①Unresectable Colorectal Liver Metatases
 It has been known that there are a certain number of cases of colorectal liver metastases that can be cured by resection alone even in the era without effective chemotherapy. In recent years, several effective chemotherapy regimens have become available, but the median survival time obtained with chemotherapy alone is estimated to be at most 2.5 years (30 months). Unfortunately, there is currently no other way than resection that can lead cure or long-term survival for such advanced colorectal cancers. In patients with multiple liver metastases, especially in cases where the number of tumors exceeds 4, it has often been considered incurable, so many surgeons still refrain from surgical resection. However, it is also true that selected patients may be benefitted from surgery.
 Here is an example, this is a lady in her 50’s presenting with a very large liver metastasis that cannot be resected in this situation (left). However, after 4 courses of chemo, the tumor was markedly shrunk and radical resection became possible (right). She is now doing well at 2.5 years with no evidence of intrahepatic recurrence. Treatment that brings such an unresectable situation to a resectable situation by chemotherapy is called “conversion”.

 Various observational studies have reported that patients who were successfully converted to curative resection show significantly favorable prognosis compared to those who were not resectable (Kopetz S, et al. J Clin Oncol 2009; Adam R, et al. Oncologist 2012).
 However, there are several tips for treatments that attempt these conversions. There are two essential points for successful conversion: 1) short-term chemotherapy and 2) selection of optimal chemotherapeutic agents for expecting optimal response for successful resection. This is often misunderstood among doctors involved in the treatment of colorectal cancer. Regarding #1, chemotherapy is basically a “poison” to our body, and prolonged treatment can damage the liver. Most of the cases aiming for conversion require a major hepatectomy, so overdoing chemotherapy may increase the risk of surgery and miss the chance of conversion. Therefore, it is necessary to go to surgery at an early stage under control of tumor growth before liver damage occurs. In this context, it is important to consult with a liver surgeon at the time of diagnosis and formulate an optimal treatment plan.
 Regarding #2, the reason why surgery is considered difficult is not only because the tumor is large as in the above case. In cases where the number of tumors is as large as 10 or 20, or where metastases are present outside the liver, it is unclear whether surgery can really remove all the metastatic lesions. In such cases, it is much important to expect tumor necrosis than shrinkage of tumor to decrease the risk of recurrence after surgery. The case presented below is a 50s gentleman who presented multiple large liver metastases and huge lymph node metastases at the hepatic hilum. The CT before and after chemotherapy is compared up and down, and you can see that the tumor in the liver is clearly blackened with clear margins in the enhanced CT after chemotherapy. This is called a morphologic response of colorectal liver metastases and large part of the tumor nodules are expected to be replaced by necrotic tissues (Chun YS, et al. JAMA 2009; Shindoh J, et al. J Clin Oncol 2012). Since this patient presented severe hepatic injury due to steatohepatitis, two-stage hepatectomy was performed to clean-up all the lesions and he is now free from cancer at 28 months after surgery.

 It is important to collaborate with specialists such as colorectal surgeons, liver surgeons, oncologists, and radiologists in treatments that attempt to convert to surgery. Based on the results of our hospital, the results of 25 conversion cases I worked on showed favorable outcomes compared to all stage IV patients treated last 10 years with 5-year survival rate of 58.6%.

②Advanced hepatocellular carcinoma
 Advanced hepatocellular carcinoma accompanying tumor thrombus, severe hepatic injury, and multiple lesions are generally difficult to cure (see Treatment for hepatocellular carcinoma for details). Treatment of hepatocellular carcinoma is more difficult than metastatic liver cancer because the liver is damaged due to underlying liver disease and it is generally refractory to radiation and chemotherapy. Therefore, multidisciplinary treatment approach is highly required including hepatologist, hepatobiliary surgeon, medical oncologist, interventional radiologist. In Japan, although number of hepatocellular carcinoma related to hepatitis B or C is decreasing, there are increasing number of patients with hepatocellular carcinoma related to metabolic syndrome.
 As with metastatic liver cancer, effective chemotherapy is needed to expand the treatment potential for advanced hepatocellular carcinoma. In recent years, several effective drugs have become available one after another for hepatocellular carcinoma, and the possibility of curative treatment for advanced cancer is expanding. Although the number remains small, conversion cases of advanced hepatocellular carcinoma is increasing and we provide the best treatment for each case under active discussion and cooperation of multidisciplinary treatment team.