Key Words: Care
Methods: Literature + Questionnaire + Interview
Places: Shanghai Sixth People's Hospital + Ottawa Civic Hospital/General Hospital

Mission One——Interview in Shanghai

Time: Afternoon, August 13th, 2018
Place: GI endoscopy division of Shanghai Sixth People’s Hospital
Interviewee: Doctor Zheng Haiming
Interviewer: iGEM2018 SJTU-BioX-Shanghai team mumber Qingwei Fang, Shiyu Sun
Topic: Clinical application of colonoscopy

  • Interview Q & A

    1.What are the symptoms patients have that come over to do colonoscopy in general?

    • ①Changes in the character of excrement (including shape, number, bleeding, etc.);

    • ②Physical examination (thickening of the intestinal wall, mass);

    • ③Most from gastroenterology dept or general surgery department

    • 2.What is general examination result?
      ①No obvious abnormality
      ②In pathological conditions, intestinal polyp is the most, followed by inflammation, then tumor.
      ③In the case of cancer, most patients are found to be in an advanced stage.
      ④Early tumors account for 60% of the tumors (early + late) found in Japan but less than 10% in China.
      3.What is the effect of colonoscopy for early detection of colon cancer?
      ①Almost is the only way to detect early colon tumors
      ②The early marker of colon tumors -polyps can be found. Polyps are responsible for 80% of colorectal cancer (non-hereditary).
      ③In the colonoscopy, the biopsy forceps attached to the colonoscopy can be used to remove the polyps and prevent further development.
      4. Is the colonoscopy included in the general medical examination?
      Not included.
      5. Is the colonoscopy included in the optional inspection program, and if so, how many people will selecte?
      Yes., but you need to make an appointment in advance (anesthesia colonoscopy: 2-3 months, common colonoscopy, 1-2 months). 1-2%.
      6. What are the reasons for hindering the colonoscopy into a widespread one?
      ①The popularization of medical knowledge is insufficient, and many people do not know about items with colonoscopy;
      ②Afraid of colonoscopy;
      ③Medical resources are limited. One time of colonoscopy is about 20-30 minutes, and a skilled colonoscopy doctor can only examine about 20 patients a day. The demand for endoscopy doctors in China is about 200,000-300,000, but currently there are only about 2-3 million.
      7. What is the impact and degree of pain of colonoscopy and other intestinal examinations?
      ①Colonoscopy: entering from the anus;
      ②Enteroscopy: entering from the mouth and anus, docking; a enteroscopy should take 2-3 hours; charge 2-3k RMB; painful; hospitals are less profitable and most are reluctant to do it;
      ③Capsule endoscopy: can not take biopsy; uncontrolled; 3k RMB; not suitable for large intestine examination (can not see, power is not enough).
      8. What are other clinical examination methods of colonoscopy other than colonoscopy?
      ①There is currently no way to completely replace colonoscopy;
      ②Abdominal enhancement CT;
      ③Barium enema (can not take biopsy, not as clear as the colonoscopy).
      9. What is the ratio of anesthesia colonoscopy to normal colonoscopy?
      10. What assessments are needed before an anesthesia colonoscopy? What kind of people is not suitable for anesthesia colonoscopy?
      ①Body type: can not be too fat (anesthesia for too fat people may have breathing risk);
      ②ECG: can not have inflammatory arrhythmia, ventricular arrhythmia, and have done a heart stent.
      ③Medical history: no allergies, asthma, high blood pressure, diabetes (the heart is generally damaged, and need to control the diet 3 days before the colonoscopy, can not resist);
      ④Prolonged bleeding time: the risk of major bleeding is not suitable for colonoscopy.
      11. What is the side effects of anesthesia?
      ①Respiratory depression;
      ②Blood oxygen reduction;
      ③Heart rate reduction;
      ④Major side effects: cough, heart rate disorders, etc.
      12. What is the side effect after the colonoscopy?
      ①General: abdominal distension (aerate the patient's intestines when inspect);
      ②Serious: collapse (a, stimulating vagal reflexes, nausea; b, colonoscopy 3d control diet; hypoglycemia; c, pain).
      13. What are the requirements for the patient's diet before the colonoscopy?
      ①Slag and semi-flow diet two days before check and treat, do not drink milk and soy milk;
      ②Liquid diet the day before check;
      ③Fasting in the check day morning ;
      14. What are the key people who doctor want them take a colonoscopy?
      ①People over 40 years old;
      ②Tool contains blood;
      ③Family history of tumors (all tumor types, causes: lung cancer, stomach cancer, intestinal cancer are three high-grade tumors);
      ④Had intestinal polyps before;
      ⑤Appendectomy patients (appendectomy is easy to cause intestinal flora disorder, increase the risk of intestinal cancer).
      15. As a clinician, are there any hopes and suggestions for improving the inspection method?
      ①In the colonoscopy, the operation of the rectal intestine requires the operator to learn for a long time to master, which is difficult;
      ②Colonoscopy operation requires operator to stand for a long time, thus the physical requirements for the doctor is higher. In addition, due to the long-term holding of the colonoscopy, the colonoscopy doctor has occupational diseases in joint and finger injuries. I hope there can be some methods can reduce the physical burden of the doctor.
      ③Doctors need to be highly concentrated when do colonoscopy, and can not miss the diseased tissue. I hope that the instrument can be used to help doctors find out the lesions to reduce the burden on doctors.
      16. From the doctor's point of view, what kind of examination the patient is more willing to accept, not too excluded?
      Safe and painless.

Mission Two——Interview in Ottawa

Ottawa Hospital

Time: Afternoon, August 16th, 2018
Place: Ottawa Civic Hospital, Cancer Centre
Ottawa General Hospital, Oncology department
Interviewee: Dr.Davis and the sick population of the day
Interviewer: iGEM2018 SJTU-BioX-Shanghai team mumber Bozitao Zhong, Shiyu Bai
Topic: The current dilemma of clinical diagnosis of colon cancer

1. Interview with Professor of Ottawa Hospital
According to the professor, we learned about the various methods of early diagnosis of colon cancer, and the problems faced by these means:

  • Colonoscope

    Advantages: Colonoscopy is more accurate than barium enema X-ray, especially when detecting small polyps. If colon polyps are found, they are usually removed by colonoscopy and sent for pathological analysis. The pathologist examines the polyps under the microscope to check for cancer.
    Disadvantages: Most of the polyps that are removed by colonoscopy are benign, and many are precancerous lesions. Removal of precancerous polyps prevents colon cancer from developing of these polyps in the future. But this is not an efficient method!

  • Sigmoidoscopy

    Sigmoidoscopy is the process of examining the left colon and rectum using a shorter range of dimensions.
    Advantages: It is easier to prepare and perform than a full colonoscopy, and sigmoidoscopy can be used for polypectomy and cancer biopsy.
    Disadvantages: However, it has significant limitations in not being able to assess right and lateral colons.

  • CEA carcinoembryonic antigen method

    Advantages: Indirect. If cancer is suspected, medical personnel can obtain the Carcinoembryonic Antigen (CEA) - called the "tumor marker" to do blood test. CEA is a substance produced by some colon and rectal cancer cells as well as some other types of cancer. Colon cancer patients have higher levels of CEAS.
    Disadvantages: Not all patients’ CEA is elevated though their cancer has spread. (Some colon cancers do not produce CEA.) In addition, some patients without cancer may also have high levels of CEA.

It can be roughly presented in the following table:

Table 1. Comparison between three diagnosis methods

Later, we learned from the professors about the current incidence of colon cancer in North America: According to the World Health Organization, colon cancer is already the second most common cancer in both men and women after lung cancer. In North America, the incidence of colon cancer is 2% in people over 50 years of age, and the incidence of colon cancer has little to do with gender. It has been learned from the database of professors in recent years that the age of the onset of colon cancer is decreasing year by year.

All kinds of data suggest that colon cancer needs to receive more attention.
At the same time, after understanding the design of our project, Professor Dr. Davis said that our project is expected to be a convenient and early screening method for colon cancer. According to the World Health Organization (WHO), colorectal cancer is the second most common tumor in men and women after lung cancer. About 2% of people over the age of 50 will eventually develop colorectal cancer in North America. Colorectal cancer often has the same effect on men and women. However, men tend to develop it at a younger age.

2. Hospital population interview
Our project is for the public, not for the doctor. Therefore, it is necessary for us to interview the masses and listen to the voices of the masses; instead of just referring to the professor's recommendations and the doctor's clinical data.
We divided the mass interview into two parts, interviewing the masses and interviewing patients. The reason why we want to treat the respondents in two categories is because the problems we prepare are different from the information we need.
The masses are almost undiseased population, which is a direct target for our early diagnosis of colon cancer. We need to introduce to the masses to promote our products and inspection process, and to investigate the acceptance of the masses.
For people:

  • If this test is included in a routine test, will you participate in the test?
  • How much do you think this test should cost?
  • What are your expectations for this project?

For patients, we focus on pain points in patients. Under the condition of not touching the patient's privacy, we try to interviewee the patient's about their living status and the early examination of colon cancer experienced as much as possible from their mouth.
For patients (general level):

  • How did you find yourself sick?
  • How long have you been sick?
  • How long have you been treated?
  • How is your treatment effect?
  • How do you do with your life after long-time treatment?
  • Is there any change that the cancer gives to you?
  • From your level of awareness, do you think our project makes sense?

The conclusion is:
With the improvement of science and technology, colon cancer is no longer as painful as before, and most people are acceptable. However, considering the individual tolerance, patients can choose painless colonoscopy according to their own wishes. Painless colonoscopy is performed under general anesthesia. However, it is also necessary to consider the risks of general anesthesia, such as anesthesia accidents, sometimes anesthesia recovery process is longer, and the cost is more expensive.

Before taking the colonoscopy, you need to take laxatives and discharge the excretions in the intestines. This is a painful process: the colonoscopy is still very painful. The tube is pushed from the anus and then the intestines. Keep deepening according to the shape of colon. Because the intestines have ascending colon, descending colon, sigmoid colon, etc., when the tube comes to turning, it is very painful and generally difficult to bear.

One patient revealed that he had had a colonoscopy. After doing it, he did not even have the strength to walk. Patient can choose painless colonoscopy, which is the state of anesthesia, and it can alleviate the pain. The instrument for colonoscopy is a flexible fiber hose with a length of about 140CM. The front end is a fiber hose with a miniature electronic camera with a light source. The rear side is connected with an imaging display. The doctor operates the moving direction of scope according to the image on the display to the intestine. After entering the anus, the colonoscopy passes through the rectum, sigmoid colon, descending colon, transverse colon, ascending colon and cecum.

In order to see the road conditions in the intestine during the examination, the doctor will continue to inflate and pump the intestines in the intestines. The stomach will have a feeling of bloating when inflated. This pain is within an acceptable range. If the above picture can be displayed, you can see that the colonoscopy will go through three curves during the on-going process, the first is the sigmoid colon, the second is the spleen of the descending colon to the transverse colon, and the third is the transverse colon to the hepatic curvature of ascending colon. It is a great test for doctors and patients going through these three corners. If the doctor is skilled and can lightly pass these three corners, the patient will not have much pain. However, if the doctor is not skilled, it will be a painful thing. These three corners, recalled by people who have completed the course, the pain levels from high to low are the spleen, sigmoid colon and hepatic curvature, which means that the second one is the most difficult, which is consistent with the colonoscopy operation skill I found: over the spleen is the most difficult test for doctor's patience and technology. This bend will generally take a long time, and need to try more times technologically. Once the spleen is over, the most difficult part of the colonoscopy is cleared, and the next one should be affordable. When the scope is retreated, it is said that there is no pain.

Mission Three——Questionnaire in Shanghai & Ottawa

We designed a questionnaire for the quality of life of patients with colorectal cancer in conjunction with the European Cancer Survey and Treatment Tissue Quality of Life Center questionnaire (EORTC QLQ-C30), trying to understand the living conditions of the survey population through some simple and easily measurable questions and does not touch patient privacy.

Fig 1.European Cancer Survey and Treatment Tissue Quality of Life Center Questionnaire

According to the 78 questionnaires we collected from Ottawa and 65 from Shanghai. We draw the following conclusions:
The physical condition of the Ottawa test population is better than that of the Shanghai area. Interestingly, the scores of the questionnaire related to dietary modules ofthe participants in the Shanghai area were better than those in the Ottawa area. We speculate whether this result is due to differences in dietary habits between the two regions. The diet in Shanghai is milder. Does it indirectly affects the incidence of intestinal diseases such as colon cancer? Due to the limited number of people we test, we don't know the result. I hope that in the future, big data analysis can tell us the answer.But at the same time, we have reason to believe that our indirect diagnosis of colon cancer by ultrasound examination of bubbles will have wider recognition and significance in North America.


After we decided to choose the direction of colon cancer diagnosis, we interviewed Zhang Shiyi, a professor who is engaged in the research of colon cancer and cancer prognosis. We hope he can give us some advice in a specific direction. After Professor Zhang Shiyi listened to our vision of the project direction , he gave us such guidance and impressions:

There are many approaches to the current treatment of colon cancer, but the treatment effect for advanced colon cancer is not ideal. The key to colon cancer prevention is not to focus on advanced conditions doing hard treatment, but how to find them earlier. The team members need to understand more about the current diagnosis and treatment methods later, and then consider whether you can focus on diagnosis rather than advanced treatment if you want to make more contributions to the diagnosis and treatment of colon cancer.

There are many approaches to the current treatment of colon cancer, but the treatment effect for advanced colon cancer is not ideal. The key to colon cancer prevention is not to focus on advanced conditions doing hard treatment, but how to find them earlier. The team members need to understand more about the current diagnosis and treatment methods later, and then consider whether you can focus on diagnosis rather than advanced treatment if you want to make more contributions to the diagnosis and treatment of colon cancer.

In order to explore more possibilities in the practice of the project, we communicated with several teachers at the School of Pharmacy. We propose to use certain materials to protect the bacteria into the intestine and realize the possibility of oral administration. Professor Guo Shengrong, who is mainly engaged in the research of polymer materials and drug delivery systems for emerging medicines, believes that the use of gastric juice insoluble API materials, such as pH sensitivity. The enteric coating can be achieved and a brief explanation of how to design the bacterial coating is given. Further, we consulted Professor Qiu Mingfeng, who is engaged in research on new drugs and new dosage forms, and determined the feasibility of preparing the freeze-dried powder into a commercially available enteric-coated capsule shell, and was fortunate to have a capsule-making process in his laboratory. We also consulted Associate Professor Qian Xiuping who is engaged in microbiology research. She also affirmed the feasibility of oral capsules and learned that she had done similar experiments. I believe that our project will have a wide application space.

Visit Shanghai F. Hoffmann-La Roche Ltd

Time: September 7, 2018, morning
Shanghai Roche Pharmaceutical Co., Ltd-1100 Longdong Da Road
Contact: Zhou Lingjie (Quality Assurance)
Interview: Shanghai Jiaotong University: Yao Kuan, Zhang Xinyu
Tongji university: Zhang Yue, Song Zhiwei
Theme: Technology in the pharmacy of engineering bacteria

Roche is the world's first biopharmaceutical company, the world's leading cancer drug research and development company, in 2008 the world's top 500 pharmaceutical companies ranked fourth. So far, Roche's research offices have won three Nobel Prizes. Shanghai Roche Pharmaceutical Co., Ltd. is one of the world's top 10 pharmaceutical companies Roche Group of Switzerland's first joint venture in China, founded in 1994, located in Pudong Zhangjiang high-tech park, with a total investment of $62.357 million. Shanghai Roche provides all kinds of prescription drugs in various key therapeutic fields such as oncology, virology, transplantation and so on, and strives to fundamentally improve people's quality of life, producing various types of antibiotics and anti-tumor drugs.

Fig 1. Visiting Roche, Shanghai

Shanghai Roche has been awarded "Shanghai civilized Unit" (4 consecutive years 19992006), "Shanghai employees are the most important" Satisfactory Enterprises "(two consecutive sessions of 20032006)," High-tech Enterprises ", "Advanced Enterprises with Foreign Investment", China Red Cross "Humanitarian Service Medal" and a series of awards. In 2006, the current General Manager Mr. Zhou Pingshan won the Shanghai Magnolia Award. Roche was ranked third best employer by Science magazine in 2006.

Investigate the production line:
The production line is mainly responsible for pharmaceutical preparations, including tablet and capsule production process, several key processes are weighing system, dust isolation system, granulator, capsule packaging, metal screening, dust filtration, on-line cleaning and drying system. Anti-pollution gating system, sheet press negative pressure vacuum system includes: sheet press vacuum area, vacuum system, air compressor, sensor and control system. The vacuum area of the sheet press is connected with the vacuum system, the other end of the vacuum system is connected with the air compressor, the sensor is arranged in the vacuum area of the sheet press, and the sensor is connected with the control system. Through the Venturi tube of the vacuum system, the vacuum pipe is connected with the working area of the sheet press, and the vacuum degree can be changed at any time by changing the compressed air flow rate(patent number CN205836067U).

Fig 2. Cooperating with Tongji_China

Pharmaceutical widget on-line cleaning and drying equipment: cleaning bin, hot air pipe, track, support, cleaning platform water conveyance system and cleaning system, hot air pipe and bin wall connection, track and bottom surface connection of cleaning bin, The support is fixed on the track, the water conveyance system is connected with the cleaning system, and the cleaning system is arranged at the upper end of the support. The utility model realizes the automatic process of cleaning and drying, only needs the staff to install the parts to the cleaning table, and then, together with the cleaning table, it is sent into the cleaning bin for washing, and after the cleaning, the equipment enters into the drying state. After drying, the equipment itself is airtight and will not pollute the surrounding environment. (patent number CN205659919U)

what are the options for drug formulation?
According to the different physicochemical properties of drugs and the different characteristics of absorption and metabolism in vivo, in order to achieve the therapeutic effect, reduce the toxic side effects and adverse reactions, it is necessary to adopt appropriate prescription design and production technology in the production and processing of drugs.

The Chinese Pharmacopoeia divides different dosage forms into solid dosage forms (such as granules, pills, granules, capsules, tablets, etc.) and semi-solid dosage forms (such as ointment, etc.). The main business of the company is the production of capsules and tablets, liquid formulations (such as solution, aromatic water, injection, etc.) and gas formulations (such as aerosols, inhalants, etc.).

We know that your company has tablets and capsule products. What is the basis for your selection? What is the patient's acceptance?

The advantage of capsule are
1. High bioavailability: capsule preparation is not like tablet need to add binder, digestion in the gastrointestinal tract quickly, easy to absorb;
2. Can improve drug stability: to light, wet, heat-sensitive drugs can be put into capsules, so that the drug from the role of light, moisture, and so on;
3. Shape adjustable: some powder, granular drugs can be encapsulated in capsules, some liquid drugs can not be made into tablets can be made into soft capsules, such as vitamin E;
4. can achieve slow release, controlled release, targeted release;
5. Can cover up the bad smell of drugs, good compliance.
6. With the development of materials and technology, more and more functions can be realized simultaneously in tablets and capsules, which means that these functions are no longer unique advantages of capsules, such as rapid release, enteric dissolution, for the protection of Guang Min water sensitive drugs, tablets can also be used to achieve process comparison: for tablet production, drugs and excipients need to be weighed first, and then mixed. Make a dough with adhesives and moisturizers (drier and looser than the dough), then use a sieve with a fixed pore size, squeeze the dough down, squeeze it into a lot of small particles, or cut the dough into a lot of small particles with a rotating blade. Then take it into the oven and dry it, then take it out and press it out. Finally, the tablet needs to be coated or printed on the outside. The capsule is relatively simple, the drug excipient is mixed up, and then it can be sent to the capsule to be filled in.
After metal detection, polishing dust can be removed. Generally speaking, capsule shells are produced by outsourcing companies. They can choose enteric-soluble capsule shells according to their demand. They are acid-resistant and can completely deliver drugs to the absorption sites of the intestines, without being affected by gastric acid, and only begin to dissolve in the environment above pH5.
Of course, the process of Chang-soluble tablets has been very mature, but compared to the capsule process is more complicated, generally lower capsule cost. Most oral drugs can be made into capsules and tablets. No more than the difficulty, some of the properties of API special, can not be made into granules, or poor compressibility, capsule more suitable. In terms of patient experience, most Chinese patients report that capsules are easier to swallow.

In view of the complexity of the production process for tablets, it is recommended that capsules be encapsulated in the form of capsules.