godfather of surgery

Chapter 1299 We can only cure illnesses, not change other people's fates.

Six o'clock in the morning in the Pancreatic Surgery Intensive Care Unit of Ruijin Hospital in Shanghai.

Forty-nine-year-old patient Shen Guohua lay in his hospital bed, his abdomen swollen high with a large amount of ascites, resembling that of a woman seven months pregnant. His skin and the whites of his eyes were yellowish, a sign of obstructive jaundice caused by a pancreatic tumor compressing the bile duct. The numbers on the monitor were not optimistic: heart rate 112 beats per minute, blood oxygen saturation 92%, and body temperature 38.5°C.

His wife, Zhou Min, held his withered hand, her eyes red and swollen. For the past three months, they had traveled between Beijing and Shanghai, only to receive the same diagnosis: late-stage pancreatic cancer with liver metastasis, and an estimated survival of three to six months. There were no more effective treatments available, and Shen Guohua had lost weight from 160 pounds to less than 100 pounds.

"Mr. Shen, Ms. Zhou." Department Director Chen led a young doctor in. "This is Dr. Li, who just returned from further training at Nandu Sanbo Hospital. He brought a new treatment plan that might be effective."

Perhaps it will work?

For Shen Guohua, this was a lifeline.

Dr. Li was one of the first Chinese trainees in the Triple Botox K therapy training course. He explained in detail the treatment principles, possible immune responses, and most importantly, the success rate.

“K therapy has no precedent for treating pancreatic cancer and has only recently been applied to this cancer. The actual success rate is unknown. Based on existing theoretical data, the overall efficacy of K therapy for pancreatic cancer is estimated at about 35%, with a complete remission rate of less than 5%. Mr. Shen's case is more complex, as he has already developed liver metastases and jaundice, so the efficacy rate may be even lower, estimated to be between 15% and 20%.” Dr. Li’s tone was calm and frank. “Furthermore, because adenovirus needs to be metabolized by the liver, your current liver function may affect the distribution and efficacy of the medication.”

Shen Guohua's voice was weak but clear: "If I don't do it, how much longer do I have?"

"It's difficult to predict precisely, but based on past experience, it might take one to two months. This is also a theoretical prediction."

"If we do it, what would be the best outcome?"

"If effective, the tumor may shrink, jaundice may subside, and pain may lessen. The best-case scenario is obtaining the opportunity for surgery, but the probability is very low." Dr. Li did not gloss over the possibility. "The worst-case scenario is that the treatment is ineffective or triggers a severe immune response, accelerating the progression of the disease."

Zhou Min's tears welled up again: "Dr. Li, we're willing to try, we'll pay any price..."

“Cost is not a problem,” Dr. Li interrupted her. “As Mr. Shen’s case is difficult to treat, the treatment costs are covered by their research fund. What we need to decide now is whether to treat him or not.”

Shen Guohua stared at the ceiling, remaining silent for a full minute. The beeping of the monitor was exceptionally clear in the ward.

"Treat it!" he finally said. "A 15% chance is no better than waiting to die. It's better to take a gamble than to risk it."

"Okay, I'll arrange it for you!" Dr. Li said.

Shen Guohua's hemoglobin was only 78g/L, albumin was 28g/L, and multiple liver function indicators were abnormal. His overall condition was very pessimistic, and he was not suitable for any treatment that would harm his body.

However, compared to other treatment options, K therapy requires less patient tolerance, and it needs a large number of patients to validate its ultimate limits.

Noon, at the Nandu Sanbo Research Institute Remote Consultation Center.

Yang Ping, Song Ziming, Xu Zhiliang, Tang Shun, Lu Xiaolu, and Academician Chen Yongnian, who is at Tsinghua University, held a joint consultation via video link. All of Shen Guohua's data—gene sequencing, imaging data, and biochemical indicators—were simultaneously displayed on the large screen.

“The tumor cells do indeed highly express that rare receptor, which is good news,” Yang Ping said, pointing to the target detection data. “The bad news is that his neutralizing antibody test shows a high titer of pre-existing immunity to adenovirus type 5. If standard formulations are used, most of the vectors may be cleared before entering the tumor.”

Academician Chen pulled up data from the mixed vector library: "He was negative for both adenovirus type 26 and type 35 antibodies. We can use the type 26 vector, which is one of the most targeted versions we modified. But the problem is that the production process of the type 26 vector is still being optimized. Currently, there is only laboratory-level production, which is only enough for one treatment."

“One chance,” Song Ziming pondered. “If I fail, there will be no second chance.”

Xu Zhiliang added: "Moreover... there is insufficient long-term safety data for the new vector. Although animal experiments have shown good results, this is the first time it has been used in humans."

People face the most common ethical dilemma in medical innovation: should we use a new technology that is not yet mature enough to save a patient who has almost no other hope, or wait for more validation, but the patient may not live to see that time?
"Professor Yang, it's your decision," Academician Chen finally said. "This is your patient, this is your technology."

Regarding the new K therapy, Academician Chen felt that he was merely a "raw material" supplier.

Yang Ping looked at Shen Guohua's imaging data on the screen. The tumor resembled an evil octopus, coiled around the head of the pancreas, its tentacles already reaching towards the liver and invading blood vessels. This was a typical, textbook case of late-stage pancreatic cancer, representing one of the most formidable fortresses in the treatment of solid tumors.

“Use the new vector.” Yang Ping’s voice was calm. “We need to prepare an immunosuppression plan in advance to prevent a possible cytokine storm; and inform the patient and their family that this is the world’s first treatment using this vector, and the risks are unknown.”

After making the decision, Academician Chen immediately arranged for the laboratory's only two bottles of type 26 vector preparation to be sent to Nandu via special plane. The preparation was stored in a liquid nitrogen tank at -80 degrees Celsius. Sanbo Institute will use the type 26 vector gene recombinant K preparation.

To facilitate his treatment, Shen Guohua was transferred from Ruijin Hospital in Shanghai to Sanbo Research Institute, and Dr. Li accompanied him to the institute.

Five days later, the treatment began.

Shen Guohua had already signed the thick twelve-page informed consent form, three pages of which specifically explained the experimental nature of the new carrier. His eyes were calm, even with a strange sense of relief. At least he was fighting to live, rather than passively waiting for death. For a terminally ill patient, hope, even the slightest glimmer, is extremely important.

Yang Ping assigned Dr. Li to treat Shen Guohua, his patient. Everyone in the ward was on high alert.

“Mr. Shen, we’re about to begin,” Dr. Li said. “The process is like a regular IV infusion, about twenty minutes. Afterwards, you may experience fever, chills, and muscle aches. These are side effects of the medication, and we have experience dealing with them; they are manageable.”

Shen Guohua nodded, closed his eyes, and the medicine entered his vein through the intravenous catheter.

The treatment lasted twenty minutes, followed by seventy-two hours of close observation. These seventy-two hours were a life-or-death test for Shen Guohua and a technological validation for Yang Ping's team. K-therapy had begun its challenge against the "King of Cancers."

……

Around the world, the first batch of trainees who graduated from the Sanbo training program began their first independent treatment after returning home.

At the São Paulo Cancer Center in Brazil, Dr. Carlos encountered an unexpected problem.

His first patient was a 56-year-old woman with advanced breast cancer, whose tumor had metastasized to her bones and lungs. Following standard procedure, Carlos performed an adenovirus antibody screening before treatment, which revealed that the patient was positive for moderate to severe antibodies against types 5, 26, and 35.

“This means that all existing vectors may not be effective,” Carlos explained to the patient’s family. “We can try pretreatment with immunosuppressants to lower antibody levels before treatment, but this increases the risk of infection.”

The patient's daughter, a lawyer in her early thirties, raised a pointed question: "Doctor, this treatment hasn't been officially approved for marketing in Brazil yet; it's only in clinical trials. If my mother's treatment doesn't work, can we sue the hospital or the Chinese technology provider?"

Carlos was stunned. In the training camp, they had learned techniques, operations, and how to handle complications, but no one had taught them how to deal with this distrust. This was no longer a technical issue, but a sociological one.

“The informed consent form signed before treatment already explained all the risks.” He tried to remain professional, “but as a doctor, I must tell you the truth: there is uncertainty in any treatment, especially experimental treatments with innovative therapies.”

Ultimately, the family decided to temporarily forgo treatment and wait for a more suitable treatment plan.

Carlos watched the patient being wheeled out of the consultation room, his heart filled with mixed emotions. In the training course, they discussed how to save more lives; in reality, the first hurdle was trust.

The same problem has emerged in a different form in Mumbai, India.

Dr. Rajiv's first patient was a poor man with advanced colon cancer. Under the tiered pricing of the Universal Care framework, the patient would have to pay approximately $3000 out of pocket—an astronomical sum for a rural Indian family.

“Doctor, we need to sell our land and everything of value to raise this money,” the patient’s son said. “But if we spend all this money and my father still passes away, my younger siblings will have nothing left.”

Rajiv couldn't answer the question. The training course taught him medicine, but not how to measure the value of life or how to advise a family to take the risk of treatment when it might plunge them into abject poverty.

He called Song Ziming, a teacher at the training course at Southern Metropolis Daily. Song Ziming was silent for a long time on the other end of the phone, and then said, "Dr. Rajiv, this is the most realistic problem in the global promotion of the inclusive framework. What we can do is ensure that the data on the effectiveness and safety of treatments are true and transparent, so that patients and their families can make choices with full information. As for the choice itself, that is the right and destiny of each family. We can only treat illnesses, we cannot change other people's destinies."

After hanging up the phone, Rajiv looked at the dozens of patients queuing outside the clinic. They all shared the same desire to live. The K therapy in his hand might be hope for some, but for others, it might be a heavy burden.

We can only cure diseases, not change other people's fates.

Rajiv silently repeated this sentence to himself.

Ultimately, the patient's family gave up on treatment, believing it was not worth it.

……

Ten days after the Zurich conference, the European Commission’s Directorate-General for Health issued an 80-page interim guidance document on the cross-border transfer of data on certain breakthrough medical technologies.

This document does not amend the GDPR, but it creates a special pathway: for innovative therapies that have undergone rigorous evaluation and significantly improve the survival of patients with no other treatment options, necessary cross-border data transfers are permitted when the following conditions are met:

The data recipient must pass the EU's data security certification;
The transmitted data is limited to the minimum necessary for clinical decision-making;
A joint oversight committee will be established, with the EU having real-time monitoring and veto power over data access;

All data must be stored in a complete mirror within the EU;
A reassessment will be conducted three years later, and a decision will be made based on technological advancements regarding whether to continue or modify the certification. This is a compromise, but also a breakthrough. "The next step is to see if you can meet those stringent certification requirements," Ms. Windsor told Huang Jiacai over the phone.

Huang Jiacai immediately organized his team to study the details of the document. The certification conditions were indeed stringent: it required building a data center that met EU standards, hiring EU-certified security experts, accepting quarterly audits without prior notice, and bearing high compliance costs.

"Preliminary estimates suggest that fully meeting these conditions would incur additional costs exceeding €2000 million annually," the CFO reported.

"Invest!" Huang Jiacai said without hesitation. "This isn't a cost, it's a ticket. Moreover, if we can become the first non-EU medical technology company to be certified, the certification itself will become a brand asset. If we want to go global, we must learn to deal with different markets, adhere to our principles while being familiar with and respecting the rules of others. Look at it from another angle: why can those multinational giants operate with ease in our country, while we often struggle when expanding overseas? It's because most of our companies lack a global perspective and global capabilities."

He was more concerned about the fourth point: data mirroring storage.

This means that a mirror center needs to be built in Europe, synchronized in real time with the main data center of Nandu. Technically feasible, but it would mean that complete data for all European patients would be stored within Europe.

"Professor Yang, from a research perspective, what impact will this have?" Huang Jiacai asked over the phone.

Yang Ping was analyzing the first batch of data after Shen Guohua's treatment, without looking up: "As long as we can access the core data needed for treatment decisions in real time, and can also obtain the anonymized data needed for scientific research on a regular basis, there will be no impact. Moreover, storing data in the EU may increase the willingness of European research institutions to participate in the analysis, which may be a good thing in the long run. There are some principles we must adhere to, but we cannot be too narrow-minded about some things."

Aren't you worried that the data will be misused or used to develop competing technologies?

"If we lose technological dominance because of a little data, then should we reflect on whether our technological threshold is too low?" Yang Ping finally raised his head. "Besides, if European scientists can use this data to develop better treatments, patients all over the world will benefit. Isn't that our original goal?"

Huang Jiacai looked at Yang Ping and felt that purity again.

In an era where everyone wants to build barriers and protect intellectual property rights, Yang Ping's thoughts are still on "what's best for patients."

“Okay,” Huang Jiacai said. “Then we’ll build it at the Frankfurt Fujian Mirror Center. Not only will we build it, but we’ll build it even better than they’re asking for, making it a landmark project for Sino-European medical technology cooperation.”

A week later, Ruixing partnered with Deutsche Telekom's data center to launch construction of the Frankfurt mirror center. Ms. Windsor's foundation provided partial funding and facilitated the participation of top research institutions such as Heidelberg University in Germany and the Pasteur Institute in France as academic oversight bodies.

Meanwhile, the European Medicines Agency (EMA) launched a comprehensive evaluation of K therapy, planning to begin full-scale clinical trials as soon as possible. Contrary to previous speculation, this evaluation was exceptionally swift, partly because relatives of several high-ranking EU officials were awaiting treatment.

The draft assessment report was quickly released, and the conclusions were generally positive, but seventeen improvement requests were proposed, including: increasing long-term safety data in European populations; optimizing the delivery system to reduce the first-pass effect in the liver; developing solutions to address pre-existing immune issues; and establishing an independent European adverse reaction monitoring committee.

These requirements highly overlapped with the problems that Yang Ping's team was solving. Huang Jiacai keenly realized that this might be due to guidance from experts within the EMA, who were not making obstructive demands, but rather constructive directions for improvement.

“This is a good thing,” Academician Chen Yongnian said at the joint analysis meeting. “It shows that the EMA professionals truly understand the technology, and their requirements are to make the therapy more perfect and safer. If we can respond to and resolve each issue one by one, we will not only get approval, but also win the respect of the European medical community.”

As a result, a series of improvement plans were formulated: launching a long-term safety study involving 1,000 people in Europe; accelerating the clinical translation of hybrid vector libraries; inviting European experts to join the adverse reaction monitoring committee...

“Sometimes, the strictest regulations can become the best driving force for technological progress,” Huang Jiacai wrote in a letter to all employees, “because it forces us to do our best.”

……

Shen Guohua on the seventh day after receiving treatment.

These seven days were like a rollercoaster ride. On the second day after treatment, he experienced the expected immune response: a high fever of 39.8°C, chills, and severe muscle pain. Doctors used hormones and antipyretics to control the symptoms. On the fourth day, the fever subsided, but the jaundice worsened, with total bilirubin soaring from 187 μmol/L before treatment to 312 μmol/L.

“Hepatic inflammatory response,” Dr. Li reported to Yang Ping. “The retention of the carrier in the liver triggered an immune attack, which, although temporary, exacerbated the existing liver function damage.”

On the fifth day, Shen Guohua began to show early symptoms of hepatic encephalopathy: confusion and disorientation. This was a dangerous sign, indicating that his liver's detoxification function was severely impaired.

Yang Ping convened an emergency meeting to discuss whether to continue supportive treatment or switch to palliative care to alleviate the pain. This was a difficult decision.

“From the perspective of tumors, the treatment may be working.” Song Ziming pulled up the latest PET-CT images. “The metabolic activity of the primary pancreatic lesion has decreased by 30%, and the liver metastases have also shown some response. However, the liver itself is severely damaged, which may offset the benefits of tumor treatment.”

“What if we…stop immune support now and let…the liver rest?” Xu Zhiliang suggested.

“That could cause the immune system to attack dying tumor cells, triggering more severe systemic inflammation.” Yang Ping stared at the data. “We are now walking on a tightrope, with cliffs on both sides.”

Just then, the patient's wife, Zhou Min, came to Professor Yang: "Professor Yang, my husband was awake for a few minutes just now. He asked me to tell you: continue treatment. He said that if he is destined to die, he would rather die on the road of battle than on the bed of waiting."

This statement silenced the meeting room.

“And,” Zhou Min continued, “this morning when they drew blood, the nurse said my husband’s blood was a little lighter in color than it had been a few days ago. I don’t know what that means, but maybe…maybe things are getting better?”

Yang Ping immediately retrieved the latest blood test data. Sure enough, Shen Guohua's hemoglobin level rose from 78 g/L to 85 g/L, and his reticulocyte count began to increase, which were signs of improved bone marrow hematopoietic function.

“The tumor may be regressing, and the suppression of bone marrow is lessening,” Yang Ping quickly analyzed. “If liver function can withstand this acute phase, there may really be a turning point.”

He made a decision: to strengthen liver support therapy—plasma exchange to remove bilirubin, an artificial liver support system to reduce the burden on the liver, and to continue to maintain appropriate immune monitoring. This was an expensive and complex support program, costing more than 50,000 yuan per day.

"What about the costs?" Dr. Li asked hesitantly.

“Ruixing will cover all the costs,” Yang Ping said. “Mr. Shen is paving the way for all similar patients, and his treatments are accumulating valuable experience for us. Money is not an issue.”

On the seventh night, a miracle occurred.

Shen Guohua's jaundice began to subside, and his total bilirubin level dropped from its peak to 276 μmol/L. His level of consciousness improved, and he was able to recognize his family members. Abdominal ultrasound showed that the ascites volume had not continued to increase.

More importantly, the tumor marker CA19-9 decreased from 12800 U/mL before treatment to 8700 U/mL—although still very high, this was the first decrease since diagnosis.

"The tumor is responding," Dr. Li said excitedly on the phone. "Although the liver damage is severe, the treatment is definitely working!"

This is not the final victory, and we are still far from it, but at least it proves that the new vector is indeed effective against this type of refractory pancreatic cancer. No matter how effective it is, it is at least a first step.

Yang Ping didn't cheer. He stared at Shen Guohua's latest single-cell sequencing data and discovered a worrying phenomenon: the tumor cells that survived the treatment had changed the expression of surface markers, seemingly exhibiting adaptive resistance.

“Tumors are learning,” he told the team. “After being attacked, they change their surface features to evade the next attack. This means that if Mr. Shen can get through this, future treatment strategies may need to be adjusted.”

“But at least we’ve proven that this road is passable,” Song Ziming said.

“Yes.” Yang Ping finally smiled. “That’s enough.”

……

When the news came that Shen Guohua's condition had stabilized, Huang Jiacai came to the Sanbo Research Institute again.

“Shen Guohua’s treatment costs have already exceeded 800,000 yuan,” Huang Jiacai said. “If we include the entire support team and resources, it may exceed 1.5 million yuan, and the success rate may still be less than 20%.”

“Without cases where patients take the initial risks, K therapy cannot expand its scope of application,” Yang Ping said.

Huang Jiacai looked at him and said, “I was just thinking that when K therapy benefits tens of thousands of patients in the future, people will only remember the successful cases, not the price paid by pioneers like Mr. Shen, not the pain suffered by families in those failed cases, and not the struggles of doctors in the face of uncertainty.”

Yang Ping was silent for a moment: "Medical progress is never linear. Behind every successful case are countless attempts, failures, and adjustments. What we can do is make every attempt valuable, whether successful or unsuccessful."

“Because data from failures is often more valuable than data from successes,” Yang Ping continued. “It tells us where the boundaries are, where the problems are, and where to go next. Shen Guohua’s case, regardless of the final outcome, has already pointed us in the direction we need to improve: reducing the first-pass effect in the liver, addressing tumor adaptive resistance, and optimizing support programs for patients with liver dysfunction. If this is successful, it will prove that common targets can also help expand the indications for K therapy, rather than requiring stable targets like those for osteosarcoma. Therefore, for any tumor, before a specific stable target is found, common targets can be used to solve the problem.”

“Wu Dechang’s open-source platform released its first tool module yesterday.” Huang Jiacai changed the subject. “The adenovirus vector basic construction scheme is completely open source. Six domestic research institutions have already started working on this module, and it is estimated that foreign countries will follow suit soon.”

"That's a good thing."

"Aren't you worried?"

"What are you worried about?" Yang Ping countered. "Worried that someone will develop better technology?"

Huang Jiacai smiled and said, "Professor Yang, I am just a businessman, a pragmatic businessman. So, from a purely commercial perspective, Wu Changde and his supporters want to take this opportunity to replace us with counterfeit products and cover us up."

"There's absolutely no need to worry. Did Microsoft worry about rampant piracy back then?" Yang Ping said calmly.

Huang Jiacai was taken aback; he seemed to understand something.