A Phase II study of palonosetron, aprepitant, dexamethasone and olanzapine for the prevention of cisplatin-based chemotherapy-induced nausea and vomiting in patients with thoracic malignancy.

BACKGROUND: The three-drug combination of a 5-hydroxytryptamine type 3 receptor antagonist, a neurokinin 1 receptor antagonist and dexamethasone is recommended for patients receiving highly emetogenic chemotherapy. However, standard antiemetic therapy is not completely effective in all patients. METHODS: We conducted an open-label, single-center, single-arm Phase II study to evaluate the efficacy of olanzapine in combination with standard antiemetic therapy in preventing chemotherapy-induced nausea and vomiting in patients with thoracic malignancy receiving their first cycle of cisplatin-based chemotherapy. Patients received 5 mg oral olanzapine on Days 1-5 in combination with standard antiemetic therapy. The primary endpoint was complete response (no vomiting and no use of rescue therapy) during the overall Phase (0-120 h post-chemotherapy). RESULTS: Twenty-three men and seven women were enrolled between May and October 2015. The median age was 64 years (range: 36-75 years). The most common chemotherapy regimen was 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed, which was administered to 14 patients. Complete response rates in acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy) and overall phases were 100%, 83% and 83% (90% confidence interval: 70-92%; 95% confidence interval: 66-93%), respectively. There were no Grade 3 or Grade 4 adverse events. Although four patients (13%) experienced Grade 1 somnolence, no patients discontinued olanzapine. CONCLUSIONS: The addition of 5 mg oral olanzapine to standard antiemetic therapy demonstrates promising efficacy in preventing cisplatin-based chemotherapy-induced nausea and vomiting and an acceptable safety profile in patients with thoracic malignancy.

[A case of hemorrhagic cholecystitis associated with Churg-Strauss syndrome].

A woman in her 70s with Churg-Strauss syndrome presented with epigastric pain. She was being treated with steroids at the time of admission. Computed tomography showed swelling of the gallbladder, and percutaneous transhepatic cholangiography revealed bloody secretion. On duodenoscopy, bleeding was observed from the orifice of the major duodenal papilla. Emergency cholecystectomy was performed under a diagnosis of hemorrhagic cholecystitis;intraoperatively, extensive hematoma was detected in the thickened wall of the gallbladder. Subsequent histopathological examination revealed mucosal ulceration with infiltration of inflammatory cells, torn small vessels, and extensive transmural bleeding and abscess formation in the thickened wall of the gallbladder. We considered that the hemorrhagic cholecystitis was induced by either vasculitis or corticosteroid therapy. To the best of our knowledge, this is the first report of hemorrhagic cholecystitis associated with Churg-Strauss syndrome.

Organ Correlation in IgG4-Related Diseases.

IgG4-related disease (IgG4-RD) is a potentially multiorgan disorder. In this study, clinical and serological features from 132 IgG4-RD patients were compared about organ correlations. Underlying pathologies comprised autoimmune pancreatitis (AIP) in 85 cases, IgG4-related sclerosing cholangitis (IgG4-SC) in 12, IgG4-related sialadenitis (IgG4-SIA) in 56, IgG4-related dacryoadenitis (IgG4-DAC) in 38, IgG4-related lymphadenopathy (IgG4-LYM) in 20, IgG4-related retroperitoneal fibrosis (IgG4-RF) in 19, IgG4-related kidney disease (IgG4-KD) in 6, IgG4-related pseudotumor (IgG4-PT) in 3. Sixty-five patients (49%) had multiple IgG4-RD (two affected organs in 36 patients, three in 19, four in 8, five in 1, and six in 1). Serum IgG4 levels were significantly higher with multiple lesions than with a single lesion (P<0.001). The proportion of association with other IgG4-RD was 42% in AIP, the lowest of all IgG4-RDs. Serum IgG4 level was lower in AIP than in other IgG4-RDs. Frequently associated IgG4-RDs were SIA (25%) and DAC (12%) for AIP; AIP (75%) for IgG4-SC; DAC (57%), AIP (38%) and LYM (27%) for IgG4-SIA; AIP (26%) and LYM (26%) for IgG4-DAC; SIA (75%), DAC (50%) and AIP (45%) for IgG4-LYM; SIA (58%), AIP (42%) and LYM (32%) for IgG4-RF; AIP (100%) and SIA (67%) for IgG4-KID; and DAC (67%) and SIA (67%) for IgG4-PT. Most associated IgG4-RD lesions were diagnosed simultaneously, but IgG4-SIA and IgG4-DAC were sometimes identified before other lesions. About half of IgG4-RD patients had multiple IgG4-RD lesions, and some associations were seen between specific organs.

Clinical features of IgG4-related dacryoadenitis.

BACKGROUND: To elucidate the clinical characteristics of IgG4-related dacryoadenitis. METHODS: Clinical features, laboratory findings, radiological findings, associated diseases, treatment, and prognosis were prospectively examined in 12 patients (seven men, five women; mean age, 60.9 ± 15.1 years) with IgG4-related dacryoadenitis. RESULTS: In addition to eyelid swelling, other ophthalmologic symptoms were observed in seven patients, including diplopia (n = 4), ptosis (n = 2), visual field disturbance (n = 2), eye pain (n = 2), decrease of visual acuity (n = 2), eye-movement disturbance (n = 1), dry eye (n = 1), corneal ulcer (n = 1), and epiphora (n = 1). Swelling of the lacrimal glands was bilateral in half of the patients. Other IgG4-related diseases were present in nine patients, including sialadenitis (n = 5), autoimmune pancreatitis (n = 4), retroperitoneal fibrosis (n = 2), and lymphadenopathy (n = 8). Serum IgG4 levels were significantly higher in patients with other IgG4-related disease (1070 ± 813 mg/dl) than in those without (197 ± 59 mg/dl, p = 0.017). Allergic histories and elevated serum IgE levels were each detected in six patients. Eight patients showed inflammatory extension beyond the lacrimal gland, such as thickened rectus muscle (n = 6), inflammation of the optic nerve (n = 2), and retrobulbar inflammation (n = 3). Steroid therapy was effective in seven patients, but dacryoadenitis relapsed in two patients with markedly higher serum IgG4 levels and autoimmune pancreatitis. CONCLUSIONS: IgG4-related dacryoadenitis showed various ophthalmologic symptoms due to extensive inflammation beyond the lacrimal gland, frequent association with other IgG4-related disease or allergic phenomena, and steroid responsiveness.

Intraductal papillary mucinous neoplasm of the pancreas and IgG4-related disease: a coincidental association.

BACKGROUND/AIMS: Coexistence of autoimmune pancreatitis (AIP) and pancreatic cancer, elevation of serum IgG4 levels in pancreatic cancer patients, and infiltration of IgG4-positive plasma cells in peritumorous pancreatitis have been described in a few reports. This study examined the relationship between intraductal papillary mucinous neoplasm (IPMN) of the pancreas and peritumorous IgG4-positive lymphoplasmacytic infiltrates. METHODS: Serum IgG4 levels were measured in 54 patients with IPMN (median 70 years, 26 males and 28 females; 13 main duct type and 41 branch duct type). Histological findings focusing on dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis were reviewed, and immunostaining with IgG4 and IgG was performed in 23 surgically resected IPMN cases (18 main duct type and 5 branch duct type). The presence of IgG4-positive plasma cells >10/hpf and an IgG4-positive/IgG-positive plasma cell ratio >40% were considered significant. RESULTS: Serum IgG4 levels were elevated in 2 (4%) IPMN patients. Significant infiltration of IgG4-positive plasma cells was detected in 4 IPMN cases (17%). The IgG4-positive/IgG-positive plasma cell ratio was >40% in all 4 cases. In one case with a markedly elevated serum IgG4 level (624 mg/dL), typical lymphoplasmacytic sclerosing pancreatitis (AIP type 1) lesions surrounded the whole IPMN. In the 3 other cases, infiltration of IgG4-positive plasma cells with fibrosis was focally detected mainly in the periductal area around the IPMN. CONCLUSIONS: In a few patients with IPMNs, IgG4-positive plasma cell infiltration can occur in the peritumorous area. The association of an IPMN with AIP type 1-like changes seems to be exceptional and coincidental.

[A successfully treated case of type 4 gastric cancer with intraperitoneal free cancer cells undergoing a curative resection followed by neoadjuvant chemotherapy with S-1 plus cisplatin].

A 41-year-old female complained of epigastric pain and was referred to our hospital. Gastrofiberscopy revealed that type 4 gastric cancer located at the whole gastric body. Although abdominal computed tomography showed that no distant metastasis but regional lymph node metastasis existed, staging laparoscopy and cytological diagnosis revealed that there were intraperitoneal free cancer cells without overt peritoneal metastasis(P0CY1). She received neoadjuvant chemotherapy with S-1 plus cisplatin for consecutive 21 days followed by 7 days of rest as a course. After 3 courses of the chemotherapy, intraperitoneal free cancer cells were not found, and she underwent curative gastrectomy. Pathological examination showed that the therapeutic effect was Grade 2. S-1 as postoperative chemotherapy had been prescribed for 10 months without relapse. However, she suffered from anorexia and abdominal distension and peritoneal metastasis was confirmed on the 575th day after curative operation. She has received a weekly paclitaxel therapy as second-line chemotherapy.

Clinical characteristics of autoimmune pancreatitis with IgG4 related kidney disease.

PURPOSE: To clarify the clinical characteristics of autoimmune pancreatitis (AIP) in immunoglobulin (Ig)G4-related kidney disease (IgG4-RKD). PATIENTS AND METHODS: A total of 92 patients with AIP were divided into an IgG4-RKD-positive group (RKD-P group, n = 13) and an IgG4-RKD-negative group (RKD-N group, n = 79) on the basis of the diagnostic criteria for IgG4-RKD. Clinical characteristics, including: age; sex; the presence of extrapancreatic lesions other than renal lesions, proteinuria, and hematuria; serum concentrations of IgG, IgG4, IgE, and creatinine; and urinary concentrations of liver-type fatty acid binding protein, α1-microglobulin, ß2-microglobulin, and N-acetyl-ß-d-glucosaminidase were compared between the RKD-P and RKD-N groups. The clinical course of the RKD-P group was also characterized. RESULTS: The prevalence of extrapancreatic lesions other than renal lesions was significantly higher in the RKD-P group (84.6% vs 43.0%,p < 0.01). Serum creatinine (1.19 mg/dl versus 0.74 mg/dl, p < 0.05), urinary ß2-microglobulin (6609.8 µg/l vs 265.8 µg/l, p < 0.05), and the prevalence of proteinuria (30.7% vs 7.6%, p < 0.05) were significantly higher in the RKD-P group. Nine out of thirteen patients in the RKD-P group had multiple low-density renal lesions on enhanced computed tomography, 3 patients had multiple high-intensity lesions on diffusion-weighted magnetic resonance images, and 1 patient had diffuse thickening of the renal wall, with a smooth intra-luminal surface. CONCLUSIONS: Patients who had AIP with IgG4-RKD were more likely to have extrapancreatic lesions other than those in the kidney, and their serum creatinine and urinary ß2-microglobulin concentrations were significantly higher than in those without IgG4-RKD.

Hypothyroidism in patients with autoimmune pancreatitis.

AIM: To examine thyroid function and clinical features of hypothyroidism in autoimmune pancreatitis (AIP) patients. METHODS: We examined thyroid function in 77 patients with type 1 AIP (50 males, 27 females; median age 68 years, range 33-85) diagnosed according to the Japanese diagnostic criteria for AIP 2011. We compared clinical and serological findings between patients with and without various categories of hypothyroidism. The change in hypothyroidism after steroid therapy was also examined. RESULTS: Eight patients (10%) had hypothyroidism of 6 patients had subclinical hypothyroidism with a normal serum free thyroxine (FT4) and high thyroid stimulating hormone (TSH) level, and 2 patients had central hypothyroidism with low serum free triiodothyronine (FT3), FT4 and TSH levels. A significant goiter of the thyroid was not observed in any patient. There were no significant differences in age; male to female ratio; serum concentrations of IgG and IgG4-related disease (IgG4-RD); presence of anti-thyroglobulin antibody, antinuclear antigen or rheumatoid factor; or presence of extrapancreatic lesions between the 6 patients with subclinical hypothyroidism and patients with euthyroidism. After steroid therapy, both subclinical and central hypothyroidism improved with improvement of the AIP. CONCLUSION: Hypothyroidism was observed in 8 (10%) of 77 AIP patients and was subclinical in 6 patients and central in 2 patients. Further studies are necessary to clarify whether this subclinical hypothyroidism is another manifestation of IgG4-RD.

Biliary carcinogenesis in pancreaticobiliary maljunction.

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall. Because of the excessive length of the common channel in PBM, sphincter action does not directly affect the pancreaticobiliary junction, which allows pancreatic juice to reflux into the biliary tract. According to the results of a nationwide survey, bile duct and gallbladder cancers were found in 6.9 and 13.4 % of adult patients with congenital biliary dilatation, respectively, and in 3.1 and 37.4 % of those with PBM without biliary dilatation, respectively. Biliary tract cancers develop about 15-20 years earlier in patients with PBM than in individuals without PBM; they sometimes develop as double cancers. Carcinogenesis is strongly associated with stasis of bile intermingled with refluxed pancreatic juice. Epithelial cells in the biliary tract of PBM patients are under constant attack from activated pancreatic enzymes, increased secondary bile acids, or other mutagens. This can result in hyperplastic change with increased cell proliferation activity, and in turn, oncogene and/or tumor suppressor gene mutations in the epithelia, leading to the biliary tract carcinogenesis. The carcinogenesis of biliary tract cancer accompanying PBM is considered to involve a hyperplasia-dysplasia-carcinoma sequence induced by chronic inflammation caused by the reflux of pancreatic juice into the biliary tract, which differs from the adenoma-carcinoma sequence or the de novo carcinogenesis associated with biliary tract cancers in the population without PBM. Patients with a relatively long common channel have a similar, albeit slightly lower, risk for gallbladder cancer compared with PBM patients.

A case of pancreaticobiliary maljunction with a connecting duct without a long common channel.

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall, usually forming an abnormally long common channel. In PBM, since the long common channel defeats the effect of the sphincter of Oddi, pancreatobiliary reflux frequently occurs, resulting in high rates of biliary tract cancers. We present the case of a 68-year-old female with advanced gallbladder cancer concomitant with bile duct cancer associated with PBM without biliary dilatation that had an extremely rare configuration showing a connecting duct without a long common channel. Pancreatography in the selectively cannulated main pancreatic duct showed the terminal portion of the common bile duct via an abnormal connecting duct. Cholangiography in the selectively cannulated lower bile duct showed the main and accessory pancreatic ducts via the connecting duct. The bile amylase level was markedly elevated. This case of a rare configuration of PBM with a connecting duct without a long common channel is the first such reported case in the English literature.

Clinical features of IgG4-related rhinosinusitis.

PURPOSE: IgG4-related disease is a systemic disease that affects various organs of the body. Aim of this study is to elucidate the clinical characteristics of IgG4-related rhinosinusitis. MATERIAL AND METHODS: Clinical features, laboratory findings, radiological and endoscopic findings, associated disease, treatment and prognosis were retrospectively examined in 10 patients with IgG4-related rhinosinusitis. RESULTS: The age was 59.1±11.3 years old and male-to-female ratio was 1:1. The chief nasal complaints were hyposmia (n=4), nasal obstruction (n=3), and nothing (n=3). Serum IgG4 levels were elevated in all patients and the value was 740.4±472.4mg/dl. Other IgG4-related diseases were associated in all 10 patients, including IgG4-related sialadenitis (n=6), IgG4-related dacryoadenitis (n=5), and autoimmune pancreatitis (n=5). Imaging findings on CT/MRI were obstruction of the way of elimination (n=10), thickening of the sinus mucous membrane (n=10), and fluid in the sinus (n=6). All of the cases had bilateral findings. Nasal endoscopic findings were chiefly deviated nasal septum (n=5), polyps (n=4), edema of the mucous membrane (n=3). Histologically, abundant infiltration of IgG4 positive plasma cell and lymphocyte and an elevated IgG4+/IgG+ cell ration was detected in all 8 patients and 5 patients, respectively. Endoscopic sinus surgery was performed in 8 patients. Eight patients were treated with steroid therapy for other associated IgG4-related diseases. Symptoms improved in all 6 patients after an initial treatment (endoscopic surgery (n=5) and steroids (n=1)), but one patient suffered relapse. CONCLUSIONS: IgG4-related rhinosinusitis is a distinct entity of IgG4-related disease, and is associated in patients with multiple IgG4-related diseases.

A case of annular pancreas with Wirsung's duct encircling the duodenum: embryological hypothesis based on cholangiopancreatographic and immunohistochemical findings.

We present a resected case of annular pancreas in which Wirsung's duct encircled the duodenum and continued directly to the main pancreatic duct in the body and tail. Furthermore, Wirsung's duct coursed along the right side of the lower bile duct near the major duodenal papilla. Histologically, the islets of Langerhans in the annular pancreas were irregular in shape and were characterized by a striking abundance of pancreatic polypeptide (PP)-positive cells. The PP-rich area that encircled the duodenum was fused with the PP-poor area in the head of the pancreas. The following embryological hypothesis is proposed. The tip of the ventral pancreatic anlage adhered to the duodenal wall and stretched to form a ring during clockwise rotation. The rotation was incomplete, and the pancreatic duct did not cross over the lower bile duct. Since there was adequate ventral anlage in the lower part of the head of the pancreas, fusion between the ducts of the ventral and dorsal anlagen did not occur. The tip of the ventral anlage overgrew and adhered to the dorsal anlage, and the annular duct fused with the main duct of the dorsal anlage.

Assessment in steroid trial for IgG4-related sclerosing cholangitis.

PURPOSE: Response to steroids is included in the diagnostic criteria for IgG4-related sclerosing cholangitis (IgG4-SC). To assess how to appropriately conduct steroid trials for IgG4-related SC, we examined the clinical pictures of steroid responsiveness in IgG4-SC patients. MATERIAL AND METHODS: A total of 29 patients with IgG4-SC (lower bile duct involvement, n=29; hilar/intrahepatic bile duct involvement, n=6) initially treated with steroids were enrolled in this study. Blood biochemistry was examined at about 5, 10 and 15 days after commencing steroid therapy. Endoscopic retrograde cholangiography (ERC) and magnetic resonance cholangiopancreatography (MRCP) were performed after steroid administration in 18 and 25 patients, respectively. RESULTS: In 19 patients without biliary drainage, elevated serum levels of total bilirubin, alanine aminotransferase, and alkaline phosphatase were halved in 50%, 25%, and 44% of patients at about 5 days after starting steroids, and in 17%, 38%, and 44% at about 10 days. Responsiveness to steroids could be evaluated at 1-2 weeks on ERC or MRCP, but response was lower in the hilar/intrahepatic bile duct than in the lower bile duct. CONCLUSIONS: Steroid responsiveness of IgG4-SC is recommended to be assessed by blood biochemistry at 5 and 10 days and on MRCP and/or ERC at 1-2 weeks after starting steroid.

Characteristic findings of endoscopic retrograde cholangiopancreatography in autoimmune pancreatitis.

BACKGROUND/AIMS: Diffuse or segmental irregular narrowing of the main pancreatic duct (MPD), as observed by endoscopic retrograde cholangiopancreatography (ERCP), is a characteristic feature of autoimmune pancreatitis (AIP). METHODS: ERCP findings were retrospectively examined in 40 patients with AIP in whom irregular narrowing of the MPD was detected near the orifice. The MPD opening sign was defined as the MPD within 1.5 cm from the orifice being maintained. The distal common bile duct (CBD) sign was defined as the distal CBD within 1.5 cm from the orifice being maintained. Endoscopic findings of a swollen major papilla and histological findings of specimens obtained from the major papilla were examined in 26 and 21 patients, respectively. RESULTS: The MPD opening sign was detected in 26 of the 40 patients (65%). The distal CBD sign was detected in 25 of the 32 patients (78%), which showed stenosis of the lower bile duct. The patients who showed the MPD opening sign frequently showed the distal CBD sign (p=0.018). Lymphoplasmacytic infiltration, but not dense fibrosis, was histologically detected in biopsy specimens obtained from the major papilla. CONCLUSIONS: On ERCP, the MPD and CBD adjacent to the major papilla are frequently maintained in patients with AIP involving the pancreatic head. These signs are useful for diagnosing AIP on ERCP. (Gut Liver 2015;9113-117).

Pancreaticobiliary maljunction and biliary cancer.

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall. Japanese clinical practice guidelines on how to deal with PBM were made in 2012, representing a world first. According to the 2013 revision to the diagnostic criteria for PBM, in addition to direct cholangiography, diagnosis can be made by magnetic resonance cholangiopancreatography (MRCP), 3-dimensional drip infusion cholangiography computed tomography, endoscopic ultrasonography (US), or multiplanar reconstruction images by multidetector row computed tomography. In PBM, the common channel is so long that sphincter action does not affect the pancreaticobiliary junction, and pancreatic juice frequently refluxes into the biliary tract. Persistence of refluxed pancreatic juice injures epithelium of the biliary tract and promotes cancer development, resulting in higher rates of carcinogenesis in the biliary tract. In a nationwide survey, biliary cancer was detected in 21.6% of adult patients with congenital biliary dilatation (bile duct cancer, 32.1% vs. gallbladder cancer, 62.3%) and in 42.4% of PBM patients without biliary dilatation (bile duct cancer, 7.3% vs. gallbladder cancer, 88.1%). Pathophysiological conditions due to pancreatobiliary reflux occur in patients with high confluence of pancreaticobiliary ducts, a common channel ≥6 mm long, and occlusion of communication during contraction of the sphincter. Once the diagnosis of PBM is established, immediate prophylactic surgery is recommended. However, the surgical strategy for PBM without biliary dilatation remains controversial. To detect PBM without biliary dilatation early, MRCP is recommended for patients showing gallbladder wall thickening on screening US under suspicion of PBM.

Major and minor duodenal papillae in autoimmune pancreatitis.

OBJECTIVE: The objective of this study was to evaluate picture of the major and minor duodenal papillae in patients with autoimmune pancreatitis (AIP). METHODS: Endoscopic features of the major and minor papillae were examined in 59 and 13 patients with AIP. After steroid therapy, changes of the major and minor papillae were observed in 5 and 6 patients. The major and minor papillae were observed with narrow band imaging in 24 and 6 patients. Biopsy specimens from the major (n = 50) and minor (n = 13) papillae were immunostained using an anti-IgG4 antibody. RESULTS: Endoscopic features of the major and minor papillae were abnormal in 26 patients (44%; swelling [n = 20] and redness [n = 14]) and 5 patients (38%; swelling [n = 5]). Swelling of the pancreatic head, irregular narrowing of the main pancreatic duct of the pancreatic head, stenosis of the lower bile duct, and abundant infiltration of IgG4-positive plasma cells were more frequent in the patients with an abnormal major papilla compared with those with a normal major papilla. On narrow band imaging, dilated vessels were observed in abnormal papillae. After therapy, swelling of the major and minor papillae improved in all 4 and 2 patients. CONCLUSIONS: Endoscopic features of the major and minor papillae were abnormal in 44% and 38% of the patients with AIP.

Allergen-specific IgE antibody serologic assays in patients with autoimmune pancreatitis.

OBJECTIVE: To clarify the allergic manifestations in patients with autoimmune pancreatitis (AIP). METHODS: We assessed 67 AIP patients, before they received steroid therapy, for a past history of allergic disease, the peripheral eosinophil count (n=62) and the serum IgE level (n=53). Allergen-specific IgE antibody serologic assays were performed in 15 patients. RESULTS: A positive past history and/or the presence of active allergic disease were found in 24 AIP patients (36%), including 15 patients with acute allergic rhinitis and eight patients with bronchial asthma. Peripheral eosinophilia and elevation of the serum IgE level were detected in 16% (10/62) and 60% (32/53) of the patients, respectively. Allergen-specific IgE antibody serologic assays were positive in 13 patients (87%). There were no differences between the assay-positive and -negative patients regarding the clinical profiles. CONCLUSION: In conclusion, 87% of the 15 AIP patients tested had positive allergen-specific IgE antibody serologic assays. Allergic mechanisms may be related to the occurrence of AIP.

Immunoglobulin G4-related gastrointestinal diseases, are they immunoglobulin G4-related diseases?

In immunoglobulin G4 (IgG4)-related disease (RD), organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis are seen in various organs. Although infiltration of many IgG4-positive plasma cells is detected in the gastric and colonic mucosa and major duodenal papilla of patients with autoimmune pancreatitis, it cannot be diagnosed as a gastrointestinal lesion involved in IgG4-RD, because none of the following is observed in these lesions: a mass-like formation; dense fibrosis; or obliterative phlebitis. Based on our review of the literature, there appear to be two types of IgG4-related gastrointestinal disease. One is a gastrointestinal lesion showing marked thickening of the wall of the esophagus and stomach, consisting of dense fibrosis with abundant infiltration of IgG4-positive plasma cells, which usually show submucosal spreading. The other is an IgG4-related pseudotumor occurring in gastrointestinal regions such as the stomach, colon, and major duodenal papilla, showing polypoid or mass-like lesions. Most solitary IgG4-related gastrointestinal lesions that are not associated with other IgG4-RD appear to be difficult to diagnose. It is of utmost importance to rule out malignancy. However, these lesions may respond to steroid therapy. To avoid unnecessary resection, IgG4-related gastrointestinal diseases should be considered in the differential diagnosis.

Clinical features of 10 patients with IgG4-related retroperitoneal fibrosis.

OBJECTIVE: To elucidate the clinical characteristics of IgG4-related retroperitoneal fibrosis (RF). METHODS: IgG4-related RF was diagnosed when all of the following three criteria were fulfilled: retroperitoneal soft tissue masses surrounding the aorta and/or adjacent tissues, elevation of the serum IgG4 levels, and abundant infiltration of IgG4-positive plasma cells in at least one organ or site. Ten patients were diagnosed as having IgG4-related RF. RESULTS: The mean age at diagnosis was 70.1 years, and the male-to-female ratio was 1:0.6. Only two patients had initial symptoms predominantly related to RF (back pain and edema of the lower extremities), while the remaining eight patients reported initial symptoms due to associated diseases. On laboratory examination, a severe inflammatory reaction was observed in one patient. Elevation of the levels of serum IgG and IgE, eosinophilia and positivity of antinuclear antibodies were detected in seven, five, two and seven patients, respectively. The retroperitoneal masses were detected primarily in the left renal hilus in four patients, in the periaortic region in five patients and in both regions in one patient. Hydronephrosis was present in five patients. The histological diagnosis was confirmed in the retroperitoneal masses (resection, n=1 biopsy, n=2) and extraretroperitoneal lesions (n=7). Twenty-four other IgG4-related diseases were found to be associated with IgG4-related RF in nine patients (autoimmune pancreatitis (n=2), sialadenitis (n=4), dacryoadenitis (n=5), lymphadenopathy (n=9), pulmonary pseudotumor (n=1) and pituitary pseudotumor (n=1)). Seven patients underwent steroid therapy, all of whom responded well and showed no instances relapse. CONCLUSION: IgG4-related RF has several clinical characteristic features. Our diagnostic criteria may be helpful in obtaining a correct diagnosis.