Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

IgG4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4+ plasma cells Although IgG4-RD is not rare and is clinically important, its clinical diagnostic criteria have not been established Comprehensive diagnostic criteria for IgG4-RD, including the involvement of various organs, are intended for the practical use of general physicians and nonspecialists Two IgG4-RD study groups, the Umehara and Okazaki teams, were organized by the Ministry of Health, Labor and Welfare Japan As IgG4-RD comprises a wide variety of diseases, these groups consist of physicians and researchers in various disciplines, including rheumatology, hematology, gastroenterology, nephrology, pulmonology, ophthalmology, odontology, pathology, statistics, and basic and molecular immunology throughout Japan, with 66 and 56 members of the Umehara and Okazaki teams, respectively Collaborations of the two study groups involved detailed analyses of clinical symptoms, laboratory results, and biopsy specimens of patients with IgG4-RD, resulting in the establishment of comprehensive diagnostic criteria for IgG4-RD Although many patients with IgG4-RD have lesions in several organs, either synchronously or metachronously, and the pathological features of each organ differ, consensus has been reached on two diagnostic criteria for IgG4RD: (1) serum IgG4 concentration >135 mg/dl, and (2) >40% of IgG+ plasma cells being IgG4+ and >10 cells/high powered field of biopsy sample Although the comprehensive diagnostic criteria are not sufficiently sensitive for the diagnosis of type 1 IgG4-related autoimmune pancreatitis (IgG4-related AIP), they are adequately sensitive for IgG4-related Mikulicz’s disease (MD) and kidney disease (KD) In addition, the comprehensive diagnostic criteria, combined with organ-specific diagnostic criteria, have increased the sensitivity of diagnosis to 100% for IgG4-related MD, KD, and AIP Our comprehensive diagnostic criteria for IgG4-RD are practically useful for general physicians and nonspecialists

Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011

Autoimmune pancreatitis (AIP) is occasionally associated with other autoimmune diseases. To investigate the pathophysiology of AIP, we immunohistochemically examined the pancreas and other organs in eight patients with AIP, and in controls, using anti-CD4-T and CD8-T cell subsets, as well as IgG4 antibodies. In AIP patients, severe or moderate infiltration of IgG4-positive plasma cells associated with CD4- or CD8-positive T lymphocytes was detected in the peripancreatic tissue (6/6), bile duct (8/8), gallbladder (8/8), portal area of the liver (3/3), gastric mucosa (5/7), colonic mucosa (2/2), salivary glands (1/2), lymph nodes (6/6), and bone marrow (2/2), as well as in the pancreas (8/8). There were few IgG4-positive plasma cells at the same sites in controls. These results suggest that AIP is not simply pancreatitis but that it is a pancreatic lesion involved in IgG4-related systemic disease with extensive organ involvement. We propose a new clinicopathological entity, of a systemic IgG4-related autoimmune disease in which AIP and its associated diseases might be involved.

A new clinicopathological entity of IgG4-related autoimmune disease

Although IgG4-related disease (IgG4-RD) is a novel and important disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells, its clinical diagnostic criteria have not been fully established. Many patients with IgG4-RD have lesions in multiple organs, either synchronously or metachronously, and the pathological features of each organ differ. We established comprehensive diagnostic criteria for IgG4-RD for the practical use of specialists and nonspecialists.

Comprehensive Diagnostic Criteria for IgG4-Related Disease

https://www.nejm.org/doi/pdf/10.1056/NEJMra1104650

IgG4-related disease

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(02)08359-9.pdf

Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis

Herein, we encountered an 89-year-old woman with pancreatic cancer who presented with fever without infective focus, leukocytosis of 45,860 /μL, and elevation of serum granulocyte-colony stimulating factor (G-CSF). The patient could not receive any curative therapy due to an extremely aggressive clinical course. Specimens taken at necropsy revealed an adenosquamous carcinoma positive for G-CSF by immunohistochemistry; it was only the second reported case to date. She was finally diagnosed with G-CSF-producing pancreatic cancer. In light of the above, clinicians should consider the presence of G-CSF-producing tumors, including pancreatic cancer, when presented with patients showing leukocytosis of unknown origin and fever without infective focus.

Granulocyte-Colony Stimulating Factor-Producing Pancreatic Adenosquamous Carcinoma Showing Aggressive Clinical Course

A 58-year-old man developed polyneuropathy, or-ganomegaly, gynecomastia, skin pigmentation, and multiple myeloma (IgG-Λ type). Although transient clinical improvement was obtained with prednisolone and cyclophosphamide, his general condition deteriorated progressively, and he died 3 years after onset. Lymph nodes showed angiofollicular hyperplasia, and the sural nerve revealed segmental demyellnation. At autopsy, the glomeruli were enlarged and showed mild mesangial cell proliferation with segmental mesangiolysis and proliferation of endothellal cells forming abnormal vessels. The massive volume of ascites contained a high level of inter-leukin-6 (IL-6). IL-6, a multifunctlonal cytokine, may be the pathogenic factor which induces the various clinical symptoms and pathological features of Crow-Fukase (POEMS) syndrome. Acta Pathol Jpn 42: 651–656,1992.

An autopsy case of Crow-Fukase (POEMS) syndrome with a high level of IL-6 in the ascites. Special reference to glomerular lesions.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840130205

Ultrastructural studies of hepatocyte cytoskeletons of phalloidin-treated rats by quick-freezing and deep-etching method.

Granulocyte-colony stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation and maturation of precursor cells in the bone marrow into fully differentiated neutrophils. Several reports of G-CSF-producing malignant tumors have been published, but scarcely any in the hepatobiliary system, such as in hepatocellular carcinoma (HCC). Here, we encountered a 69-yr-old man with a hepatic tumor who had received right hepatic resection. He showed leukocytosis of 25,450/µL along with elevated serum G-CSF. Histological examination of surgical samples demonstrated immunohistochemical staining for G-CSF, but not for G-CSF receptor. The patient survived without recurrence for four years, but ultimately passed away with multiple bone metastases. In light of the above, clinicians may consider G-CSF-producing HCC when encountering patients with leukocytosis and a hepatic tumor. More cases are needed to clarify the clinical picture of G-CSF-producing HCC.

/pdf/a-case-of-granulocyte-colony-stimulating-factor-producing-1oh6c7lrec.pdf

Koh Nakazawa

Papers

Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis

Granulocyte-Colony Stimulating Factor-Producing Pancreatic Adenosquamous Carcinoma Showing Aggressive Clinical Course

An autopsy case of Crow-Fukase (POEMS) syndrome with a high level of IL-6 in the ascites. Special reference to glomerular lesions.

Ultrastructural studies of hepatocyte cytoskeletons of phalloidin-treated rats by quick-freezing and deep-etching method.

A Case of Granulocyte-Colony Stimulating Factor-Producing Hepatocellular Carcinoma Confirmed by Immunohistochemistry