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.     

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。      

Optimizing outcomes for patients with gastric cancer peritoneal carcinomatosis

Peritoneal carcinomatosis (PC) from gastric cancer has traditionally been considered a terminal progression of the disease and is associated with poor survival outcomes. Positive peritoneal cytology similarly worsens the survival of patients with gastric cancer and treatment options for these patients have been limited. Recent advances in multimodality treatment regimens have led to innovative ways to care for and treat patients with this disease burden. One of these advances has been to use neoadjuvant therapy to try and convert patients with positive cytology or low-volume PC to negative cytology with no evidence of active peritoneal disease. These strategies include the use of neoadjuvant systemic chemotherapy alone, using neoadjuvant laparoscopic heated intraperitoneal chemotherapy (NLHIPEC) after systemic chemotherapy, or using neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) in a bidirectional manner. For patients with higher volume PC, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been mainstays of treatment. When used together, CRS and HIPEC can improve overall outcomes in properly selected patients, but overall survival outcomes remain unacceptably low. The extent of peritoneal disease, commonly measured by the peritoneal carcinomatosis index (PCI), and the completeness of cytoreduction, has been shown to greatly impact outcomes in patients undergoing CRS and HIPEC. The uses of NLHIPEC and NLHIPEC plus NIPS have both been shown to decrease the PCI and thus increase the opportunity for complete cytoreduction. Newer therapies like pressurized intraperitoneal aerosol chemotherapy and immunotherapy, such as catumaxomab, along with improved systemic chemotherapeutic regimens, are being explored with great interest. There is exciting progress being made in the management of PC from gastric cancer and its’ treatment is no longer futile.     

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.     

Multidisciplinary therapy for peritoneal dissemination using peritonectomy

An aggressive approach to peritoneal dissemination involves peritonectomy procedures combined with preoperative intraperitoneal chemotherapy, intraoperative chemo-hyperthermia, and postoperative systemic chemotherapy. We have been performing multimodal therapy consisting of peritonectomy plus perioperative chemotherapy for the treatment of patients with peritoneal dissemination. Fifty-seven patients with established peritoneal dissemination from gastric cancer (n = 32), colon cancer (n = 17), ovarian cancer (n = 7), and mesothelioma (n = 1) have been treated with peritonectomy and intraoperative chemo-hyperthermia. Five-year survival rates of patients with gastric and colon cancer were 18% and 38%, respectively. Among various clinical factors, complete tumor resection was the most significant prognostic factor, and the prognosis of patients who underwent complete cytoreduction was significantly better than those who received incomplete cytoreduction. A multimodal therapy consisting of perioperative chemotherapy and peritonectomy with complete cytoreduction may be the most powerful method to treat patients with established peritoneal dissemination.     

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.     

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.     

Downstaging of lymph node metastasis after neoadjuvant intraperitoneal and systemic chemotherapy in gastric carcinoma with peritoneal metastasis

PurposeThe aim of the present study was to evaluate the clinical features and prognosis of lymph node metastasis (LNM) in gastric cancer patients with peritoneal metastasis (PM) after neoadjuvant intraperitoneal and systemic chemotherapy.MethodsA total of 69 gastric cancer patients with PM and LNM who received neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) of intraperitoneal docetaxel (DXT) and cisplatin (CDDP); intravenous chemotherapy of DXT and CDDP and oral S-1in Kishiwada Tokushukai Hospital between January 2008 and February 2017. After surgical resection, the response of LNMs was studied to confirm the effect of NIPS on LNMs.ResultsAfter NIPS, 197 lymph nodes (LNs) (42.5%) were graded as G3, the progression in LNMs were significantly better than in the primary tumors. Until the last follow-up, 1-year overall survival rate was 82.6%, and the median survival period was 22.0 ± 3.7 months. In the group of patients who had achieved a more than 50% G3 grade of the response of LNMs, the median survival period is 38 months; in the less than 50% G3 grade group, it is 14 months, that is a significantly different result. Multivariate analyses showed that the factors PCI, Post-therapeutic N status and response of the LNMs were found to be as independent prognostic factors.ConclusionDownstaging of LNMs were achieved in patients of gastric cancer with PM who received NIPS. Downstaging of LNMs after NIPS is related with the prognosis of gastric cancer and should be valued in subsequent surgery for gastric cancer with peritoneal and lymph nodes metastasis.     

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.     

An effective treatment by chemotherapy with S-1 and CDDP intraperitoneal administration for the peritoneal dissemination of gastric cancer--a case report

The most common treatment for patients of peritoneal dissemination of gastric cancer is a systemic chemotherapy, but the prognosis of these patients is very poor. For these diseases, some have reported the usefulness of intraperitoneal chemotherapy with cisplatin (CDDP), because of the direct cytotoxicity. Here, we report an effective treatment by chemotherapy with S-1 plus CDDP, intraperitoneal administration for the patients of peritoneal dissemination of gastric cancer. The patient was a 41-year-old male with upper abdominal pain. Upper gastrointestinal endoscopy showed a large type 3 gastric cancer from the cardia to antrum. Intraoperative peritoneal lavage cytology and dissemination was positive, thus we performed the total gastrectomy and implanted the intraperitoneal (IP) port in the Douglas's pouch. S-1 was given orally twice daily for the first 3 weeks of a 5-week cycle. CDDP was given as an intraperitoneal infusion on day 8 of each cycle. After 10 courses, he was treated with S-1 alone because he had an allergic reaction of CDDP. In 35 courses, he had survived for 5 years as disease free. Intraperitoneal chemotherapy may be a promising treatment for the patients who have peritoneal dissemination from gastric cancer.     

The use of intraperitoneal chemotherapy for gastric malignancies

Introduction: Gastric cancer is the fourth/fifth most common malignancy worldwide, with only a quarter of patients achieving a 5-year survival rate. It has been estimated that 15–50% or more of patients have peritoneal disease upon surgical exploration. Until the early 1990s, peritoneal metastasis was considered as terminal stage of the disease; in the late 1990s, selected patients with peritoneal metastasis were recategorized as local disease. Over the past two decades, the treatment of peritoneal involvement has transformed, and cytoreductive surgery plus intraperitoneal therapy have drastically altered the natural course of several malignancies.

Areas covered: We performed a review of studies available on PubMed from 1 January 2014 to 31 July 2019 and the analysis of their reference citations. We describe the most current intraperitoneal chemotherapy opportunities in the treatment of gastric cancer: hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC), laparoscopic hyperthermic intraperitoneal chemotherapy (LHIPEC), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), LHIPEC + NIPS, extensive intraoperative peritoneal lavage (EIPL), early postoperative intraperitoneal chemotherapy (EPIC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC).

Expert opinion: Comprehensive treatment consisting of CRS combined with perioperative intraperitoneal/systemic chemotherapy can, today, be considered an effective strategy to improve the long-term survival of gastric cancer patients with peritoneal metastasis.     

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.     

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.     

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.     

Peritoneal lavage cytology under local anesthesia for detection of peritoneal recurrence after surgery

Gastric cancer with positive peritoneal lavage cytology shows a very poor prognosis due to frequent peritoneal recurrence after surgery. Therefore, we have introduced neoadjuvant intra-peritoneal and systemic chemotherapy( NIPS) for gastric cancer with peritoneal microscopic and/or microscopic dissemination before surgery. In patients subjected to the strategy, we have experienced two cases of advanced gastric cancer with CY1, which had been treated with NIPS and curative surgery, had been performed with second peritoneal lavage cytology two years after surgery. In those two cases, S-1 was discontinued due to the negative results of peritoneal lavage cytology. We will present the cases.     

腹腔热灌注化疗联合全身系统化疗及阿帕替尼转化治疗对胃癌腹膜转移的疗效

  目的  通过腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）联合腹腔局部加全身系统化疗（neoadjuvant intraperitoneal and systemic chemotherapy,NIPS）及阿帕替尼转化治疗胃癌腹膜转移（P1CY1）患者,评价其临床安全性及有效性。  方法  回顾性分析2017年10月至2018年10月河北医科大学第四医院收治的32例经腹腔镜探查后证实为P1CY1胃癌患者,所有患者均进行HIPEC联合NIPS及阿帕替尼靶向治疗。在进行6个周期转化治疗后再次进行腹腔镜探查评估,根据评估结果对患者进行进一步治疗。  结果  32例患者经转化治疗后均进行疗效评价,其中客观缓解率（objective response rate,ORR）为62.50%,疾病控制率（disease control rate,DCR）为90.63%。所有患者均进行二次腹腔镜探查,PCI评分较之前下降者24例（75.00%）,上升者8例（25.00%）,其中R0切除率为18.75%。中位随访时间25.2个月,中位生存期（median overall survival,mOS）为16.2（13.5~22.5）个月,中位无进展生存期（median progression-free survival,mPFS）为14.9（11.4~20.3）个月。常见不良反应主要包括骨髓抑制、周围感觉神经病变、消化道反应及口腔黏膜炎,无不良反应相关死亡病例。  结论  HIPEC联合NIPS及阿帕替尼靶向治疗可以提高腹膜转移胃癌患者的R0切除率和疾病控制率,同时化疗不良反应可控,是一种安全有效的转化治疗方案,值得深入研究。      

Surgery combined with peritonectomy procedures and intraperitoneal chemohyperthermia in abdominal cancers with peritoneal carcinomatosis: a phase II study.

PURPOSE: To evaluate the tolerance of peritonectomy procedures (PP) combined with intraperitoneal chemohyperthermia (IPCH) in patients with peritoneal carcinomatosis (PC), a phase II study was carried out from January 1998 to September 2001. PATIENTS AND METHODS: Fifty-six patients (35 females, mean age 49.3) were included for PC from colorectal cancer (26 patients), ovarian cancer (seven patients), gastric cancer (six patients), peritoneal mesothelioma (five patients), pseudomyxoma peritonei (seven patients), and miscellaneous reasons (five patients). Surgeries were performed mainly on advanced patients (40 patients stages 3 and 4 and 16 patients stages 2 and 1) and were synchronous in 36 patients. All patients underwent surgical resection of their primary tumor with PP and IPCH (with mitomycin C, cisplatinum, or both) with a closed sterile circuit and inflow temperatures ranging from 46 degrees to 48 degrees C. Three patients were included twice. RESULTS: A macroscopic complete resection was performed in 27 cases. The mortality and morbidity rates were one of 56 and 16 of 56, respectively. The 2-year survival rate was 79.0% for patients with macroscopic complete resection and 44.7% for patients without macroscopic complete resection (P =.001). For the patients included twice, two are alive without evidence of disease, 54 and 47 months after the first procedure. CONCLUSION: IPCH and PP are able to achieve unexpected long-term survival in patients with bulky PC. However, one must be careful when selecting the patients for such an aggressive treatment, as morbidity rate remains high even for an experienced team.     

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.     

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.     

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.