Possibility of sandwiched liver surgery with molecular targeting drugs, cetuximab and bevacizumab on colon cancer liver metastases: a case report

ABSTRACT: A 31-year-old man with sigmoid colon cancer with concomitant simultaneous multiple liver metastases had received FOLFIRI (leucovorin, fluorouracil and irinotecan) and FOLFOX6 (leucovorin, fluorouracil and oxaliplatin) after an ordinary sigmoidectomy. However, his serum carcinoembryonic antigen (CEA) level increased rapidly during the fifteen months after the operation while he was on FOLFOX6. Abdominal computed tomography revealed expanding multiple liver tumors. As the third line chemotherapy, a combination therapy of cetuximab with irinotecan was given, which markedly reduced his levels of serum CEA, and the size and number of liver tumors. He underwent lateral segmentectomy of the liver and microwave coagulation of the liver metastases in the remnant liver. Thereafter, a good quality of life with tumor dormancy was obtained for 6 months. However, his serum CEA started to rise again in the absence of liver tumors. Therefore, FOLFOX 6 with bevacizumab was chosen as the fourth line chemotherapy, and the serum CEA was reduced with tumor dormancy. A good quality of life was obtained again at 3 years after the first surgery. This report indicates the effectiveness of sandwiched liver surgery with the molecular targeting drugs cetuximab and bevacizumab on multiple liver metastases of colon cancer, and suggests the possibility of a regimen consisting of bevacizumab following cetuximab.     

Recent results of irinotecan therapy in colorectal cancer

New results presented at ASCO Conference in 2003 added further important data to our knowledge on successful use of irinotecan in colorectal cancer (CRC). Irinotecan - just like oxaliplatin - given as neoadjuvant therapy with 5-FU - folinic acid (FUFA) can render originally unresectable liver or lung metastases of CRC resectable, giving the hope of long-term survival for a proportion of patients. Irinotecan combined with 5-FU is an essential part of the most successful palliative sequential chemotherapy of stage IV CRC. Sequential FOLFIRI before or after FOLFOX combination ensures the longest possible progression-free and overall survival for metastatic CRC patients in the palliative setting. In order to achieve the longest survival time, sequential use of both 5-FU, irinotecan and oxaliplatin is necessary. The French GERCOR Group achieved 26 months median overall survival with the sequential use of continuous infusional FUFA, oxaliplatin and irinotecan combinations in stage IV CRC. The analysis of large phase III trials using 5-FU, irinotecan and oxaliplatin revealed that the higher proportion of patients was treated with all three drugs, the longer overall survival was achieved. If applied with caution, toxicity and efficacy of irinotecan in elderly patients is not significantly different from that seen in younger population. The anti-VEGF bevacizumab increases the efficacy of first-line irinotecan therapy, while the addition of cetuximab restores irinotecan sensitivity in second line treatment of stage IV CRC. The combination of irinotecan with oral capecitabine is safe and effective in advanced CRC.     

Dietary glycine protects from chemotherapy-induced hepatotoxicity

Hepatotoxic side effects of neoadjuvant chemotherapy for colorectal liver metastases increase perioperative morbidity and mortality. Glycine protects liver from injury in various animal models. Thus, this study was designed to assess its effect on liver after chemotherapy. Sprague–Dawley rats (200–220 g) were fed a synthetic diet containing 5% glycine for 5 days. Subsequently, chemotherapy (FOLFIRI: irinotecan, folinic acid and fluorouracil, or FOLFOX: oxaliplatin, folinic acid and fluorouracil) was administered at standard doses. Transaminases, histology, immunohistochemistry and in vivo microscopy were used to index liver injury, to monitor intrahepatic microperfusion and activation of Kupffer cells. Glycine significantly decreased transaminases after chemotherapy to 25–50% of control values (p < 0.05). Microvesicular steatosis was significantly reduced from 18.5 ± 3.4 and 57.1 ± 8.6% in controls to 9.5 ± 1.8 and 37.7 ± 4.4% after FOLFIRI and FOLFOX, respectively. Furthermore, phagocytosis of latex beads was reduced by about 50%, while leukocyte adherence in central and midzonal subacinar zones decreased to 60–80% after glycine (p < 0.05). Glycine significantly reduced expression of inducible nitric oxide synthase after chemotherapy, while hepatic microcirculation was increased (p < 0.05). This study shows for the first time that glycine reduces chemotherapy-induced liver injury. The underlying mechanisms most likely include Kupffer cells and an improved intrahepatic microperfusion.     

Economic Evaluation of First-Line Adjuvant Chemotherapies for Resectable Gastric Cancer Patients in China

Background

First-line postoperative adjuvant chemotherapies with S-1 and capecitabine and oxaliplatin (XELOX) were first recommended for resectable gastric cancer patients in the 2010 and 2011 Chinese NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer; however, their economic impact in China is unknown.

Objective

The aim of this study was to compare the cost-effectiveness of adjuvant chemotherapy with XELOX, with S-1 and no treatment after a gastrectomy with extended (D2) lymph-node dissection among patients with stage II-IIIB gastric cancer.

Methods

A Markov model, based on data from two clinical phase III trials, was developed to analyse the cost-effectiveness of patients in the XELOX group, S-1 group and surgery only (SO) group. The costs were estimated from the perspective of Chinese healthcare system. The utilities were assumed on the basis of previously published reports. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were calculated with a lifetime horizon. One-way and probabilistic sensitivity analyses were performed.

Results

For the base case, XELOX had the lowest total cost ($44,568) and cost-effectiveness ratio ($7,360/QALY). The relative scenario analyses showed that SO was dominated by XELOX and the ICERs of S-1 was $58,843/QALY compared with XELOX. The one-way sensitivity analysis showed that the most influential parameter was the utility of disease-free survival. The probabilistic sensitivity analysis predicted a 75.8% likelihood that the ICER for XELOX would be less than $13,527 compared with S-1. When ICER was more than $38,000, the likelihood of cost-effectiveness achieved by S-1 group was greater than 50%.

Conclusions

Our results suggest that for patients in China with resectable disease, first-line adjuvant chemotherapy with XELOX after a D2 gastrectomy is a best option comparing with S-1 and SO in view of our current study. In addition, S-1 might be a better choice, especially with a higher value of willingness-to-pay threshold.     

Classifying the Stage IV Colorectal Cancer: Prognostic Impact of Radical Resection for Colorectal liver Metastases and Proposal for a New Staging System

Currently, there is no universally accepted system to classify the stage IV colorectal cancer. Here, we analyze the prognostic impact of radical resection for colorectal liver metastases and propose a new staging system for stage IV colorectal cancer. A retrospective review was undertaken of 126 consecutive patients who underwent surgical treatment for colorectal liver metastases from January 1997 to January 2004. Based on the overall survival rates (Kaplan–Meier method) and surgical outcomes, we propose a new staging system for stage IV colorectal cancer. Patients were divided into two groups: patients who underwent initial hepatic resections (R0 resection) for liver metastases (group 1, n = 22), and patients who underwent palliative resection for unresectable liver metastases (group 2, n = 104). The overall survival rates in group 1 at 1, 3, and 5 years were 68.2 % (15/22), 40.9 % (9/22), and 18.2 % (4/22), respectively. The overall survival rates in group 2 at 1, 3, and 5 years were 54.8 % (57/104), 16.3 % (17/104), and 0 % (0/104), respectively. There was a significant difference in overall survival rates between both groups (p < 0.05). Based on the study results, we propose a new staging system where all distant metastases are grouped within stage IV and subclassified into resectable (R0 resection) and unresectable stages. Curative surgical treatment is a critical prognostic factor in colorectal liver metastases. The proposed new staging system for stage IV colorectal cancer is simple and is clinically useful to estimate the prognosis.     

Chronotherapy of colorectal cancer

Chronotherapy consists of chemotherapy delivery according to circadian rhythms. These genetically based rhythms modulate cellular metabolism and cell proliferation in normal tissues. As a result, both the host tolerance and antitumor efficacy of 5-fluorouracil (5-FU) and oxaliplatin (L-OHP), like 30 other anticancer drugs, vary largely according to the dosing time in laboratory rodents. The transfer of this concept to the clinic is aimed primarily at increasing the dose-intensity of the therapy through adjustment of drug-delivery to 24h rhythms in host tolerance. A specific technology (programmable-in-time infusion pumps) enables administration of chronotherapy to fully ambulatory patients. Phase I-III clinical trials show chronotherapy significantly increases tolerance to high doses of cancer drugs and improves antitumor activity in patients with metastatic colorectal cancer. These safe conditions of drug-delivery led to the first demonstration of the high activity of the 5-FU-leucovorin-L-OHP protocol. Chronotherapy with these three drugs also allows surgical removal of previously unresectable liver and lung metastases. This novel medico-surgical management provides hope for the cure of metastatic disease in patients with unresectable colorectal cancer metastases.     

FOLFOX4和XELOX两周方案用于进展期胃癌新辅助化疗的随机对照研究

目的:观察FOLFOX4和XELOX新辅助化疗方案治疗局部进展期胃癌的疗效和毒副作用。方法:68例初治确诊为局部进展期胃癌的患者,随机分为两组,每组各34例,分别采用XELOX和FOLFOX4化疗方案行术前两个疗程的化疗治疗。结果:XELOX组总有效率为47.06%,FOLFOX4组总有效率为41.08%,两组间无显著性差异。不良反应方面,FOLFOX4组恶心、呕吐,白细胞减少和口腔黏膜炎发生率较高,而XELOX组手足综合症发生率较高。结论:XELOX方案作为胃癌新辅助化疗方案,疗效与FOLFOX4方案相似,但XELOX方案副作用较轻且均可控制,化疗时间短,对机体损伤小,易于接受,值得在临床工作中进一步研究和推广。     

Comparison of efficacy of different route of administration of chemotherapy on unresectable, advanced gastric cancer

ABSTRACT: BACKGROUND: The aim of this study was to compare the efficacy of two neoadjuvant chemotherapies (FLEEOX and XELOX) with different routes of administration for unresectable gastric cancer. METHODS: A total of 85 patients with unresectable gastric cancer hospitalized from January 2007 to December 2009 received neoadjuvant chemotherapy. The FLEEOX group (48 patients) received the FLEEOX regimen(fluorouracil, leucovorin, epirubicin, epotoside, and oxaliplatin), which combined arterial with venous administration for one or two cycles, while the XELOX group (37 patients) received XELOX (capecitabine plus oxaliplatin) via venous administration for two to four cycles. The clinical response and overall survival of the two groups were compared. RESULTS: In the FLEEOX group, the clinical response rate (RR) of chemotherapy was 85.4% (41 of 48 patients) and the median survival time was 25 months. The 1-year and 2-year disease-free survival (DFS) rates were 85.4% and 45.8%, respectively. In the XELOX group, the clinical RR was 59.5% and the median survival time was 9 months, while the 1-year and 2-year survival rates were 35.2% and 8.3%, respectively. The clinical RR, the R0 resection rate, the median survival time, and the 1-year and 2-year DFS rates were significantly better (P <0.05) in the FLEEOX group than in the XELOX group. In addition, there were no significant differences in the rates of toxic and adverse reactions or post-operative complications between the two groups. CONCLUSIONS: For patients with a preoperative diagnosis of unresectable gastric cancer, the efficacy of the FLEEOX regimen, which combines arterial with venous administration, was better than that of the XELOX regimen, using venous administration only. This combination of arterial and venous administration could be useful for improving the efficacy of neoadjuvant chemotherapy for gastric cancer.     

Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study

Background

Adjuvant chemotherapy for colorectal cancer is mainly based on the combination of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4). The pharmacological target of oxaliplatin remains intracellular and therefore dependent on its entry into cells. The intracellular distribution of oxaliplatin is mediated by organic cation transporters 1, 2 and 3 (OCT1, 2 and 3), copper transporter 1 (CTR1) and ATPase Cu²⁺ transporting beta polypeptide (ATP7B) and may modulate the efficacy of oxaliplatin-based chemotherapy. The aim of this study was to perform a retrospective study to assess the relation between the expression of oxaliplatin transporters in colorectal cancer before chemotherapy and the response to FOLFOX-4 adjuvant chemotherapy in responder and non-responder patients.

Methods

This retrospective study was conducted at a single center (University Hospital of Clermont-Ferrand, France). The target population was patients with resectable colorectal cancer operated between 2006 and 2013. Inclusion criteria were defined for the responder patients as no cancer recurrence 3 years after the end of chemotherapy, and for the non-responder patients as cancer recurrence within 1 year. Other inclusion criteria were stages IIb–IV cancers, first-line adjuvant FOLFOX-4 chemotherapy, and the availability of resected primary tumor samples. Exclusion criteria were preoperative chemotherapy and/or radiotherapy, a targeted therapy, other anticancer drugs, cancer recurrence between the first and the third year after the end of chemotherapy and follow-up < 3 years. Immunostaining of oxaliplatin transporters (OCT1, 2, 3, CTR1 and ATP7B) and Ki-67 was assessed in tumor samples.

Results

Retrospectively, 31 patients have been selected according to inclusion and exclusion criteria (15 responders and 16 non-responders). Before FOLFOX-4 regimen, OCT3 expression was significantly lower in responder patients compared to non-responders (p<0.001). According to multivariate analysis, OCT3 remains an independent criterion for adjuvant FOLFOX chemotherapy response (p = 0.039). No significant relation is reported between chemotherapy response and the expression of OCT1 (p = 0.49), OCT2 (p = 0.09), CTR1 (p = 0.45), ATP7B (p = 0.94) and Ki-67 (p = 0.34) in tumors.

Conclusions

High expression of OCT3 could be an independent factor related to resistance to FOLFOX-4 chemotherapy.     

A Pilot Study of Cryochemotherapy for Hepatic Metastases from Colorectal Cancer

Cryosurgery of hepatic metastases from colorectal carcinoma is a form of local therapy for unresectable disease. After curative resection, failures occur in the liver, and at extrahepatic sites. This pilot study evaluated the toxicity and tolerance to cryotherapy and intraoperative chemotherapy for unresectable hepatic metastases from colorectal cancer. If after exploratory celiotomy for potential curative resection of hepatic metastases the patient was deemed unresectable because of location and/or number of lesions, cryosurgery and intraoperative chemotherapy with systemic 5-fluorouracil 600 mg/m²and leucovorin 500 mg/m²was performed. Four patients were treated with cryochemotherapy. All patients developed toxicity. Two patients developed grade III leukopenia on Postoperative Days 2 and 12, and grades II and III diarrhea on Postoperative Days 5 and 7, respectively. Grade III hyperbilirubinemia and thrombocytopenia occurred in one patient on Postoperative Days 3 and 7. Acute respiratory distress syndrome, postoperative ileus, and grade II mucositis occurred in one patient each. All patients had delays and dose reductions on their subsequent chemotherapy treatments secondary to toxicity. Two patients had disease progression, one had stable disease, and one is “disease free.” Combining the tumoricidal effects of chemotherapy and cryosurgery is in theory a good concept. However, the toxicity of 5-FU and leucovorin is enhanced by this approach.     

Molecular markers in circulating tumour cells from metastatic colorectal cancer patients

The prognosis of metastatic cancer patients is still largely affected by treatment failure, mainly due to drug resistance. The hypothesis that chemotherapy might miss circulating tumour cells (CTCs) and particularly a subpopulation of more aggressive, stem‐like CTCs, characterized by multidrug resistance, has been recently raised. We investigated the prognostic value of drug resistance and stemness markers in CTCs from metastatic colorectal cancer patients treated with oxaliplatin (L‐OHP) and 5‐fluoruracil (5‐FU) based regimens. Forty patients with metastatic colorectal cancer were enrolled. CTCs were isolated from peripheral blood and analysed for the expression of aldheyde dehydrogenase 1 (ALDH1), CD44, CD133 (used as markers of stemness), multidrug resistance related protein 5 (MRP5 used as marker of resistance to 5‐FU and L‐OHP) and survivin (used as a marker of apoptosis resistance). CTCs were found in 27/40 (67%) patients. No correlation was found between the expression of either CD44 and CD133 in CTCs and the outcome of patients, while a statistically significant shorter progression‐free survival was found in patients with CTCs positive for the expression of ALDH1, survivin and MRP5. These results support the idea that isolating survivin and MRP5⁺ CTCs may help in the selection of metastatic colorectal cancer patients resistant to standard 5‐FU and L‐OHP based chemotherapy, for which alternative regimens may be appropriate.     

Chronotherapy of colorectal cancer

Chronotherapy consists of chemotherapy delivery according to circadian rhythms. These genetically based rhythms modulate cellular metabolism and cell proliferation in normal tissues. As a result, both the host tolerance and antitumor efficacy of 5-fluorouracil (5-FU) and oxaliplatin (l-OHP), like 30 other anticancer drugs, vary largely according to the dosing time in laboratory rodents. The transfer of this concept to the clinic is aimed primarily at increasing the dose-intensity of the therapy through adjustment of drug-delivery to 24h rhythms in host tolerance. A specific technology (programmable-in-time infusion pumps) enables administration of chronotherapy to fully ambulatory patients. Phase I–III clinical trials show chronotherapy significantly increases tolerance to high doses of cancer drugs and improves antitumor activity in patients with metastatic colorectal cancer. These safe conditions of drug-delivery led to the first demonstration of the high activity of the 5-FU–leucovorin–l-OHP protocol. Chronotherapy with these three drugs also allows surgical removal of previously unresectable liver and lung metastases. This novel medico-surgical management provides hope for the cure of metastatic disease in patients with unresectable colorectal cancer metastases.     

射波刀立体定向放疗技术治疗结直肠癌肝转移癌的疗效观察

目的:探讨射波刀立体定向放疗技术治疗结直肠癌肝转移癌的疗效观察。方法:选择2014年1月至2016年2月我院收治的64例结直肠癌肝转移癌患者为研究对象,按照随机数字表法随机分为对照组(32例)和治疗组(32例),对照组患者给予FOLFOX6全身化疗方案,治疗组患者给予FOLFOX6全身化疗和肝脏病灶立体定向放疗(射波刀)治疗。观察患者的治疗3个月后的近期临床疗效和不良反应,6个月后患者生存率和局部控制率,并评价患者的生活质量。结果:治疗3个月后,治疗组患者的总有效率为78.13%,高于对照组的53.13%,差异有统计学意义(P0.05);治疗6个月后,治疗组的生存率(96.88%)和局部控制率(87.50%)均高于对照组(81.25%和65.63%),差异有统计学意义(P0.05);治疗6个月后,治疗组患者的情绪功能、认知功能、角色功能、躯体功能、社会功能评分均高于对照组,差异有统计学意义(P0.05)。两组患者的不良反应发生率比较差异无统计学意义(P0.05)。结论:射波刀立体定向放疗技术治疗结直肠癌肝转移癌具有较好的近期临床疗效,可提高患者的生存率和局部控制率,改善患者生活质量,且不良反应发生率低,值得临床推广应用。     

Liver Resection for Non-Colorectal,Non-Carcinoid,Non-Sarcoma Metastases: A Multicenter Study

Background

The role of liver resection for non-colorectal, non-neuroendocrine, non-sarcoma (NCNNNS) metastases is ill-defined. This study aimed to examine the oncologic outcomes of liver resection in such patients.

Methods

A retrospective analysis of liver resection for NCNNNS metastases was performed at two large centers. Liver resection was offered selectively in patients with stable disease. Oncologic outcomes were examined using the Kaplan-Meier method.

Results

Fifty-two patients underwent liver resection for NCNNNS metastases. Overall 5-year survival was 58%. Five-year survival was 85% for breast metastases, 66% for ocular melanoma, 83% for other melanomas, 50% for gastro-esophageal metastases, and 0% for renal cell carcinoma metastases. A contemporary colorectal liver metastasis cohort had a survival of 63% (p=0.89).

Conclusions

Liver resection is an effective option in the management of selected patients with NCNNNS metastases which have been deemed stable. Five-year survival rates were comparable to that of a contemporary cohort of patients with colorectal liver metastases in carefully selected patients. Further, larger studies are required to help identify potential prognostic variables and aid in decision-making in this heterogeneous population.     

Prospective analysis of KRAS wild-type patients with metastatic colorectal cancer using cetuximab plus FOLFIRI or FOLFOX4 treatment regimens

Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor, has proven to be efficient in the treatment of metastatic colorectal cancer. We made a prospective study of the efficacy and toxicities of cetuximab-combination first-line (FOLFOX4) versus second/third-line (FOLFIRI) chemotherapy in 98 KRAS wild-type patients who had metastatic colorectal cancer. Wild-type KRAS had been identified by direct sequencing. Associations between clinical response/progression-free survival/overall survival/toxicities and cetuximab-combination chemotherapy timing were evaluated. The overall response rate was significantly higher for first-line treatment than for second/third-line treatment (relative risk = 1.707, 95% confidence interval = 1.121-2.598). Both progression-free survival and overall survival indicated significantly longer survival of first-line treatment than second/third-line treatment patients. This study is a validation of a molecular analysis of KRAS wild-type status for the prediction of response to cetuximab-combination chemotherapy for metastatic colorectal cancer patients; its predictive role was less prominent in the second/third-line than in the first-line treatment patients.     

Effect of Neoadjuvant Chemotherapy in Patients with Resectable Colorectal Liver Metastases

Background

Whether patients with resectable colorectal liver metastases (CRLM) receive survival benefit from neoadjuvant chemotherapy remains controversial.

Methods

We retrospectively analyzed 466 patients with resectable CRLM between 2000 and 2010. Patient characteristics and survival data were recorded.

Results

The patients were divided into one group with neoadjuvant chemotherapy (group NC, n = 121) and another without (group WN, n = 345). There was no difference in 5-year survival (52% vs. 48%) between the two groups. No significant differences were identified between the two groups in terms of 30-day mortality (1.7% vs. 1.2%) or morbidity (33.9% vs. 25.8%). A primary tumor at stage T4, ≥4 liver metastases, the largest liver metastasis ≥5 cm in diameter, and a serum CEA level ≥5 ng/ml were independent prognostic factors. By assigning one point to each, the patients were divided into a low-risk group (0–2) and a high-risk (3–4). The patients in the low-risk group received no survival benefit from neoadjuvant chemotherapy, whereas those in the high-risk group received survival benefit (5-year survival, 39% vs. 33%, P = 0.028).

Conclusions

Preoperative neoadjuvant chemotherapy did not increase mortality or complications. Not all resectable patients, only those with >2 independent risk factors, received survival benefit from neoadjuvant chemotherapy.     

Safety of simultaneous resections of colorectal cancer and liver metastases

Liver resection is the only potentially curative method for patients with colorectal cancer metastases and 5-year survival rates are 20%-40%. Simultaneous resection of colorectal cancer and synchronous liver metastases has been recommended if minor hepatectomy is indicated. The purpose of this paper is to analyze the treatment of hepatic colorectal secondaries and to assess the safety of simultaneous and delayed liver resections and relations of morbidity to the extensiveness of hepatectomy and perioperative factors. Analyzed were 21 patients with liver metastases from colorectal cancer operated between 1997 and 1999 in the Clinical Hospital "Sestre milosrdnice". Operating time for simultaneous colorectal and liver resections was not significantly longer compared to liver resections alone. No significant difference in complication rate was found after simultaneous procedures and liver resection alone (38% vs. 31%). Complication rate after major liver resections was not significantly greater than after minor resections (38% vs. 31%). No statistically significant differences were found in operation time and blood replacement between patients who developed postoperative complications and those who did not. In conclusion, simultaneous resections of primary colorectal cancer and liver metastases may be considered safe. Morbidity rates are not significantly different from those after liver resections alone, nor depend significantly upon the extensiveness of liver resection, providing that the operation time and blood loss are within the range observed in this study.     

Cytoreductive Surgery of Colorectal Peritoneal Metastases: Outcomes after Complete Cytoreductive Surgery and Systemic Chemotherapy Only

Background

Cytoreductive peritoneal surgery (CRS) associated with hyperthermic peritoneal chemotherapy (HIPEC) has long been considered the standard treatment for colorectal peritoneal metastases (CPM). However, although efficacy of surgery has been demonstrated, evidence supporting HIPEC’s role is less certain.

Method

Overall survival (OS), progression-free survival (PFS) and morbidity were analysed retrospectively for fifty consecutively included patients treated for colorectal CPM with complete CRS and systemic chemotherapy only.

Results

Median peritoneal cancer index (PCI) was 8 (range 1-24). 23 patients had liver or lung metastases (LLM). 22 patients had synchronous CPM. 27 complications occurred (12 Grade 1/2, 14 Grade 3, 1 Grade 4a, 0 Grade 5). Median follow-up was 62.5 months (95 %CI 45.4-81.3), median survival 32.4 months (21.5-41.7). Three- and 5-year OS were 45.5% (0.31-0.59) and 29.64% (0.17-0.44) respectively. Presence of LLMs associated with peritoneal carcinomatosis was significantly associated with poorer prognosis, with survival at 5 years of 13.95% (95 %CI 2.9-33.6) vs. 43.87% (22.2-63.7) when no metastases were present (P= 0.018). Median PFS was 9.5 months (95 %CI 6.2-11.1).

Conclusion

With an equivalent PCI range and despite one of the highest rates of LLM in the literature, our survival data of CRS + systemic chemotherapy only compare well with results reported after additional HIPEC. Tolerance was better with acceptable morbidity without any mortality. Extra-hepatic metastasis (LLM) is a strong factor of poor prognosis. Awaiting the results of the randomized PRODIGE trial, these results indicate that CRS + systemic chemotherapy only is a robust hypothesis to treat colorectal CPM.     

Incidence and detection of occult hepatic metastases in colorectal carcinoma.

Isotope liver scan, ultrasonography, and computed tomography of the liver were performed during the postoperative period in 43 consecutive patients undergoing laparotomy for colorectal carcinoma. Obvious hepatic metastases were detected in six patients at the time of surgery. Eleven patients considered to have a disease-free liver at laparotomy developed hepatic metastases during the two-year follow-up period. These patients were considered to have had occult hepatic metastases at the time of surgery. Postoperative isotope liver scan, ultrasonography, and computed tomography detected the presence of overt metastases in four, five, and six patients respectively. Of the 11 patients with occult metastases, isotope liver scan, ultrasonography, and computed tomography detected one, three, and nine respectively. These observations suggest that 29% of patients undergoing apparently curative resection for colorectal carcinoma possess occult hepatic metastases and that computed tomography is superior to ultrasonography and isotope liver scan in detecting them.