[A Case of Medullary Carcinoma of the Colon].

The patient is a 79-year-old woman who visited her local doctor with a chief complaint of abdominal pain. A lower gastrointestinal endoscopy revealed a circumferential type 3 mass in the transverse colon. The patient was diagnosed with transverse colon cancer (cT3N0M0, cStage Ⅱa)and underwent laparoscopic transverse colectomy(D3). The postoperative course was good, and she was discharged on POD 9. Pathological results showed a diagnosis of medullary carcinoma(pT3N0M0, pStage Ⅱa)with MSI-high. The patient was treated with UFT/UZEL for 6 months as postoperative adjuvant chemotherapy. The patient has been recurrence-free for 1 year and 6 months postoperatively and is under outpatient follow-up. Medullary carcinoma is a rare histologic type that is estimated to account for 2-3% of all colorectal cancers. Medullary carcinoma of the colon is more common in elderly patients, women, and the right side of the colon, with a relatively favorable prognosis. We report a case of medullary carcinoma of the transverse colon in which the patient had a relatively long survival, with some discussion of the literature.

[A Case on the Long‒Term Effect of Imatinib on GIST of Unknown Primary Origin with Multiple Liver Metastases, Peritoneal Dissemination, and Bone Metastasis].

A 61‒year‒old woman observed that she had a lower limb edema approximately 1 month ago and began to feel a general malaise. The symptom was caused by multiple liver metastases, and the primary lesion was suspected to be an ovarian cancer. Peritoneal disseminations throughout the abdominal cavity were found in the exploratory laparotomy. No obvious primary lesion could be found in the searchable gastrointestinal tract. The patient was diagnosed with a gastrointestinal stromal tumor(GIST)based on the biopsy results of the peritoneal dissemination. Treatment with imatinib mesylate(imatinib) was initiated 13 days after surgery. The severe lower extremity edema disappeared within 2 months. Computed tomography (CT)scan showed a reduction of the multiple liver metastases and peritoneal dissemination, and the appearance and increase of calcifications in the tumor and cystic degeneration inside the liver metastasis. The abnormal accumulation observed by bone scintigraphy also disappeared. Imatinib has a long‒term effect on GIST of unknown primary origin with multiple liver metastases, peritoneal dissemination, and bone metastasis. Five years after the initiation of the treatment, the patient is still alive, and new lesions have not developed.

[A Case of Thyroid and Endotracheal Metastasis from Rectal Cancer].

A 75-year-old woman previously underwent low anterior resection for rectal cancer(pT3N0M1a[PUL1], Stage Ⅳa)in October 2012. We administered 7 courses of mFOLFOX6 plus bevacizumab(BV)followed by oral UFT/LV for 6 months. In November 2014, we performed partial lung resection for relapsing metastatic lung tumor. In April 2017, we performed right lower lobectomy for recurrence at the site of partial resection. In October 2018, since serum CEA was gradually elevated, FDG-PET was performed for metastasis. FDG-PET indicated FDG accumulation in the left neck and the trachea. Enhanced CT revealed the thyroid tumor, an enlarged cervical lymph node and a small nodule in the trachea. Needle aspiration cytology of the thyroid tumor and the lymph node showed Class Ⅴ(adenocarcinoma). Bronchoscopy indicated a polypoid tumor Class Ⅴ(adenocarcinoma). After 18 courses of FOLFIRI plus BV, all metastases were reduced significantly. We conclude that FOLFIRI plus BV seems to be effective for patients with thyroid and endotracheal metastasis from rectal cancer.

[A Case of Metaplastic Squamous Cell Carcinoma of the Breast Successfully Treated with S-1].

Metaplastic squamous cell carcinoma(MSCC)of the breast is very unusual and is histologically characterized by rapid progression. Conventionalchemotherapy for ductalcarcinoma of the breast is ineffective against MSCC. Here, we report a case of MSCC of the breast successfully treated with S-1. A 57-year-old woman was admitted to our hospital because of a left breast tumor. A tumor approximately 10 cm in diameter was palpable in the lower-outer quadrant(D region)of the left breast. Core needle biopsy indicated estrogen receptor(ER)-negative, progesterone receptor(PR)-negative, and human epidermalgrowth factor receptor 2(HER2)-negative MSCC of the breast. Computed tomography(CT)showed left axillary lymph node metastases but did not indicate distant metastasis. A diagnosis of T4N3cM0, Stage ⅢC, MSCC of the left breast was made. Each treatment course consisted of the administration of S-1(120mg/body/day)for 4weeks, followed by 2 drugfree weeks. After the second course, significant tumor and lymph node reduction was observed. We concluded that S-1 chemotherapy seems to be effective for patients with MSCC of the breast.

Analysis of finger vein variety in patients with various diseases using vein authentication technology.

In finger vein authentication technology, near-infrared rays penetrate the finger and are absorbed by the hemoglobin in blood. The veins appear as dark areas. The finger vein pattern images of patients with various diseases were acquired; a new evaluation method applying image processing technique ("E value") was developed, and it was examined whether the patterns have any characteristics differentiating them from those of healthy volunteers. As a result, low E values appeared in systemic sclerosis, mixed connective tissue disease, Sjögren's syndrome, and polymyositis/dermatomyositis. No statistical reduction in E value was shown in patients with rheumatoid arthritis, pernio (without rheumatic diseases), arteriosclerosis obliterans, diabetes, hypertension, hypothyroidism and alopecia areata. This technology could be used for screening and evaluation of some diseases and their conditions with impaired peripheral venous circulation. E value may be useful as an indicator of venous circulation.

Hybrid method with explorative laparoscopy and anterior open approach for re-recurrent inguinal hernia.

The new guidelines of the HerniaSurge group recommend that only an expert hernia surgeon should repair a re-recurrent inguinal hernia. We report the efficacy of the hybrid method with explorative laparoscopy and anterior open approach for re-recurrent inguinal hernia repair. A 61-year-old man underwent anterior open preperitoneal mesh repair for right inguinal direct hernia and laparoscopic transabdominal preperitoneal repair for recurrence. Two years after the second surgery, re-recurrent inguinal hernia was confirmed. We carried out explorative laparoscopy for the re-recurrent inguinal hernia, which revealed a re-recurrent hernia orifice. We performed the anterior open approach while observing from the abdominal cavity. Explorative laparoscopy can help in accurately determining the orifice of the re-recurrent inguinal hernia. Based on that information, the hernia sac can be reached through the shortest route using the anterior open approach.

Combined therapy using interventional radiology and surgical management for a ruptured pseudoaneurysm of the iliac artery: A case report.

INTRODUCTION: An optimal treatment strategy for a ruptured pseudoaneurysm of the iliac artery must necessarily control bleeding and prevent ischemia in the ipsilateral lower extremity. PRESENTATION OF CASE: A 69-year-old man underwent resection of a metastatic lymph node from rectal cancer, which had invaded the sigmoid colon, the left internal iliac artery and vein, and his left ureter. The metastatic lymph node and the organs it invaded were resected together. Owing to postoperative complications, the patient was required to undergo a 2nd and 3rd operation after the initial surgery. During his 3rd surgery, sudden intraoperative bleeding was identified, which was diagnosed as a ruptured pseudoaneurysm of the internal iliac artery. After achieving temporary surgical hemostasis, the lesion was successfully treated using combined therapy comprising catheter embolization and an axillofemoral bypass. DISCUSSION: Even after temporary surgical hemostasis has been achieved, it is perhaps safer to block the arterial flow prophylactically to avoid recurrence of a pseudoaneurysm owing to infection. CONCLUSION: Combined therapy using catheter embolization and surgical revascularization is a minimally invasive and effective treatment option for a ruptured pseudoaneurysm of the iliac artery.

[A Case of Advanced Breast Cancer with Improvement in the Quality of Life by Local Treatment Using Mohs Paste and Systemic Pharmacotherapy].

Locally advanced breast cancer with skin invasion often causes malodor, bleeding, and massive exudates, which degrades patients' quality of life(QOL). A 61-year-old woman presented with locally advanced breast cancer with malodor and massive exudates, which had carcinomatous pleurisy causing dyspnea. We administered endocrine therapy and chemotherapy and used Mohs paste for local therapy. The exposed part of the tumor was fixed using Mohs paste. After continuing to apply Vaseline over the fixed part, the lesion spontaneously detached without surgical removal and completely epithelized, and malodor and exudates disappeared. Cancerous pleurisy also improved, and dyspnea disappeared. Local treatment using Mohs paste and systemic pharmacotherapy dramatically improved her QOL.

[A Case of Chest Wall Metastasis after Surgery for Lower Bile Duct Carcinoma].

A 76-year-old woman with lower bile duct carcinoma underwent subtotal stomach-preserving pancreaticoduodenectomy (SSPPD)after percutaneous transhepatic biliary drainages(PTBD). Nine months after the operation, chest computed tomography revealed a mass in the subcutis of the right chest wall, which was a different lesion from that in the PTBD site. The aspiration biopsy cytology and needle biopsy indicated no malignant findings. However, the mass was growing and was suspected to be a metastasis of bile duct cancer. We resected the mass, including portions of the sixth and seventh ribs. The pathological diagnosis was metastasis of bile duct carcinoma. The postoperative course was uneventful. Now, 2 years have passed since the resection of the primary lesion and 9 months since the resection of the chest wall metastasis. Thus far, no manifestations of recurrence have been observed, and the patient has been in a favorable condition. We report this case with a literature review.

[Three Cases of Remnant Pancreatic Cancer after Surgery for Invasive Ductal Carcinoma of Pancreas].

We report here 3 cases of remnant pancreatic cancer after surgery for invasive ductal carcinoma. Case 1 was a 73-year-old male who underwent distal pancreatectomy(pap, pT3, pN0, M0): fStage II A(JPS 7th). He developed a remnant pancreatic cancer 39 months later, and total remnant pancreatectomy was performed. He died from sepsis 9 months after surgery. Case 2 was a 72-year-old female who underwent subtotal stomach-preserving pancreatoduodenectomy(SSPPD)(tub2, pT1c, pN1a, M0): fStage II B. She developed a remnant pancreatic cancer 82 months later. This lesion seemed to be resectable. But she hoped to take a best supportive care, and died 13 months after diagnosis. Case 3 was a 68-year-old female who underwent SSPPD(tub1, pT3, pN1a, M0): fStage II B. She developed a remnant pancreatic cancer 20 months later and was successfully treated by chemotherapy and carbon-ion radiotherapy.

Disease flare patterns and predictors of systemic lupus erythematosus in a monocentric cohort of 423 Japanese patients during a long-term follow-up: The JUDE study.

OBJECTIVE: To clarify the clinical features of systemic lupus erythematosus (SLE) patients, factors associated with flares, and changes over time. METHODS: Patients having SLE with a visiting history were entered into the Juntendo University Database of Erythematosus. We included 423 cases in the long-term follow-up analysis, and 383 cases were followed for 10 years after the initiation of any therapeutic intervention (comparative analysis: 1973-1982, 82 cases; 1983-1992, 141, and 1993-2002, 160). We assessed changes in the patients' background characteristics, disease symptoms, flare rates, etc. RESULTS: Among the 423 cases, the mean follow-up period was 25.9 years, and mean number of flares was 0.51. Of those, 31.9% had ≥1 flares. Thrombocytopenia at onset contributed to the flares. For disease symptoms at onset, a recent trend in increasing thrombocytopenia was observed. The combination rate of immunosuppressive agents for diseases other than lupus nephritis was slightly increased, and there was no improvement until the first flare or in the flare rate. CONCLUSIONS: Thrombocytopenia at onset is predictive factor for flares. Since SLE is a diverse disease with varying symptoms at recurrence, the treatment guidelines should be improved for thrombocytopenia from a long-term perspective.

The synovial grade corresponding to clinically involved joints and a feasible ultrasound-adjusted simple disease activity index for monitoring rheumatoid arthritis.

OBJECTIVES: To determine which grade of ultrasound (US) synovitis corresponds to clinically involved joints in rheumatoid arthritis (RA) and develops a new US-adjusted composite measure. METHODS: Clinical and US examinations were performed on 137 patients with RA (28 joints). Synovial effusion, hypertrophy, and blood flow were semiquantitatively graded from 0 to 3 using gray scale (GS) and power Doppler (PD) modes. We calculated US-adjusted simple disease activity index (SDAI) and assessed feasibility, and external validity by comparing with erythrocyte sedimentation rate (ESR), and modified health assessment questionnaires (MHAQ). RESULTS: GS ≥2 and PD ≥0 corresponds to clinically swollen joints, and GS ≥2 and PD ≥1 corresponds to tender joints. The US-adjusted SDAI showed the highest correlation when US-determined swollen joints were defined as PD ≥2 with ESR, and GS ≥3 and PD ≥2 with MHAQ. A feasible US-adjusted SDAI examining only clinically involved joints still showed a higher correlation with ESR and MHAQ than SDAI. CONCLUSION: Our composite measure complemented by US only for clinically involved joints is feasible and reliable for monitoring disease activity.

Predictive grade of ultrasound synovitis for diagnosing rheumatoid arthritis in clinical practice and the possible difference between patients with and without seropositivity.

OBJECTIVE: To determine the degree of contribution and the contributing factors of ultrasound in the diagnosis of rheumatoid arthritis (RA) in daily clinical practice and the predictive differences depending on seropositivity. METHODS: We included 122 patients who presented with the main complaint of finger and/or wrist joint pain but for whom no definite diagnosis was reached or treatment strategy was provided. Ultrasound was performed on at least 22 joints (both wrist joints, proximal interphalangeal joint, and metacarpophalangeal joints), and patients were followed for ≥6 months. Factors contributing to RA diagnosis were determined and compared between seropositive and seronegative RA patients. RESULTS: RA was diagnosed in 52 of 122 patients, in whom the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria (odds ratio [OR] = 4.74, P = 0.01) and gray scale (GS) grade of 3 (OR = 3.64, P = 0.04) for ≥ 1 joint were the contributing factors. In seropositive RA, the ACR/EULAR criteria (OR = 15.53, P < 0.001) and power Doppler (PD) ≥ 2 for ≥ 1 joint (OR = 10.48, P = 0.0048) were the contributing factors. In seronegative RA, PD ≥ 1 for ≥ 1 joint contributed the most (OR = 20.00, P = 0.0044), but the ACR/EULAR criteria did not contribute to RA diagnosis (P = 0.57). CONCLUSION: Ultrasound findings contributed to RA diagnosis in clinical practice. The contributing factors are different in the presence or absence of seropositivity, and ultrasound complementation was particularly useful in seronegative RA patients.

Second-to-fourth Digit Ratio in Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) occurs predominantly in women, and sex hormones play an important role in SLE. Variation in the second-to-fourth digit ratio (2D4D ratio) is attributed to sex hormone exposure. Therefore, we evaluated the relationship between sex hormones and SLE by measuring 2D4D ratios. METHODS: We measured 2D4D ratios in 100 patients with SLE and 200 normal healthy controls (NHC). RESULTS: Patients with SLE had a lower 2D4D ratio than NHC. CONCLUSION: Our study suggests that patients with SLE have experienced high prenatal testosterone and low prenatal estrogen. To our knowledge, this is the first study evaluating the association between 2D4D ratio and SLE.

Predictive value of bone destruction and duration of clinical remission for subclinical synovitis in rheumatoid arthritis patients.

OBJECTIVES: Treatment for rheumatoid arthritis (RA) should aim to achieve full remission. The aim of this study was to investigate predictors of persistent subclinical synovitis and whether longer clinical remission is effective in reducing subclinical synovitis. METHODS: Forty-four RA patients who achieved DAS28ESR clinical remission for at least 3 months were enrolled in this study and underwent ultrasound examination of 22 joints (bilateral proximal interphalangeal joints, metacarpophalangeal joints, and wrists); bilateral hand X-ray; and blood examination. The severity of synovial effusion, synovial hypertrophy, and blood flow were semi-quantitatively graded from 0 to 3 using gray-scale (GS) and power Doppler (PD) modes. RESULTS: Among patients with DAS28ESR-defined clinical remission, 59.1% (26/44) demonstrated residual synovitis (≥ PD1) in at least one joint. Genant-modified total Sharp score (TSS) demonstrated the highest statistical difference between patients with and without residual subclinical synovitis (p = 0.0057), and full remission was only observed in patients with low TSS. A nonsignificant trend for decreased residual synovitis with longer sustained clinical remission was also observed (p = 0.724). CONCLUSION: Residual synovitis can persist during clinical remission, particularly in patients with progressive bone destruction. Early treatment and longer sustained clinical remission prior to bone destruction are critical for full remission.

Weighting with the Lansbury articular index improves the correlation of ultrasound score with serum matrix metalloproteinase-3 level in rheumatoid arthritis patients.

OBJECTIVE: To determine whether weighting improves the correlation of ultrasound (US) score with serum matrix metalloproteinase-3 (MMP-3) level in rheumatoid arthritis (RA). METHODS: As ultrasound examination was performed on 100 RA patients, and the severity of synovial effusion and synovial hypertrophy and the blood flow were semi-quantitatively graded from 0 to 3 by using the gray-scale (GS) and power Doppler (PD) modes. We then calculated the sums of the scores of the 28 joints of each patient in the 2 modes, that is, the GS28 and PD28 scores, as well as the respective scores weighted using the Lansbury articular index (LAI, shoulder and elbow, × 12; wrist, × 8; and knee, × 24)-Lans GS28 and Lans PD28 scores. RESULT: The Lans PD28 score showed a higher correlation with MMP-3 (r = 0.591; 95% confidence interval, 0.446-0.705, p < 0.0001) than the existing measures. The scores of the large joints-the knee, shoulder, and elbow-correlated well with the serum MMP-3 level. CONCLUSION: Weighting with the LAI can improve the correlation of US findings with serum MMP-3 level. Bidirectional approach based on both serum MMP-3 level and US scores can further improve the assessment of disease activity in RA patients.

Increased serum concentration of BAFF/APRIL and IgA2 subclass in patients with mixed connective tissue disease complicated by interstitial lung disease.

B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are known to be crucial for B cell maturation and survival, and increased expression of these factors in various autoimmune diseases has been reported. Human B cells produce two IgA subclasses: IgA1 and IgA2, the latter being abundant in the distal intestine, saliva, colostrum and bronchial fluid. We investigated these parameters in patients with mixed connective tissue disease (MCTD) complicated by interstitial lung disease (ILD+), and compared them with those in MCTD patients without ILD (ILD-). Sixty-three MCTD patients were divided into two groups: 21 ILD+ patients and 42 ILD- patients. In each patient group we analyzed soluble BAFF/APRIL using ELISA, and IgA1 and IgA2 using double immunodiffusion. Furthermore, we analyzed BAFF-APRIL receptors, BCMA, BAFF-R and TACI, using flow cytometry. The ILD+ patients had significantly higher levels of BAFF/APRIL than the ILD- patients. There were significant correlations between BAFF/APRIL, BAFF/KL-6 and APRIL/KL-6. Although there was no significant inter-group difference in the serum IgA1 level, ILD+ patients had a significantly elevated IgA2 level in comparison with ILD- patients. Moreover, although there were no significant inter-group differences in the expression of BCMA, BAFF-R and TACI on B cells, the expression of BAFF-R was significantly decreased in the ILD+ patients. In recent years, relationships between BAFF/APRIL and IgA subclass have been reported. Our results suggest that an elevated level of BAFF/APRIL drives the maturation of B cells, subsequently leading to IgA2 class switching, and possibly to the development of ILD in patients with MCTD.

Can routine clinical measures predict ultrasound-determined synovitis and remission in rheumatoid arthritis patients?

OBJECTIVES: The purpose of this study was to determine if routine clinical measures can predict the presence and severity of ultrasound synovitis in rheumatoid arthritis (RA) patients. METHODS: Bilateral 1-5 MCP (metacarpopharangeal) and wrist joints were examined using power Doppler (PD) ultrasound (US). Correlations between PD scores and routine clinical measures of RA - swollen joint count (SJC), tender joint count, patient's global assessment (GA), physician's GA, CRP, ESR, MMP-3, RF and anti-CCP antibody - were determined and used to identify significant predictors of PD score. Clinical measures were then compared between two groups (patients with and without PD) and analysed using multiple logistic regression, to derive a model that predicted the absence of PD signals. RESULTS: SJC was the most significant predictor of PD score (R2 = 0.4566, p value <0.0001), but was an inadequate predictor of PD signal remission. However, the combination of Steinbrocker's stage I or II (odds ratio [OR] 9.23, p=0.0049), SJC=0 in 1-5 MCP and wrist joints on both sides (OR 6.60, p=0.0039), and SDAI (or CDAI) remission (OR 5.06, p=0.0450) had a positive predictive value of 100%, predicting the absence of PD signals in all study patients meeting the 3 criteria. CONCLUSIONS: PD score and absence of PD signals can be predicted using routine clinical measures. When used in combination, Steinbrocker's stage, SJC and SDAI (or CDAI) can estimate disease activity and identify patients likely to have synovitis and requiring US.

Clinical miscount of involved joints denotes the need for ultrasound complementation in usual practice for patients with rheumatoid arthritis.

OBJECTIVES: Ultrasound (US) examination can visualise and clarify involved joints anatomically in patients with rheumatoid arthritis (RA), and it enables physicians to verify the accuracy of clinical assessments of involved joints. Here, we studied the practical 'miscount'- calculated by subtracting US-determined involved joint count from clinically determined involved joint count - and analysed possible contributing factors for increased miscount. METHODS: The study population consisted of 137 patients with RA. Physical joint examination was performed by 3 assessors with different levels of experience in rheumatology, followed by US joint examination. Clinical and US examinations were performed on 28 joints (proximal interphalangeal, metacarpophalangeal, wrist, elbow, shoulder, and knee on both sides). Miscount was calculated for all patients, and multivariate analysis was conducted on possible contributing factors for miscount, including age, sex, body mass index, disease duration, Steinbrocker stage, erythrocyte sedimentation rate (ESR), C-reactive protein level, patient global assessment (GA), evaluator GA, matrix metalloproteinase-3 level, and power Doppler (PD) score. RESULTS: A high variability in concordance rate among the joint sites was observed among the 3 assessors. The average miscount was 1.07 (SD, 5.19; range, 18 to -11). ESR and patient GA were determined as significant contributing factors for false-positive miscount, whereas PD score and age were significant factors for false-negative miscount. CONCLUSIONS: In addition to the condition of the involved joint distribution and the assessor's clinical examination skills, the patients' background can also lead to increased miscount. Assessors should be blinded to patients' background information, and US complementation should be included in usual clinical joint examinations.