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Biomedical subjects

P M Chen

Publications and source records attributed to P M Chen.

At least 19 recordsLinked to original sources

Calcium binding protein containing neurons in the gliotic mouse hippocampus with special reference to their afferents from the medial septum and the entorhinal cortex.

In CA1 area and the hilus of the dentate gyrus of the mouse hippocampus, drastic reduction of NeuN, calbindin, calretinin, or parvalbumin immunopositive neurons was shown at 3, 7 and 60 days after pilocarpine-induced status epilepticus. In gliotic CA1 area at 60 days, few dendritic branches of calcium binding protein immunopositive neurons could be found suggesting reorganization of the afferents of surviving calcium binding protein immunopositive neurons. Calbindin, calretinin, or parvalbumin and 5-bromo-2'-deoxyuridine (BrdU) double labeling showed that calcium binding protein immunopositive neurons in gliotic CA1 area at 60 days were surviving instead of newly generated neurons. Iontophoretic injection of Phaseolus vulgaris leucoagglutinin into the medial septum and the nucleus of the diagonal band of Broca or the lateral entorhinal cortex showed contacts between Phaseolus vulgaris leucoagglutinin immunopositive en passant and terminal boutons and surviving calcium binding protein immunopositive neurons in the hippocampus. The presence in the gliotic hippocampus of enlarged and/or aggregated bouton-like structures 60 days after pilocarpine-induced status epilepticus is indicative for the reorganization of connections between the hippocampal afferents and surviving hippocampal neurons. This reconstruction could be a factor in the ongoing epileptic activity in this model of mesial temporal lobe epilepsy.

Afferent Pathways↗

Colorectal carcinoma: from tumorigenesis to treatment.

Colorectal carcinoma (CRC) is a complicated and often fatal genetic disease. Fortunately, owing to rapid expansion of knowledge and technology development in oncology, much progress has been made regarding the diagnosis, understanding of the molecular genetics and malignant progression, as well as the novel regimens of CRC. In this review, we summarize the staging system, the most critical genetic and epigenetic alterations, the pleiotropic effects of MMP-7, the controversial roles of Hedgehog signaling, the intriguing involvement of thymosin beta-4, and the possible contribution of the putative colon (cancer) stem cells in CRC tumorigenesis. Current treatments as well as several potentially applicable therapeutic strategies for CRC are also discussed.

Animals↗

The economic impact of incorporating flexible endoscopy into a community general surgery practice.

BACKGROUND: Flexible endoscopy is a vital component of gastrointestinal surgery. It has and will replace many of the surgical procedures now commonly performed. Flexible endoscopy, unfortunately, is not an integral part of surgical residency training based on resident operative experience as reported by the Residency Review Committee. Moreover, general surgeons have deferred the practice of flexible endoscopy to the gastroenterologists because of concerns over turf battles and referral patterns. The purpose of this study was to assess the overall case load and the economic impact of flexible endoscopy on the practice of general surgery in a community hospital setting. METHODS: This retrospective review was performed over a 6-month period. The total cases and the total billings of inpatient and outpatient procedures for a group practice of five general surgeons in a community hospital were evaluated. The billings were the actual charges based on current procedural terminology (CPT) codes for these procedures using the Medicare fee schedule. RESULTS: Of the 2,159 procedures performed, 1,154 involved flexible endoscopy cases accounting for 54% of all cases (1,154 of 2,159) performed from February 1, 2003 to July 31, 2003. Flexible endocopy accounted for 43% of the total charges. A. total of 46 surgical procedures and 216 future endoscopies were generated from the flexible endoscopic procedures. Future endoscopic cases were for surveillance of colonic neoplasia and Barrett's esophagus. CONCLUSIONS: Flexible endoscopy contributed to a major portion of the caseload and revenue generated by the general surgery group studied. The overall impact of flexible endoscopy is even greater than reported because of the future endoscopic surveillance cases or surgical interventions generated on the basis of endoscopic findings.

Ambulatory Surgical Procedures↗

Relatively favorable outcomes of post-transplant pulmonary function in patients with chronic myeloid leukemia receiving non-myeloablative allogeneic hematopoietic stem cell transplantation.

Pulmonary function tests were performed in 20 patients with chronic myeloid leukemia before and after human leukocyte antigen-matched allogeneic sibling hematopoietic stem cell transplantation (HSCT) to identify any conditioning treatment effects on post-transplant function from January 1995 to December 2002. Of 20 patients, eight received non-myeloablative conditioning treatment and 12 received conventional myeloablative conditioning treatment. Pulmonary function tests including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and diffusion capacity for carbon monoxide (DLCO) were performed pretransplant, 6 and 12 months post-transplant. Possible pre-HSCT and post-HSCT risk factors were evaluated for association with pulmonary function. The results showed that myeloablative conditioning treatment had greater negative impact on FEV1, FVC, and DLCO than non-myeloablative conditioning therapy. We conclude that non-myeloablative allogeneic HSCT may apply a better transplant choice in patients who need special concern with post-transplant pulmonary function changes.

Adult↗

Hematopoietic stem cell transplantation for severe aplastic anemia--experience of an institute in Taiwan.

Hematopoietic stem cell transplantation (HSCT) is an accepted treatment strategy for patients with severe aplastic anemia (SAA). We report our experience in a general hospital in Taiwan. From March 1985 to July 2001, 79 consecutive SAA patients, 46 male and 33 female, with a median age of 22 (4-43) years, received 80 courses of transplantation. Cyclophosphamide and total body radiation were used for the conditioning regimen, and cyclosporine-A and methotrexate for graft-versus-host disease (GVHD) prevention. Patients were followed for a median of 39 months (from 8 days to 194 months). Myeloid and platelet engraftment occurred in a median of 15 (8-27) days and 18 (8-77) days, respectively. Three patients had primary and three patients secondary graft failure. Five patients (6.8%) had grade II-IV acute GVHD in 73 evaluable patients. Chronic GVHD occurred in 23 (34.8%) patients, with extensive stage in six. Only two patients had CMV disease. The projected 3- and 5-year overall survival rates estimated by the Kaplan-Meier method were 76.08 and 74.13%, respectively. Age at transplant, non-sibling donor, mononuclear cell dose, grade II-IV acute GVHD, interval from diagnosis to transplant, and red blood cell and platelet transfusion before transplant were poor prognostic factors for overall survival by univariate analysis. Grade II-IV acute GVHD was the only prognostic factor affecting overall survival after multivariate Cox regression analysis (P=0.040). In conclusion, SAA patients receiving HSCT have good long-term survival. The low incidence of acute GVHD in our patients may be related to ethnicity.

Adolescent↗

Comparative genomic hybridization of esophageal squamous cell carcinoma: correlations between chromosomal aberrations and disease progression/prognosis.

BACKGROUND: Esophageal carcinoma is a major cause of cancer-related deaths among males in Taiwan. However, to date, the genetic alterations that accompany this lethal disease are not understood. METHODS: Chromosomal aberrations of 46 samples of esophageal squamous cell carcinoma (EC-SCC) were analyzed by comparative genomic hybridization (CGH), and their correlations with pathologic staging and prognosis were analyzed statistically. RESULTS: In total, 321 gains and 252 losses were found in 46 tumor samples; thus, the average gains and losses per patient were 6.98 and 5.47, respectively. Frequent gain abnormalities were found on chromosome arms 1q, 2q, 3q, 5p, 7p, 7q, 8q, 11q, 12p, 12q, 14q, 17q, 20q, and Xq. Frequent deletions were found on chromosome arms 1p, 3p, 4p, 5q, 8p, 9p, 9q, 11q, 13q, 16p, 17p, 18q, 19p, and 19q. It was found that deletions of 4p and 13q12-q14 and gain of 5p were significantly correlated with pathologic staging. Losses of 8p22-pter and 9p also were found more frequently in patients with advanced disease. Gain of 8q24-qter was seen more frequently in patients with Grade 3 tumors. A univariate analysis found that pathologic staging; gains of 5p and 7q; and deletions of 4p, 9p, and 11q were significant prognostic factors. However, pathologic staging became the only significant factor in a multivariate analysis. CONCLUSIONS: CGH not only revealed novel chromosomal aberrations in EC-SCC, but also found possible genotypic changes associated with disease progression. Despite all of the possible associations of chromosomal aberrations with disease progression, the most important prognostic factor for patients with EC-SCC was pathologic staging.

Adult↗

Carcinoembryonic antigen in monitoring of response to systemic chemotherapy in patients with metastatic colorectal cancer.

The response to chemotherapy of solid tumors is generally assessed by measuring tumors visualized by imaging. However, the response assessment based on imaging is not always feasible because patients often have disease not measurable by imaging, such as diffuse peritoneal dissemination. We evaluated the correlation between the change on imaging and change in CEA levels for assessing chemotherapeutic response of patients with metastatic colorectal cancer. Between July 1993 and August 1999 we retrospectively examined 136 patients with metastatic colorectal carcinoma, all of whom had measurable lesions. Forty patients received oral tegafur-uracil (300 mg/m2/day) plus folinic acid (60 mg/day) for 4 weeks, repeated every 5 weeks, as the firstline treatment. Another 96 patients received either a weekly intravenous bolus injection of 5-fluorouracil (400 mg/m2) plus folinic acid (20 mg/m2), or an intravenous bolus injection of 5-fluorouracil (425 mg/m2) plus folinic acid (20 mg/m2) for 5 consecutive days every month. Responders, based on CEA assessment, were defined as those with a greater than 50% drop in CEA level for more than 4 weeks. The pretreatment CEA levels were elevated beyond the normal cutoff value in 110 (81%) patients. A response rate of 18.4% (95% CI, 11.9-24.9%), including 8 complete remissions and 17 partial remissions, was achieved according to imaging studies. The response rate assessed by CEA was 25% (34/136). Sixteen responders (47%) based on CEA had no remission on imaging. The sensitivity of change in CEA levels in the prediction of true responders and progressive diseases on imaging were 72% and 81%, respectively. In terms of the positive predictive value, change in CEA levels in the prediction of true responders and progressive disease on imaging were 53% and 85%, respectively. Patients with remarkable falls on CEA levels survived significantly longer than nonresponders (P < 0.001, log-rank test). At follow-up of 48 months the median survival for responders and nonresponders assessed by CEA was 28 months and 13 months, respectively. These data suggest that measurement of CEA levels might be helpful in monitoring chemotherapeutic response when imaging study is unsuitable for assessing the response in clinical practice. Furthermore, measurement of CEA levels may be helpful in determining the prognosis of patients with metastatic colorectal cancer receiving chemotherapy.

Adult↗

Tamoxifen and colchicine-modulated vinblastine followed by 5-fluorouracil in advanced renal cell carcinoma: a phase II study.

OBJECTIVES: Chemotherapy resistance of renal cell carcinoma (RCC) has been attributed in large part to multidrug resistance (MDR). Reported MDR-modulated chemotherapy for RCC, however, has resulted in only marginal response benefits. In this study, the MDR-modulated effect of paired tamoxifen and colchicine on vinblastine and the possible additive effect of 5-fluorouracil (5-FU) were investigated in the treatment of advanced RCC. METHODS: Chemotherapy was administered every 4 weeks with biweekly vinblastine (4 mg/m(2)/day, intravenously on days 1 and 15) modulated by oral tamoxifen (100 mg/day) and colchicine (1 mg/day) from days -1 to 2 and from days 13 to 16. 5-FU (800 mg/m(2)/day from days 2 to 5) was administered after vinblastine administration as a continuous infusion. RESULTS: Of 17 eligible patients with advanced RCC available for evaluation, 1 achieved a complete response (CR) and 3 a partial response (PR), with an overall response (CR plus PR) rate of 23.5%. The median overall survival time of all patients was 10 months (95% confidence interval [CI] 3.5 to 16.5); that of our patients with poor, intermediate, and favorable risks as stratified by Motzer's model was 6 (95% CI 1.7 to 10.3), 10 (95% CI 7.9 to 12.2), and 26 (95% CI 24.4 to 27.6) months, respectively. These results are encouraging in view of the poor efficacy of chemotherapy in RCC observed previously. Additionally, the treatment toxicity was limited: toxicity of grade 3 or greater occurred in only 1 patient with leukopenia, and no treatment-related mortality was found. CONCLUSIONS: The encouraging response rates and overall survival with limited toxicity warrant further investigation of this combination therapy as an integrated part of immunochemotherapy for RCC.

Adult↗

Relapse of Graves' disease after successful allogeneic bone marrow transplantation.

As shown in many reports, allogeneic BMT can help cure autoimmune diseases. Conversely, we present a 24-year-old woman with Graves' disease, which was diagnosed just before BMT for CML. The Graves' disease remitted immediately after BMT but relapsed 18 months later. Since the donor was free from thyroid diseases and the patient showed a rapid shift to complete donor chimerism after BMT, the autoimmune problem seemed neither to arise directly from the donor nor simply from the recipient's residual lymphocytes. On the contrary, it was most likely compounded by chronic GVHD as suggested by the accompanying GVHD symptoms and the absolute donor karyotype in bone marrow cells. A Graves' disease-susceptible HLA allele was also shared between recipient and donor, possibly enhancing the chances of this condition developing. Thus, allogeneic BMT may facilitate relapses in autoimmune diseases as well as alleviating them.

Adult↗

Complete atrio-ventricular block as a major clinical presentation of the primary cardiac lymphoma: a case report.

It is uncommon for malignant lymphomas to present primarily with cardiac invasion as the main clinical feature. What we are interested in is not only where the disease is, but also those symptoms that it may induce. Sudden onset of complete atrio-ventricular block is one of the most common clinical presentations. Cardiac tamponade is another common disease entity which, if it locates over outlets of great vessels, may also exert symptoms of obstructive vessels. Diagnosis can be made by needle aspiration under the guidance of transcutaneous or transesophageal echocardiography. Both CT scan and MRI play positive roles in the diagnosis of cardiac lymphomas, and the latter can even provide much more image information than the former. We report a 70-year-old male with primary cardiac lymphoma with initial clinical pictures of sudden onset of complete atrio-ventricular block. Chemotherapy was utilized with cyclophosphamide, vincristine and prednisolone (COP) initially for four courses and followed by adding doxorubicin (CHOP) for another three courses. The patient was still in remission status after treatment for 2 years.

Aged↗

Salvage therapy with single-agent paclitaxel by three-hour infusion in metastatic breast cancer: an experience in Taipei Veterans General Hospital.

BACKGROUND: Paclitaxel is an active agent in the treatment of breast, ovarian, lung and head and neck cancers. In previous phase I and II trials, it exerted novel cytotoxic effect on several malignancies. Various doses and regimens of paclitaxel have been assessed in metastatic breast cancer, with responses between 20 and 62%. However, combination therapy with other anti-cancer drugs leads to a high incidence of side effects. Our aim was to evaluate the efficacy of paclitaxel given by 3 h infusion as salvage chemotherapy for patients with metastatic breast cancer. METHODS: Between May 1999 and April 2000, 14 women with metastatic breast cancer were enrolled in this study and all the patients had to have measurable lesions. The median age of the patients was 48.7 years (range 39-56 years). All of them were definitely evidenced as having metastatic breast cancer and received complete courses of anthracycline-containing agents before applying paclitaxel. The protocol was single-agent paclitaxel (Anzatax, Faulding, Australia) at a moderate dosage of 175 mg/m(2) by 3 h intravenous infusion every 3 weeks. RESULTS: A total of 75 cycles were administered to these 14 patients with a median of four delivered cycles (range 3-14) and the response rate was 28.6% (95% CI: 21-40%), including four partial remission, three stable disease and seven progressive disease. The median time to progression was 3 (range 3-7) months. Hematological toxicities were minimal with no evidence of severe (grade 3 or 4) leukopenia and thrombocytopenia. Hepatic toxicities were observed in 12 cycles with five in grade 3. CONCLUSIONS: Our study indicates that utilizing single-agent paclitaxel exerts moderate activity on anthracycline-refractory metastatic breast cancer patients without excessive toxicities.

Adult↗

Chronic hepatitis C virus infection associated with primary warm-type autoimmune hemolytic anemia.

Autoimmune hematologic abnormalities are not well recognized in chronic hepatitis C virus infection. We demonstrate an unusual association between primary autoimmune hemolytic anemia and chronic hepatitis C virus infection. A 69-year-old woman who had a history of hepatitis C virus-related liver cirrhosis was found to have deteriorating anemia with reticulocytosis when admitted to the hospital. Laboratory work revealed both positive direct and indirect Coombs' tests, and warm-type immunoglobulin G against surface antigens of red blood cells. After prednisolone therapy, her anemia improved dramatically. To our knowledge, this is the first reported case of chronic hepatitis C virus infection linked with autoimmune hemolytic anemia in its natural course, not related to prior interferon treatment. Our report suggests that isolated autoimmune hemolytic anemia may be one of the unusual hematologic manifestations of chronic hepatitis C virus infection.

Aged↗

Molecular analysis of mucosa-associated lymphoid tissue (MALT) lymphoma of ocular adnexa.

Lymphomas of mucosa-associated lymphoid tissue (MALT) are a distinct subgroup of extranodal B-cell non-Hodgkin's lymphomas. Most studies have failed to demonstrate the clonal rearrangement of BCL-1, BCL-2 or c-MYC genes for MALT lymphomas. Further, alteration of the p53 gene is rarely demonstrated in low-grade MALT lymphomas, but can be detected in high-grade disease. Lymphomas of the ocular adnexa represent approximately eight percent of all extranodal lymphomas, most of which are MALT lymphomas, but few studies had explored the alterations of BCL-1, BCL-2, c-MYC and p53 genes specifically for ocular MALT lymphomas. We investigated the changes to BCL-1, BCL-2, c-MYC and p53 genes in these lymphomas for Taiwanese patients. Clonal rearrangement for immunoglobulin heavy-chain (IgH), BCL-1, BCL-2, c-MYC and p53 genes was examined for 16 cases of ocular MALT lymphoma. Restriction-length polymorphism and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) of the DNA, corresponding to exons 5 through 9, followed by DNA sequencing, were utilized to analyze the possible mutations of the p53 gene for these tumors. Thirteen of the cases revealed rearranged IgH genes using Southern blotting or PCR. No rearrangement of BCL-1, BCL-2, c-MYC or p53 genes was discovered, with point mutation of the p53 gene in one case. As for other types of MALT lymphomas, BCL-1, BCL-2 and c-MYC genes are not implicated in the pathogenesis of the ocular sub-group. Although alteration of the p53 gene is rare for low-grade ocular MALT lymphoma, its role in disease progression merits further research.

Adolescent↗

Protection against ischemic injury in primary cultured mouse astrocytes by bis(7)-tacrine, a novel acetylcholinesterase inhibitor [corrected].

The effects of bis(7)-tacrine, a novel acetylcholinesterase inhibitor, on ischemia-induced cell death and apoptosis were investigated in primary cerebral cortical astrocytes of mice. Following a 6 h in vitro ischemic incubation of the cultures, a marked decrease in the percentage of viable cells was observed by lactate dehydrogenase (LDH) release assay. Furthermore, using bisbenzimide staining, we determined that approximately 65% of the cells underwent apoptosis. Treatment with bis(7)-tacrine (1-10 nM) during ischemic incubation effectively inhibited the ischemia-induced apoptosis, as demonstrated by morphological and biochemical tests. Our results demonstrated that bis(7)-tacrine could protect astrocytes against ischemia-induced cell injury, indicating that the drug might be beneficial for the treatment of vascular dementia, in addition to Alzheimer's disease.

Alzheimer Disease↗

Lack of mutations of BCL6 and BCL10 genes in mucosa-associated lymphoid tissue lymphomas of the orbital adnexa.

Knowledge regarding the molecular pathogenesis and progression of mucosa-associated lymphoid tissue (MALT) lymphomas of ocular adnexa is limited. Eleven cases of ocular MALT lymphoma were analyzed by clonal rearrangement of antigen receptor genes using Southern blot hybridization. Polymerase chain reaction-single stranded conformational polymorphism analysis and DNA sequencing was utilized to analyze the mutations of BCL6 and BCL10 genes. Clonal rearrangement of immunoglobulin heavy genes was found in all 11 patients. No point mutation was found in BCL6 or BCL10 genes in any of the samples analyzed. We suggest that mutations of BCL6 and BCL10 genes are rare in low-grade MALT lymphoma of ocular adnexa and are unlikely to be involved in the pathogenesis of the disease. But the role of alterations of both BCL6 and BCL10 genes in the disease progression of low-grade MALT lymphoma require additional study.

Adaptor Proteins, Signal Transducing↗

Vaginal obliteration after total body irradiation and chemotherapy as treatment for acute myeloid leukemia.

Although radiotherapy is an integral part in the management of certain types of hematological malignancies, its effect on the reproductive system has been well documented. We report a rare complication where a patient had complete vaginal obliteration after receiving a dose of total body irradiation (1575 cGy) as part of her treatment for acute myeloid leukemia. A 37-year-old married woman, G3P2, underwent high-dose cyclophosphamide accompanied by high dose (1575 cGy) total body irradiation (TBI) as part of her treatment for acute myeloid leukemia (AML: m1) when she was 35 years of age. After TBI, the patient developed ovarian failure and amenorrhea, which was confirmed by hormonal evaluation. Nevertheless, she did not receive any hormonal replacement therapy and stopped her sexual life for two years. Fortunately, no recurrence of AML was noted. The patient visited our clinic due to difficulty in performing coitus. Physical examination showed a 2-cm short and blinded vaginal pouch. She initially received hormonal replacement therapy followed by surgical correction via vaginoplasty and two months of dilatory replacement and frequent coitus with satisfactory result. To our limited knowledge, vaginal obliteration as a complication of condition regimen has never been reported before. In the present case report, it is unclear whether spontaneous vaginal obliteration resulted from chemotherapy, total body irradiation, or another unknown cause such as a concomitant leukemic infiltration of the vaginal wall, severe bacterial and fungal infection before treatment, or from any combination of the above. However, due to this case presentation, we suggest that such patients must receive hormonal replacement therapy and be encouraged to have a normal sexual life to avoid this possible problem.

Adult↗

Preoperative carcinoembryonic antigen level as an independent prognostic factor in colorectal cancer: Taiwan experience.

BACKGROUND: Preoperative carcinoembryonic antigen (CEA) level is considered as a factor predictive of survival in colorectal cancer patients. Patients with normal (<5 ng/ml) or lower preoperative CEA levels were reported to have significantly longer survival. This study was carried out in an effort to evaluate the prognostic significance of preoperative CEA levels of patients with colorectal cancer in Taiwan. METHODS: Between 1990 and 1994, 218 patients with histologically confirmed colorectal cancers were evaluated retrospectively at the Veterans General Hospital-Taipei. All the patients had undergone potentially curative surgery. Patients with metastatic diseases were not included. 5-Fluorouracil-based adjuvant chemotherapy was administered if the patients had Dukes' C disease. Reference to the Dukes' classification was according to the classical criteria described in 1932 for carcinoma of the rectum and adapted for use in colonic tumors. Data on gender, age, degree of tumor differentiation, location of the tumor, tumor size, lymph node metastasis, penetration of the bowel wall and preoperative CEA levels were analyzed to determine their association with survival. Blood samples for CEA measurement were taken a few days before operation and were analyzed using the radioimmunoassay method. Multivariate analysis by Cox's proportional hazards regression model was performed to determine the most important predictors of survival among all of the possible variables. RESULTS: By univariate analysis, the size of the tumor (p = 0.012), lymph node metastases (p = 0.007), penetration of the bowel wall (p < 0.001) and preoperative CEA levels (p < 0.001) were found to be significant prognostic factors, while gender, age, degree of tumor differentiation and location of the tumor were not significant. By multivariate Cox analysis, lymph node metastases (p = 0.003), penetration of the bowel wall (p = 0.0001) and preoperative CEA levels (p = 0.0001) were found to be independent prognostic factors in colorectal cancer patients. CONCLUSIONS: The data from our study indicate that in addition to lymph node metastases and penetration of the bowel wall, the preoperative CEA levels are also an independent prognostic factor in non-metastatic colorectal cancer patients after curative surgery. This could serve as an appropriate modification to the initial Dukes' scheme in colorectal cancer.

Adenocarcinoma↗

Venous gangrene in a patient with adenocarcinoma of the lung.

Cancer-related thromboembolism is a severe but not uncommon paraneoplastic syndrome in mucinous cancer patients. However, cancer-induced venous gangrene is extremely rare and has never been reported in the English literature. Here, we present a case of lung cancer complicated with venous gangrene of the left foot. An elevated serum anticardiolipin level was detected during hospitalization, but the patient's clinical condition stabilized after heparinization. We suggest that in cancer patients, an elevated serum anticardiolipin antibody level might be a warning sign of an impending thrombotic event and that low-molecular-weight heparin is a sensible choice in treating this kind of cancer-related thromboembolism.

Adenocarcinoma↗