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Summary of Medical doctoral thesis: Research on the clinical, pathological characteristics and treatment results of nonepithelial cancer of the gastrointestinal tract at Viet Duc university hospital

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Description of the clinical and anatomic morphology of nonepithelial gastrointestinal tract cancer; description of surgical methods and evaluation of surgical treatment results for non-epithelial gastrointestinal tract cancer.

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Nội dung Text: Summary of Medical doctoral thesis: Research on the clinical, pathological characteristics and treatment results of nonepithelial cancer of the gastrointestinal tract at Viet Duc university hospital

  1. MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY PHẠM GIA ANH RESEARCH ON THE CLINICAL, PATHOLOGICAL CHARACTERISTICS AND TREATMENT RESULTS OF NON- EPITHELIAL CANCER OF THE GASTROINTESTINAL TRACT AT VIET DUC UNIVERSITY HOSPITAL Specialized : Digestive surgery Code : 62720215 SUMMARY OF MEDICAL DOCTORAL THESIS HANOI – 2022
  2. THIS THESIS WILL BE COMPLETED AT: HANOI MEDICAL UNIVERSITY Scientific advisors: Prof. PhD. Trinh Hong Son Reviewer 1: Reviewer 2: Reviewer 3: The thesis defense shall be held by the university-level Thesis Assessment Board at Hanoi Medical University. Time: Date: , 20 This thesis could be found at: - The National Library of Vietnam - The Hanoi Medical University Library
  3. LIST OF OF THE AUTHOR’S SCIENTIFIC ARTICLES RELATED TO THE THESIS 1. Pham Gia Anh, Trinh Hong Son. Review of diagnostic and therapeutic methods for malignant lymphoma of the gastrointestinal tract. Vietnam medical journal, 2020, 6(1), 205- 213. 2. Pham Gia Anh, Trinh Hong Son. A report of 5 rare cases of primary malignant melanoma in the gastrointestinal tract operated at Viet Duc University Hospital in 10 years. Vietnam medical journal, 2020, 6(2), 185-188. 3. Pham Gia Anh, Trinh Hong Son. A report of 4 rare cases of leiomyosarcoma in the gastrointestinal tract operated at Viet Duc hospital in 10 years and a review of the literature. Vietnam medical journal, 2020, 6(2), 196-201. 4. Pham Gia Anh, Trinh Hong Son. A report 1 case of rhabdomyosarcoma in the gastrointestinal tract. Clinical features, pathophysiology and literature review. Vietnam medical journal, 2020, 6(2), 209-213. 5. Pham Gia Anh, Trinh Hong Son. A report of 7 rare cases of liposarcoma in the gastrointestinal tract operated at Viet Duc Hospital in 10 years. Vietnam medical journal, 2020, 7, 106- 110. 6. Pham Gia Anh, Trinh Hong Son. A rare case report: Angiosarcoma of the rectum. Vietnam medical journal, 2020, 7, 51-54. 7. Pham Gia Anh, Trinh Hong Son. Clinical characteristics of non- epithelial gastrointestinal tract cancer operated at Viet Duc University Hospital for 10 years. Vietnam medical journal, 2021, 1(2), 138-142. 8. Pham Gia Anh, Trinh Hong Son. Evaluation of surgical results of non-epithelial gastrointestinal cancer at Viet Duc University Hospital in 10 years. Vietnam medical journal, 2021, 1(2), 214- 217.
  4. 1 INTRODUCTION Non-epithelial cancer of the gastrointestinal (GI) tract includes the mesothelioma group and the lymphoma of the GI tract, accounting for less than 5% of all cancers of GI tract, there are more than 10 different types, including the group that accounts for a small percentage than having histopathology images and diagnostic criteria similar to soft tissue tumors in other organs such as lipoma, leiomyoma, shwannoma, angioma, rhabdomyoma ... and the other group accounts for the majority of them heterogeneously is called gastrointestinal stromal tumor (GIST) and lymphoma. In the world and Vietnam, there are existing studies on non-epithelial cancer, however, the authors often study a type of lesion on one or more organs without a comprehensive study of the the type of non-epthelial tumor of the entire GI tract. With the important role of pathology, especially the application of immunohistochemistry (IHC) technology to confirm the nature of tumor cells and determine the risk of malignancy of the disease has helped a lot in the treatment process. Recently, there have been many new discoveries and changes in the diagnosis and the treatment of non-epithelial tumors of the GI tract. Although they account for a much lower ratio than the epithelial tumors, non-epithelial gastrointestinal cancers also have many serious complications of emergency nature that can be fatal (such as digestive hemorrhage, perforation, obstruction intestinal, intussusception ...) and these complications are rarely seen clinically, therefore, it is of great importance to understand thoroughly the clinical features as well as the need for definitive diagnosis of stromal tumors, lymphoma and other mesenchymal tumors of the GI tract to develop appropriate and effective treatment for the patient. Therefore, we conducted this research project with two goals: 1.Description of the clinical and anatomic morphology of non- epithelial gastrointestinal tract cancer. 2.Description of surgical methods and evaluation of surgical treatment results for non-epithelial gastrointestinal tract cancer. CONTRIBUTIONS OF THE THESIS 1. This was the first research thesis having the longest follow-up time on all types of non-epithelial gastrointestinal malignancies consisting of all segments of the gastrointestinal tract from the esophagus to the anus. 2. The first dissertation researched in a comprehensive demonstration, giving details of clinical features, pathology, treatment methods and necessary recommendations for all types of non-epithelial gastrointestinal malignancies of the gastrointestinal tract. 3. The long-term large research database had statistical significance, including many rare cases not only in Vietnam but also in the world, contributing to further research in the country and on international scale. STRUCTURE OF THE THESIS The thesis has 126 pages, including: introduction (2 pages), overview (46 pages), subjects and methodology (15 pages), results (23 pages), discussion (39 pages), conclusion (2 pages), recommendations (1 page). The thesis has 27 tables, 8 graphs, 36 pictures, 215 references (32 Vietnamese, 183 English).
  5. 2 CHAPTER 1 - LITERATURE OVERVIEW 1.1. Physiological and anatomical characteristics of the gastrointestinal tract. The gastrointestinal (GI) tract starts from the esophagus to the end of the anus, each segment has a different function. In addition to the special structures of each segment, the wall of the GI tract has the same overall structure, consiting of 4 layers: mucosal layer (epithelial layer, stroma layer, mucosal layer). When the tumor is located in different positions of the GI tract, there will be different clinical symptoms. 1.2. Overview of clinical morphology and pathology of non-epithelial GI cancer. Depending on the location of the lesion at different locations of the field, the symptoms and clinical morphology will be different, such as signs of swallowing often found when tumors in the esophagus, intestinal obstruction is more common in the small intestine and colon. , very rarely in the stomach, intussusception is common when tumors in the ileum. At the same time, different types of tumors will have different specific lesions such as GIST tumors or have high social symptoms (stomach, jejunum), while peritonitis, intestinal perforation causes peritonitis. Lymphoma and more often present in the ileum. According to the latest classification of the World Health Organization, gastrointestinal tract tumors are divided into 3 large groups: tumors of epithelial origin, tumors of non- epithelial origin and secondary cancers. . Morphological codes according to the international classification of disease for oncology, anatomically classifying non- epithelial tumors of thymus include granulomatous cell tumors, GIST tumors, smooth muscle tumors, skeletal muscle tumors, Kaposi tumors, melanoma, lymphoma, hemangioma, adipoma, angioma, and nerve sheath tumors. 1.2.1. Malignant smooth muscle tumor (Leiomyosarcoma): Malignant smooth muscle tumor is a type of malignant tumor of cell origin that is smooth muscle fibers, usually occurring in middle age or elderly people. The tumor is usually large in size, has a shell, can become a zone, a solid grayish-white density, can progress to ulcers, alternate bleeding, necrosis. There are cases where the tumor grows in the form of a polyp, which is stiff and infiltrated. According to Conlon, the recurrence rate is 44% after complete resection of the tumor in an average period of 9 months, blood-borne metastasis usually to the liver, invasiveness of surrounding organs, rare lymphatic and elbow metastases. bad amount. With tumors ≥ 5 cm, the survival rate over 5 years is 27% (O'Riordan et al.), If the tumor is highly malignant, the rate of liver metastasis and recurrence also increases as in the 17/21 field study. Collaboration by Chou et al. or other authors also recommend that the smaller the tumor size, the lower the mitosis index, the better the prognosis is. According to research by Rajshekar, if there is metastasis, it is by blood sugar with 65% metastatic to liver, 15% to other part of digestive system and 4% to lung. With the development of IHC, it is very helpful in definitive diagnosis when positive for SMA, Desmin and H-caldesmon; negative for CD117 and DOG1.1. 1.2.2. Malignant Lymphoma: The first malignant lymphoma (MLP) was described by Billroth in 1871. Lymphoma in TH lymphoma accounts for 1-4% of malignant tumors of the gastrointestinal tract, accounting for 30-40% of MLP.
  6. 3 extra-lymphadenopathy and 10-15% of non-Hodgkin's MLP. The lymphatic organization of the gastrointestinal tract is the tissue that is not the same as the lymphoma, spleen (clinical, anatomical, progressive), the most common group is diffuse large cell B lymphoma, second is the lesion group. The lesions develop from the mucosa associated with lymphoid tissue (MALT). Mainly non-Hodgkin tumors of B cell origin (90%), T cell origin are rarer (10%). The location is more common in the stomach 75%, small intestine 8.6%, ileum 7%, colon 0.2-1.2% and 0.1-0.6% in the rectum. In the studies, there is a close association between lymphoma of the gastrointestinal tract and the presence of HP bacteria as in the case of MALT type lymphoma of the stomach. For patients with acquired immunodeficiency syndrome, among types of cancer, non-Hodgkin lymphoma ranks second after Kaposi cancer. In terms of pathology, the first widely accepted classification is that of Rappaport (1956), but so far the most commonly used disease staging classification for lymphoma is that of Ann ArBor (1971) and revised according to Cotswolds (1988), the latest Lugano classification (2014), the authors have included the role of PET-CT in diagnosing, evaluating treatment effectiveness, disease progression, eliminating the unclear, favorable points in comparing patient results. 1.2.3. Gastrointestinal stromal tumor (GIST): GIST was first described by Mazur and Clark in 1983. Gastrointestinal stromal tumors are digestive mesenchymal tumors of spindle cells and / or epithelial cells with over 95% expressing CD117, 75-80% with c-kit gene mutation. GIST accounts for 1% of all GI tract cancers and 3/4 mesothelioma tumors, can be found in all sites of the GI tract but mainly in the stomach (50-70%), small intestine (20-30%), colorectal (5- 15%) and esophagus (
  7. 4 peripheral nerve tumors, originating from Schwann cells, accounting for 2-6% of OTH non-epithelial tumors. Tumors mainly found in the stomach and small intestine (the stomach is more common than the small intestine 10 times), very rare in the esophagus, colon, rectum; The ratio is equal between the sexes and is usually over the age of 65. Malignant neurosomal tumors often combine 40% in Von Recklinghausen's disease, and in patients with this disease the malignancy potential of buccal tumors menstruation increased to 4600 times. In diagnosis is often confused with muscle tumor and GIST. Immunohistochemistry is required for a definitive diagnosis: protein S 100 is a protein of the central and peripheral nervous cells. Protein S 100 (+) for all benign Schwann cell tumors and 50% - 90% of malignant Schwann cell tumors, elevated p53 and Ki67 were also implicated in the suggestion of malignant lesions of the tumor. It is necessary to think of Malignant Schwann cell tumors when microscopic organisms have a strong proliferation of atypical, chaotic arrangement, multiple cell division. Negative for SMA, desmin, myosin, CD34 and c-Kit. 1.2.5. Liposarcoma: Liposarcoma is one of the most common soft tissue tumors in adults, originating from fat cells, usually benign, aged between 40 and 60 years old, less Common in children, more common in obese people. The pathogenesis is not clear, some risk factors such as environmental pollution, eating and drinking, radioactivity, immunosuppressive drugs, immunodeficiency virus, exposure to certain chemicals or dioxin In general tumors often have clear margins, yellow, microscopic cells are polygonal cells with eccentric nucleus. Tumors that grow 90% into the lumen, vary in size from 1cm or larger. Molluscum, pale yellow, often solitary, covered with normal mucosa, sometimes ulcerative. 1.2.6. Kaposi's Cancer (Kaposi's Sarcoma's - KS): This type of lesion was first described in 1872, is a form of endothelial tumor associated with HHV8 virus, low malignancy; very common in HIV-infected patients can be at any stage of the disease with the rate of 15-20%, and in patients KS patients are over 95%. Lesions in the GI tract are usually inconspicuous (81.5%) or mild such as nausea, vomiting, some more severe such as GI hemorrhage, abdominal pain, intestinal obstruction or intussusception. Kaposi cancer has 4 types. Immunohistochemistry: positive for CD31, CD34, but for differential diagnosis with other types of cancer, it is necessary to confirm the presence of HHV-8 virus. 1.2.7. Malignant angioma (Angiosarcoma): A rare type of tumor, a low rate of 1-2% of the total soft tissue cancers, mainly found in the skin and subcutaneous, less than in the liver, spleen, and upper kidney and very rare in the gastrointestinal tract (usually in the stomach and small intestine). So far in the literature not many reports about this type of cancer: about 30 cases. The etiology is unclear, but there have been studies on the association of tumors with chemicals such as vinyl, arsenic and thorium dioxide, radiation, genetic related diseases, abdominal pain symptoms, and bleeding or congestion of the intestine; or gastroscopy, angiogram is needed to find bleeding point in case of tumor in the small intestine. IHC: (+) with CD31 CD34, Vimentin, VEGF, (-) with CD117 and S-100. 1.2.8. Melanoma Malignant: Occurs in the gastrointestinal tract can be primary or metastasis from elsewhere; Primary melanoma can be in all sections of the gastrointestinal tract, accounting for a small proportion of 1-3% of all types of
  8. 5 malignancies here, difficult to diagnose in the early stage, very high level of malignancy. and the prognosis is very poor, the average postoperative life is 6 to 10 months. The prevalence in men is 4 times higher than that of women, between the ages of 20 and 70, the main symptoms are abdominal pain, anemia, gastrointestinal bleeding in which nearly one third of cases have acute complications. counted as bleeding, intestinal obstruction, perforation that require surgical intervention. Diagnosis by CT, PET (in the detection of metastases), endoscopy, pathological biopsy, immunohistochemical staining with HMB45 and S100. IHC: (+) with Vimentin, S-100, HMB45, Melan-A. 1.2.9. Glomus Tumors: This type of tumor is usually benign, accounting for 2% of the total soft tissue tumors and very rare manifestations in the internal organs. Malignant tumors were first described in 1939 by Kirschbaum et al. There have been many other reports of malignancies in the stomach even at a very young age as by Yannopoulos with the patient group: young women from 12-14 years old. According to Folpe et al., Assessment of tumor malignancy with invasive macroscopic properties of surrounding organizations, tumor location and size (> 2 cm), nuclear and cell variability, multiplication index abnormalities (> 5 / 50HPF), tumor necrosis and lymph node invasion are factors in assessing the degree of malignancy of the tumor, but distant metastases are very rare. IHC (+) with SMA, calponin, H-Caldesmon, vimentin, ki-67, BCl-2, p53; (-) with CD34, CD117 and S100. 1.2.10. Granular Cell Tumor: A rare type of tumor originating from nerves (Schwann cells), mainly located in the skin, under the skin, mouth and tongue; 5- 9% of these tumors are located in the gastrointestinal tract, of which 75% are found mainly in the esophagus (2/3 of tumors located in the lower esophagus), followed by the colorectal (21%), stomach. thick, usually in the middle aged 40- 50, the male / female ratio is 3/2. Malignant granulomatosis is very rare, malignant properties manifest: recurrence, rapidly growing tumor, larger than 4 cm in size, proliferation and abnormal cells. 1.2.11. Malignant rhabdomyosarcoma (Rhabdomyosarcoma): The more rare this tumor is found in the gastrointestinal tract; For example, in the duodenum until 2014, only 3 cases of rhabdomyolysis (not in Vater's ball) were reported, most recently the authors Asahi Sato et al (Japan) published in the newspaper. Surgical Today (2014), Stout and Lattes reported 4 cases of the esophagus and 2 cases of the stomach, Templeton and Heslin describe a case in a 3-year-old child with a stomach tumor and a male case 54 age with lesions in the esophagus. IHC (+) with Desmin, HHF-35 and SMA, (-) with PTAH, CD68, CD34, c-kit and S100. 1.3. Overview of treatment for non-epithelial cancer cells. 1.3.1. Leiomyosarcoma: Although there are many opinions in treatment such as postoperative or postoperative chemotherapy, according to author Berna O., the prognosis of malignant smooth muscle tumors in the rectum is still poor with the survival rate 5 Only 20% a year after surgery. Surgery is still the basic treatment for malignant smooth muscle tumors, chemotherapy is only partially effective, radiotherapy is almost ineffective, and chemicals are effective. is very limited, as doxorubicin and ifofamide response rates are only 15-20%.
  9. 6 1.3.2. Malignant lymphoma: In the types of non-epithelial tumors, MLP is the type of lesion with good response to chemicals, this is the first choice in the treatment of MLP when detecting the disease, surgery only when there are variables. such as intestinal obstruction, perforation or bleeding. 1.3.3. Gastrointestinal stromal tumors So far, Imatinib (Glivec) is the drug of choice in cases where the tumor cannot be cut and those with distant metastases. Sunitinib is an alternative drug in this case (second line option). Immunotherapy with immunostimulating effects against cancerous cells such as nivolumab (Opdivo) and ipilimumab (Yervoy) is being studied in the treatment of GIST. Surgery is still a basic treatment with primary GIST with a effective surgery rate of up to 70-80% of cases. 1.3.4. Malignant schwannoma: Surgery remains the first and only option in the treatment of malignant neural envelopes. Adjuvant therapy, chemotherapy (Doxorubicin, ifosfamide), and radiotherapy are ineffective for this type of lesion, often indicated in the event of recurrence of the tumor or inadequate surgery. 1.3.5. Liposarcoma: surgery is still the most effective method, it is necessary to try to remove all lesions (R0) to avoid recurrence, especially the atypical group of tumors with high malignancy and high probability of recurrence at place as well as distant recurrence. Radiation therapy in case the tumor cannot be removed, chemotherapy can use doxorubicin and ifosfamid when monitoring the tumor recurrence, assessing the effectiveness of treatment with CT or MRI every 2 cycles. 1.3.6. Kaposi Sarcoma: Until now there is no standard treatment regimen for this type of cancer, can be surgery, cryotherapy, chemotherapy, radiotherapy or antiviral drugs or use Imatinib as in GIST treatment (for patients positive for CD117). The preferred chemical in treatment is Liposomal Doxorubicin (Caelyx, Myocet or Doxil), essentially the drug doxorubicin covered by a layer of fat called liposome. Interferon-Alpha and several other drugs are also being studied, such as thalidomide, IM-862 or Retinoid. 1.3.7. Angiosarcoma: Primarily surgical, with radical surgery (R0) being the primary criterion of treatment strategy. Radiation therapy is given when lesions are located in the rectum at a dose of at least 60-65 Gy. Chemotherapy is often ineffective, but more and more research is being done to increase the tumor's response to chemotherapy, often treatment with taxanees (paclitaxel) is the first choice or a combination of gemcitabine. . Recently, target drugs have also been investigated for the treatment of malignant hemangiomas such as PD-1 and PD-LI inhibitors, VEGF inhibitory monoclonal antibodies (bevacizumab) or beta blockers (β-Blocker). 1.3.8. Malignant melanoma: Mainly surgery and curettage, supportive treatment such as chemotherapy with interferon, interleukin, immunotherapy with vaccine from tumor cells ... but not really effective. Radiation therapy is given when the tumor is in the anorectal role in a supportive role in controlling the tumor, but also does not help improve survival. Chemicals commonly use Dacarbazine (DTIC) and temozolomide (Temodar). For the target treatment of Vemurafenib, when no longer response, a second regimen with Ipilimumab is used. Interferon-β, INF-2
  10. 7 or IFN-2b support and palliative therapy help control tumor progression and recurrence. 1.3.9. Glomus tumour: Surgical treatment is the main thing, ensuring a wide enough cut area and safe rarely recurs, but also need to guide periodic monitoring for patients. There is no need for supportive treatment. 1.3.10. Granular cell tumour: Mainly by surgery. For small tumors that can be cut through flexible endoscopy, radical surgery is required when identifying malignancies, invading the deep layer of the OTH wall, unnecessary radiation and chemotherapy for benign tumors and no effect with malignant lesions. Recent target therapy with Pazopanib. 1.3.11. Rhabdomyosarcoma: radical surgery to remove the bowel with the tumor is the best, multiple chemotherapy is applied including chemotherapy and radiation. 1.4. Research situation of non-epithelial cancer of the Gastrointestinal tract in Vietnam: Since the 1970s, author Nguyen Duc Ninh, 38 cases of small bowel tumors by Nguyen Phuc Cuong, Nguyen Trung Tuan. Authors Nguyen Nhu Bang, Truong Nam Chi, Pham Kim Binh studied 422 gastric cancer cases in 5 years (1976-1980) found 4% of non-epithelial cancers, of which 9 cases were malignant lymphomas. and 6 cases of malignant neuroma. In 1993, the author, Do Duc Van, through 1908 people who received surgical treatment had 14 cases of malignant lymphoma and 8 cases of malignant nerve tumors. The study through 359 cases of colon tumors was operated in Viet Duc for 8 years (1986-1993), with 15 cases of non-epithelial tumors, including 13 cases of malignant lymphoma and 2 cases of malignant fatty tumors. In 1997, Trinh Hong Son studied "clinical morphology of small bowel tumors" through 42 cases, including benign and malignant tumors (1998). In 1998, there were 23 cases in the period 1993-1999 at Viet Duc hospital of the authors Trinh Hong Son, In 2000, another study on 12 cases of malignant smooth muscle tumors of small intestine by Trinh Hong Son, Pham Duy Hien. About "malignant lymphoma of the small intestine" author Trinh Hong Son et al. Within 10 years, only 13 cases have been operated at Viet Duc hospital. In 2002, Le Dinh Roanh et al in the study on histopathological classification of stomach cancer on 452 cases (2002) showed that gastric stromal tumors and malignant lymphomas had an equally low incidence (1, 55%). The author has used immunohistochemistry to diagnose difficult cases and discovered 1 case with c-kit mutation. In 2002, author Nguyen Ngoc Hung studied 62 cases of non-epithelial tumors of the stomach operated at Viet Duc Hospital In 2005, there were statistics on peritonitis cases due to perforation of pathological small intestine for 5 years in Viet Duc, Hong Son et al. 2 cases of malignant tumors were smooth muscle tumors and lymphoma in a total of 14 patients. In 2007, the thesis of author Nguyen Van Mao studied histopathology and immunohistochemistry through 32 gastrointestinal tract malignant stromal tumors and proposed anatomical diagnosis. In 2011, author Nguyen Thanh Khiem's inpatient thesis on "clinical, subclinical and surgical treatment results of primary gastrointestinal lymphoma at Viet Duc hospital". In 2011, author Bui Trung Nghia's inpatient thesis on "Assessment of clinical, subclinical and surgical treatment results for gastrointestinal stromal tumor (GIST) at Vietnamese hospital." In 2017, the author
  11. 8 Do Hung Kien with research on clinical and subclinical features of gastrointestinal stromal tumors (GISTs) no longer indicated for tumor resection surgery, with CD 117 (+) and Results of treating this group of 188 patients with imatinib and a number of related factors. CHAPTER 2 - SUBJECTS AND METHODOLOGY 2.1. Research subjects: Patients diagnosed with non-epithelial cancer of the gastrointestinal tract operated at Viet Duc University Hospital during a period of 10 years, from January 2009 to April 2019. 2.1.1. Criteria for selecting patients: - Patient regardless of age, sex. - Patients receiving surgical treatment. - The results of anatomical diagnosis confirming non-epithelial malignancies of the entire gastrointestinal tract including the esophagus, stomach, duodenum, small intestine, colon, rectum and anal canal. - Having complete medical records with clinical symptoms and subclinical results, surgery records, disease anatomy results. 2.1.2. Exclusion criteria: - The anatomical result of the disease is GI tract epithelial carcinoma. - The anatomical results of the disease are benign tumors. - Patients with incomplete records, and do not have pathological results. 2.2. Research Methods 2.2.1. Research design Retrospective descriptive research methods: retrospective analysis of patients’ medical record of clinical symptoms, subclinical, pathological anatomy, imaging diagnosis, and surgical methods according to the statistical research records. Research assistants directly entered data, analyzed, contacted patients’ for postoperative follow-ups and results evaluation. 2.2.2. Sample size Convenient sample selection: All eligible patients underwent surgery during the period of 10 years from January 2009 to April 2019. 2.2.3. Study time and location - Time: from January 2009 to April 2019 - Research location: Viet Duc University Hospital 2.2.4. The method of data collection - Step 1: Collect all the results that are non-epithelial tumors of the anatomical department: Including 2 sources: data collected from the handwritten archives and from the database of the Anatomy department illness from January 2011 to April 2019. Find each morphology code according to the international classification of disease for oncology. - Step 2: From the results obtained in step 1, the name, age, clinical diagnosis of chosen patients were sent the department sends the patient and the date of reading the pathology profile. Get each patient's discharge date. Get the medical records of each patient to get the medical records for research. Check out the complete record according to the new standard taking into the research data.
  12. 9 2.3. Research target. 2.3.1. The target serves the first objective of the study: "Describe the clinical and anatomical forms of non-epithelial gastrointestinal tract cancer" 2.3.2. The target serves the second goal of the study: "Describe surgical methods and evaluate surgical treatment results of non-epithelial gastrointestinal tract cancer" 2.3.1.1. Surgical methods. - Surgical methods: probe, biopsy, biopsy combined with opening, shortening, wedge-shaped tumor resection, intestine resection (with tumor) and repeat immediate digestive circulation, rectal resection, bowel resection (with tumor) and make IHC, enlarge, transanal tumor resection. 2.3.1.2. Early post-operative result. - Patient is stable: - Complications after surgery: Bleeding, residual abscess, pleural effusion, wound infection, GI hemorrhage, gastrointestinal fistula, other complications such as early postoperative bowel obstruction, urinary infection ... were taken into account if presented. - Postoperative death: within 30 days after surgery. - Time in hospital: From surgery time to discharge. 2.3.1.3. Follow-ups. - After surgery, the patient received adjuvant treatment: chemicals, radiation therapy, targeted treatment, immunology ... - Postoperative survival time was counted from postoperative period until the patient's death (for patients who died during follow-up of the study) or the period from postoperative to the end of the study in 31 December 2019 (Patient was still alive until the end of the study follow-up of the study). - The estimated survival time and recurrence time were evaluated by Kaplan-Meier method. 2.4. Data processing methods 2.4.1. Data collection: All information on clinical symptoms, surgery methods, postoperative follow-up, were collected according to a common and unified research record. 2.4.2. Data processing: Data input, storage and analysis were conducted using SPSS 20.0 software. Duration and recurrence were estimated using the Kaplan- Meier method. CHAPTER 3 – RESULTS Throughout the study 557 cases of non-epithelial gastrointestinal cancer were operated at Viet Duc University Hospital from January 2009 to April 2019. 3.1. Clinical and subclinical characteristics 3.1.1. Age: The highest age was 88 years old, the lowest age was 3, the average age 57.1 ± 14.7. Most patients were over 50 years old, accounting for 71.6% of the study population. 3.1.2. Gender ratio: More men than women were involved, ratio: 1.13 3.1.3. The rate of non-carcinoma types in the digestive tract:
  13. 10 450 393 400 350 300 250 200 145 150 100 7 5 5 50 1 1 0 Ratio of tumor types Figure 3.2. The rate of non-epithelial gastrointestinal tumour types Comments: - Most cases were GIST tumours (70.6%), malignant lymphoma (26%). - There were no malignant schwannoma, Kaposi sarcoma, granular cell tumour, glomus tumours. 3.1.4. Location of GI tract lesions: 300 276 250 200 150 96 100 38 43 33 50 19 21 11 6 8 5 1 0 Location of GI tract injury Comments: - Occurrence were found mostly in the stomach, 176 cases (49.6%), and small intestine 24.9% (jejunum, ileum) - Only 5 cases (9%) were found in the esophagus. 3.1.5. Association between types of tumors and location of lesions in the GI tract - Lesions were mostly found in the stomach, most were GIST tumours and lymphoma, the colon was mainly associated with lymphoma. - Rarely found lesions in the esophagus (5 cases), but 3 out of 5 cases were leiomyosarcoma.
  14. 11 - Lesions found in the cecum were lymphoma, mainly GIST in the rectum. - Most melanoma occurred in the rectum, liposarcoma could be found in various organs. Other rarely seen tumours (glomus, rhabdomyo) was located in the colorectal section. 3.1.6. Gender relevance to types of tumors and location of lesions. - Men were more likely to have lymphoma and leiomyosarcoma. - GIST tumours and other types of tumors did not differ much in gender. - Occurences in the esophagus, cecum and other lower GI tract segments: male> female. 3.1.7. Relate age to the type of tumor and the location of the lesion - The widest age distribution was lymphoma and GIST (both children and adolescents), the youngest was 3 years old, the oldest was 88 years old. Average age was 57.1 years old. - Average age with tumors in the esophagus (49.4) and sigma colon (47.8) was the lowest, while the highest relating to the stomach (58.9) and rectum (58.9). 3.1.8. Associated symptoms, clinical syndrome and gastrointestinal tract site lesions - Bowel obstruction was mainly found in the small intestine and the right colon, GI hemorrhage was more common (mostly in the stomach and jejunum). - Peritonitis mainly due to damage in the small intestine. 3.1.9. Associated clinical symptoms and syndromes of various types of tumors - Abdominal pain and cancer-related symptoms were the two most common signs. - GI hemorrhage: found in lymphoma and GIST patients, of which 4/5 melanoma had this symptoms. - Peritonitis due to intestinal perforation or necrosis was more common among lymphoma cases. - Intestinal obstruction and semi-obstruction were only found in GIST and lymphoma cases. 3.1.10. Association between the reason for admission and the type of injury - Most patients were hospitalized because of abdominal pain (69%) - Followed by hemorrhage (17.4%) and palpation of the abdominal tumor (7%). - As for tumors in the esophagus, the main symptom was difficulty swallowing (80%). 3.1.11. Association between the reason of admission and lesion location in the GI tract - 37 cases were detected by chance (6.6%) 3.1.12. Association between the types of tumors, organs injury that required emergency surgery - Emergency surgery occured in 2 tumors cases, of which were lymphoma and GIST tumors. - Lesions mainly in the small intestine, not seen in the esophagus and colorectal
  15. 12 3.1.13. Related the cause of emergency surgery with the type of tumor 25 2 20 8 13 15 10 4 12 5 5 0 GIST Lymphoma VFM Intestinal Obstruction GI Hemorrhage Figure 3.5. The cause of emergency surgery is related to the type of tumor Comment: - Peritonitis due to perforation, necrosis of the intestine, intestinal obstruction was common in lymphoma cases. - Hemorrhage was common among GIST tumor patients. 3.1.14. Subclinical characteristics - 62.3% of cases detected the tumors via ultrasound. - 81.3% did CT scan, the rate of detecting tumors was relatively high (83.6%). MRI was rarely indicated, tumors mainly located in the pelvic area. - The rate of gastric tumor detection through endoscopy was 61,2% (249/407), in the rectum, colon and cecum 32,2% (66/205). - 1/4 of PET-CT scans showed no lesion. Table 3.10. Results of some indicated laboratory diagnosis Diagnosis Count (n) X ± SD Alpha FP (ng/ml) 397 3,29 ± 4,35 CEA (ng/ml) 409 2,19 ± 5,08 CA199 (U/ml) 409 15,40 ± 24,13 Comment: tumor markers were within the normal range 3.2. ANATOMY PATHOLOGY FINDINGS: - The majority of non-epithelial tumor lesions were a bulging mass that protrudes into the lumen of the intestine, the surface of the tumor was placenta, or into a mass (56.2%). - Infiltration form: was not seen in liposarcoma, rhabdomyosarcoma, melanoma and angiosarcoma. Among lymphoma cases, this rate was 25% and for GIST tumor was 14.7%. General characteristics - 48% of tumors were 5-10 cm in size,> 10 cm. 72% of tumors were GIST - The majority of lesions were a protruding tumor, the surface of the tumor had many zones or into a mass, accounting for 46.2%.
  16. 13 - Bright color tumors account for the majority of 71%, molluscum density accounts for 52%, rate of shell and boundary was 55.6%, of which GIST tumors were mainly 87%. - Lymphoma usually occured as the infiltrative type into plaque. - The role of IHC was very important, helping to diagnose and determine the origin of undifferentiated tumors, distinguish between similar lesions. Immunohistochemistry of lymphoma: - Mainly 75.3% large B-cell lymphoma. - The rate of having IHC done was not high (242/557 = 43.4%) 3.3. RESULTS OF SURGERY TREATMENT 3.3.1. Features and methods of surgery Ratio Count (n) (%) Type of surgery Opened surgery 458 82,2 Laparoscopy 99 17,8 Scheduled surgery – Emergency surgery Scheduled surgery 513 92,1 Emergency surgery 44 7,9 Methods of surgery Probe biopsy 3 0,5 Bypass anastomos 6 1,1 Ostomy surgery 21 3,8 Wedge-shaped surgery 149 26,8 Partial resection 344 61,8 Partial resection, ostomy 11 2,0 Extended resection 2 0,4 Rectum amputation 9 1,6 Transanal excision 12 2,2 Total 557 100 Comments: - Most cases were (82.8%) opened surgery, 61.8% of cases had the tumors removed and immediately restore the digestive circulation. Lymphoma is predominantly GIST - There are 9 cases (1.6%) of complicated lesions that only probe for biopsy, short connection or diagnostic nature. Related surgical procedures and organs: - The rate of gastric partial resection and wedge-shaped surgery was nearly 132/136. - In the small intestine (92.7%) most cases had partial resection and digestive circulation was restored immediately. In the colon this rate was 75.4%. - The rate of local tumors excision in the rectum and anus was the highest, 12/33 cases (36.4%), the rectum amputation rate was quite high (28.1%).
  17. 14 - Wedge-shaped surgery was most performed in the stomach. - Partial resection, ostomy (Hartmann surgery) mainly in the left colon, cecum, sigma colon. - 98% of the cases that have a wedge-shaped tumor were GIST. - 5/6 lymphoma cases had to perform non-excision bypass. - All 3 biopsy cases were GIST tumors. 3.3.2. General results and post-operative complications - The majority of patients with good results were discharged from the hospital (97.5%). - 13/15 deaths / severe cases were diagnosed lymphoma ( 7 emergency operations). Post-operative complications: - 1 case of post-operative peritonitis lymphoma and then worsen, discharged. - 5 cases of postoperative hemorrhage are all GIST. - 3 cases of gastrointestinal fistula including 1 GIST tumor and 2 lymphoma. 3.3.3. Follow-ups - The research tracked 460 cases. Average survival time: 36.9 ± 28 (months). - The longest survival was 121.1 months. - The longest follow up was 132 months, the shortest was 9 months. 35 (29,9) ≥ 5 năm 104 (31,9) 139 (30,2) 43 (36,8) ≥ 4 năm 144 (44,2) 187 (40,7) Số lượng (%) 57 (48,7) ≥ 3 năm 195 (59,8) 253 (55,0) 66 (56,4) ≥ 2 năm 248 (76,1) 319 (69,4) 87 (74,4) ≥ 1 năm 316 (96,9) 417 (90,6) 0 100 200 300 400 500 U Lympho U GIST Chung Graph 3.6. Survival time of tumour patients by year Comment: 1-year, 3-year, and 5-year postoperative survival rates for GIST tumors were higher than for lymphoma and overall non-epithelial gatrointestinal cancers.
  18. 15 Graph 3.7. Post-operative survival time of different tumour type (month) Comment: The possibility of postoperative survival of GIST tumors was highest compared to other non-epithelial gastrointestinal cancers. - The survival time was 50,7 months average. GIST and Lymphoma tumors were higher than other tumors at 53.1 months and 47.2 months, respectively. - Malignant angiosarcoma was rare but the severity of malignancy was very high, surival time after surgery was short. - The rate of patients receiving postoperative adjuvant treatment remained low (19.1%). CHAPTER 4 - DISCUSSION 4.1. Clinical characteristics 4.1.1. Demographic: The incidence rate was higher in men than in women, the highest age was 88, the minimum age was 3 and the mean age was 57 years. In the individual studies of non-epithelial gastrointestinal cancers of the GI tract, from various authors such as Chandrajit about soft organ cancer, Bui Trung Nghia about GIST, Nguyen Thanh Khiem about lymphoma, Trinh Hong Son for leiomyosarcoma or Nguyen Ngoc Hung about non-epithelial gastric cancers, the common age was commonly on 50 years old as in the time of this study. Regarding gender, according to the US statistics on soft tissue cancers, this rate was 7240 men / 5510 women (2019), this result also coincided with the rate of men more than women as in our study (296 men / 261 female). 4.1.2. The incidence of non-epithelial gastrointestinal cancers and tumour locations. Of the 557 patients with non-epithelial gastrointestinal cancers of the entire GI tract in this study, GIST and malignant lymphoma had the highest incidence of 70.6% and 26%, respectively. Lesion locations of non-epithelial gastrointestinal cancers, in the stomach accounts for the highest percentage (49.6%). Other domestic and foreign publications had many studies on a type of non-carcinoma of one; a type of non-epithelial cancer of malignant, including epithelial, non- epithelial tumors of the entire GI tract (e.g. malignant leiomyosarcoma of the GI tract including carcinoma and non-epithelial gastrointestinal cancer), or whole, non-epithelial cancers of an individual organ (eg stomach only). Our researches studied all types of non-carcinoma (malignant leiomyosarcoma, malignant lymphoma ...) of the entire organs of the digestive tract (esophagus, stomach, small intestine ...). Therefore, the findings of our study so far did not have existing data from other studies to make comparison. We would like to discuss in depth
  19. 16 the clinical, subclinical, pathological symptoms of each type of non-epithelial gastrointestinal cancer with lesion sites (organs), and vice versa of each segment of the GI tract with the types of tumour. Throughout the results tables in the study with vertical columns were the types of non-epithelial cancers (smooth muscle tumors, lymphoma, adipoma, rhabdomyoloma, melanoma, angioma and GIST) or the site of the lesion. quotient - and horizontal row were related parameter variables (clinical features, subclinical characteristics, pathology, surgical treatment results). 4.1.3. Characteristics of age, gender and location of tumors of each type of non-epithelial gastrointestinal cancer. 4.1.3.1. Liposarcoma We met 7 cases, including 3 men and 4 women, the mean age was 58 years, the youngest was 42 years old while the oldest being 74 years old, no children were found; the mean age was 61.2, the highest was 72 years old and the lowest was 56 years old. This result was consistent with other studies such as author Sawayama (2017) or Matone (2016). In terms of location, we met 5 cases in the colon, 1 case of duodenal tumors and 1 case tumors in the jejunum. Statistics in the literature on the location of malignant fatty tumors in the esophagus and stomach were very rare, from 1983 to 2016, 35 cases of primary malignant adipoma in the esophagus were reported with the first case described by Mansour, There were 29 cases of malignant stomach fat tumors reported in the literature, tumors originating under the lining of the stomach, pushing out and sticking to the wall, usually located on the small curvature of the stomach. In our study, there was no case of liposarcoma in the esophagus, stomach and rectum. 4.1.3.2. Leiomyosarcoma Among soft melanoma, smooth muscle tumors accounted for about 7%, mainly in the stomach (40%), uterus (24%) and retroperitoneal (19%), at the gastrointestinal tract where the most common The gastrointestinal tract was less common, while the esophagus, colorectal and duodenum were much rarer. In our study, out of 5 patients with malignant smooth muscle tumors of whole GI tract, there was no case in the stomach, colorectal, but 3 cases in the esophagus, 2 cases in the small intestine (1 in the jejunum and 1 in the ileum). Male patients were four times more likely to have mentioned conditions. The average age was 45 years, the highest was 75 years old and the lowest was 24 years old, of which 4 cases were in middle age, not seen in children. Leiomyosarcoma accounted for only 0.5% of all types of malignant lesions here, mainly in the middle and lower 1/3, in the middle age and more common in men, all 3 cases in the study were male, with tumour location starting from 1/3 middle esophagus to the lower segment and mostly in the middle age (34, 36 and 56 years old). Smooth muscle tumors in the stomach accounted for about 50% of the entire gastrointestinal smooth muscle tumors of which 75% were benign tumors. Although we had quite a few benign smooth muscle tumors, there were no malignancies of the stomach segment. In the small intestine, smooth muscle tumors here were more often malignant. According to a study published in the World Journal of Cancer Surgery 2005, small bowel cancer accounted for 2% of all cancers of the gastrointestinal tract, locating mainly in the jejunum, less in the ileum and duodenum. Another study included 26 cases, with 7 cases being in the duodenum, 6 cases in the jejunum and 6 other cases locating in the ileum, matched with the ratio of 1: 1 as in our results. Colorectal and anal canal were very rare, we did not have any cases in our study; as reported by Evans for many years of malignant smooth muscle tumor in the rectum with 56 cases in 10 years with 4 cases,
  20. 17 Randleman with 22 cases in 35 years and Walsh reported 48 cases in 31 years. Particularly in the anal canal, it was very rare with only 9 cases described in the literature, of which the first case was discovered in 1977 by Wolfson and Oh. 4.1.3.3. Malignant Melanoma In the study, all 5 patients were diagnosed with primary melanoma in the GI tract and were ordered for surgery. All 5 patients were over 60 years old. The average age was 70, the proportions of males and females were 60% and 40% respectively. In our study, the most common sites were the rectum, stomach, duodenum and small intestine. Moore DW (1857) described the first clinical case of melanoma in the anal rectum, accounting for 0.5% of malignant lesions here, but it is the 3rd most common place of postcutaneous melanoma. and eyes, moreover, are the most common locations in the OTH. The patients in our study are similar to those reported by other authors around the world as well as by author Huynh Ngoc Linh reporting a 72-year-old male with primary malignant melanoma on the spot. colon (2007). In 5 patients in this study, there was 1 case of injury in the stomach, duodenum and small intestine, invading the gallbladder, the patient was also an elderly male (73 years old). This is the first case reported in Vietnam by primary melanoma in the stomach, duodenum, and small intestine. 4.1.3.4. Rhabdomyosarcoma In the world there are a number of articles reporting single malignant rhabdomyolysis cases of GI tract such as author Asahi Sato on duodenal tumors, Aceves with tumors in the colon ... However, at the time of the study we had not seen any reports in Vietnam about this type of tumor in the gastrointestinal tract. In our 557 study we only had 1 case, an 83-year-old male patient with a 15 cm large tumor in the left colon, this was a very rare case, such as location in the duodenum until 2014 only 3 cases of rhabdomyolysis (not in the shadow of Vater) were reported, most recently the authors Asahi Sato et al (Japan) published in Surgical Today (2014). 4.1.3.5. Angiosarcoma In our study, there was 1 case of a 57-year-old male patient with definitive diagnosis of malignant hemangioma of the rectal wall. This type of lesion is particularly rare in OTH, but if it is often present in the stomach and small intestine, the tumor can develop from the blood vessels or lymphatic vessels, the prognosis is very poor, where the recurrence often occurs. Regional and lung lymph nodes followed by liver and spleen. About the age of the patient is nearly 60 years old as reported by other authors around the world, in Vietnam we have not seen any reports of malignant hemangioma in the rectum. 4.1.3.6. Malignant Lymphoma According to the authors at Saint-Louis Hospital (Paris), at the lesion sites on the body, lymphoma in the gastrointestinal tract accounted for 50%, in which the stomach is the largest followed by the jejunum. According to Pinire, this rate in the stomach is the highest from 60-75%, followed by the small intestine, the ileum and rectum respectively. This result is similar to our study with 52/145 (35.8%) cases in the stomach and 40/145 cases in the small intestine (27.6% of which the ileum accounts for 13.1%). , cecum 19/145 (13.1%) and colon 23/145 (15.9%), had 3 cases in rectum, 4 cases in duodenum, not seen in esophagus, lower than in stomach of Author Anusha ST with the corresponding rates of stomach, small intestine, cecum and many locations is 74.8%, 8.6%, 7% and 6.5%. This result is similar to Pinire Theo A. Wotherspoon et al. the same proportion of men and women, the mean age is 50
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