https://blog.naver.com/ham1sh/224276052095

introduction

1) Seoul National University Professor Shin Hee-young’s paper presentation materials
2) Discovery of IMT and Partial Resection
3) Initial visit after recurrence
4) After 6 months of using MSG0500 as a herbal monotherapy)

introduction

While reviewing my previous lecture materials, I would like to include the treatment process of an IMT patient as one of the cases worth preserving. Although treatments such as crizotinib, which acts as an ALK inhibitor, are currently being used for inflammatory myoblastoma, the drug was not approved by the FDA until 2011; therefore, no medication was available in 2004, when this patient was being treated. In 2004, only a portion was resected via minor surgery, and in November of the same year, Professor Shin Hee-young referred the case to me when surgery had become impossible due to tumor spread.

At the time, Professor Shin Hee-young of the Department of Pediatric Hematology and Oncology at Seoul National University referred the case to me because reoperation was impossible due to a recurrence following surgery at Seoul National University. Treatment was completed by 2009, and it was confirmed that there had been no recurrence since then. Although a small residual area remained in the right kidney region at the time of treatment completion, it remained in a somewhat reduced state until 2014, with no spread to other areas or recurrence.

And this case is included in Professor Shin Hee-young’s paper titled “Experience with Alternative Medicine in 7 Cases of Intractable Digestive Hematological Oncological Diseases That Were Difficult to Explain with Modern Medicine.”

Professor Shin Hee-young is an authority on pediatric cancer at Seoul National University. After retiring, she served as the President of the Korean Red Cross and is currently lecturing at Kangwon National University. Her dedication to children with leukemia is immense; she struggled tirelessly to provide financial assistance to these children through the Korea Children’s Leukemia Foundation and has made significant contributions to the advancement of pediatric leukemia and cancer treatment. In particular, driven by a humanitarian concern for pediatric patients in North Korea, she has consistently spared no effort in supporting North Korean children. She truly deserves to be respected as an exemplary physician.

He is someone with whom I have been classmates from elementary school through college, and we exchange medical views. We understand the results of Korean traditional medicine without prejudice, and he is making efforts to conduct research by integrating it with Western medicine.

1) Seoul National University Professor Shin Hee-young’s paper presentation materials

I will reproduce the text of this paper exactly as it is.

A male patient born in 1994 visited the hospital in March 2004 complaining of abdominal pain. An abnormality was discovered during a gastroscopy, and a biopsy was performed; however, as no definitive conclusion could be reached, open surgery was performed. Surgical findings revealed abnormal lesions, including tumors and extensive thickening of the intestinal wall extending from the stomach to the duodenum and small intestine.

The biopsy confirmed a diagnosis of an inflammatory myofibroblastic tumor. An attempt was made to perform extensive resection, such as a Whipple procedure, but it was determined that resection was impossible due to the excessively long length required, so only a biopsy was performed. Although gastric lymphoma and MALToma were suggested as differential diagnoses, the final conclusion was an inflammatory myofibroblastic tumor.

As further surgery was deemed impossible, the patient was transferred from the Department of Pediatric Surgery to the Department of Pediatrics and Adolescent Medicine. Since the condition was not suitable for chemotherapy, it was decided to administer herbal medicine at the request of the guardian, and MSG500 herbal medicine was initiated.

After administration of medication, abdominal CT scans showed a gradual decrease in the thickness of the duodenum, small intestine, and stomach wall, and all symptoms, including abdominal pain, disappeared. Although medication was discontinued after one year, no deterioration in clinical symptoms or CT findings was detected. Even on the last CT scan in 2011, although a slight increase in stomach wall thickness remained, it was continuously maintained well without significant change (Fig. 4).

At the time, Professor Shin Hee-young was unable to obtain accurate information regarding the medication, leading to a misunderstanding that the treatment was discontinued after one year; however, the child actually received herbal medicine treatment for five years, grew normally, and experienced no recurrence. Today, I would like to discuss the treatment process and the interpretation of this disease. I will create a separate section later to explain the Sasang Constitutional Medicine perspective and the composition of the prescription.

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2) Discovery of IMT and Partial Resection

Due to environmental factors, the child had more opportunities to encounter meat than others because their parents ran a butcher shop, and they consumed a lot of pork, which is unsuitable for a Taeeumin.

This is a patient with a true Taeeumin constitution, where both parents are Taeeumin. Although this disease cannot be discussed based on just one case, it appears to be one of the true Taeeumin diseases similar to medulloblastoma, retinoblastoma, etc.

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📄 Case 3. Inflammatory Myofibroblastoma (IMT)

This case is an inflammatory myofibroblastoma that occurred in a 13-year-old boy. Although it showed rapid progression after initial surgery, it showed a stabilized clinical course through long-term treatment.

The patient was diagnosed with inflammatory myofibroblastoma in February 2004 and underwent tumor resection at Seoul National University Hospital in May 2004. However, around November 2004, about six months after the surgery, the tumor was found to have progressed more than twice as much as it had at the time of surgery.

At this point, the lesion had spread beyond the local area to the liver, stomach, and pancreas, and was therefore determined to be an unresectable disease. The patient visited our hospital around the same time and began aggressive treatment.

Subsequently, continuous treatment was administered for approximately three years from November 2004 to August 2007. As a result, the tumor stabilized without further progression and maintained a clinically sound condition without signs of recurrence during the follow-up period. From then until 2013

It was followed up and there was no recurrence.

This case suggests the characteristics of aggressive IMT that showed rapid progression within a relatively short period following initial surgery; however, it is also an important clinical example demonstrating that long-term disease control is possible through appropriate therapeutic intervention. In particular, given that the patient maintained a stable state without recurrence for an extended period despite being unable to undergo surgery due to multi-organ involvement, this case is evaluated as significant in that it illustrates both the biological diversity and treatment responsiveness of IMT.

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The primary lesion identified during surgery was a palpable soft tissue mass located between the gallbladder, pylorus, first duodenum, and liver S6; it was observed to be an ill-defined mass approximately 3 cm in size. The gallbladder wall was thickened and accompanied by edematous changes, while the stomach and duodenum showed diffuse thickening centered around the areas in contact with the mass. Additionally, a severe inflammatory reaction was present around the gastroduodenal ligament.

Intraoperative frozen section biopsy revealed some neutrophils in the main mass, showing results consistent with overall inflammation.

The surgery began with the complete resection of the main mass, followed by a cholecystectomy. During the operation, a perforation of the pylorus was identified at the site where the mass was attached to the gallbladder, and treatment was subsequently performed on the affected area. A full-thickness stomach wall biopsy was performed on the perforation site, after which the site was repaired with a primary closure. An omentopexy was additionally performed to enhance the stability of the suture, and the surgery was concluded with thorough irrigation and hemostasis of the surgical site.

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Contrast-enhanced abdominal CT performed on October 7, 2004 demonstrates a recurrent ill-defined soft tissue mass located in the region of the pylorus, duodenal bulb, and adjacent hepatic segment S6. The lesion shows heterogeneous attenuation with indistinct margins and appears to infiltrate surrounding structures, including the gastric antrum and proximal duodenum.

There is associated wall thickening of the stomach and duodenum, as well as surrounding fat stranding, suggesting an active inflammatory process. The overall findings are consistent with recurrent inflammatory myofibroblastic tumor (IMT) with local invasion.

Contrast-enhanced abdominal CT performed on October 7, 2004, revealed a recurrence of an ill-defined soft tissue mass located in the pylorus, duodenal bulb, and adjacent hepatic S6 region. The lesion exhibited heterogeneous opacity, had indistinct boundaries, and showed signs of infiltration into surrounding structures, including the gastric antrum and proximal duodenum.

In addition, thickening of the walls of the stomach and duodenum is present, and increased fat stranding in the surrounding fat layer is observed, suggesting an active inflammatory response. The overall findings are consistent with a recurrence of inflammatory myofibroblastic tumor (IMT) with local infiltration.

4) 6 months after using MSG0500 as a herbal monotherapy

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🟢 After Herbal Treatment (2005.04, 6 months after MSG0500)

Follow-up contrast-enhanced CT performed in April 2005, after approximately 6 months of herbal treatment (MSG0500), demonstrates a marked decrease in the size of the previously noted mass.

The lesion shows significant regression with reduction in mass effect and improvement of the previously observed gastric and duodenal wall thickening. Surrounding inflammatory changes, including fat stranding, are also substantially decreased.

No definite evidence of newly developed lesions or disease progression is identified. The imaging findings suggest a favorable therapeutic response with partial remission of the previously recurrent IMT.

A follow-up contrast-enhanced CT performed in April 2005, about 6 months after MSG0500 herbal medicine treatment, showed a significant reduction in the size of the previously observed mass.

The lesion showed distinct regression with a reduced mass effect, and the previously observed thickening of the gastric and duodenal walls also improved. Inflammatory changes (fat stranding) in the surrounding fat layer also significantly decreased.

No newly developed lesions or findings suggesting disease progression were observed, and imaging findings suggest a favorable treatment response, including partial remission, for previously recurrent IMT.

(Inflammatory Myofibroblastoma)

Inflammatory myofibroblastic tumors were previously understood as simple inflammatory pseudotumors, but are now classified as low-grade tumors with confirmed molecular biological evidence. The pathological core of this disease lies in the coexistence of a neoplastic element consisting of proliferating spindle-shaped myofibroblasts and various inflammatory cells—particularly lymphocytes, plasma cells, and eosinophils—surrounding it. This structure reflects a unique pathogenesis in which neoplastic and immune responses operate simultaneously, rather than a simple inflammatory response.

Histologically, spindle cell proliferation is observed along with a fibrotic stroma, and immunohistochemical staining shows SMA positivity and partial desmin positivity. Of particular importance is the confirmation of ALK gene rearrangements in more than half of the patients. This ALK rearrangement acts as a major driver that induces sustained tyrosine kinase activation to maintain cell proliferation signals while simultaneously triggering an inflammatory response. Recently, the discovery of fusion genes such as ROS1 and NTRK in some patients, in addition to ALK, has further clarified that this disease is a tumor with distinct molecular targets.

Clinically, IMT often follows a relatively benign course, but in some cases, it exhibits an aggressive pattern involving rapid progression or invasion into surrounding organs. It occurs frequently in children and adolescents and can appear in various sites, including the lungs, abdominal cavity, mesentery, liver, and bladder. Imaging often reveals ill-defined masses accompanied by hypertrophy and inflammatory responses in surrounding tissues, making differentiation from malignant tumors a critical issue.

The basis of treatment is complete surgical resection. If the lesion is localized and resectable, a cure can be expected through surgery alone. However, in cases like this one, where surgery is impossible due to multi-organ involvement, the treatment strategy changes. In the past, treatment often relied on steroids, non-specific chemotherapy, or simple observation, but currently, molecular targeted therapy has established itself as a key therapeutic pillar.

In particular, when ALK positivity is confirmed, ALK inhibitors are used as a highly effective treatment. Crizotinib is typically used as a first-line treatment, and if resistance develops or the response is insufficient, next-generation drugs such as alectinib or lorlatinib may be applied. These drugs selectively inhibit ALK kinase activity, thereby blocking tumor growth signals and simultaneously reducing inflammatory responses. In fact, dramatic responses in which tumors significantly shrink have been reported in some patients, even in cases where surgery is not possible.

Meanwhile, in ALK-negative patients, it is important to identify other fusion genes such as ROS1 or NTRK and apply the corresponding targeted therapy. When molecular targets are not identified, steroids or anti-inflammatory treatments may still be effective to some extent, and it is understood that the inflammatory nature of the disease influences the treatment response.

Ultimately, inflammatory myofibroblastoma is a disease situated in between a simple tumor and simple inflammation, and modern medicine understands it as an “inflammation-driven neoplasm.”

​Due to these characteristics, treatment also requires a multi-layered approach combining surgical resection, immunomodulation, and molecular targeted therapy. The fact that long-term stabilization can be achieved even in a progressive state where surgery is not possible, as in this case, holds significant clinical implications, demonstrating both the biological diversity and therapeutic potential of this disease.

​The mechanism of Western medical treatment for inflammatory myofibroblastoma is, in essence,

It is based on the concept of “directly blocking driver mutations (especially ALK).”

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Modern treatment of inflammatory myofibroblastoma begins with a precise understanding of the tumor’s molecular biological mechanisms. In a significant number of cases of this disease, ALK gene rearrangements are present, and the resulting ALK fusion proteins act as continuously activated tyrosine kinases. Cell proliferation signals, which normally require regulation by external signals, remain in a continuously autonomously activated state in this instance.

This abnormal ALK activity simultaneously stimulates multiple intracellular signaling pathways. Notably, the PI3K–AKT pathway enhances cell survival and anti-apoptosis signaling, while the RAS–MAPK pathway promotes cell proliferation and division.

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​Furthermore, the JAK–STAT pathway increases the secretion of inflammatory cytokines, creating a persistent inflammatory environment around the tumor. Consequently, IMT is not merely a tumor where cells proliferate, but possesses a structure that maintains an environment favorable for its own growth by accompanying an inflammatory response.

The core of Western medical treatment is to block the source of these “driver signals.” ALK inhibitors selectively bind to the ATP binding site of ALK proteins to inhibit kinase activity. As a result, downstream signaling pathways are simultaneously blocked, preventing cells from receiving proliferation signals and inducing apoptosis. At the same time, the production of inflammatory cytokines is reduced, thereby alleviating the inflammatory environment surrounding the tumor.

Crizotinib, a representative drug, was the first ALK inhibitor developed and is characterized by inhibiting not only ALK but also kinases such as ROS1. Subsequently developed drugs such as alectinib and lorlatinib were designed to overcome resistance to existing drugs while providing even stronger ALK inhibitory effects.

In particular, these drugs have improved penetration into the central nervous system, so they can be effective even when tumors have metastasized to the brain.

Meanwhile, in the case of ALK-negative patients, other fusion genes such as ROS1 or NTRK may be present, and in such cases, using targeted therapies tailored to the corresponding genes becomes the key to treatment. In other words, modern treatment takes the form of precision medicine, determined not simply by tissue type but by “what genetic abnormalities exist.”

Ultimately, Western medical treatment views IMT as a “tumor driven by specific genes” and employs a strategy of directly blocking its key switch. This approach is highly effective in rapidly reducing tumor size and inhibiting disease progression, and it has established itself as an important treatment option, particularly for advanced patients for whom surgery is not possible.

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Crizotinib was not a drug developed to target ALK from the beginning, but rather a drug whose development began around 2005 at Pfizer with the goal of inhibiting MET tyrosine kinase. At that time, because the understanding of molecular targets in tumors was not as precise as it is now, the general approach was to first develop candidate substances that inhibit specific kinases and then expand the applicable targets.

Subsequently, the situation changed significantly in 2007 when ALK gene rearrangement was identified as a key pathogenesis in non-small cell lung cancer. Researchers confirmed that Crizotinib, which was already under development, had a strong inhibitory effect on ALK kinase as well as MET, and this led to a shift in the drug’s direction toward becoming an ALK-targeted treatment.

Subsequently, Crizotinib quickly garnered attention as very high response rates were observed in ALK-positive patients during early clinical trials conducted between 2008 and 2010. In particular, as significant tumor reductions were observed even in patients who had not responded to conventional anticancer drugs, the drug established itself as a representative success story in targeted therapy.

Ultimately, based on these clinical results, Crizotinib received FDA approval in 2011 and officially began to be used as the first ALK inhibitor. This point is considered not merely the emergence of a new drug, but a significant turning point marking the transition of cancer treatment from histological classification to the era of precision medicine, which directly targets genetic abnormalities.

From the perspective of Sasang medicine, Taeumin is a constitution with a potential for lipid or fibrous tumors.

The patient was the son of a butcher and consumed an excessive amount of meat, especially pork, in his daily diet.

People with a Yin constitution have a tendency for their Na concentration to always be low; when the Na concentration in the intestines drops, lipid intake increases more than amino acid intake.

this patient is a true Taeeumin.

Both of his parents are Taeeumins, which further lowers his Na concentration and improves lipid absorption. Additionally, he had frequent environmental exposure to pork. It is inferred that the disease was cured because the genetic factor of the disease, low Na, combined with the environmental factor, excessive lipid absorption.

Therefore, herbal medicine was administered to the patient along with a diet suitable for Taeeumin.

Excessive fat accumulation is not merely a matter of energy storage, but serves as a crucial starting point for reorganizing signaling systems at the cellular level. When fat accumulates excessively, free fatty acids and inflammatory cytokines increase, particularly in the liver and visceral fat regions.

These changes promote the activation of the mTOR signaling pathway within cells that induce insulin resistance. While mTOR is inherently a central regulator controlling cell growth and synthesis, if continuously activated, cells deviate from normal equilibrium and transition to a “growth and accumulation-centered state.”

In this process, protein synthesis and lipid synthesis increase, and autophagy is inhibited,
As a result, unnecessary substances and damaged structures within the cell accumulate without being removed.
This condition goes beyond simple metabolism
It induces structural change at the organizational level, namely “remodeling.”

Meanwhile, **ALK (Anaplastic Lymphoma Kinase)** is
As a receptor tyrosine kinase, when activated
It plays a role in amplifying various growth signals, including the PI3K/AKT/mTOR axis.

Chronic inflammation and increased growth signals caused by lipids create an environment favorable for the activation of tyrosine kinase signaling, such as ALK. Specifically, by binding with the already activated mTOR pathway, cells receive stronger proliferation and survival signals, leading to the gradual loss of normal tissue structure and the initiation of reorganization.

At this point, the critical turning point is fibrosis. In a chronic inflammatory environment, TGF-β signaling increases, and
Fibroblasts are activated, and collagen and extracellular matrix accumulate excessively.

Ultimately, metabolic changes initiated by fat accumulation create a state of intracellular accumulation through the sustained activation of mTOR; when growth signaling axes such as ALK are added to this, the tissue moves in the direction of “proliferation + accumulation + reconstruction.” The result is fibrotic tissue, and in some cases, tumor-forming lesions. This entire process is not merely a simple metabolic disease.

It is a single continuous pathological flow leading from “fat → signal → structural change,” and This pathway may be even more pronounced, especially in constitutions with a strong tendency toward accumulation and hypertrophy.