Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders.

OBJECTIVE: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). METHODS: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models. RESULTS: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens. CONCLUSION: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset.

A Case of Acute Kidney Injury Caused by Myoglobin Cast Nephropathy With Sars-Cov-2 Infection in a Living-Donor Kidney Transplant Recipient.

When COVID-19 affects patients with risk factors such as chronic kidney disease or on immunosuppressive drugs, they often rapidly become seriously ill. We describe a 50-year-old man who was affected with SARS-CoV-2 and had undergone an ABO-compatible living-donor kidney transplantation from his father 14 years ago because of end-stage renal failure due to hypertensive nephrosclerosis. He had continued on immunosuppressive drugs and completed vaccination twice (9 months ago and 6 months ago) with messenger RNA (mRNA) vaccines against SARS-CoV-2. However, he was temporarily on a mechanical ventilator due to respiratory failure and hemodialysis due to acute kidney injury (AKI). He was finally weaned from the ventilator and hemodialysis by taking steroid and antiviral drugs. Echo-guided renal biopsy revealed myoglobin cast nephropathy. We experienced 14 outpatients after living-donor kidney transplantation infected with SARS-CoV-2, but only this case developed AKI.

[A Case of Primary Adenocarcinoma of the Duodenal Bulb with Laparoscopic Distal Gastrectomy].

A 66-year-old male presented with a torose lesion at the duodenal bulb, detected via endogastroduodenoscopy(EGD) during a medical check-up. It was histopathologically diagnosed as a low-grade adenoma. He was referred to the Department of Gastroenterology for follow-up observation. An endoscopic mucosal resection(EMR)was performed due to the increasing tumor size. The pathological findings of the resected specimen showed a tubular adenoma. The patient was then followed up as an outpatient. Two months later, a follow-up EGD revealed a mass lesion, suspected to be a remnant tumor. A laparoscopic distal gastrectomy, #3, #4sb, #5, #6 dissection, and Billroth Ⅱ+Braun anastomosis reconstruction were performed. Pathological examination showed a tubular adenocarcinoma in adenoma, tub1, with depth M, and no lymph node metastasis. Non-papillary duodenal carcinoma is a rare disease that has no established guidelines for radical surgery and the extent of lymph node dissection. Pancreaticoduodenectomy is often performed in advanced cases. However, due to the increasing number of patients and the risk of complications, limited resection should be considered as an alternative management option.

[A Case of IgG4-Related Disease Arising in Female Periurethra].

A 67-year-old female, with a past medical history of IgG4-related Mikulicz disease, was referred to our department for a periurethral mass revealed by contrast-enhanced computed tomography. She presented with weak urine flow a half year before the first consultation. Magnetic resonance imaging (MRI) revealed a periurethral mass, 39×39×29 mm, extending from the bladder neck to the urethral meatus. Serum IgG4 level was elevated to 580 mg/dl. Histological examination by the transvasinal biopsy revealed a lymphocytic infiltrate with IgG4-positive plasmacytoid predominance, leading to the diagnosis of IgG4-related disease arising in the periurethra. She was treated with prednisolone for 4 months, and urinary disturbance disappeared. MRI showed that the periurethral mass decreased in size.

[Laparoscopic Surgical Treatment of Differentiated Intramucosal Gastric Cancer with Lymph Node Metastasis-A Case Report].

A 78‒year‒old man was admitted to our hospital with the chief complaint of 5 kg weight loss in 6 months. An esophagogastroduodenoscopy revealed a 0‒Ⅱa lesion in the posterior wall of the antrum, and biopsy findings showed a well‒differentiated adenocarcinoma. Endoscopic ultrasonography did not show an obvious invasion of the submucosal layer. Contrast‒ enhanced abdominal computed tomography(CT)revealed an enlargement of the #11p lymph node to approximately 30 mm, and positron emission tomography(PET)‒CT showed an accumulation in the same lymph node. Since no other apparent distant metastases were observed, laparoscopic distal gastrectomy and D2 dissection were performed. The postoperative pathological diagnosis was L, 7×8 mm, 0‒Ⅱa, tub1, pT1a, ly0, v0, pPM0(73 mm), pDM0(35 mm), N2, and pStage ⅡA. We report this case because the successful laparoscopic resection of a differentiated gastric mucosal cancer with lymph node metastasis has been considered to be extremely rare.

[A Case of Long-Term Survival after Multidisciplinary Treatment for Neuroendocrine Carcinoma of the Anal Canal].

A 75-year-old man presented to a local clinic with anal pain, and a palpable anal tumor on was found on digital examination of the rectum. A biopsy led to the diagnosis of neuroendocrine carcinoma. Besides the anal tumor, an right-inguinal lymph node was revealed on computed tomography(CT). Positron emission tomography-CT showed abnormal uptake in the 2 regions. He was diagnosed with lymph node metastases from anal canal carcinoma, and an abdominoperineal resection was performed. The resected specimen included the anal canal tumor with a size of 27×18 mm in diameter. On immunohistochemistry, the anal canal tumor was strongly positive for synaptophysin and positive for chromogranin A, with a Ki- 67 positivity index of 70%. After the surgery, he was administered chemotherapy with 4 courses of cisplatin and CPT-11. One year after the surgery, CT revealed lymph node recurrence. Therefore, cisplatin and CPT-11 therapy was repeated. After 11 courses of the cisplatin and CPT-11 treatment, tumor regrowth was still detected. The treatment protocol was changed to an amrubicin monotherapy regimen. However, the patient's general condition worsened after the therapies, and he died 38 months after the surgery.

[A Case of Long-Term Survival after Chemotherapy for Gastric Cancer with Peritoneal Dissemination].

The patient was a 58-year-old man who had undergone wide gastrectomy for gastric ulcer at 22 years of age. Endoscopic examination revealed an advanced type 3 gastric cancer in the anastomotic region. We performed total gastrectomy and D1 lymph node dissection because of the bleeding from the tumor, although peritoneal dissemination was found during the surgery. A post-operative pathological diagnosis of gastric cancer pT4b(SI, abdominal wall)N0M1(PER), pStage Ⅳ, was made. After the surgery, he was administered chemotherapy with S-1 and cisplatin. After 9 courses of the treatment, the treatment protocol was changed to an S-1 therapy regimen because of general fatigue. Four years and 8 months after the surgery, the tumor marker had increased, and CT scans revealed a dissemination nodule at the left back side of the bladder. Therefore, PTX plus Rmab therapy was administered as a second-line chemotherapy. Treatment with PTX plus Rmab resulted in tumor reduction, with an improvement of the QOL of the patient; partial response was maintained for 12 months. After 16 courses of the PTX plus Rmab treatment, tumor regrowth was detected. The treatment protocol was changed again to a nivolumab regimen. After 4 courses, the tumor marker was normalized, and CT scans revealed that the peritoneal dissemination had shrunk. Although the prognosis of gastric cancer with dissemination is very poor, it is possible to prolong survival with chemotherapy.

[A Case of HER2-Positive Gastric Cancer with Multiple Liver Metastases Treated with Curative Conversion Therapy after Chemotherapy].

A 66-year-old man underwent chemotherapy with S-1 plus cisplatin plus trastuzumab to treat advanced gastric cancer that was diagnosed as cStage Ⅳ adenocarcinoma(T3N1M1[P0, CYX, H1]). After 8 courses, liver metastases were absent on contrast-enhanced MRI. The patient underwent a laparoscopic distal gastrectomy with D2 lymphadenectomy. The gross appearance of the surgically resected specimen showed a shrunk gastric tumor measuring 1 mm. The postoperative course was uneventful, and the patient has been well, receiving maintenance chemotherapy of S-1 plus trastuzumab without evidence of recurrence for 15 months following the operation. Conversion surgery following chemotherapy might be an effective treatment for patients with advanced gastric cancer; however, further studies are needed to establish this treatment strategy.

[A Case of Ipsilateral Multifocal Renal Cell Carcinoma Treated with Robot-Assisted Partial Nephrectomy].

A 55-year-old male was referred to our hospital for left lower back pain. Computer tomography suggested a left ureteral stone and two left renal tumors at ventral and lateral sites. The ventral tumor measured 7 mm, and it showed intense early enhancement. On the other hand, the lateral tumor measured 22 mm, and it was enhanced weakly. We performed a single-stage robot-assisted partial nephrectomy, because he had chronic renal insufficiency and the two tumors appeared to be different types of renal cell carcinoma. Pathological examination revealed the ventral tumor was clear cell renal cell carcinoma, while the lateral tumor was papillary renal cell carcinoma. He is free of recurrence 1 year and 2 months after operation.

Accelerated Atherogenicity in Tangier Disease.

We report a case of Tangier disease with Leriche syndrome and bleeding tendency. In this male patient, nasal hemorrhage had been observed frequently throughout childhood. At 46 years old, he experienced effort angina, and coronary angiography demonstrated 75% stenosis in the right coronary artery. Orange-colored tonsils, mild hepatosplenomegaly and very low levels of serum high-density lipoprotein cholesterol (HDL-C) were observed, and the patient was diagnosed with Tangier disease. At 52 years old, effort angina recurred. Coronary angiography revealed 75% stenosis of the left main trunk, left anterior descending, and right coronary arteries. Stenosis of the brachiocephalic and right common iliac arteries was also recorded. Stents were implanted, and coronary artery bypass surgery was performed. At 53 years old, 15 months after surgery, the patient reported intermittent claudication, coldness of feet, and impotence. Aortic angiography showed progression of the stenosis at the bifurcation of the common iliac artery. The patient was diagnosed with Leriche syndrome, and aorta-left external iliac artery graft bypass surgery was performed. After surgery, oozing from subcutaneous tissue and leaking from the anastomotic region were observed. Additional analysis revealed two single-nucleotide polymorphisms (V825I and N935T) in the ATP-binding cassette transporter A1 (ABCA1) gene, and accumulation of small dense low-density lipoprotein together with low levels of HDL-C. In Tangier disease, HDL-C is markedly decreased because of ABCA1 deficiency. However, this is the first reported case to exhibit extensive atherosclerosis and bleeding tendency. This patient had atypical extensive and multiple atherosclerotic lesions, accompanied by Leriche syndrome and uncontrollable bleeding.

[A Case of Appendiceal Adenocarcinoma with Vesico-Appendiceal Fistula Treated by Additional Laparoscopic Excision].

A 40-year-old woman was admitted to our hospital with the chief complaint of miction pain. MRI showed fundal wall thickening of the bladder in contact with the appendix. Under cystoscopy, redness of the mucous membrane was found in the posterior wall of the bladder. Therefore, laparo-appendectomy with partial cystectomy was performed. Microscopically, adenocarcinoma cells were observed in the lumen of the appendix, invading the wall of the urinary bladder at the fundus of the appendix. We performed laparo-ileocecal resection for a regional lymphadenectomy. Thus, the patient was diagnosed with adenocarcinoma of the appendix[V, type 3, 16×7 mm, tub2, pT4b(SI, urinary bladder), int, INF b, ly0, v0, pN0, cM0, pStage Ⅱ]. The patient has been receiving adjuvant chemotherapy using capecitabine for 6 months. There was no evidence of recurrence after 9 months of follow-up.

[Primary Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma with Large Cell Transformation of the Prostate : A Case Report].

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate is rare. MALT lymphoma with large cell transformation like a diffuse large B-cell lymphoma (DLBCL) of the prostate is extremely rare. To the best of our knowledge, only one case has been previously reported. A 65-year-old man with difficulty on urination was referred to our department, in April 2014, because of abnormal findings of magnetic resonance imaging (MRI) and positron emission tomography-computed tomography imaging. Routine laboratory tests including prostate specific antigen and soluble interletkin-2 recepter were within normal limits, and the physical examination was unremarkable. In July 2007 and August 2009, he was submitted for a transrectal prostate biopsy, and then a histological examination for chronic prostatitis. In addition to the biopsy, transurethral resection of the prostate was performed. Histological examination revealed primary MALT lymphoma with large cell transformation of the prostate. Complete clinical investigation, including bone marrow biopsy, did not show any involvement of other sites by lymphoma, he received 3 cycles of chemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) followed by radiation therapy with a total dose of 46 Gy. The patient has been in complete remission for 6 months after the chemoradiation therapy.

[A Case of Cecal Cancer with Multiple Cutaneous Metastases].

We encountered a case of cutaneous metastases from colorectal carcinoma. A 63-year-old woman underwent laparoscopic-assisted ileocecal resection for cecal cancer. Computed tomography (CT) showed multiple liver metastases. The tumor was diagnosed as a well-differentiated adenocarcinoma and was staged as pSE, pN1, sH2, ly1, v1, CP0cM0, fStage Ⅳ. She was treated with 33 courses of the 5-fluorouracil, Leucovorin, and irinotecan (FOLFIRI) regimen and 15 courses of the 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab regimen. Thirty-four months after resection, multiple cutaneous tumors were noted, predominantly on the lower abdomen, and we resected 2 of them. Histologically, the specimens were diagnosed as well-differentiated adenocarcinoma, which was similar to that of cecal carcinoma. After 1 course of regorafenib, she died 3 years after the primary surgical resection.

BioGlue® coronary embolism during open heart surgery.

In cases of iatrogenic coronary embolism during cardiac surgery or percutaneous coronary intervention, small air bubbles or foreign bodies are directly injected, which usually result in serious adverse events if not treated promptly. We herein describe the case of a patient who developed acute myocardial infarction resulting in shock due to BioGlue® (CryoLife, Atlanta, GA, USA)-induced coronary embolism during the surgical repair of aortic dissection and was treated for retrieval of the material using a thrombectomy catheter. .

Resolution of gelatinous bone marrow transformation following hormone replacement therapy in a patient with primary insufficiency of the adrenal and thyroid glands.

A 59-year-old man with recurrent oral cancer presented with severe pancytopenia, hyponatremia and hypoglycemia. Endocrine testing showed a partial primary adrenal insufficiency and primary hypothyroidism. The bone marrow biopsy showed a gelatinous transformation with hypocellularity and fat atrophy. His pancytopenia, hyponatremia and hypoglycemia resolved following treatment with corticosteroids and thyroid hormone replacement therapy. The follow-up bone marrow biopsy demonstrated a resolution of the gelatinous transformation. This case is a rare example of a patient with a primary insufficiency of the adrenal and thyroid glands that is associated with gelatinous bone marrow transformation (GMT). The GMT was resolved through the administration of corticosteroids and thyroid hormone replacement therapy.

The Efficacy of Mizoribine (Inosine Monophosphate Dehydrogenase Inhibitor) for ANCA-Associated Vasculitis with Hepatitis B Virus Carrier.

A 42-year-old female who was an asymptomatic carrier of hepatitis B virus (HBV) was diagnosed with antineutrophil cytoplasm antibody- (ANCA-) associated vasculitis and was induced to remission with 30 mg/day prednisolone nine years ago. Four years ago, she suffered recurrence of ANCA-associated vasculitis and with 30 mg/day prednisolone was induced to remission. This time, laboratory data showed 3-fold increase in myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) levels. Administration of 30 mg/day prednisolone was started. Three days later, she was admitted to our hospital suffering from fatigue. After admission, urinalysis showed glomerular hematuria. Despite administration of 30 mg/day prednisolone, MPO-ANCA titer had been of high level, ranging from 42 to 83 EU for 2.5 months. Furthermore, the adverse effects of steroid were seen. We decided the tapering of prednisolone (25 mg/day) and the start of mizoribine (4-carbamoyl-1-ß-D-ribofuranosyl imidazolium-5-olate) administration. After mizoribine treatment, MPO-ANCA titer was decreased without any mizoribine-related adverse effects. Six months later, MPO-ANCA titer was decreased to normal levels and she was induced to clinical remission without reactivation of HBV. We describe the effectiveness of mizoribine for the ANCA-associated vasculitis complicated with HBV-carrier.

Presence of B-cell clones in T-cell lymphoma.

OBJECTIVES: The presence of B-cell clones in 76 cases with peripheral T-cell lymphoma (PTCL) and precursor T-lymphoblastic lymphoma (T-LBL) and its correlation with Epstein-Barr virus (EBV) was studied. METHODS: DNA was extracted from paraffin sections and/or fresh-frozen samples and then used for clonality analysis using a modified BIOMED-2 polymerase chain reaction (PCR)-based method. RESULTS: T- and B-cell clones were detected in 59 (77.6%) and 14 (18.4%) of 76 patients, respectively: 90% and 30% of cases with PTCL, not otherwise specified, 76.4% and 17.6% of cases with angioimmunoblastic T-cell lymphoma, 77% and 7.6% of cases with adult T-cell lymphoma, 50% and 0% of cases with anaplastic large T-cell lymphoma, 62.5% and 12.5% of cases with T-LBL, and 50% and 0% of cases with intestinal T-cell lymphoma, respectively. Histological and immunohistochemical analyses revealed the presence of large B cells in lesional tissues, which were occasionally monoclonal. The presence of B-cell clones was highly associated with EBV positivity, as revealed by in situ hybridization. In two cases that were evaluated by serial histological and molecular examination, EBV-positive cells persisted in one and disappeared in the other. CONCLUSIONS: These findings suggest a role for EBV in the evolution of B-cell clones in T-cell lymphomas.

Epstein-barr virus in diffuse large B-Cell lymphoma in immunocompetent patients in Japan is as low as in Western Countries.

According to previous reports, the frequency of Epstein-Barr virus (EBV) positivity in diffuse large B-cell lymphoma is higher in East Asia (approximately 9%) than in Western countries. The presence of the EBV genome was examined in diffuse large B-cell lymphoma patients registered with the Osaka Lymphoma Study Group (OLSG) in Osaka, Japan, situated in East Asia. The EBV-positive rate was examined with in situ hybridization (ISH) in 484 immunocompetent diffuse large B-cell lymphoma patients registered with OLSG. The male-to-female ratio was 1.29, with ages ranging from 16 to 95 (median, 68) years. ISH with EBV-encoded small RNAs (EBER) probes revealed positive signals in the nuclei of tumor cells: the frequency of positively stained cells among all tumor cells was almost none in 458 cases, 5-10% in 5, 10-20% in 5, 20-50% in 11, and >50% in 5. When the frequency was >20% or >50%, the EBV-positive rate in the present series (3.3% or 1.0%) was rather similar to that reported in Western cases. Careful evaluation of patient backgrounds, including age distribution, type of lymphomas, exclusion of immunocompromised patients, and establishment of definite criteria for EBV positivity (>20%, >50%, or almost all tumor cells) are essential in comparing geographical differences.