Two-stage hepatectomy combined with converting chemotherapy achieved a successful treatment for initially unresectable multiple bilobar colorectal liver metastases

A 60-year-old man having metachronous multiple bilobar colorectal liver metastases was referred to our institution. The lesions were diagnosed unresectable due to a lack of the estimated future remnant liver volume. He underwent 13 courses of mFOLFOX6 + bevacizumab as down-staging chemotherapy. The periodic abdominal CT scans revealed metastatic lesions to become PR. We had decided to perform two-stage hepatectomy to preserve a hepatic functional reserve. After the rest of chemotherapy for 4 weeks, four tumors were resected and right branch of the portal vein embolization was performed at the first operation. Right hemihepatectomy was performed 5 weeks after the first operation to achieve curative resection. Postoperative course was uneventful and the patient was discharged at 17 days after the operation. He has no signs of tumor recurrence during the follow-up. The combination of two-stage hepatectomy and neoadjuvant systemic chemotherapy may contribute to improve prognoses of initially unresectable multiple bilobar colorectal liver metastases, leading to prolonged survival.     

Successful treatment with cetuximab combination chemotherapy in a case of FOLFOX-refractory rectal cancer with previously unresectable multiple liver metastases leading to complete resection

Most colorectal cancer patients with liver metastases are not resectable upon initial diagnosis. Recently, chemotherapy improves overall survival of initially unresectable patients by allowing tumor downstaging and complete resection. We report a FOLFOX-refractory rectal cancer patient with unresectable multiple liver metastases, whose tumors could be downstaged and completely resected after initiation of FOLFIRI with cetuximab. Case: A 41-year-old male demonstrated rectal cancer with unresectable multiple liver metastases. He was treated by FOLFOX4 therapy as first-line chemotherapy. After initiating 14 courses, he was treated by FOLFIRI with cetuximab because of disease progression. After initiation of chemotherapy, radiographic examination demonstrated remarkable reduction of primary rectal tumor and metastatic liver tumors. He underwent complete rectal tumor resection after 13 courses of chemotherapy, and metastatic liver tumor resection after 18 courses of chemotherapy.     

A long survival case of sigmoid colon cancer patient with initially unresectable hepatic metastases

The prognosis of a colorectal cancer patient with unresectable hepatic metastases is extremely poor. To improve the prognosis, when the hepatic metastases were initially unresectable, we performed second-look hepatectomy (s-l hepatectomy) after neoadjuvant hepatic arterial 5-FU infusion plus UFT (HAI-PMC). Here, we report the case of a sigmoid colon cancer patient with initially unresectable hepatic metastases showing a prolonged survival (6.5 years) by second-look operation after HAI-PMC. A 57-year-old woman was diagnosed with sigmoid colon cancer with unresectable liver metastases. Sigmoidectomy and hepatic arterial catheterization were performed in the initial operation, and HAI-PMC was performed 6 months after. Metastatic foci of the liver had shrunk (90.9%), but solitary metastatic lung cancer was detected during HAI. As no other metastatic lesion was observed, partial resection of the liver and lung was performed as a second-look operation, 6 months after the initial operation. The woman continued venous infusion chemotherapy as an outpatient, and she survived for 6.5 years after the initial operation. This result suggests that strategic multidisciplinary treatment utilizing s-l hepatectomy after neoadjuvant chemotherapy can lead to better prognosis for colorectal cancer patients with hepatic metastases.     

A successfully resected case of colorectal cancer with multiple liver metastases treated with FOLFIRI after failure of mFOLFOX6

A sixty-year-old man was admitted with anorexia and abdominal mass. Colonoscopy revealed type 2 tumor at sigmoid colon. Computed tomography (CT) demonstrated multiple liver metastases. The patient was diagnosed as sigmoid colon cancer with multiple liver metastases. The patient was treated with mFOLFOX6 as neoadjuvant chemotherapy because the liver metastases were unresectable. However, after 2 cycles of mFOLFOX6, the level of CEA and CA19-9 much increased. The regimen was replaced by FOLFIRI. The level of CEA and CA19-9 decreased after 2 cycles of FOLFIRI. CEA and CA19-9 further decreased and colonoscopy and CT revealed a partial response after 5 cycles of FOLFIRI. The patient was subjected to curative resection. Sigmoidectomy and liver resection were performed. Histological response was Grade 1b at liver metastasis. The patient was discharged and had an uneventful recovery. Six months after surgery, CEA and CA19-9 decreased to normal level, and the patient is free of recurrence. Neoadjuvant chemotherapy for metastatic colorectal cancer may render some unresectable patients resectable, affording these patients the possibility of prolonged survival. However, the optimal approach is unknown.     

A successful treatment with down-staging chemotherapy for sigmoid colon cancer with unresectable multiple liver and lung metastases

A 63-year-old woman was diagnosed as having a sigmoid colon cancer with synchronous unresectable multiple liver and lung metastases. After sigmoidectomy, she was treated with S-1 combined with CPT-11 as a down-staging chemotherapy. After 3 courses of chemotherapy, the liver and lung metastases reduced in size as partial response. In March 2005, extended right hepatectomy combined with MHV resection was performed. She was treated with 2 courses of chemotherapy after hepatectomy, and furthermore she underwent left lung upper lobectomy. She has been alive without any signs of recurrence for 33 months from the initial surgery. Recently, a progression of the systemic chemotherapy for colorectal cancer has been a promising modality to improve a poor prognosis for unresectable multiple liver or extrahepatic metastases from advanced colorectal cancer.     

Determinants of unresectability and outcome of patients with occult colorectal hepatic metastases

BACKGROUND: Patients chosen for liver resection of colorectal liver metastases are a select group with minimal disease, favorable tumor biology and earlier presentation when compared to unresectable patients. Despite intense preoperative assessments, operative detection of occult unresectable disease is inevitable for a small group of patients. The aim of this study was to evaluate determinants of occult unresectability, and to establish if patients with occult unresectable disease demonstrate survival benefits similar to resected patients, or more similar to patients diagnosed with metastatic disease who were never explored. METHODS: A retrospective medical record review was performed on 171 patients with colorectal hepatic metastases who underwent exploration with the intent of performing a curative liver resection. Patient and tumor characteristics, operative findings and survival were evaluated. Univariate and multivariate analysis were performed to evaluate determinants of unresectability, and survival was determined by Kaplan-Meier analysis. RESULTS: One hundred forty-six patients were completely resected and 25 patients were found to have occult unresectable disease during exploration. Of these 25 patients, 10 had more extensive hepatic disease than expected which precluded resection, while 15 patients had unexpected extrahepatic disease. Of the 15 patients with extrahepatic disease, 7 had otherwise resectable liver metastases. Only bilobar disease was a statistically significant finding associated with occult unresectability on multivariate analysis (P = 0.05). Resected patients had a median survival of 37 months, while unresected patients had a median survival of 17 months (P < 0.005). At 3 and 5 years, the overall survival for resected patients was 52% and 29%. The survival at 3 years for patients with occult unresectable disease was only 5%, with no 5 year survivors. CONCLUSIONS: The majority of patients with occult unresectable colorectal hepatic metastases had bilobar disease or extrahepatic spread. Despite the process of patient selection that leads to an attempt for curative resection, patients with occult unresectable disease identified at exploration suffer from poor survival that approximates the outcome of patients never considered for resection.     

A case of liver metastasis from gastric cancer responding to S-1/CDDP chemotherapy, allowing partial gastrectomy and left hepatectomy

A 63-year-old man was found to have an upper abdominal mass, and was referred to our hospital. Endoscopic examination and abdominal CT showed gastric cancer with liver metastasis. A large metastatic tumor of the liver invaded the hepatic hilus, making curative resection impossible. We started chemotherapy using S-1(120 mg/body/day), orally administered for three weeks followed by 2-week rest period, and cisplatin(100mg/body), administered intravenously on day 8 as 1 course. After 5 courses of chemotherapy, the liver tumor reduced markedly and the gastric cancer pathologically disappeared, enabling partial gastrectomy and left hepatectomy. Histological examination showed a well-differentiated adenocarcinoma in the mucosal layer of the resected stomach. A resected specimen of the liver showed a moderately-differentiated adenocarcinoma with signet-ring cells, compatible to liver metastasis from gastric cancer. Bile leakage the remaining liver occurred, but he recovered soon. Gastrointestinal examination revealed another early gastric cancer after seeing him for 2 years on an outpatient basis. We conducted subtotal gastrectomy, and the patient remains alive 30 months after the first operation. This case suggests that S-1/CDDP chemotherapy may reduce the stage of unresectable liver metastasis from gastric cancer and make a curative operation possible.     

Two cases of resection of synchronous bilobar multiple liver metastases from colorectal cancer after hepatic arterial infusion chemotherapy

We report 2 cases of synchronous bilobar multiple liver metastases from colorectal cancer which are hepatectomised following a hepatic arterial infusion chemotherapy. Both cases were considered unresectable metastases before chemotherapy. Case 1: A 55-year-old male, with rectal cancer and multiple hepatic metastases, was performed a low anterior resection. Hepatic arterial infusion chemotherapy (5-FU 1 g/m2 5h qw) and systemic chemotherapy (5-FU/LV) were administered. Twelve months after the first surgery, hepatectomy was performed. Case 2: Right hemicolectomy was performed on a 66-year-old male, with cancer of the transverse colon and multiple hepatic metastases. Hepatic arterial infusion chemotherapy was administered 38 times. Thirteen months after the first surgery, hepatectomy and MCT were performed. Even among the cases of unresectable hepatic metastases from colorectal cancer, there are some in which resection is possible followed by hepatic arterial infusion chemotherapy. Re-evaluation for hepatectomy is needed for the cases where hepatic arterial infusion chemotherapy is administered.     

A phase II study of radiofrequency ablation of unresectable metastatic colorectal cancer with hepatic arterial infusion pump chemotherapy

BACKGROUND: Adjuvant hepatic arterial infusion (HAI) chemotherapy has been demonstrated to improve disease-free survival for colorectal cancer liver metastases. It is unclear if this improvement can be extrapolated to unresectable liver metastases that undergo RFA. The aim of this study was to evaluate the combination of RFA and HAI chemotherapy for unresectable liver metastases. METHODS: Phase II study was conducted from November 2000 to July 2003 evaluating the use of complete extirpation by RFA, or resection/ablation with adjuvant HAI consisting of FUDR for 6 months. RESULTS: Twenty-one patients had successful resection and/or RFA with HAI pump, which included treatment for 100 liver metastases (22 resected, 78 ablated; mean 4.8 tumors/patient). Four of 21 patients completed the full 6-month course of HAI. Six of these patients had 12 adverse events related to HAIP, most commonly elevated liver enzymes. After a median follow-up of 24 months, the median liver specific disease-free and overall survival rates for the entire group were 17 and 30 months, respectively. CONCLUSIONS: Given the complications and toxicity associated with HAI pump chemotherapy, adjuvant HAI chemotherapy after RFA of liver metastases may not be warranted as a first line treatment option.     

A case of multiple liver metastases from nonfunctioning neuroendocrine pancreatic tumor curatively resected after successful intra-arterial chemotherapy

We report a case of 33-year-old woman for nonfunctioning neuroendocrine pancreatic tumor with synchronous multiple liver metastases. For the primary pancreatic legion, we performed pylorus-preserving pancreatoduodenectomy at first. Three weeks after the surgery, the patient started to undergo intra-arterial chemotherapy with a weekly administration of high-dose 5-FU (1,000 mg/body) for residual liver metastases. Any severe adverse events were not observed. After 20 courses, a partial response was achieved and she underwent curative operation with partial resection for 4 metastatic legions and RFA for others. Histopathological findings of resected specimens revealed no viable neoplastic tissues. She is alive with no sign of recurrence 3 months after the surgery. Although a surgical resection is accepted as the standard therapy for liver metastases of nonfunctioning neuroendocrine pancreatic tumor, intra-arterial chemotherapy might be an alternative therapeutic option for unresectable case.     

Three cases of multiple colorectal liver metastases responding to hepatic arterial infusion chemotherapy undergoing liver resection

We encountered three cases of multiple liver metastases of colorectal cancer treated with hepatic resection after hepatic arterial infusion. Case 1: A 55-year-old female underwent sigmoidectomy for sigmoid colon cancer and six liver metastases. After responding postoperatively to hepatic arterial infusion chemotherapy (HIA), she underwent resection of liver metastases. Case 2: A 66-year-old man underwent colectomy and hepatic resection for cecal colon cancer and liver metastasis. Multiple liver metastases appeared six months after the operation. HIA resulted in a complete response. Liver metastases recurred twice and liver resection was performed each time. Case 3: A 52-year-old female underwent partial resection of colon and liver for ascending colon cancer and multiple liver metastases. After she responded postoperatively to HIA and systemic chemotherapy, the patient underwent resection of liver metastases. Case 1 has lung metastases at this writing. The other two patients are alive and well, and have been free from recurrence as of 4 years after operation.     

A case of unresectable rectal cancer with severe pelvic infiltration responding to FOLFOX

The patient was a 54-year-old male with a huge advanced rectal cancer tumor. Abdominal CT showed liver metastasis and local progressive cancer of the rectum measuring 13 × 9 × 7 cm in diameter, which invaded the urinary bladder and sacrum. We established a diagnosis of unresectable rectal cancer and then performed sigmoid colostomy. After 16 courses of FOLFOX4, abdominal CT revealed the liver metastases to have disappeared, and the large-sized advanced rectal cancer had also remarkably decreased in size. Consequently, the patient underwent a resection of the rectum while his bladder was preserved. For 2 years 10 months after surgery, no local recurrence or distant metastasis has been observed, and the patient has received no postoperative chemotherapy. FOLFOX may therefore be a useful preoperative chemotherapy for the patients with unresectable primary rectal cancer.     

A case of lung metastasis from colon cancer controlled effectively by the stereotactic radiotherapy

A 73-year-old man underwent a sigmoid colon resection and an insertion of a hepatic arterial infusion catheter for multiple liver metastases from sigmoid colon cancer. After the hepatectomy, the patient was detected a lung metastasis and was scheduled to undergo mFOLFOX6 chemotherapy. The tumor lesion was reduced once in size, but it has grown again after the chemotherapy. So, we underwent a stereotactic radiotherapy (60 Gy/10 Fr). The tumor lesion became a scar and the patient was doing well without any recurrence at 21 months after undergoing stereotactic radiotherapy. Lung resection has a better result than other treatments for a lung metastasis caused from colon cancer, but there are some cases with no indication of the operation due to a complication. Stereotactic radiotherapy can be an effective treatment for lung metastasis from colon cancer with no indication of the operation.     

A case of unresectable liver metastases from rectosigmoid colon cancer with survival for over 3 years after multidisciplinary treatment

A 61-year-old man underwent curative low anterior resection for rectosigmoid colon cancer. Follow-up ultrasonography revealed unresectable multiple liver metastases at 10 months after surgery. Arterial infusion therapy with 5-fluorouracil (5-FU) was given at 1,500 mg every 2 weeks up to a total dose of 37.5 g, resulting in complete remission (CR) of the liver metastases. However, recurrence was seen 4 months after CR. Following partial hepatectomy and local ablation therapy, he received multidisciplinary treatment including local ablation therapy, arterial infusion of 5-FU and mitomycin C, and systemic chemotherapy with 5-FU/Leucovorin/CPT-11. The patient died of liver failure at 3 years and 7 months after the detection of hepatic metastases. If arterial infusion therapy achieves CR of unresectable hepatic metastases from colorectal cancer, the patient may survive for several years with multidisciplinary treatment including surgery, local ablation therapy, and systemic chemotherapy.     

Panitumumab as third-line chemotherapy shrank unresectable multiple liver metastases from rectal cancer, making them resectable - report of a case

We report a case of unresectable multiple liver metastases, in which there was such a good response to panitumumab as third-line chemotherapy, that they were converted into resectable metastases. A 67-year-old man was admitted to our department for rectal cancer with synchronous unresectable multiple liver metastases. After the primary lesion was resected, modified FOLFOX6 regimen was started as first-line chemotherapy. After 10 courses of FOLFOX6 followed by 14 courses of sLV5FU2 regimen, the liver metastases became smaller and were thought to be resectable. Before hepatectomy, we performed portal vein embolization to enlarge the remnant liver, but the tumor grew larger again and we had to cancel the operation. Then, the second-line chemotherapy with FOLFIRI regimen failed. As third-line chemotherapy, panitumumab alone was administered to him and the tumor greatly shrank after 5 courses. We were able to resect the liver metastases with extended right posterior segmentectomy and partial resection. He has been well without recurrence for one year since hepatectomy. This case is rare in that panitumumab alone as third-line chemotherapy shrank unresectable liver metastases and made them resectable. The result is highly suggestive for management, including chemotherapy and operation of multiple liver metastases from colorectal cancer.     

A case of liver failure associated with liver damage due to mFOLFOX 6 after resection for multiple liver metastases from colorectal cancer

A case of colorectal cancer in a 60-year-old man became resectable after downstaging was achieved with mFOLFOX 6 for multiple liver metastases from colorectal cancer. The patient received 8 cycles of mFOLFOX 6 on the basis of a diagnosis of multiple liver metastases in the right and left lobes and a single metastasis in the right lung. After chemotherapy, the liver metastases showed partial response, and the lung metastasis stable disease. Because the lung metastasis was controlled and radical cure of the liver metastases was thought possible by resection, we performed right lobectomy of the liver. Postoperative progress was good, and we then planned a staged partial resection of the lung. However,on postoperative day 28, the patient was hospitalized again with liver dysfunction, which evolved into liver failure, in spite of conservative treatment. The patient died on postoperative day 95. The needle biopsy specimens of the liver taken on readmission showed bile duct occlusion, portal hypertension, and perisinusoidal fibrosis, and histopathology of the surgical non-tumoral liver specimen showed the same findings. We think that liver failure was triggered by resection of the liver which had been damaged by mFOLFOX 6. Recently, liver damage due to oxaliplatin was reported, and evaluation of liver injury is considered important before liver resection for colorectal liver metastases with neoadjuvant FOLFOX.     

Hepatic artery infusion in the treatment of colorectal cancer metastases

The most common site of metastasis from colorectal carcinoma is the liver. Surgical resection of hepatic metastases can result in long-term survival. The majority of patients have unresectable disease, however, and even if hepatic metastases are resected, most patients will still experience relapse, often in the liver. Hepatic arterial infusion (HAI) of chemotherapy allows high concentrations of a drug to be delivered directly to hepatic metastases with minimal systemic toxicity. HAI therapy has been used to treat unresectable isolated hepatic metastases of colorectal cancer and has also been investigated as adjuvant therapy after resection. This review examines the role of HAI as therapy for both unresectable and resectable hepatic metastases.     

A Successfully Resected Case of Recurrent Lung and Liver Metastases of Rectal Cancer Treated with XELIRI + Bevacizumab Therapy

It has been reported that many colorectal cancer (CRC) patients with synchronous or metachronous liver metastases underwent surgery subsequent to neoadjuvant combination chemotherapy with folinic acid, fluorouracil, and oxaliplatin (FOLFOX), folinic acid, fluorouracil, and irinotecan (FOLFIRI), or capecitabine and oxaliplatin (XELOX). However, there are very few reports of the use of capecitabine and irinotecan (XELIRI). We herein report a successfully resected case of recurrent lung and liver metastases of rectal cancer treated with combination chemotherapy with XELIRI + bevacizumab (BV) therapy. A 63-year-old male developed recurrence of a solitary nodule in the right lower lobe of the lung and multiple liver metastases after low anterior resection for rectal cancer 1 year previously. Partial resection of the right lower lobe of the lung was performed and treatment with XELIRI + BV was initiated. A computed tomography scan revealed a reduction in tumor size without any new lesions after four cycles of XELIRI + BV therapy. Partial hepatectomy of S1, S5, and S7 was safely performed. The patient is now undergoing adjuvant chemotherapy and has been free from recurrence for 18 months following surgery. There are only few studies with relatively low patient numbers reporting on the outcome after resection of both pulmonary and hepatic metastases of CRC. We therefore report a patient who underwent sequential resection of pulmonary and hepatic metastases with XELIRI + BV therapy.Key words: Colorectal cancer, Liver metastasis, XELIRI     

Long survival in a case of unresectable hepatic metastasis from rectal carcinoma treated with second-look hepatectomy plus pharmacokinetic modulating chemotherapy (PMC)

A 67-year-old female with rectal cancer and multiple liver metastases underwent low anterior resection by total mesorectal excision (TME), cholecystectomy and hepatic arterial cannulation in June 1995. She was treated with hepatic arterial infusion chemotherapy (HAI) (5-FU 600 mg/m2/day x 2 days/w) and oral UFT (400 mg/body, 5 days/w) once a week for 6 months on an outpatient basis. As the metastatic foci of the liver significantly decreased (83.3%) and extrahepatic disease were not observed, partial resection of the liver (second-look hepatectomy) was performed in March 1996. She continued arterial infusion PMC and venous infusion PMC as an outpatient. During the follow-up period a lung metastasis appeared in November 1997. Her regimen was changed to modified PMC with MMC (mitomycin C) and CPT-11. She has been managed at our outpatient clinic while the lung metastasis remained but with no liver metastasis for 57 months after the first operation, until the present. Second-look hepatectomy and PMC with a two-way port system was a useful option for unresectable hepatic metastases from colorectal carcinoma.     

不同治疗方法对结直肠癌肝转移患者预后的影响

目的 探讨不同治疗方法对结直肠癌肝转移患者预后的影响.方法 对300例结直肠癌首发肝转移患者的诊治过程及肝转移后生存情况进行回顾性分析.结果 结直肠癌肝转移灶完全切除者、姑息切除者和无法切除者的肝转移后中位生存期分别为48、19和18个月(P=0.000).对于无法行肝转移灶完全切除的患者,肝转移后化疗联合局部治疗和不治疗患者的肝转移后中位生存期分别为23个月和6个月(P=0.000).一线治疗有效患者和无效患者的肝转移后中位生存期分别为24个月和16个月(P=0.000).单因素生存分析结果显示,原发肿瘤的治疗方式、肝转移灶的手术方式、肝转移后的综合治疗以及一线治疗的疗效均与预后相关(均P<0.05).多因素分析结果显示,肝转移灶的手术方式、肝转移后的综合治疗和肝转移后一线治疗的疗效是影响结直肠癌肝转移患者预后的独立因素(P<0.05).结论 肝转移灶完全切除、肝转移后进行综合治疗以及肝转移后一线治疗有效的结直肠癌肝转移患者预后好.