Peritoneal carcinomatosis from colorectal cancer

BACKGROUND: Aggressive therapeutic regimens have been advocated for the treatment of peritoneal carcinomatosis from colorectal cancer. It is essential to understand the clinical and histological features that govern the natural history of this condition if the efficacies of novel therapeutic approaches are to be assessed adequately. METHODS: A database of 3019 colorectal cancers was used to identify patients with synchronous peritoneal carcinomatosis, patients who developed metachronous peritoneal carcinomatosis, and those without carcinomatosis. Clinical, histological and survival data for the groups were collated and subjected to statistical analysis. RESULTS: Some 349 patients (13 per cent) with peritoneal carcinomatosis were identified; 214 had synchronous disease and 135 had metachronous carcinomatosis. Some 125 patients (58 per cent) in the synchronous group were free of systemic metastases; 80 of these patients had localized disease. Liver metastases, tumour (T) stage, nodal stage, and venous and perineural invasion were independent predictors of metachronous carcinomatosis. The median survival of patients with synchronous disease was 7 months; survival was adversely affected by the extent of peritoneal carcinomatosis and the T stage of the primary cancer. CONCLUSION: Peritoneal carcinomatosis is a common mode of disease progression in patients with colorectal cancer. For the majority of patients the prognosis is poor, but a small number with localized disease may be suitable for further aggressive therapy.     

Peritoneal cytology in colorectal cancer: incidence and prognostic value

BACKGROUND: The value of peritoneal washing cytology on prognosis is not clear yet. The aims of our prospective study were to consider the incidence and prognostic value of peritoneal cytology. METHODS: From 1996 to 2003, washing cytology was performed in 88 patients who underwent surgery for colorectal cancer. Before exploration and manipulation of the tumor, each of the peritoneal cavities next to the tumor site, subhepatic and rectovesical recesses, were irrigated with 50 mL saline, and then the aspirates were taken for cytological evaluation. RESULTS: Thirteen (14.7%) of 88 patients had positive cytology. Although necrosis, depth of invasion, differentiation of the tumor, macroscopic peritoneal dissemination, and ascites were correlated with positive cytology; multivariate analyses revealed the depth of invasion, presence of necrosis, and differentiation of the tumor as the factors affecting the cytology. The disease-free and overall-survival times in patients with positive and negative peritoneal washing cytology were 56.36, 61.40 and 52.08, 63.94 months, respectively (P > .05). CONCLUSION: The presence of free malignant cells in the peritoneal cavities of patients who underwent curative resection for colorectal cancer provides no further prognostic value over the current staging systems.     

Surgical treatment of peritoneal carcinomatosis: current treatment modalities

Background

Selected patients with peritoneal surface malignancies (PSM) have been treated effectively by the combination of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Purpose

The purpose of this study is to summarize the treatment outcomes and general considerations regarding definitions and staging systems of current CRS and HIPEC modalities in malignant peritoneal mesothelioma and in secondary peritoneal malignancies such as peritoneal metastasis from appendiceal, colorectal, gastric, and epithelial ovarian cancers.

Conclusion

Disease progression within the peritoneal cavity has in the past been regarded as a terminal event. Accumulating evidence underlines the therapeutic potential and the acceptable morbidity and mortality rates of CRS and HIPEC in selected patients.     

Peritoneal carcinomatosis from colorectal cancer and small bowel cancer treated with peritonectomy

BACKGROUND: This study aims to assess the survival of patients who underwent peritonectomy, to assess the morbidity and mortality associated with the procedure and to review the published reports on the survival of patients with peritoneal spread of colorectal cancer (CRC). METHODS: Peritonectomy involves resection of all visible peritoneal tumour and is followed by heated intraperitoneal chemotherapy. Peritonectomy with heated intraperitoneal chemotherapy is associated with a 3-year survival of 30-50% in patients with low peritoneal cancer index (PCI) with peritoneal carcinomatosis from CRC. There are approximately 1000 patients in phase 2 studies and a large survival advantage was shown in a randomized control trial. We have carried out over 100 peritonectomy procedures. This study describes 22 patients with peritoneal spread of gastrointestinal cancer treated with peritonectomy between 1996 and March 2005. Twenty of these patients had primary colorectal cancer and two patients had primary small bowel cancer. RESULTS: Of the 22 patients who underwent peritonectomy, 8 patients are now deceased. The median follow up is now 16.1 months. At 12 months, the survival was 61.5% and at 24 months the survival was 46.1%, which are creditable results comparable with the world published reports. We found that those patients with all macroscopic residual tumour removed at the end of the procedure (completeness of cancer resection, CCR O) had improved 24-month survival compared with patients in whom there was incomplete tumour resection (53.3% survival vs 22.2%, respectively, P = 0.024). Patients with a PCI score less than 13 had better survival (P = 0.0003). CONCLUSIONS: Peritonectomy for peritoneal carcinomatosis from CRC offers patients improved survival. Our results are consistent with the published data with respect to improved survival in patients with low PCI and complete cytoreduction.     

Peritoneal carcinomatosis. Surgical treatment, including hyperthermal intraperitoneal chemotherapy]

Colorectal cancer is a common malignant disease with increasing incidence and a significant cause of death in cancer patients. More than 10% of patients with colorectal cancer show peritoneal carcinomatosis at initial diagnosis. Moreover, peritoneal metastasis is a common sign of recurrence. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a new treatment strategy for highly selected patients with peritoneal carcinomatosis. Numerous studies show prolonged survival after CRS and HIPEC with acceptable morbidity and mortality rates. Accurate preoperative diagnostics and patient selection play a pivotal role in postoperative patient outcome. This promising treatment strategy is discussed regarding surgical technique, intraperitoneal chemotherapy, and patient outcome.     

Intraperitoneal chemohyperthermia and attempted cytoreductive surgery in patients with peritoneal carcinomatosis of colorectal origin

BACKGROUND: Colorectal cancer with peritoneal carcinomatosis is usually considered incurable. The purpose of this study was to evaluate the efficacy of intraperitoneal chemohyperthermia (IPCH) following cytoreductive surgery in patients with colorectal carcinomatosis. METHODS: Between January 1989 and August 2002, 53 patients (mean age 48.6 years) were treated by IPCH with mitomycin C. IPCH was performed in 34 patients following extensive cytoreductive surgery (more than two peritonectomy procedures). Five patients underwent two operations and one patient three operations. RESULTS: Operative morbidity and mortality rates were 23 and 4 per cent respectively. At a median follow-up of 59.5 months, the overall median survival was 12.8 months. The extent of carcinomatosis, completeness of cytoreduction and histological differentiation were significant prognostic indicators by univariate analysis. The median survival was 32.9 months for patients whose resection was classified as completeness of cancer resection (CCR) 0 (complete cytoreduction), 12.5 months for those whose operation was CCR-1 (diameter of residual nodules 5 mm or less) and 8.1 months for patients who had a CCR-2 resection (diameter of residual nodules more than 5 mm) (P < 0.001). Completeness of cytoreduction was the only significant independent predictor of survival by multivariate analysis. CONCLUSION: IPCH combined with cytoreductive surgery seems to be an effective therapy for carefully selected patients with carcinomatosis from colorectal cancer. This strategy was most effective in patients with carcinomatosis of limited tumour volume or when cytoreductive surgery allowed sufficient downstaging (residual tumour nodules smaller than 5 mm).     

Hyperthermic intraperitoneal chemotherapy and cytoreductive surgery for peritoneal carcinomatosis of colorectal origin: a novel treatment strategy with promising results in selected patients

Peritoneal carcinomatosis is a major cause of treatment failure in colorectal cancer with few options for treatment. Recent reports, including a single randomized trial, suggest that localized peritoneal carcinomatosis, in the absence of other metastases, could be considered regional metastatic disease analogous to liver metastases, and thus amenable to locoregional therapy. Optimal treatment involves complete tumour removal by complex surgical techniques, combined with hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment strategy has significant morbidity and mortality risks and careful selection is essential to avoid futile procedures. The best results are achieved in patients with limited disease who have complete macroscopic tumour removal, when the primary and peritoneal metastases are removed synchronously, and when the primary tumour is a cancer of the appendix. Improvements in cross-sectional imaging and increasing utilization of laparoscopy in colorectal cancer surgery may help in detecting suitable cases for these techniques. Selected patients with localized disease have been shown to have good outcomes with prolonged survival and perhaps a possibility of cure.     

Patient selection and treatment of peritoneal carcinomatosis from colorectal and appendiceal cancer

Colorectal cancer is a disease process that disseminates through lymphatic channels, through hematogenous routes, and by invasion through the bowel wall. These mechanisms result in lymph node metastases, liver metastases, and peritoneal seeding. Although lymphatic and venous dissemination requires an invasive local process, peritoneal seeding may occur with both high grade and low grade malignancies. Cancer dissemination that causes liver and lymphatic metastases occurs prior to surgical resection of the primary colorectal cancer. Peritoneal seeding and seeding of the resection site (local recurrence) may also occur as a result of the surgical trauma that accompanies resection of the primary lesion. Leakage of malignant cells from transected lymphatic channels may be the mechanism of this intraoperative intraperitoneal cancer dissemination. To limit the progression of peritoneal seeding and to treat large volume, low grade intraabdominal tumor deposits, combinations of cytoreductive surgery and intraperitoneal chemotherapy have been successfully employed. Selection factors that correlate with long-term benefit are (1) low grade of malignancy, (2) lack of lymph node or liver metastases, and (3) treatment of low volume disease. For patients with moderate or high grade colorectal cancer, only a low volume of disease can be treated successfully. For patients with low grade cancer, peritonectomy procedures are used to achieve minimal residual disease before initiating the intraperitoneal chemotherapy. In properly selected patients, peritoneal carcinomatosis from colorectal and appendiceal cancer is a treatable condition that may result in long-term disease-free survival.

---

Resumen El cáncer colorrectal es un proceso patológico que se disemina a través de los canales linfáticos, por vías hematógenas y por invasión de la pared del intestino. Estos mecanismos resultan en metástasis a los ganglios linfáticos, al hígado y, también, en siembras peritoneales. Aunque la extensión linfática y venosa implica la existencia de un proceso invasor local, la diseminación pertioneal puede presentarse tanto en los tumores de alto grado de malignidad como en los de bajo grado. La diseminación del cáncer que causa metástasis hepáticas y ganglionares ocurre con anterioridad a la resección quirúrgica del neoplasma colorrectal primario. La siembra peritoneal, así como la siembra del lugar del la resección (recurrencia local), pueden también ocurrir como resultado del trauma quirúrgico asociado con la resección del neoplasma primario. La filtración de células malignas a partir de canales linfáticos seccionados también puede ser un mecanismo de este fenómeno intraoperatorio de diseminación del cáncer. Con el objeto de limitar la progresión de la diseminación peritoneal y de tratar depósitos tumorales de alto volumen/bajo grado de malignidad, se han empleado exitosmente combinaciones de cirugía citorreductora y quimioterapia intraperitoneal. Los factores de selección que se correlacionan con beneficios a largo plazo son: 1) bajo grade de malignidad, 2) ausencia de metástasis ganglionares o hepáticas y 3) tratamiento de enfermedad de bajo volumen. Para los pacientes con cáncer colorrectal de grado moderado o alto de malignidad, solamente se puede tratar con éxito un proceso neoplásico de bajo volumen. En pacientes con cáncer de bajo grado, se utilizan procedimientos de peritonectomía para lograr un mínimo de enfermedad residual antes de iniciar la quimioterapia intraperitoneal. En pacientes debidamente seleccionados, la carcinomatosis peritoneal por cáncer colorrectal es una entidad eminentemente tratable que puede resultar en prolongada sobrevida libre de enfermedad.

---

Résumé Le cancer colorectal est une maladie maligne qui s'étend à distance par des voies lymphatiques, des voies hématogènes et par invasion à travers la paroi intestinale. Ces mécanismes expliquent que l'on retrouve des métastases lymphatiques, des métastases hépatiques et enfin péritonéales. Alors que les deux premiers mécanismes exigent une invasion locale, l'ensemencement péritonéal peut se voir dans les cancers d'agressivité variable, de haut ou de bas degré de malignité. La dissémination responsable des métastases hépatiques et lymphatiques a lieu avant la résection de la tumeur primitive. L'ensemencement péritonéal et du site d'origine de la tumeur peut se produire par traumatisme lors de la résection chirurgicale. Une «fuite» au niveau des canaux lymphatiques est peut-être le mécanisme de cet ensemencement. C'est pour limiter l'évolution de l'ensemencement péritonéal et pour traiter les éventuels ensemencements péritonéaux, quel que soit leur grade de malignité, que la chirurgie «cytoréductrice» et la chimiothérapie intrapéritoneale ont été employées avec succès. Les facteurs de sélection qui sont corrélés avec un bénéfice pour le patient sont 1) un degré de malignité réduit, 2) l'absence de métastase lymphatique et/ou hépatique et 3) la réduction tumorale maximale lorsque le volume tumoral est limité. Pour les patients ayant un cancer colorectal à degré de malignité modéré ou élevé, le volume de cancer doit être réduit pour être traité avec succès. Si le cancer est de bas degré de malignité, des résections péritonéales (péritonectomie) sont nécessaires pour obtenir une réduction tumorale maximale avant d'initier la chimiothérapie intrapéritonéale. Chez des patients sélectionnés, la carcinose péritonéale à partir d'un cancer colorectal est traitable et peut donner des survies à long terme.

     

Peritoneal carcinomatosis from appendiceal cancer: A paradigm for treatment of abdomino-pelvic dissemination of gastrointestinal malignancy

Summary Background Peritoneal carcinomatosis from appendix cancer is a rare disease which has generally not been studied. 104 patients treated by a uniform treatment strategy have been followed for up to 10 years. Methods The clinical features that correlate with improved survival included low vs. high histologic grade, complete vs. incomplete cytoreduction, lymph nodes negative rather than positive for metastasis and minimal vs. extensive prior surgery. By the Cox semi-parametric model the independent variables were histologic grade and completeness of cytoreduction. From these data prognostic groups 1, 2 and 3 were formulated. Results Patients in prognostic group 1 had a complete cytoreduction and a grade 1 histopathology with a 5 year survival of 90%. Patients in prognostic group 2 had a complete cytoreduction with grade 2 or 3 histopathology and a 70% 5 year survival. Patients in group 3 had an incomplete cytoreduction, and a 5 year survival of 22%. Conclusions These data accumulated on patients with appendix cancer may have relevance to the management of patients with peritoneal carcinomatosis from other gastrointestinal cancers.      

免疫检查点抑制剂在结直肠癌中的应用：当前和未来的策略

免疫检查点抑制剂（ICIs）主要包括帕博利珠单抗、纳武单抗和伊匹木单抗,已经改变了多种类型肿瘤的标准治疗方案。对于结直肠癌（CRC）,肿瘤中微卫星不稳定（MSI）或错配修复（MMR）的状态是影响ICIs疗效的最关键因素。高水平MSI（MSI-H）或MMR缺陷（dMMR）的转移性CRC（mCRC）通常有浸润T细胞的肿瘤微环境,与对ICIs的良好反应相关,但MSI-H/dMMR的比例不足5%。帕博利珠单抗和纳武单抗联合或不联合伊匹木单抗已被纳入MSI-H/dMMR mCRC的标准治疗方案。与此相反,微卫星稳定（MSS）或错配修复稳定（pMMR）的mCRC的肿瘤微环境中T细胞浸润程度低被认为是ICIs的主要耐药机制。笔者回顾现有ICIs治疗CRC的临床数据和正在进行的部分临床试验,讨论可能存在的不足。     

Peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemohyperthermia

STUDY AIM: The aim of this prospective non-randomized trial was to report a series of intraperitoneal carcinomatosis due to miscellaneous causes, treated by intraperitoneal hyperthermic perfusion (IPHP) and cytoreductive surgery. PATIENTS AND METHOD: From January 1995 to May 1999, 35 patients were treated by IPHP and 26 of them underwent maximal cytoreductive surgery. IPHP was performed for 60 minutes at an intraperitoneal temperature of 42 degrees C with Mitomycin C (10 mg/L) or cisplatinum (12 mg/L) at a flow rate of 0.9 L/min. RESULTS: There was one (2.8%) postoperative death due to respiratory complications on day 16. Three patients (8.5%) were admitted to the intensive care unit. A high morbidity rate (54%) was observed with intra-abdominal complications in 28.5% of patients, requiring reoperation in three patients. In patients with stages 1 and 2 peritoneal carcinomatosis (granulations less than 5 mm), the 12- and 24-month survival rates were 63.1% and 31.5%, respectively. In patients with advanced stage 3 (diffuse malignant nodules less than 2 cm) and stage 4 carcinomatosis (malignant nodules larger than 2 cm), the 12- and 24-month survival rates were 31.2% and 12%, respectively. Six patients survived for more than 30 months. CONCLUSION: IPHP appears to be an effective treatment for peritoneal carcinomatosis. IPHP combined with cytoreductive surgery is aggressive with a high morbidity rate. Rigorous patient selection is necessary. IPHP is still under evaluation. Prospective randomized trials with identical IPHP protocols are required.