Granulocyte-colony Stimulating Factor Producing Research Articles

Leukocytosis Associated with Esophageal Squamous Cell Carcinoma as a Predictor of Poor Prognosis - A Case Report and Review of Literature

Leukocytosis, specifically granulocytosis in malignancy is a common finding with various etiologies. Graulocytosis associated with esophageal cancer has not commonly been reported in case reports in the United States. Furthermore, granulocyte colony stimulating factor (G-CSF) producing tumors have been associated with a variety of cancers. However, G-CSF producing esophageal tumors are rare. The diagnosis is established through serum G-CSF levels and immunohistochemistry staining of tumor cells. Here, we report a case of a 72-year-old woman with persistent granulocytosis leading to the diagnosis of esophageal squamous cell carcinoma (ESCC). Although, our case did not report serum G-CSF levels, we strongly suspect it to be the underlying etiology in our case. Additionally, through our missed opportunity, we hope to emphasize and increase awareness of G-CSF producing ESCC.

Granulocyte-Colony Stimulating Factor Producing Extrahepatic Bile Duct Carcinoma: A Case Report

Granulocyte-colony stimulating factor (G-CSF) producing tumors are rare diseases and occur in various organs. However, due to the rarity of these tumors, the precise biologic characteristics and optimal therapeutic strategies are largely unknown. Previous studies have shown the extremely high malignant potential and aggressive clinical features of G-CSF producing tumors, regardless of the histologic type and tumor location. We present the case of a 59-year-old female who had large tumor in extrahepatic bile duct. She underwent surgery and adjuvant chemotherapy. Then, she also received gemcitabine and cisplatin combination chemotherapy for metastatic lesions. The therapy showed a certain effect and she survived for 17 months after surgery. To the best of our knowledge, this is the first report of multidisciplinary treatment with surgery and systemic chemotherapy for G-CSF producing extrahepatic bile duct cancer. This study highlights the potential of multidisciplinary treatment even for this lethal disease condition.

Characteristic EUS and FDG-PET features of G-CSF Producing Esophageal Squamous Cell Carcinoma: A Case Report and Review of the Literature

Purpose: Tumors producing granulocyte colony stimulating factor (G-CSF) are quite rare, and features of clinical examinations are not well known. Particularly in G-CSF producing esophageal tumors, only a few reports are available concerning EUS and FDG-PET features. Methods: We present a case of G-CSF producing esophageal squamous cell carcinoma showing interesting features of EUS and FDG-PET imaging findings, and changes of clinical examinations with a treatment course were analyzed. Results: A 58-year-old Japanese man had type I esophageal cancer with marked lymph node metastases associated with leukocytosis and elevated serum G-CSF, IL-6, CRP, and SCC. Repeated biopsy showed poorly differentiated squamous cell carcinoma, not carcinosarcoma. Although the primary lesion was negative for G-CSF by immunohistochemistry, a highly increased G-CSF m-RNA level, measured using reverse transcriptase-polymerase chain reaction in frozen sections, led to a diagnosis of GCSF-producing esohageal cancer. Before treatment, esophagoscopy showed 5 cm tumor with a steep slope in the middle thoracic esophagus, and EUS showed a low echoic mass with the mixture of a high echoic area in the 1st∼3rd layer. Contrary to the tumor size, the depth of tumor invasion was relatively shallow, T1 (SM with massive invasionor), or T2 (MP with slight invasion). FDG-PET scanning showed a significantly high uptake in the main tumor, abdominal lymph nodes and the bones. Uptake in the bone was symmetrically found in the red pulp throughout the body. This patient was diagnosed as stage 4 esophageal squamous cell carcinoma and received 1st line chemotherapy with 5-FU and cisplatin. This regimen led to progressive disease and worse performance status. He selected another chemotherapy, not best supportive care, and 2nd line treatment with irrinotecan monotherapy enabled partial response during five months. He died 10 months after the 2nd line chemotherapy with irrinotecan due to the progression of tumors. Throughout the treatment course, FDG uptake in the bone changed along with the change of the leukocytes, serum G-CSF, IL-6, CRP and SCC. Conclusion: When detecting esophageal tumor with a steep slope, serum G-CSF, IL-6, and CRP must be checked in consideration of G-CSF producing cancer. EUS and FDG-PET attribute to the diagnosis. Irrinotecan monotherapy can be one of the effective regimens for non-operable G-CSF producing esophageal cancer.

血液系腫よう随伴症候群を伴った上顎へん平上皮癌例

We report a case of maxillary cancer that caused a marked systemic inflammatory reaction including leukocytosis and high blood levels of C-reactive protein. The production of Granulocyte-colony stimulating factor (G-CSF) by tumor cells was demonstrated by immunohistochemical staining. Despite the reported poor prognosis of G-CSF producing tumors, chemoradiotherapy was highly effective and all of the inflammatory indexes settled to within normal limits. The patient is under close follow-up and has been in complete remission for eleven months after the completion of chemoradiotherapy.

Ｇ‐ＣＳＦ産生上顎癌例

A 64-year-old man with well-differentiated squamous cell carcinoma of the maxilla who presented with high levels of granulocyte-colony stimulating factor (G-CSF) is described. The extent of the tumor was staged as T4N1M0. Regional chemotherapy, radiotherapy and resection of the tumor were performed. The patient died of local recurrence and lung metastasis about four months after admission. During his clinical course, a peripheral blood analysis demonstrated marked granulocytosis and high G-CSF activity. G-CSF producing cancer cells were immunohistologically observed in the primary lesion and metastatic lymph nodes. Therefore, he was diagnosed with G-CSF producing maxillary cancer. The cancer tissue from this patient was transplanted into nude mice, and one of these mice demonstrated distant metastasis to the lung.

Granulocyte Colony-Stimulating Factor Produced by Bladder Carcinoma of a Patient with Leukemoid Reaction did not Affect Proliferation of the Tumor Cells

Bladder carcinoma associated with leukemoid reaction, though it rarely occurs, is considered highly malignant and has proved to produce granulocyte colony-stimulating factor (G-CSF). Interest exists in whether G-CSF itself or G-CSF producing ability reflects the malignant potential of such a tumor, possibly through an autocrine mechanism. In a patient with invasive bladder carcinoma, we found that the tumor cells produced G-CSF responsible for a remarkable leucocytosis. However, we could not detect the rearrangement and amplification of the G-CSF gene nor the expression of G-CSF receptor in the tumor cells. Our immunohistological and molecular biological study failed to demonstrate a crucial role for G-CSF in mediating a growth advantage for the tumor.

Intraclonal diversity of fibrosarcoma cells for the production of macrophage colony‐stimulating factor and granulocyte colony‐stimulating factor

A new cell line was established from fibrosarcoma that had spontaneously developed in a mouse. The cells were maintained growing in culture for two years and constantly produced both macrophage colony-stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF). Cloning of the cells by anchorage-independent colony formation gave subclones showing the activity of producing M-CSF and G-CSF in different proportions, whereas no subclone produced G-CSF without producing M-CSF simultaneously. Recloning of the bipotential subclones again gave clonal derivatives producing two types of CSF in various proportions. The observed heterogeneity of the cloned cells seems to be an epigenetic phenomenon, because the cells resumed the G-CSF producing activity in the absence of cell proliferation. After equilibrium was achieved, all of the subclones produced both M-CSF and G-CSF nearly in equal proportions. Tumorigenic and leukocytosis-inducing activity of the cloned cells was nearly comparable with the activity of the original tumor cells.