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Several vaccines have been approved worldwide for the prevention of morbidity and mortality against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the development of these vaccines has raised concerns regarding their adverse effects. Herein, we report the first case of intracerebral hemorrhage (ICH) due to vasculitis after the first dose of mRNA vaccine (BNT162b2, Pfizer/BioN-Tech). Although this case cannot demonstrate a direct relationship between COVID-19 vaccination and vasculitis, the clinical and histological features of this patient are highly consistent with the adverse effects of COVID-19 vaccine.

Highlights • In our case report, we suggested that reduced port laparoscopic surgery using an umbilical zigzag incision is comparable to conventional multiport laparoscopic surgery. • This method is associated with improved cosmesis and decreased wound pain. • We herein report a case involving interval resection of Meckel’s diverticulum using a transumbilical approach with a zigzag incision, which was performed three months after the appearance of symptoms., Introduction Reduced port laparoscopic surgery using an umbilical zigzag incision is comparable to conventional multiport laparoscopic surgery. This method is associated with improved cosmesis and decreased wound pain. Presentation of case A 67-year-old man visited our hospital. He presented emergency room with a chief complaint of right lower abdominal pain by walking. The patient was diagnosed Meckel’s diverticulitis by computed tomography (CT). At first, antibiotics therapy and fasting were performed. Three months later, the patient underwent resection of Meckel’ diverticulum with zigzag transumbilical laparoscopic surgery. The patient’s postoperative course was good, and he rarely felt wound pain. The patient started oral intake three days after surgery, and was discharged 10 days after surgery. Discussion Zigzag transumbilical laparoscopic surgery is very useful for resection of the small intestine. This method is associated with improved cosmesis and decreased wound pain. In the case of Meckel’s diverticulitis, we suggest that interval resection of Meckel’s diverticulum was very useful as it was an operation that could be performed easily. Conclusion Reduced port laparoscopic surgery using an umbilical zigzag incision is considered to be an excellent technique in terms of operability and aesthetic outcomes.

Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open‐label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40–160 mg/day or febuxostat 10–60 mg/day, titrated to maintain serum uric acid, This multicenter, randomised, open‐label study compared the effects of two xanthine oxidoreductase inhibitors, topiroxostat and feboxostat, on arterial stiffness, uric acid levels and blood pressure (BP) in hypertensive patients with hyperuricemia. Neither topiroxostat nor feboxostat had any significant effects on arterial stiffness (measured using the cardio‐ankle vascular index) over 24 weeks' treatment; but both agents significantly reduced serum uric acid levels and morning home systolic BP compared with baseline.

Introduction Pancreatic acinar cell carcinoma (ACC) is a relatively rare neoplasm. Furthermore, tumor rupture is extremely rare. Only 1 case of ruptured pancreatic ACC has been reported, and the long-term outcome of the case is unknown. Here, we present a case of spontaneously ruptured ACC with long-term survival after successful resection. Case Presentation A 67-year-old man was brought to our hospital by ambulance, presenting with progressive left abdominal pain. Laboratory data showed an increased inflammatory response, and contrast-enhanced computed tomography showed a mass in the pancreas tail with nonuniform enhancement in the early phase. Fluid collection was detected around the spleen to the left kidney. Spontaneous rupture of a pancreatic tumor was strongly suspected. After improvement of his general condition, the patient underwent resection of the pancreas and adjacent organs. The resected tumor was surrounded by organs and adipose tissue, so obvious exposure was not observed in the surgical margins. Pathologically, neither exposure of tumor cells at the surgical margins nor lymph node involvement was detected. The patient has survived 80 months since initial diagnosis without any evidence of recurrence. Conclusion Although ruptured pancreatic ACC has the potential for dissemination, surgical resection including adjacent organs remains an option for curative treatment.

Inhibitors of vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) signaling, such as bevacizumab (Bmab), are used for the treatment of various advanced cancers. However, these inhibitors induce renal thrombotic microangiopathy (TMA). Recently, two European cohort studies showed a distinctive histopathological pseudothrombotic pattern different from TMA in Bmab-treated patients. We analyzed 9 renal biopsies from proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors in our Japanese cohort. Clinical and laboratory features were also assessed in these patients. All 9 patients had moderate to heavy proteinuria with normal or slightly elevated serum creatinine levels. On light microscopy, a patchy pattern of hemispherical/spherical lesions along glomerular capillary walls was a characteristic finding. On immunofluorescence microscopy, staining for immunoglobulins (IgM dominant) at varying intensities was observed mainly along glomerular capillary walls. Especially, hemispherical/spherical positive staining for immunoglobulins was a characteristic pattern. Immunohistochemical studies showed positive staining for immunoglobulins and negative staining for CD61-positive platelets in capillary hemispherical/spherical lesions and positive VEGF staining in podocytes. On electron microscopy, variably electron-dense material in dilated glomerular capillaries and partial effacement of podocyte foot processes were observed. After the withdrawal of VEGF-VEGFR2 inhibitors, proteinuria improved without any specific treatment in 8 patients. Histopathological findings in our patients treated with VEGF-VEGFR2 inhibitors were consistent with those observed in the recently described new form of Bmab-associated hyaline occlusive glomerular microangiopathy. This form should be considered in proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors. Discontinuing VEGF-VEGFR2 inhibitors may lead to improvement of glomerular microangiopathy induced by these drugs.

Introduction This study was designed to identify the minimal and necessary cell morphologies to be considered for high-precision diagnosis of high-grade urothelial carcinoma (HGUC) in a routine urinary cytology practice. Materials and methods We included 338 urine cytology specimens from 11 medical facilities in Japan. Six experts evaluated these Papanicolaou-stained specimens using their own diagnostic criteria to categorize them within an initial 4-tiered classification system. Of the 338 cases, 70 HGUC and 32 benign cases (with a complete consensus diagnosis of 6 experts) were included for the analysis. Two of the cytologists evaluated the specimens for 20 specific cellular features. The results were analyzed using a contingency table and by discriminant analysis. Results Of the original 338 cases, 165 were originally diagnosed as HGUC, but only 70 (42.4%) were scored as malignant by all participating cytologists; of the 101 benign cases, only 32 (31.7%) were classified as such in all examinations. These specimens were re-evaluated by 6 experts using a panel of 20 specific cellular features used to distinguish between HGUC and benign diseases; tests of significance and discriminant analyses identified 7 critical features that were most useful for cytological diagnosis. Statistical analysis revealed that a focus on these 7 features led to a diagnosis of HGUC with a probability of over 95%. Conclusions The accuracy of our presently used method to evaluate urinary cytology is not consistently high. This novel classification system, which focuses on 7 critical features, facilitates the high accurate diagnosis of HGUC in routine cytology practice.

Background Patients with some mutations in the lamin A/C (LMNA) gene are characterized by the presence of dilated cardiomyopathy (DCM), conduction abnormalities, ventricular tachyarrhythmias (VT), and sudden cardiac death (SCD). Various clinical features have been observed among patients who have the same LMNA mutation. Here, we show a family with cardiac laminopathy with a c.475G > T, p.E159* LMNA mutation, and a family history of conduction disorder, DCM, VT, and SCD. Case presentation A proband (female) with atrial fibrillation and bradycardia was implanted with a pacemaker in her fifties. Twenty years later, she experienced a loss of consciousness due to polymorphic VT. She had a serious family history; her mother and elder sister died suddenly in their fifties and sixties, respectively, and her nephew and son were diagnosed as having DCM. Genetic screening of the proband, her son, and nephew identified a nonsense mutation (c.475G > T, p.E159*) in the LMNA gene. Although the proband’s left ventricular ejection fraction remained relatively preserved, her son and nephew’s left ventricular ejection fraction were reduced, resulting in cardiac resynchronization therapy by implantation of a defibrillator. Conclusions In this family with cardiac laminopathy with a c.475G > T, p.E159* LMNA mutation, DCM, SCD, and malignant VT occurred. Clinical manifestation of various atrial and ventricular arrhythmias and heart failure with reduced ejection fraction occurred in an age-dependent manner in all family members who had the nonsense mutation. It appears highly likely that the E159* LMNA mutation is related to various cardiac problems in the family of the current report.

Objective The long-term use of proton pump inhibitors (PPIs) may induce adverse events in many organs, including the stomach. The chronic use of PPIs has been associated with the growth of fundic gland polyps (FGPs) and of gastric black spots. This study assessed the incidence of gastric lesions with cobblestone-like appearance in PPI users. Methods The clinical characteristics and endoscopic findings of patients who underwent upper gastrointestinal endoscopy after using PPIs for at least six months were analyzed. The biopsy specimens from patients with gastric cobblestone-like lesions (GCLLs) were examined histopathologically. Patients This study analyzed 171 patients who underwent upper gastrointestinal endoscopy after more than 6 months of PPI use in Mitsugi Public General Hospital from January 1, 2015, to March 31, 2016. Results Of the 171 patients, 60 (35.1%) had GCLLs and 111 (64.9%) did not. There were no significant between-group differences in age, sex, duration of PPI use, and receipt of Helicobacter pylori eradication therapy. Atrophic gastritis of the corpus was significantly less frequent in the GCLL than in the non-GCLL group (55.0% vs. 47.8%, p=0.0097). Among the GCLL group, histological examinations of 24 patients revealed cystic dilation of the fundic gland in 19 (79.2%), parietal cell hyperplasia in 18 (75.0%), and cytoplasmic vacuolation in 7 (29.2%). Conclusion GCLLs occurred frequently in long-term PPI users, especially in patients without atrophic gastritis. The pathological findings of GCLLs included parietal cell hyperplasia and fundic gland cysts. The clinical importance of these new lesions remains uncertain, but they should be observed carefully.

The USA300 clone, which produces Panton-Valentine leukocidin (PVL), is a major highly pathogenic community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clone that is spreading throughout the world. Although the prevalence of the USA300 clone in Japan was very limited a decade ago, its incidence has been increasing in both community and hospital settings in recent years. There is great concern that the USA300 clone will cause more complicated diseases and become a serious threat to immunocompromised patients in hospital settings. Here, we report an outbreak of severe infectious diseases in a tertiary care university hospital involving the incidence of deep infections, including bacteremia, and continuous and frequent isolation of MRSA strains for five months from six patients and a healthy nursing staff member in the same ward. The genotype of all MRSA isolates was identical to that of the USA300 clone. Furthermore, pulsed-field gel electrophoresis analysis indicated that all MRSA had the same patterns. These data demonstrate that a USA300 clone outbreak had occurred in the hospital. Fortunately, this outbreak was terminated subsequent to the interventions of the infection control team and all patients recovered following the appropriate therapies. Our report demonstrates that patients carrying highly pathogenic CA-MRSA have the potential to become a source of nosocomial outbreaks that can spread to healthy healthcare workers. Therefore, stricter standard precautions should be applied for all patients at the time of admission to prevent such nosocomial outbreaks.

The aim of this retrospective study was to evaluate the prognostic significance of lymphopenia associated with chemotherapy in patients with colorectal cancer who received adjuvant chemotherapy after undergoing potentially curative surgery. Lymphocyte plays an important role in antitumor immunity. Lymphopenia is sometimes induced during the period of adjuvant chemotherapy after potentially curative surgery for colorectal cancer. However, the prognostic significance of lymphopenia associated with chemotherapy is unknown. One hundred fifteen patients who received adjuvant chemotherapy after potentially curative surgery for stage II/III colorectal cancer were enrolled in this study. All patients were classified into 2 groups, the lymphopenia group and the normal group, according to minimum lymphocyte count during the period of adjuvant chemotherapy. Lymphopenia was defined as a lymphocyte count of less than 1000/μL. Lymphopenia associated with chemotherapy was found in 17 of the 115 patients (14.8%). Lymphopenia was associated with a worse disease-free survival (P = 0.018) and overall survival (P = 0.022). Moreover, in a multivariate analysis, lymphopenia associated with chemotherapy was identified to be an independent prognostic factor for disease-free survival (hazard ratio, 2.296; 95% confidence interval, 1.089–4.840; P = 0.029) and overall survival (hazard ratio, 2.995; 95% confidence interval, 1.021–8.790; P = 0.046). Lymphopenia associated with chemotherapy is an independent prognostic factor in patients with colorectal cancer who receive adjuvant chemotherapy after undergoing potentially curative surgery.

Few studies have been conducted on the long-term prognosis of patients with amyloid light chain (AL) and amyloid A (AA) renal amyloidosis in the same cohort. We retrospectively examined 68 patients with biopsy-proven renal amyloidosis (38 AL and 30 AA). Clinicopathological findings at the diagnosis and follow-up data were evaluated in each patient. We analyzed the relationship between clinicopathological parameters and survival data. Significant differences were observed in several clinicopathological features, such as proteinuria levels, between the AL and AA groups. Among all patients, 84.2 % of the AL group and 93.3 % of the AA group received treatments for the underlying diseases of amyloidosis. During the follow-up period (median 18 months in AL and 61 months in AA), 36.8 % of the AL group and 36.7 % of the AA group developed end-stage renal failure requiring dialysis, while 71.1 % of the AL group and 56.7 % of the AA group died. Patient and renal survivals were significantly longer in the AA group than in the AL group. eGFR of >60 mL/min/1.73 m2 at biopsy and an early histological stage of glomerular amyloid deposition were identified as low-risk factors. A multivariate analysis showed that cardiac amyloidosis and steroid therapy significantly influenced patient and renal survivals. Our results showed that heart involvement was the major predictor of poor outcomes in renal amyloidosis, and that the prognosis of AA renal amyloidosis was markedly better than that in previously reported cohorts. Therapeutic advances in inflammatory diseases are expected to improve the prognosis of AA amyloidosis.

Objective We have recently discovered new gastric lesions with black spots. There have been no reports about black spots and their clinicopathological features. We therefore report the clinicopathological features of black spots and assess their causes and mechanisms. Methods Sixty-four patients with black spots among 26,620 Japanese patients that underwent endoscopy between May 2012 and October 2014 were enrolled. Endoscopic findings of black spots were defined as black pigmentations in the gastric mucosa by conventional endoscopy. We investigated the clinicopathological characteristics, including gender, age, underlying diseases and medications, endoscopic and pathologic findings of patients with black spots. Results The prevalence of patients with black spots was 0.24%. Of sixty-four cases, 44 (68.8%) were taking proton pump inhibitors (PPIs). Eight (12.5%) were taking corticosteroids. There were 10 cases (15.6%) with decreased renal function. All black spots were identified only in the fundic gland region. Forty-one (64.1%) patients had multiple (more than ten) black spots. There were two different types: black spots on the flat mucosa and black spots on fundic gland polyps. Pathologically, parietal cell protrusions, fundic gland cysts and brownish pigmentation in fundic gland cysts were seen in 26 (76.5%), 23 (67.6%) and 6 (17.6%) patients, respectively. Conclusion We herein describe gastric black spots as a new gastric mucosal finding that arises only in the fundic gland region. The black spots are pathologically brownish pigmentations in fundic gland cysts. Adverse events of PPIs and parietal cell protrusion caused by PPI use are strongly considered to be one of the etiologies of black spots.

Background/aim A meta-analysis was conducted to evaluate and compare the short- and long-term outcomes of robot-assisted (RAS) and conventional laparoscopic surgery (LAS) for rectal cancer. Materials and methods We searched MEDLINE for relevant papers published between 2010 and December 2017 by using specific search terms. We analyzed outcomes over short- and long-term periods. Results We identified 23 papers reporting results that compared RAS for rectal cancer with LAS. Our meta-analysis included 4,348 patients with rectal cancer; 2,068 had undergone RAS, and 2,280 had undergone LAS. In the short- and long-term period, 27 and 7 outcome variables were examined, respectively. RAS for rectal cancer was significantly associated with a greater operative time and a lower conversion rate to open surgery in the short-term, and results in almost similar outcomes in the long-term, compared to LAS. Conclusion RAS may be an acceptable surgical treatment option compared to LAS for rectal cancer.

Rationale & Objective Epidemiologic and clinical studies have suggested that urate-lowering therapy may slow the progression of chronic kidney disease (CKD). However, definitive evidence is lacking. Study Design Randomized, double-blind, placebo-controlled trial. Setting & Participants 467 patients with stage 3 CKD and asymptomatic hyperuricemia at 55 medical institutions in Japan. Intervention Participants were randomly assigned in a 1:1 ratio to receive febuxostat or placebo for 108 weeks. Outcomes The primary end point was the slope (in mL/min/1.73 m2 per year) of estimated glomerular filtration rate (eGFR). Secondary end points included changes in eGFRs and serum uric acid levels at 24, 48, 72, and 108 weeks of follow-up and the event of doubling of serum creatinine level or initiation of dialysis therapy. Results Of 443 patients who were randomly assigned, 219 and 222 assigned to febuxostat and placebo, respectively, were included in the analysis. There was no significant difference in mean eGFR slope between the febuxostat (0.23 ± 5.26 mL/min/1.73 m2 per year) and placebo (−0.47 ± 4.48 mL/min/1.73 m2 per year) groups (difference, 0.70; 95% CI, −0.21 to 1.62; P = 0.1). Subgroup analysis demonstrated a significant benefit from febuxostat in patients without proteinuria (P = 0.005) and for whom serum creatinine concentration was lower than the median (P = 0.009). The incidence of gouty arthritis was significantly lower (P = 0.007) in the febuxostat group (0.91%) than in the placebo group (5.86%). Adverse events specific to febuxostat were not observed. Limitations GFR was estimated rather than measured, and patients with stages 4 and 5 CKD were excluded. Conclusions Compared to placebo, febuxostat did not mitigate the decline in kidney function among patients with stage 3 CKD and asymptomatic hyperuricemia. Funding Funded by Teijin Pharma Limited. Trial Registration Registered at the UMIN (University Hospital Medical Information Network) Clinical Trials Registry with study number UMIN000008343.

Background The aim of this study was to clarify the operative mortality and long-term survival of gastrectomy for elderly patients with gastric cancer. Methods A total of 461 patients who underwent gastrectomy for gastric cancer in our hospital were classified as elderly group (≥80 years-old, 95 patients) and control group (60–69 years-old, 366 patients). Results The frequency of comorbidities was significantly (P

The aim of the present study was to investigate the efficacy of intracorporeal reinforcing sutures for preventing anastomotic leakage (AL) after laparoscopic surgery for rectal cancer. This was a retrospective single-institution study consisting of 201 consecutive patients who underwent laparoscopic proctectomy with double-stapling anastomosis for primary rectal cancer between August 2007 and December 2013. The data for patients who received intracorporeal reinforcing sutures were compared with those of patients who did not receive reinforcing sutures. Patient-, tumor- and surgery-related variables were collected and examined using univariate and multivariate analyses. The overall incidence of AL was 9.0 % (18/201). No significant correlations were observed between the various clinicopathological factors and the use of reinforcing sutures. The multivariate analyses revealed the distance of the tumor from the anal verge, tumor size and presence of reinforcing sutures to be independent risk factors for AL. We classified the patients into two risk groups using a combination of the tumor site and tumor size: a low-risk group (patients without any risk factors, n = 134) and a high-risk group (patients with one or two risk factors, n = 67). The frequency of AL was significantly lower (p

Background Common complications of pelvic fractures include visceral injury, large-volume hemorrhage, genitourinary injury, rectal injury, and pulmonary embolism. On the other hand, traumatic hernia is a rare complication, especially in association with pelvic fractures. We report a case of bowel perforation due to traumatic hernia at a pelvic fracture site. Case presentation A 65-year-old female was presented at our hospital for further examination and treatment of ileus. She was diagnosed with bowel perforation due to traumatic hernia at a pelvic fracture site, and an emergency operation was thus immediately performed. We performed segmental jejunum resection and constructed jejunostomy, and the iliac bone fracture was fixed with four pins. In the postoperative course, she received antibiotics and vasopressors for septic shock. However, there was no need for either a ventilator, dialysis or admission to the ICU. At seven days after the operation, a residual abscess was detected in the pouch of Douglas. We performed percutaneous drainage (Clavien-Dindo IIIa) and jejunostomy closedown 35 days after the first operation. The postoperative course was without complication, but she received rehabilitation until she was able to walk unaided. She was discharged 64 days after the first operation. Conclusion The occurrence of traumatic hernia is rare, especially in association with pelvic fractures. Although its rarity, traumatic hernia follows a severe course. Thus, proper diagnosis and effective treatment are necessary. Surgeons treating patients with pelvic injuries should consider the possibility of any complications and perform a work-up examination in order to achieve an accurate diagnosis at an earlier time point.

Patients with overweight reportedly have more comorbidities, including diabetes mellitus and cardiovascular disease, and longer operating times as well as more blood loss during surgery compared with those with normal weight. However, the impact of overweight on the short-term outcome after transthoracic esophagectomy for patients with esophageal squamous cell carcinoma (ESCC) remains unclear. We hypothesized that overweight has a negative impact on short-term surgical outcomes after esophagectomy for patients with ESCC.A total of 304 patients who underwent transthoracic esophagectomy for ESCC were included in this study. Body mass index (BMI) was classified into three categories,18.49, 18.50-24.99, and25.00 (kg/m(2)), defined as low, normal, and high BMI, respectively, according to the World Health Organization criteria. We investigated the association of BMI status with patient demographics and surgical outcomes after esophagectomy for patients with ESCC. In addition, overall survival and relapse-free survival stratified by BMI were compared.Fifty-nine (19.4 %) and 41 (13.4 %) patients were classified to low BMI and high BMI, respectively. The high-BMI group had significantly higher comorbidity rates of diabetes mellitus (p 0.01) and anastomotic leakage (p = 0.011) than the normal-BMI group. There were no significant association between high BMI and another various complications except for an anastomotic leakage, severe complications defined by Clavien-Dindo classification and in-hospital mortality. In multivariate analysis, high BMI was a significant risk factor for anastomotic leakage (p = 0.030, hazard ratio; 3.423, 95%CI; 1.128-10.38). On the other hand, no significant association was observed between low BMI and short surgical outcomes. There were no significant differences in overall and relapse-free survival among the three BMI groups in univariate and multivariate analysis (p = 0.128 and p = 0.584, respectively).The surgical treatment should not be denied for patients with ESCC due to overweight and underweight. However, intraoperative prevention and postoperative careful monitoring for anastomotic leakage might be required after esophagectomy for overweight patients with ESCC.

Previous studies have revealed that an elevated preoperative serum C-reactive protein (CRP) level is associated with a poor prognosis in patients with various malignant tumors. The aim of this study was to determine the clinical significance of the preoperative serum CRP level in patients with stage IV colorectal cancer.We enrolled 144 patients who underwent surgery for stage IV colorectal cancer. A total of 53 patients with a serum CRP level of ≥ 1.0 mg/dl were classified as the high CRP individuals. The association between the preoperative serum CRP level and survival was retrospectively assessed.The cancer-specific survival of the patients with a high CRP level was significantly worse than that of the patients with a low CRP level. A multivariate analysis indicated that the curability (non-curative surgery), the number of organs with metastasis (more than one organ), the tumor diameter (≥ 5 cm), lymphatic involvement, histological differentiation (non-differentiated) and a high CRP level (≥ 1.0 mg/dl) were independent risk factors for a poor survival.A high preoperative serum CRP level is a convenient biomarker for identifying patients with a poor prognosis for stage IV colorectal cancer.

Intraductal/intracystic papillary carcinoma (IPC) of the breast is defined as a malignant non-invasive papillary tumor arising from the ductal-lobular system. Based on the presence of myoepithelial cells in the cystic wall, IPC is distinguished from encapsulated papillary carcinoma (EPC). Here, we report a case of an intracystic apocrine papillary tumor in the breast of a 49-year-old woman. Histopathologic examination revealed that the entire papillary structures and cyst wall were comprised of apocrine cells, some of which showed nuclear atypia with macronucleoli. Immunohistochemical examination revealed a lack of myoepithelial cells in the papillary fronds and cyst wall. Although the dense proliferation of apocrine cells mimicked a cribriform pattern, detailed examination identified a delicately intermingled interstitium in the cribriform-like growth area in the present case. We judged the current case to be benign apocrine papilloma. Only a few apocrine variants of IPC or EPC have been reported to be malignant or potentially malignant. Since even benign apocrine lesions are known to lack myoepithelial cells, histopathologic evaluation regarding malignant potential requires caution in apocrine variants. The detection of clearly benign areas and knowledge of the "pseudo-cribriform" pattern should provide clues to distinguish between benign and malignant apocrine papillary tumors., Pathology - Research and Practice, 209(12), pp.808-811; 2013

A 25-year-old woman was admitted because of proteinuria. A renal biopsy showed mesangial/endocapillary proliferative glomerulonephritis with IgG2-κ deposits. Electron microscopy showed immune complex-type deposits. She also had Coombs-positive hemolytic anemia, anticardiolipin antibodies, and antinuclear antibodies. Middle-dose steroid therapy led to improvement of proteinuria and hemolytic anemia. Six years later, she developed crescentic glomerulonephritis with IgG2-κ deposits during pregnancy. Middle-dose steroid therapy improved renal dysfunction. This is an exceptional case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a recently described rare dysproteinemia-related glomerulonephritis, associated with autoimmune disease. This case also suggests that crescentic glomerulonephritis can be superimposed on PGNMID.

A 45-year-old man presented with moderate proteinuria and hematuria. A renal biopsy showed mesangial/endocapillary proliferative glomerulonephritis, linear deposition of monoclonal immunoglobulin γ1 C(H) 2 heavy chain along glomerular and tubular basement membranes (GBMs and TBMs), granular deposition of κ light chain within the mesangial area, and continuous linear deposits of finely granular electron-dense materials along GBMs and TBMs. Dual immunostaining showed essentially discrete glomerular localization of γ1 C(H) 2 heavy chain and κ light chain. Monoclonal protein was not detected in urine and serum. A bone marrow aspiration showed no abnormalities. Steroid therapy led to the improvement of proteinuria and hematuria. We would classify this case as a new variant of monoclonal immunoglobulin deposition disease, light chain/heavy chain deposition disease. In contrast with light and heavy chain deposition disease, the remarkable characteristics of this variant are separate deposition of monoclonal heavy chain and light chain, deposition of largely deleted γ heavy chain lacking the C(H) 1 domain, and good response to steroid therapy.

Atypia is admittedly a difficult topic to cover no matter what the organ system it is in. The most important reason for this is its subjective nature – it is in the eye of the beholder. In keeping with the mantra of The Paris System for Reporting Urinary Cytology, the goal for the “atypical urothelial cells” (AUC) category is to capture the cases worrisome for high-grade urothelial carcinoma that fall short of the “suspicious for high-grade urothelial carcinoma” (SHGUC) category. It is important to ensure that known causes of atypia such as polyomavirus change, treatment effect, etc., are classified as “negative for high-grade urothelial carcinoma” (NHGUC), and not under the AUC category. In order to make this a tangible and more objective category we have set forth criteria for AUC using four main cytomorphologic features: nuclear to cytoplasmic (N/C) ratio, nuclear chromasia, chromatin pattern, and features of the chromatinic rim. From a clinical standpoint, whenever the diagnosis of AUC is rendered on a case, this inconclusive category may create confusion and anxiety in the patient, and may lead to unnecessary procedures. Therefore, we recommend that the “AUC” interpretation should be kept at a minimum, and not be used as a waste basket.

We conducted a meta-analysis to evaluate and compare the outcomes of laparoscopic and open surgery for the treatment of patients with acute appendicitis. We searched MEDLINE, EMBASE, Science Citation Index, and the Cochrane Controlled Trial Register for relevant papers published between January 1990 and February 2012. We analyzed 22 outcomes of laparoscopic and open surgery for acute appendicitis. We identified 39 papers reporting results from randomized controlled trials that compared laparoscopic surgery with open surgery for acute appendicitis. Our meta-analysis included 5,896 patients with acute appendicitis; 2,847 had undergone laparoscopic surgery, and 3,049 had undergone open surgery. Compared with open surgery, laparoscopic surgery was associated with longer operative time (by 13.12 min). However, compared with open surgery, laparoscopic surgery for acute appendicitis was associated with earlier resumption of liquid and solid intake; shorter duration of postoperative hospital stay; a reduction in dose numbers of parenteral and oral analgesics; earlier return to normal activity, work, and normal life; decreased occurrence of wound infection; a better cosmesis; and similar hospital charges. Laparoscopic surgery may now be the standard treatment for acute appendicitis.

A 62-year-old splenectomized woman was admitted because of upper respiratory tract symptoms, general fatigue, and purpura. Laboratory data demonstrated microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure, and a positive Streptococcus pneumoniae (SP) urinary antigen test. A renal biopsy showed thrombotic microangiopathic changes. She was diagnosed with hemolytic uremic syndrome (HUS) secondary to SP infection. Methylprednisolone pulse therapy in addition to antibiotic therapy led to prompt improvement of her symptoms and laboratory abnormalities. This is the first adult case of SP-associated HUS successfully treated without hemodialysis. SP infection should be considered as a causative etiology in all splenectomized patients with HUS.

We report previously undescribed renal lesions associated with monoclonal gammopathy in a 59-year-old man with Waldenstrom macroglobulinemia (IgM-κ). Light microscopy showed mesangial proliferation and thickening of glomerular basement membranes (GBMs) and tubular basement membranes (TBMs). Neither intraglomerular thrombi nor nodular glomerulosclerosis was observed. Immunofluorescence studies disclosed essentially discrete localization of IgM heavy chain within the mesangial area and κ light chain along GBMs and TBMs. Electron microscopy showed continuous linear deposits of finely granular electron-dense material along the inner aspect of GBMs and TBMs. Repeated rituximab treatment and chemotherapy (melphalan and prednisolone) led to the improvement of proteinuria.

Purpose: We conducted a meta-analysis to evaluate and compare the short- and long-term results of laparoscopy-assisted colectomy (LAC) and open colectomy (OC) for colon cancer. Methods: We searched MEDLINE, EMBASE, Science Citation Index, and Cochrane Controlled Trial Register for relevant papers published between January 1990 and October 2011 by using the search terms “laparoscopy,” “laparoscopy-assisted,” “surgery,” “colectomy,” “colon cancer,” and “randomized clinical trials (RCTs)”. We analyzed the outcomes of each type of surgery over short- and long-term periods. Results: We selected 12 papers reporting RCTs that compared LAC with OC for colon cancer. Our meta-analysis included 4614 patients with colon cancer; of these, 2444 had undergone LAC and 2170 had undergone OC. In the short-term period, we found that the rates of overall postoperative complications and ileus in LAC were lower than in OC groups. LAC was associated with a reduction in intraoperative blood loss, a shorter duration of time to resumption and hospital stay, and lower rates of overall complication and ileus over the short-term, but with similar long-term oncologic outcomes such as overall and cancer-related mortality, overall recurrence, local recurrence, distant metastasis, and wound-site recurrence, compared to OC. Conclusions: It is suggested that LAC may be preferred to OC for colon cancer.

Invasive micropapillary carcinoma (IMPC) is a rare subtype of epithelial tumor of the breast listed in the 2003 World Health Organization histologic classification of tumors of the breast. It is characterized by inside-out micropapillary morphology, frequent lymph vessel invasion (LVI), and lymph node metastasis; however, its etiology remains unknown. This study investigated the incomplete inside-out growth pattern (IGP) in invasive ductal carcinoma, not otherwise specified (NOS), and examined the association between incomplete IGP and clinicopathologic features, including the presence of intratumoral lymph vessels (ILV), LVI, nodal metastasis, and prognosis. Tumor tissues from 166 invasive duct carcinomas NOS and 10 IMPCs were immunostained using an anti-epithelial membrane antigen antibody to detect IGP and with D2-40 antibody to determine the presence of ILV and LVI. Incomplete IGP was detected focally in 88 (53%) of 166 invasive duct carcinomas NOS. Transition areas between IMPC and invasive duct carcinoma NOS also showed prominent incomplete IGP in 9 (90%) of 10 IMPCs. Incomplete IGP in invasive duct carcinomas NOS was associated with larger tumor size, higher frequencies of ILV, LVI, nodal metastasis, and poorer recurrence-free survival by univariate analysis. Incomplete IGP, ILV, and tumor size independently affected LVI by multivariate analysis. These findings indicate that incomplete IGP of tumor cell clusters is not uncommon and is a useful tool for predicting LVI in invasive duct carcinoma NOS of the breast., Virchows Archiv, 458(2), pp.159-169; 2011

妊娠中に発症した急性虫垂炎は，しばしばその診断に苦慮することも多く，他の産婦人科的疾患との鑑別が必要になる．本症例は妊娠18週の患者で，上腹部痛を主訴に来院し，臨床所見および術前画像検査で急性虫垂炎が疑われたものの確定診断には至らなかった．腹腔鏡を施行のうえ，急性虫垂炎と診断し，腹腔鏡下にて虫垂切除術を安全に施行した．術後，合併症なく退院し，その後の妊娠経過も良好であった．腹腔鏡手術は妊娠時期により安全に施行できる点や，診断的治療が可能である点において有効であると考えられた．

小腸原発肉腫様癌の1例を経験した．症例は74歳の男性で，近医にて貧血を指摘され当院を受診した．小腸造影検査にて下部小腸に陰影欠損，腹部CTにて小腸間膜内のリンパ節腫大を認め，小腸原発悪性腫瘍の診断で手術を行った．回盲弁より70cm口側の回腸に約4cm大の腫瘍性病変を認め，また同部を栄養する上腸間膜動脈周囲に腫大したリンパ節を伴っており，これらを一括して切除した．病理組織学的および免疫組織化学的検索にて腫瘍細胞はAE1/AE3，CAM5.2やEMAなどの上皮性マーカーに加え間葉系マーカーであるvimentinが陽性で，CEA，c-kit，CD34は陰性であり，小腸原発の肉腫様癌と診断した．術後は肝転移の急速な増悪を認め，術後40日目に死亡した．小腸原発の肉腫様癌は自験例を含めて22例の報告があるのみとまれであり，文献的検討を加えて報告する．

Background A very few cases of biopsy-proven tubulointerstitial nephritis (TIN) in patients with primary biliary cirrhosis (PBC) have been reported. Although the clinical importance of this association has been suggested, information on its clinicopathological features and prognosis is limited. Methods We reviewed 5955 renal biopsies processed at our department, and identified four patients with TIN associated with asymptomatic PBC. We evaluated clinicopathological features and outcomes in these patients, and reviewed the previously reported cases of TIN associated with PBC. Results Our four patients were female. The patients' age at the time of renal biopsy ranged from 36 to 77. Three patients had been treated with ursodeoxycholic acid. All patients had urinary abnormalities such as proteinuria and elevated levels of urinary β(2)-microglobulin, and three patients had renal insufficiency. All patients had distal renal tubular acidosis (RTA), and two patients also had Fanconi syndrome. Renal biopsy showed severe lymphocyte infiltration in the tubules and interstitium with mild-to-moderate tubular atrophy and fibrosis. All patients responded well to steroid therapy. On review of the previously reported five cases, all patients were female. The patients' age ranged from 42 to 68. Apparent symptoms linked to PBC were not described. All patients had renal insufficiency. Three patients suffering from bone pains or bone fractures also had Fanconi syndrome. Marked or transient improvements were observed after steroid therapy in three patients. Conclusions TIN and RTA of different types are extremely rare but one of the important extrahepatic complications of PBC. Steroid therapy can be beneficial in treating PBC patients with these renal complications.

We conducted a meta-analysis to evaluate and compare the advantages of laparoscopy-assisted distal gastrectomy (LADG) over open distal gastrectomy (ODG) for treating early gastric cancer (EGC). We searched MEDLINE, EMBASE, Science Citation Index, and Cochrane Controlled Trial Register for relevant papers published between January 1990 and January 2010 by using the following search terms: laparoscopy-assisted gastrectomy, laparoscopic gastrectomy, and early gastric cancer. The following data were analyzed: operative time, estimated blood loss, number of harvested lymph nodes, time required for resumption of oral intake, duration of hospital stay, frequency of analgesic administration, complications, tumor recurrence, and mortality. We selected four papers reporting randomized control studies (RCTs) that compared LADG with ODG for EGC. Our meta-analysis included 267 patients with EGC; of these, 134 and 133 had undergone LADG and ODG, respectively. The volume of intraoperative blood loss, frequency of analgesic administration, and rate of complications were significantly lesser for LADG than for ODG. However, the time required for resumption of oral intake and duration of hospital stay did not significantly differ between LADG and ODG. The operative time for LADG was significantly longer than that for ODG; further, the number of harvested lymph nodes was significantly lesser in the LADG group than in the ODG group. LADG is advantageous over ODG because it results in lesser blood loss, is less painful, and is associated with a low risk of complications. Additional RCTs that compare LADG and ODG and investigate the long-term oncological outcomes of LADG are required to determine the advantages of LADG over ODG.

A 68-year-old man developed proteinuria and renal insufficiency. A renal biopsy showed mesangial proliferation and double contour in almost all glomeruli. Congo red staining for amyloid was negative. Immunofluorescence microscopy revealed no deposition of immunoglobulins. Electron microscopy showed unusual deposits of striated structures mainly in the subendothelial space and the mesangium. These deposits contained regularly stacked straight electron-dense bands. Microfilament-like deposits were also observed. The patient did not respond to steroid therapy and developed end-stage renal disease. All known disease entities with non-amyloid non-immunoglobulin-derived organized glomerular deposits were excluded. Progressive glomerulopathy in our patient might be a new disease entity.

症例は80歳，男性．脳梗塞で近医入院中に腹部腫瘤を疑われ，精査加療目的にて当院紹介となった．精査でも確定診断には至らず，診断も兼ねた手術を施行した．腫瘍は膀胱前腔から腹膜前腔に存在し，表面平滑な小児頭大の巨大腫瘤を呈していたが，消化管や腸間膜との癒着は認めなかった．膀胱頂部と強固に癒着しており剥離は困難であったため，正中臍索を切離し，膀胱部分合併切除にて腫瘤を摘出した．免疫組織学的検査で尿膜管起源の低悪性度粘液性腫瘍の診断に至った．本疾患は非常に稀であり有効な治療法は確立されておらず，若干の文献的考察を加えて報告する．

CA19-9産生脾嚢胞で極めて稀な破裂症例を経験したので報告する．症例は15歳の男性．2004年12月より脾嚢胞の診断で経過観察されていた．2008年9月，腹部打撲直後より腹痛出現し緊急入院した．入院時血中CA19-9は1,044U/mlと上昇していた．腹部CTで，虚脱した脾嚢胞と多量の腹水が認められ，脾嚢胞破裂の診断で緊急手術を行った．手術は開腹下に脾嚢胞天蓋切除・嚢胞底焼灼術を行った．腹水および嚢胞内容液は茶褐色でCA19-9は419×104U/mlと異常高値を示したが，細胞診は陰性であった．組織学的にはCA19-9免疫染色で強陽性に染色された扁平様上皮に覆われた良性の真性嚢胞と診断された．手術後，血中CA19-9は基準値内に復した．術後再発は認めていないが，長期成績の報告は少ないため今後も経過観察が必要と考えられた．

We report the cases of three patients with granulomatous lobular mastitis (GLM), who were treated successfully with low-dose steroid therapy. Furthermore, the findings of our review of 271 patients reported in the literature suggest that steroid therapy is the treatment of choice for GLM., Surgery today, 39(8), pp.695-699; 2009

This study aimed to investigate whether adipose tissue invasion (ATI) of cancer cells at the tumor margin influenced lymph node status and prognosis in patients with invasive ductal carcinoma of the breast. Data for 245 patients with breast cancer with marginal ATI were clinicopathologically compared with data for 65 patients without ATI. We also examined the value of the combination of ATI and peritumoral lymphatic vessel invasion (LVI). The frequency of axillary lymph node metastases was 40.7% in patients with ATI (99/243) and 11.3% in patients without ATI (7/62; P < .0001), and ATI was an independent factor influencing nodal metastasis. Patients with ATI had a poorer prognosis than patients without ATI (10-year disease-free survival, 76% and 94%, respectively; P = .0323). In addition, patients without ATI or LVI had neither lymph node metastasis (n = 52) nor recurrent disease (n = 53). ATI is one of the biologic indicators of tumor aggressiveness.

Calorie restriction (CR) is an experimental intervention in laboratory animals that attenuates age-associated increases in morbidity, mortality, and functional impairment. It is characterized by mild ketosis, hypoinsulinemia and hypoglycemia. In this study, we examined whether metabolic simulation of CR by a diet of isocaloric ketogenic or hypoinsulinemic diets ameliorated the learning and memory deficit in a strain of senescence-accelerated prone mice (SAMP8), a mouse model of age-dependent impairments in learning and memory. Male SAMP8 mice were fed high carbohydrate (CHO), high fat (FAT), or high protein (PRO) diets after weaning, and calorie intake was adjusted to 95% (sub ad libitum, sAL) or 70% (CR) of the mean calorie intake of control mice. At 28 weeks of age, we found CR ameliorated the performance defects of SAMP8 mice in a passive avoidance task. Neither FAT nor PRO diets affected performance of the task when fed sAL level, although a diet of these compositions partially mimicked the serum parameters of CR mice. These results suggest restriction of calorie intake is important for the prevention of learning and memory deficits, and that the simulation of serum changes induced by CR is not sufficient to prevent the cognitive defects of SAMP8 mice.

We attempted to elucidate the current status of endoscopic self-expanding metal stents for palliation of malignant gastroduodenal obstruction in comparison with surgical gastroenterostomy.Original articles and abstracts published from January 1990 to September 2006 were searched in Medline, EMBASE, and Cochrane Controlled Trials Register databases. Clinical appraisal and data extraction were independently conducted by two reviewers. Statistical analysis was performed by meta-analysis using a random effects model. Weighted mean differences with 95% confidence intervals (CI) were used to analyze continuous variables. Odds ratios with 95% CI were calculated for dichotomous variables.The outcomes of 307 procedures from nine studies were analyzed. Endoscopic stenting was found to be associated with higher clinical success (P = 0.007), a shorter time from the procedure to starting oral intake (P0.001), less morbidity (P = 0.02), lower incidence of delayed gastric emptying (P = 0.002), and a shorter hospital stay (P0.001) than surgical gastroenterostomy. There was no significant difference between the two groups in the analysis of 30-day mortality.Endoscopic stenting may be a feasible alternative to surgery for the palliation of inoperable malignant gastroduodenal obstruction, with a high clinical success and low morbidity rate. Additional well-designed randomized controlled trials with larger sample sizes are expected to further reinforce this conclusion.

A 58-year-old woman underwent laparoscopy-assisted transverse colectomy for transverse colon cancer. On postoperative day 7, she experienced sudden abdominal pain accompanied by vomiting and fever. Computed tomography showed a small bowel obstruction caused by an internal hernia. Laparotomy revealed an internal hernia through the mesenteric defect at the anastomotic colonic stumps, which had not been closed in the previous operation. Almost the entire small bowel protruding through the mesenteric defect was found in the omental bursa. We resected part of the jejunal loop, which was strangulated and congested by an adherent band. Our experience suggests that if the mesenteric defect is relatively small, it should be closed completely during laparoscopy-assisted colectomy; however, more studies are required to determine the indications for closure of the mesenteric defect to prevent this complication.

To investigate the relationship between spiculated masses at mammography and marginal adipose tissue invasion at histologic examination.The institutional review board approved this retrospective study, and the requirement to obtain informed consent was waived. A total of 478 patients with invasive breast cancer who underwent surgery between 1999 and 2009 were included in this study. Clinical-pathologic findings from patients with spiculated masses on mammograms were compared with those from patients without spiculated masses by using logistic regression models, Cox proportional hazards regression models, and the Kaplan-Meier method.There were 136 spiculated tumors and 342 nonspiculated tumors. All 136 spiculated tumors (100%) were positive for adipose tissue invasion, whereas only 264 of the 342 nonspiculated tumors (77%) were positive for adipose tissue invasion (P.001). Multivariate analysis revealed that adipose tissue invasion (P.001), histologic grade (P.001), dense breast (P = .002), and body mass index (P = .02) were independent factors associated with spiculation. With regard to survival, although many patients with spiculated tumors had a hormone-sensitive (estrogen receptor positive: P = .004; progesterone receptor positive: P = .001) or low-grade (P.001) tumor, in contrast to the patients without spiculated masses, the prognosis in the two groups was similar (disease-free survival: P = .09; overall survival: P = .23).Cancer cell interaction with adipose tissue is crucial for the finding of spiculation at mammography.

Background The pretreatment albumin to globulin ratio (AGR) has been reported to correlate with the long-term survival in patients with various cancers. However, there are no reports regarding the correlation between the pretreatment AGR and chemotherapeutic outcomes in patients with unresectable metastatic colorectal cancer. The aim of this study was to evaluate the prognostic significance of the pretreatment AGR in patients with unresectable metastatic colorectal cancer. Methods A total of 66 patients with unresectable metastatic colorectal cancer who underwent palliative chemotherapy for metastatic tumors were enrolled. The AGR was calculated as follows: Albumin/(Total protein - Albumin). Results The median pretreatment AGR was 1.254 (range: 0.849-1.840). We set 1.25 as the cut-off value based on the receiver operating characteristic curve. Based on the cut-off value of 1.25, 34 patients were classified into the high-AGR group and 32 patients were classified into the low-AGR group. The high-AGR group had a significantly higher chemotherapeutic disease control rate (p = 0.040) and better progression-free survival (p = 0.0171) and overall survival (p = 0.0360) rates than the low-AGR group. According to a multivariate analysis of survival, the AGR was identified to be an independent prognostic factor for progression-free survival (Hazard Ratio: 2.662, 95% Confidence Interval: 1.085-6.631, p = 0.033) and overall survival (Hazard Ratio: 2.247, 95% Confidence Interval: 1.069-4.722, p = 0.033). Conclusions The pretreatment AGR is a useful prognostic marker in patients with unresectable metastatic colorectal cancer who receive palliative chemotherapy.

Diffuse large B-cell lymphoma (DLBCL) with spindle cell components is extremely rare and often misdiagnosed as carcinoma or sarcoma. Here, we present a case of primary DLBCL with spindle cell components arising in the liver, for which a preoperative diagnosis by needle biopsies was unsuccessful. The patient was a 70-year-old man with a continuous cough. Thoracic computed tomography incidentally detected a mass of 5 cm in diameter in his liver. The initial and second needle biopsies from the liver mass were pathologically diagnosed as suspicious for sarcomatoid hepatocellular carcinoma. He underwent an extended left hepatectomy. Histological examination revealed a diffuse or epithelioid arrangement of round and polygonal cells, mixed with the fascicles of spindle-shaped cells. Immunohistochemically, all the morphological types of tumor cells showed positive reactions for a lymphocytic marker (CD45RB) and B-cell markers (CD20 and CD79a). Double-immunostaining revealed that the spindle-shaped tumor cells expressed CD20, but never expressed alpha-smooth muscle actin. Malignant lymphoma with a spindle cell morphology is quite uncommon, and this variant can be a diagnostic pitfall, especially in tiny biopsy specimens. We emphasize that pathologists should be reminded of lymphoma as a differential diagnosis of spindle cell tumors.

A 46-year-old woman developed nephrotic syndrome at the age of 16 in 1973. On the basis of the histological findings of the first renal biopsy, she was diagnosed as having minimal change nephrotic syndrome. Initial treatment with steroid was effective, but she had several relapses during tapering of the daily dose of steroid. The second renal biopsy, performed in 1997, disclosed glomerular lobulation, mesangial proliferation, nodular mesangial lesions, and mesangiolysis. From 2001, the degree of proteinuria increased, with urinary protein being 5 g/day in January 2003, when a third renal biopsy was performed. On light microscopy, the glomerular lesions were similar to those observed in 1997. Immunofluorescence microscopy revealed coarse granular stainings for IgG, IgA, IgM, kappa, lambda, and C3 in the mesangial area and along the capillary walls. On electron microscopy, fingerprint structures were observed in the mesangial and subendothelial deposits. There were no characteristic fibers in the nodular lesions. On the basis of clinical and laboratory findings in this patient, we excluded disease entities in which nodular mesangial lesions, mesangiolysis, and fingerprint deposits had been reported. To our knowledge, such a unique combination of glomerular lesions has not been described previously in the literature.