2016年3月20日星期日

Xu Kecheng’s Ward Round Essays: Four Cases of Pancreatic Cancer

On 26th February, 2016, it’s Friday. I made rounds of the wards and visited 14 patients including four pancreatic cancer patients which made me impressed.



The first case is a female of 58 years old with pancreatic tail ductal adenocarcinoma. She was admitted to FUDA for the first time on November last year. At that time, she suffered from severe pain on lower back. The CA 19-9 in the blood was 8000u/ml. The size of the tumor was 3*4 cm with peripancreatic lymph nodes metastasis. After having ultrasound screen and irreversible electroporation (nanoknife therapy) ablation guided by CT, the pain was relieved. Patient went back to hospital for re-examination this time, and the general condition was good. The patient complained of ambiguous pain on left abdomen, which was relieved by taking non-steriodal pain-killing drugs. And the CA19-9 dropped to 600u/ml. Then, the patient was having peripancreatic lymph nodes absolute alcohol injection guided by ultrasound screen. She was also having NK immunotherapy at the same time.  

The second case is a male of 65 years old. His waist has been painful for a month. Neck of pancreas occupying lesion is 3-5 cm with peripancreatic lymph nodes swelling. The biopsy showed adenocarcinoma. In January this year, under the guidance combined with ultrasound and CT scan, the lump of tail of pancreas and peripancreatic lymph nodes were ablated by percutaneous nanoknife (irreversible electroporation ) surgery. After surgery, abdominal pain was relieved quickly. He went back to FUDA for re-examination a week ago with mild pain on his abdomen. The MR re-examination showed that activity of original lump in the pancreas was cut by 90%. Under the guidance of ultrasound scan, he had local alcohol injection and NK cells injection for taking immunotherapy.


The third case is a male of 61 years old who comes from Hong Kong. The lump in the head of pancreas was 3cm, which suppressed common bile duct and caused obstructive jaundice. Serum bilirubin concentration was 65mmol/L. The tumor was ablated by nanoknife (irreversible electroporation) with the guidance of ultrasound and CT. After surgery, patient could walk and get ready to come back Hong Kong for having endoscopic common bile duct cathetering.  


The fourth case is female of 62 years old. She accepted surgery at a hospital of a big city which included resection of stomach, duodenum, common bile duct and the head of pancreas. And he had chemotherapy. On 15th February, 2016, he was admitted to our hospital. The CT examination showed that there were multiple metastases in liver and enlarged lymph nodes in the head and neck of pancreas. HepaSpherin microspheres intervention was injected percutaneously to hepatic artery. Recently he had percutaneous cryosurgical ablation on liver with the guidance of CT. At the same time, metastatic lymph nodes were injected with 125 iodine seeds. And he was ready to get NK cell immunotherapy. 

Recent years, the morbidity of pancreatic cancer has been increased obviously, which is the No.4 most common cancer of digestive system. Treating pancreatic cancer is still world’s challenge so far. As for the above four cases, the first three cases were accepting nanoknife (irreversible electroporation) therapy. When three cases were diagnosed as pancreatic cancer, there were metastases in peripancreatic lymph nodes and suppression in blood vessels, which was impossible to remove by surgery. As for unresectable pancreatic cancer, ablation plays an important role as alternative treatment nowadays. Cryosurgery and nanoknife are common ways to ablate tumors. In 2012, after nanoknife (irreversible electroporation) being allowed to apply in treating soft-tissue tumors in America, nanoknife for pancreatic cancer treatment attracts attention all around the world. It can ablate tumors in targeted area clearly without much harm to great vessels and intestinal wall. Nanoknife conducts nanoscale perforation to cells membrane by high voltage and short current pulse. It’s neither hot nor cold, which doesn’t cause obvious inflammation. As we know, inflammation is the main factor causing cancer’s development and metastases. Therefore, nanoknife makes fewer side effects on patients. Patients will recover sooner after surgery. 

According to the reports from ten great hospitals’ reports, nanoknife therapy for pancreatic cancer treatment has been applied in more than 3000 cases, and the therapeutic effects are good. Guangzhou Fuda Cancer Hospital has applied nanoknife therapy since last July, which was the first case of nanoknife application in the mainland of China. More than 50 cases of pancreatic cancer patients accepted nanoknife therapy. Initial follow-up shows that the ablation technique has a good therapeutic effect with slight complications.

The first three cases above accepted nanoknife therapy, which was correct. Of course, the long-term effects need to be further observed. The recent condition was steady and the pain was relieved obviously. The fourth case of pancreatic cancer patient accepted surgery at out-of-town hospital. It’s conventional treatment. Unfortunately, the lesion recurred with liver metastases. Why did it metastasize so quickly? Was it undiscovered before surgery, or was surgery promoting metastases?

In 2007, a report named “Reveal the Mystery about Treating Cancer Causing More Metastases” from America said, treating cancer by surgery, chemotherapy and radiation would probably lead to cancer cells metastases. Surgery can accelerate cancer. I don’t have direct evidence on this topic. Someone has compared the cancer metastases after cryosurgery and surgery in experimental animal mode. He found that cancer metastasis after having surgery was earlier and more severe. And he thought TGF-βincreased after surgery. It’s the factor that leaded to cancer cell proliferation. Cryosurgery and nanoknife therapy are local ablations. The damage of tissue is less, and died cancer cells after ablation release antigen, which stimulates immune cells to generate anti-cancer immunity. Then it reduce the incidence rate of cancer metastasis.   

It doesn’t deny surgery certainly. Surgery is still the main means of treating early-stage cancer with mastering indication. It’s hard to say whether the 4th case has surgical indication. The diagnosis of pancreatic cancer is often with metastases. Therefore, it should be especially cautious of evaluating patient’s condition and grasping surgical indication.

The February 26th ward-round was to solve the problem about subsequent treatment. The first three cases all accepted nanoknife therapy. It’s impossible to ablate all tumors. I am not advocating chemotherapy for its function of prolonging patient’s life is limited, especially to pancreatic cancer patient of middle and advanced stage.

Famous book Sun Tzu’s The Art of War once said that a cornered animal is a dangerous foe, which is full of philosophy. In other words, it means that not hotly pursuing an enemy who is caught in a hopeless situation. Fierce attacks make enemy to resist strongly, which leads to great cost inevitably. The right way is inducing it to capitulate and making it safe. Then, live peace with each other.

A great number of evidence shows that chemotherapy has opposite effect which not only kills no cancer cells, but makes cancer cells growing. No.4 case had chemotherapy after surgery. I can’t claim whether the opposite effect of chemotherapy promotes metastases.

I suggest the former patients taking immunotherapy mainly. At present, CIK-DC and NK cell immunotherapy are most practical among all immunotherapy adopted in our hospital.

Recently, I read a report of World J Gastrointest Pharmacol Ther.2016. It said that scholars from five units reported their result of applying DC cell-based vaccine in treating pancreatic cancer. They processed DC cell with streptococcus immunoadjuvent OK432 and made Vaccel vaccine. They found DC vaccine could promote Th1 at a favorable situation and generate IL-12 in the way they processed DC vaccine, which had a better effect on fighting against cancer. 255 inoperable pancreatic cancer patients injected the vaccine. It’s discovered that patients with positive DTH had longer survival time than patients with negative DTH. Then, the author added HLAI restrictive WT1-II and restrictive WT1-I into DC cell, which was proved to prolong survival time of pancreatic cancer patient. In Japan, OK432 is most common potentiator for boosting immunity in cancer treatment. There are medicines like OK432 at home. Such as highly agglutinative staphylococcin (HASL), it’s extracted from staphylococcin. It should be sublingual medicine for lots of sublingual lymph nodes absorbing and stimulating immunity directly. I suggest giving patient this medicine.

There is always one thing conquering another in nature. Snake is the enemy of rat; bat is the enemy of mosquito; and bird is the enemy of grasshopper. The same as in human body, to fight against cancer cells, we also can use the natural enemy of cancer cell. That is NK cell.

I read lots of literature, which demonstrated that in-vitro amplificatory and highly activated NK cell shows strong activity of fighting against cancer in vitro and vivo. Another clinical test shows that allograft NK cell is effective in treating lymphoma and progressive, recurrent and solid tumors. The author injected continually NK cell to the patients three times, and the highest number of NK cell was 3*107 (about 30 billion) per kilogram. Among 17 evaluable patients, eight patients’ condition (47.1%) tended to be steady. CD8+T cells which have killing effect on cancer cells increased and T cells correlated cytokines was up regulated. On the contrary, T cells, myeloid-derived suppressor cells and TGF-β(transforming growth factor-β) which have regulatory rather than inhibitory effect on cancer diseased. The author thought a great number of allograft NK cell injections not only were safe and available but also were important method to maintain organism’s effective immune response (Cancer Immunol Res.2016).
  
Therefore, as to the four cases of pancreatic cancer above, I suggest giving cells adoptive immunotherapy. At meanwhile, I suggest adopting traditional Chinese medicine to adjust intestine and stomach, which also helps improve immunity. A few days ago, I offered eight kinds of TCM including salvia miltiorrhizae, astragalus, dried wolfberry, dried hawthorn, dried tangerine and Mangnolia officinalis etc. to the four patients above. After taking these TCM, distending pain of upper abdomen was relieved and the eating was improved.


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