients who underwent CMV-ip was significantly better than those who received other therapies. In 26 patients with severe peritoneal dissemination who were treated with TS-1 (60 mg/m2) and taxane-ip (docetaxel 40-60 mg/body or paclitaxel 120-180 mg/body), 9 of 18 responders performed complete cytoreduction. The median survival time (MST) in these 9 patients was 944 days and a 2-year survival rate was 63%. A multimodal therapy consisting of systemic chemotherapy, intraperitoneal chemotherapy and complete cytoreductive surgery may provide good prognosis to the gastric cancer patients with peritoneal dissemination.     

Significance of peritonectomy for peritonitis carcinomatosis

We analyzed patients who underwent multimodal treatment with peritonectomy as an aggressive treatment for peritonitis carcinomatosis. Peritonectomy was treated in eighteen cases (eleven gastric cancer, seven colon cancer). Out of these eighteen cases, nine were initial operation, six were recurrence after first operation and three were for relief after palliative operation for peritoneal dissemination. Five cases of recurrence included ileus. Of all eighteen patients, ten had received preoperative chemotherapies. Peritonectomy made complete resection possible principle, and the procedure included resection of the primary lesion, subtotal colectomy and peritonectomy. An intestinal stoma was needed in nine cases, consequently. All patients cases underwent continuous hyperthermic peritoneal perfusion (CHPP). Early postoperative peritoneal chemotherapy was given in five cases. By peritonectomy for a first time operation, macroscopically complete resection was possible in six cases. In relief and recurrence cases few tumor cells remained in five cases. Ileus due to peritoneal carcinomatosia was eliminated in all cases, and caloric intake became possible. Fourteen cases had postoperative complication (morbidity 78%), and treatment-related death occurred in three cases (mortality 17%). It became possible to resect even the peritoneal dissemination that was inoperable by conventional surgery, and improvement of QOL was achieved by peritonectomy in cases of carcinomatous peritonitis. However, postoperative care is important since aggression becomes more intense.     

Subtotal peritonectomy with chemohyperthermic peritoneal perfusion for peritonitis carcinomatosa in gastrointestinal cancer

Treatment for peritonitis carcinomatosa in gastrointestinal cancer remains to be established though it is one of the commonest causes of cancer death. Subtotal peritonectomy (SP) with chemohyperthermic peritoneal perfusion (CHPP) was developed for the new therapeutic strategy for peritoneal dissemination in gastrointestinal cancer in our department. SP includes resection of stomach, colon, small bowel, spleen, gall bladder, and parietal peritoneum. CHPP was carried out by heated saline containing 25 mg/l cisplatin, 10 mg/l mitomycin C, and 20 mg/l etoposide. Intraperitoneal temperature was maintained at 42 degrees C for 60 min. Fifteen gastric cancer and three colon cancer patients with severe peritoneal dissemination underwent these procedures. The averages of operating time, intraoperative bleeding volume, and total perioperative transfused blood volume were 9 h, 4400 ml, and 5600 ml, respectively. The patients estimated as complete resection and residual disease by histopathological study numbered 11 and 7. There was no treatment-related deaths though bleeding occurred in 5 patients; perforation in 2 patients; and abscesses in 2 patients. The 1-year survival rate (1ysr) and the 2-year survival rate (2-ysr) of all the patients were 57% and 21%, respectively. The 1-ysr and the 2-ysr of the patients who underwent complete resection were 67% and 40% significantly greater than the 43% and 0% of the patients who had residual tumors (p=0.02). The combination therapy of SP and CHPP is feasible in spite of its morbidity and has great possibilities in complete resection of peritoneal dissemination and prolongation of patient's survival.     

Successful management of microscopic residual disease in large bowel cancer

Although cancer surgery has been of great benefit to patients with large bowel cancer, a flaw that has caused the death of countless patients has gone unrecognized. Although surgeons have dealt successfully with the primary tumor, they have neglected to treat microscopic residual disease. Persistent cancer cells within the abdomen and pelvis are responsible for the death of 30-50% of the patients who die with this disease and for quality of life consequences that result from intestinal obstruction caused by cancer recurrence at the resected site and on peritoneal surfaces. New surgical techniques for large bowel cancer resection minimize the surgery-induced microscopic residual disease that may result from surgical trauma. New developments in exposure, hemostasis, adequate lymphadenectomy, and qualitatively superior margins of excision have occurred. Clinical data show that a 40% improvement in survival with an optimization of surgical technique is possible. Not only should the surgical event for primary colon and rectal cancer be optimized, but also the successful treatment of peritoneal carcinomatosis should be pursued. Resected site disease and peritoneal carcinomatosis can be prevented through the use of perioperative intraperitoneal chemotherapy in patients at high risk of persistent microscopic residual disease. These are patients with perforated cancer, positive peritoneal cytology, ovarian involvement, tumor spill during surgery, and adjacent organ involvement. Patients with established peritoneal carcinomatosis can be salvaged with an approximate 50% long-term survival rate if the timely use of peritonectomy procedures, intraperitoneal chemotherapy, and knowledgeable patient selection are utilized. Peritonectomy procedures allow the removal of all visible peritoneal carcinomatosis with acceptable surgical morbidity (25%) and mortality (1.5%) rates. Heated intraoperative intraperitoneal chemotherapy using mitomycin C, in addition to early postoperative intraperitoneal 5-fluorouracil, can eradicate microscopic residual disease in the majority of patients. The peritoneal cancer index, which quantitates colon cancer peritoneal carcinomatosis by distribution and by lesion size, must be used in the selection of patients who may benefit from these advanced oncologic surgical treatment strategies. The completeness of the cytoreduction score is the most powerful prognostic indicator in this group of patients. The surgeon must be aware that there are no long-term survivors unless complete cytoreduction occurs. With a combination of proper techniques for the resection of primary disease, peritonectomy procedures for the removal of all visible peritoneal implants, intraoperative and early postoperative chemotherapy for the eradication of microscopic residual disease, and quantitative tools for proper patient selection, one can optimize the surgical treatment of patients with large bowel cancer.     

Strategies for the prevention and treatment of peritoneal carcinomatosis from gastrointestinal cancer

Background. Peritoneal surface malignancy can result from full thickness invasion of gastrointestinal cancer through the bowel wall or from dissemination of cancer cells from the trauma of cancer surgery. In the past, this clinical situation was treated only with palliative intent. Methods. An aggressive approach to peritoneal surface malignancy involves peritonectomy procedures, perioperative intraperitoneal chemotherapy and knowledgeable patient selection. The clinical assessments necessary for valid clinical judgements include the cancer histopathology (invasive vs. expansive progression), the preoperative abdominal and pelvic CT, the peritoneal cancer index and the completeness of cytoreduction score. Proper patient selection is mandatory for optimizing the results of treatment. Results. In a series of phase II studies, appendiceal tumors with peritoneal seeding became the paradigm for success with an 85% long-term survival in selected patients. Carcinomatosis from colon cancer had an overall 5-year survival of 50% with selected patients. In all malignancies, early aggressive treatment of minimal peritoneal surface dissemination showed the greatest benefit. Conclusions. Oncologists must accept responsibility for knowledgeable management of peritoneal surface dissemination of cancer because a curative approach has been demonstrated in both phase II studies and phase III studies. All historical controls show 0% long-term survival. Surgical interventions combined with perioperative intraperitoneal chemotherapy in diseases where peritoneal surface spread occurs must be considered a treatment option.     

Review of a personal experience in the management of carcinomatosis and sarcomatosis

BACKGROUND: Peritoneal surface malignancy can result from seeding of gastrointestinal cancer or abdomino-pelvic sarcoma; it can also occur as a primary disease, such as peritoneal mesothelioma. In the past, this clinical situation was treated only with palliative intent. METHODS: An aggressive approach to peritoneal surface malignancy involves peritonectomy procedures, perioperative intraperitoneal chemotherapy and knowledgeable patient selection. The clinical assessments necessary for valid clinical judgements include the cancer histopathology (invasive vs expansive progression), the preoperative abdominal and pelvic CT, the peritoneal cancer index and the completeness of cytoreduction score. Proper patient selection is mandatory for optimizing the results of treatment. RESULTS: In a series of phase II studies, appendiceal tumors with peritoneal seeding became the paradigm for success with an 85% long-term survival in selected patients. Carcinomatosis from colon cancer had an overall 5-year survival of 50% with selected patients. Also, sarcomatosis patients overall had a 40% 5-year survival in selected patients. Peritoneal mesothelioma showed a 36% 5-year survival. In all malignancies, early aggressive treatment of minimal peritoneal surface dissemination showed the greatest benefit. CONCLUSIONS: Oncologists must accept responsibility for knowledgeable management of peritoneal surface dissemination of cancer because a curative approach has been demonstrated in large phase II studies and all historical controls show 0% long-term survival. Adjuvant phase III studies with perioperative intraperitoneal chemotherapy in diseases where peritoneal surface spread occurs are indicated.     

Comprehensive approach to advanced primary and recurrent ovarian cancer: a personal experience

Despite improvements in chemotherapy agents and schedules and new drug combinations, epithelial ovarian cancer remains a leading cause of gynecologic cancer death in Western countries. It is usually diagnosed at late stages of the disease, which makes complete surgical resection technically more difficult. The targeted comprehensive approach described in this review includes cytoreductive surgery and perioperative intraperitoneal chemotherapy. The goal of this aggressive therapy is to remove all the macroscopic disease with the use of peritonectomy procedures and visceral resections, and also to eradicate microscopic disease using heated intraoperative intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy. Patients that received a complete cytoreduction followed by perioperative intraperitoneal chemotherapy had an improved survival, with reasonable morbidity and mortality, as compared with those who received incomplete cytoreduction.     

Comprehensive approach to advanced primary and recurrent ovarian cancer: a personal experience

Despite improvements in chemotherapy agents and schedules and new drug combinations, epithelial ovarian cancer remains a leading cause of gynecologic cancer death in Western countries. It is usually diagnosed at late stages of the disease, which makes complete surgical resection technically more difficult. The targeted comprehensive approach described in this review includes cytoreductive surgery and perioperative intraperitoneal chemotherapy. The goal of this aggressive therapy is to remove all the macroscopic disease with the use of peritonectomy procedures and visceral resections, and also to eradicate microscopic disease using heated intraoperative intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy. Patients that received a complete cytoreduction followed by perioperative intraperitoneal chemotherapy had an improved survival, with reasonable morbidity and mortality, as compared with those who received incomplete cytoreduction.     

Controversies in surgical treatment of gastric cancer

Conservative surgery is performed for patients with early gastric cancer, according to the guideline proposed from Japanese Gastric Cancer Society. There are many kinds of operations, such as ordinary open surgery, laparoscopic-assisted gastrectomy, laparoscopic intragastric surgery, pyrolus preserving gastrectomy, hand-assisted laparoscopic surgery. Indications of the operations are various, but it is necessary to have standard indication for each procedure. Standard operation for advanced gastric cancer in Japan is D2 gastrectomy. Surgeons in Eastern world believed that D1 + alpha or D1 + adjuvant radio-chemotherapy are the standard treatments, because of high incidence of mortality and morbidity after D2 dissection. In Japan, D4 dissection has been performed for patients with nodal involvement, and the validity of D4 dissection is now studied by two randomized trials. Combined resection for T4 tumor is believed to be mandatory. However, the validity of pancreato-splenectomy to yield a complete clearance of No. 10 or No. 11 lymph node station is in controversial, because of high incidence of the postoperative development of pancreatic fistula, anastomotic insufficiency and abscess. There was no prospective study to confirm the effect of omentectomy. Patients with advanced gastric cancer showing a serosal invasion-diameter less than 2.5 cm have less risk of peritoneal recurrence. It may be valuable to perform randomized controlled study consisting of omentum-preserving gastrectomy and gastrectomy with omentectomy. Prognosis of patients with peritoneal dissemination was improved by intraperitoneal chomo hyporthormia and peritonectomy, and prospective studies should be done to compare the effects of systemic chemotherapy and regional chemotherapy combined with peritonectomy. Furthermore, effects of neoadjuvant chemotherapy with cytoreduction with R0 resection should be confirmed by prospective studies.     

Cytoreductive surgery for ovarian cancer.

AIM: The aim of this study is to describe the technique of managing peritoneal dissemination in patients with ovarian cancer, based on radical surgical excision and, later, perioperative chemotherapy. METHOD:Treatments included complete surgical resection of the peritoneal disease, and intraperitoneal intraoperative and postoperative chemotherapy, using Adriamycin intraoperatively, and Cis-platinol next 1-5 postoperative days. RESULTS: Eleven cytoreductive procedures were performed between 1996 and 2002. Eight patients with primary ovarian cancer underwent total hysterectomy with bilateral adnexectomy, omentectomy and peritonectomy of the pelvic cavity. In 3 cases with recurrent ovarian cancer, peritonectomy alone was performed. Bowel resection was performed in all patients. The median operation time was 279 min (range 190-500min). Median total blood loss was 919 mL (range 450-1330 mL). The median survival time was 22 months. CONCLUSION: Cytoreductive procedure offers satisfactory results in peritoneal carcinomatosis in patients with advanced primary ovarian cancer.     

Clinical efficacy of cytoreductive surgery and hyperthermic chemotherapy in peritoneal carcinomatosis from gastric cancer

Evaluation of: Yang XJ, Huang CQ, Suo T et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a Phase III randomized clinical trial. Ann. Surg. Oncol. 18(6), 1575–15781 (2011).

Peritoneal carcinomatosis (PC) is the most common pattern of metastasis and recurrence in patients with gastric cancer and is associated with poor clinical outcome and survival. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) was recently established as a new treatment option for PC of gastrointestinal cancer. However, the role of cytoreductive surgery in gastric cancer and the intrinsic role of HIPEC remains unclear. The evaluated article presented a single center Phase III study, randomizing 68 patients with PC from gastric cancer to surgical cytoreduction only (CRS; n = 34) versus cytoreduction plus HIPEC with cisplatin and mitomycin (CRS+HIPEC; n = 34). Median overall was 6.5 months in the CRS group and 11.0 months in the CRS+HIPEC group (p = 0.046). Serious adverse events were acceptable in both groups. Multivariate analysis found CRS+HIPEC, synchronous PC, complete cytoreduction, systemic chemotherapy >6 cycles and no incidence of severe adverse events independent predictive factors for survival. This was the first study to show the positive effects of HIPEC in addition to CRS in PC independently of the tumor entity. In patients with gastric cancer, multimodal treatment concepts combining surgical cytoreduction and HIPEC may provide a new option in carefully selected patients.     

腹腔内全身新辅助化疗(双向化疗)对胃癌腹膜转移癌患者的疗效研究

  目的   建立联合腹腔内-全身新辅助化疗方案(NIPS)和腹膜切除术的新型多学科交叉治疗模式。   方法   2004年4月至2011年12月本研究纳入来自日本大阪草津综合病院和岸和田综合病院的胃癌腹膜转移癌患者96例, 在NIPS治疗前后, 均通过腹腔导管系统进行了腹腔冲洗液细胞学检查。患者每日按60 mg/m2剂量口服S-1, 持续21天, 随后休息一周; 在第1、8、15 d, 分别通过腹腔导管给予多西他赛30mg/m2和顺铂30mg/m2(500mL生理盐水稀释)。术前行2个周期NIPS。NIPS后3周, 82例患者符合意向性细胞减灭术(CRS), 即进行胃切除术+D2根治术+腹膜切除术获得完全细胞减灭。   结果   68例在NIPS之前细胞学检查阳性, 其中47例(69.1%)在NIPS之后细胞学检查阴性, 30例(36.8%)在NIPS治疗后达到病理学完全缓解, 12例(14.6%)患者达到肿瘤分期下降, 58例(70.7%)达到完全细胞减灭。9例患者出现4级并发症, 总体手术死亡率为3.7%(3/82)。多变量分析显示, 完全细胞减灭和病理缓解是改善患者生存的独立预后因素。   结论   该疗法的最佳适应症为病理缓解良好, PCI评分≤6, 预期可以通过腹膜切除术达到完全细胞减灭。      

Cytoreductive surgery and peri-operative intraperitoneal chemotherapy as a curative approach to pseudomyxoma peritonei syndrome.

Peritoneal carcinomatosis, regardless of primary tumour type, has always been a lethal condition. Recently special treatments using cytoreductive surgery with peritonectomy procedures combined with peri-operative intraperitoneal chemotherapy have resulted in long-term survival. Pseudomyxoma peritonei may be especially appropriate for these aggressive local regional treatments. All patients treated prior to 1999 are presented; patients left with gross residual disease after surgery were not given intraperitoneal chemotherapy, but were later treated with intravenous chemotherapy after cytoreduction. The intraperitoneal chemotherapy was given in the peri-operative period, starting with mitomycin C. For patients whose pathology showed adenomucinosis, intraperitoneal chemotherapy was limited to treatment in the operating theatre with heated mitomycin C. Patients with mucinous adenocarcinoma or pseudomyxoma/adenocarcinoma hybrid had, in addition to mitomycin C, 5 consecutive days of intraperitoneal 5-fluorouracil. A complete cytoreduction was defined as tumour nodules <2.5 mm in diameter remaining after surgery. The histopathology categorized the patients as adenomucinosis, intermediate type, or mucinous carcinomatosis. A prior surgical score was used to estimate the extent of previous surgical procedures. The morbidity of treated patients was 27% and the mortality was 2.7%. In a multivariate analysis, prognostic factors for survival included the completeness of cytoreduction (P<0.0001), the histopathological character of the appendix malignancy (P<0.001) and the extent of previous surgical interventions (P=0.001). Patients with a complete cytoreduction and adenomucinosis by pathology had a 5-year survival of 86%; while hybrid pathology survival at 5 years was 50%. Incomplete cytoreduction had a 5-year survival of 20% and 0% at 10 years. Cytoreductive surgery and peri-operative intraperitoneal chemotherapy is the current standard treatment for selected patients with peritoneal surface spread of appendiceal primary tumours. Similar strategies for other patients with peritoneal surface malignancy such as peritoneal carcinomatosis from colon or gastric cancer, peritoneal sarcomatosis, or peritoneal mesothelioma should be pursued. Copyright Harcourt Publishers Limited.     

Neoadjuvant treatment of gastric cancer with peritoneal dissemination.

AIMS: To report our experience of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) for patients having a complete resection of the primary gastric cancer and peritoneal carcinomatosis (PC). PATIENTS AND METHODS: Patients with advanced peritoneal dissemination of primary gastric cancer had the placement of a peritoneal port system. For intraperitoneal chemotherapy, 40 mg of docetaxel and 150 mg of carboplatin were introduced in 1000 ml of saline on a weekly basis. Simultaneously, 100 mg/m2 of methotrexate and 600 mg/m2 of 5-fluorouracil were infused via a peripheral vein. A minimum of two cycles and up to six cycles of NIPS were used prior to cancer resection. At surgery a complete removal of the primary gastric cancer and the peritoneal implants by peritonectomy was attempted. RESULTS: Sixty-one patients were enrolled in the study. Thirty-nine had positive intraperitoneal cytology which reverted to negative cytology after treatment in 22. Thirty-eight showed a partial response. Thirty patients came to resection and 14 patients could be made disease-free. Median survival time of all patients was 14.4 months. Patients who received a complete resection had a median survival time of 20.4 months. Grade III/IV toxicities were not found after two courses of NIPS, but did develop in seven patients after more than three courses of NIPS. CONCLUSION: NIPS can downstage large volume peritoneal dissemination of gastric cancer. When combined with gastrectomy including peritonectomy a complete surgical resection was possible in one-quarter of the patients and resulted in a prolonged survival. This combined intraperitoneal and systemic chemotherapy for PC from gastric cancer is worthy of consideration for phase III clinical investigations.     

Clinical efficacy of cytoreductive surgery and hyperthermic chemotherapy in peritoneal carcinomatosis from gastric cancer

Peritoneal carcinomatosis (PC) is the most common pattern of metastasis and recurrence in patients with gastric cancer and is associated with poor clinical outcome and survival. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) was recently established as a new treatment option for PC of gastrointestinal cancer. However, the role of cytoreductive surgery in gastric cancer and the intrinsic role of HIPEC remains unclear. The evaluated article presented a single center Phase III study, randomizing 68 patients with PC from gastric cancer to surgical cytoreduction only (CRS; n = 34) versus cytoreduction plus HIPEC with cisplatin and mitomycin (CRS+HIPEC; n = 34). Median overall was 6.5 months in the CRS group and 11.0 months in the CRS+HIPEC group (p = 0.046). Serious adverse events were acceptable in both groups. Multivariate analysis found CRS+HIPEC, synchronous PC, complete cytoreduction, systemic chemotherapy >6 cycles and no incidence of severe adverse events independent predictive factors for survival. This was the first study to show the positive effects of HIPEC in addition to CRS in PC independently of the tumor entity. In patients with gastric cancer, multimodal treatment concepts combining surgical cytoreduction and HIPEC may provide a new option in carefully selected patients.