A case of diverticulum of the appendiceal base resembling a submucosal tumor of the cecum under colonoscopy: a hitherto undescribed lesion.

BACKGROUND: Diverticulosis of the appendix is an uncommon clinical entity, and a preoperative diagnosis is often difficult. Herein we report an unusual case of appendiceal diverticulosis. CASE PRESENTATION: A 72-year-old male was referred to our hospital to examine the cause of hematochezia. A colonoscopy study showed a protruding lesion resembling a submucosal tumor (SMT), approximately 20 mm in diameter, at the site around the appendiceal orifice of the cecum. An abdominal computed tomography and magnetic resonance imaging showed a cystic lesion at the appendiceal base. The lesion was clinically diagnosed as a cystic tumor of the appendix, but the possibility of a malignant tumor could not be excluded. Therefore, a laparoscopic ileocecal resection with lymph node dissection was performed. The pathological examination of the resected specimen revealed that the lesion was a diverticulum (pseudodiverticulum) occurring solitarily at the appendiceal base, in which the mucosal layer of the appendix was invaginated into the submucosa of the adjacent cecum, thus forming an SMT-like lesion. CONCLUSION: To our knowledge, this is the first case report in the English literature showing that an appendiceal diverticulum can manifest as an SMT-like lesion in the cecum. This condition should be recognized as a differential diagnosis for such lesions.

Heterotopic ossification in lymph node metastasis after rectal cancer resection: a case report and literature review.

BACKGROUND: Heterotopic ossification (HO) is the formation of osseous tissue outside the skeleton. HO in malignant tumors of the digestive tract is extremely rare, as is ossification in metastatic lesions from HO-negative digestive tract tumors. Regarding the pathogenesis of HO, two theories have been proposed. The first is that the osteoblastic metaplasia of tumor cells (driven by the epithelial-mesenchymal transition, EMT) results in HO, and the second is that factors secreted by cancer cells lead to the metaplasia of stromal pluripotent cells into osteoblasts. However, the osteogenic mechanisms remain unclear. CASE PRESENTATION: An 83-year-old Japanese woman underwent low anterior rectal resection for rectal cancer before presentation at our institution, in June 2018. The final diagnosis was stage IIB rectal adenocarcinoma (T4aN0M0). Histological examination did not reveal HO in the primary tumor. Thirteen months after the operation, a solitary metastatic lesion in the brain 20 mm in size and a solitary metastatic lesion in a right axillary lymph node 20 mm in size were diagnosed. The patient was treated with gamma-knife therapy for the brain metastasis. One month later, she was referred to our institution. She underwent lymph node resection. Histological examination revealed that most portions of the affected lymph node were occupied by metastatic tumor cells and that central necrosis and four small ossified lesions without an osteoblast-like cell rim were present in the peripheral region. Immunohistochemical analysis showed tumor cells positive for BMP-2, osteonectin, osteocalcin, AE1/AE3, TGF-ß1, Gli2, Smad2/3, and CDX2 and negative for nestin, CD56, and CK7. CONCLUSION: This is the first English case report of HO in a metachronous metastatic lymph node after the curative resection of HO-negative rectal cancer. Unlike HO lesions in past reports, the HO lesion did not show peripheral osteoblast-like cells, and the immunohistochemical findings indicated that the present case resulted from the EMT.

Clinical characteristics of elderly pulmonary tuberculosis in an acute-care general hospital in Tokyo, Japan: A 12-year retrospective study.

OBJECTIVE: A significant feature of tuberculosis (TB) in Japan is the fact that a high proportion of cases belong to the elderly population. Furthermore, previous reports have pointed out the delayed diagnosis of pulmonary TB in acute-care settings. We aimed to examine the clinical characteristics of pulmonary TB patients in an acute-care general hospital, particularly focusing on the elderly population. METHODS: We retrospectively reviewed the medical records of patients with pulmonary TB who presented at our institution between May 2005 and December 2016. We described the overall clinical characteristics of these patients and compared them according to age. RESULTS: Overall, 289 patients were eligible for the analysis, with a median age of 58 [42-73] years, and 29.4% being older than 70 years. Among the elderly patients, 42.4% were characterized by atypical presentation. CONCLUSION: Our findings suggest that the elderly population tends to present as atypical cases lacking respiratory complaints, thereby being at a risk of misdiagnosis.

Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae ST258 isolated from a Japanese patient without a history of foreign travel - a new public health concern in Japan: a case report.

BACKGROUND: Thus far, studies on Klebsiella pneumoniae carbapenemase (KPC)-producing organisms have only been reported in those with a history of foreign travel, and a specific Japanese KPC-producing isolate has not yet been reported. CASE PRESENTATION: We describe a Japanese patient, with no history of travel to foreign countries, admitted due to aspiration pneumonia, and a KPC-producing isolate detected in his sputum. Fortunately, his pneumonia resolved. His close contacts did not have a history of foreign travel, and the isolate was not detected in other patients. CONCLUSIONS: The potential for KPC-producing organisms to become endemic in Japan is currently of great concern.

Molecular epidemiological analysis of human- and chicken-derived isolates of Campylobacter jejuni in Japan using next-generation sequencing.

In this research, we analyzed the main sequence types (ST) and ST complexes of human- and chicken-derived isolates of Campylobacter jejuni in Japan by using multilocus sequence typing (MLST). We also analyzed lipooligosaccharide biosynthesis locus classes (LOS locus classes) and the numbers of isolates carrying genes coding resistance factors against various antibiotics, and observed their relationships. ST-21 complex was the main ST complex in isolates from humans (n = 38) and chickens (n = 25). None of the isolates showed resistance to imipenem, chloramphenicol, or erythromycin. Few isolates were resistant to ampicillin and streptomycin (1.3%-15%), whereas many showed resistance to tetracycline, ciprofloxacin, and nalidixic acid (38%-48%). Among the ST-21 complex isolates, ST4526 was detected at a very high rate. Those isolates showed resistance to tetracycline and ciprofloxacin, and were susceptible to ampicillin. Among the chicken-derived isolates, 37 of the 38 isolates that showed resistance to ciprofloxacin and nalidixic acid had threonine to isoleucine amino acid substitution in GyrA at codon 86 (T86I). Among the human-derived isolates, 17 of the 47 isolates that showed resistance to ciprofloxacin and 16 of the 48 isolates that showed resistance to nalidixic acid did not have T86I amino acid mutations in GyrA. The human-derived ST-21 complex isolates were classified into LOS locus classes A, B, C, D, and E. The chicken-derived ST-21 complex isolates, with the exception of one isolate, were all classified into LOS locus classes C and D. Among chicken-derived isolates, the most prevalent was ST51 (ST-443 complex) (10 isolates) and all of those were LOS locus class E.

The first case report of infective endocarditis caused by Gemella taiwanensis.

Gemella is a facultative anaerobic Gram-positive coccus and a rare cause of infective endocarditis (IE). Gram staining may eventually misidentify the organism, which tends to easily decolorize and manifest as either Gram-negative or Gram-variable. Commercial biochemical tests are often used to identify Gemella, but the methods they employ sometimes lack accuracy. A 52-year-old woman was diagnosed with Gemella taiwanensis IE after initial identification of the pathogen as Gemella haemolysans using biochemical tests combined with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). She was treated successfully with penicillin, gentamicin, and mitral valve replacement. To our knowledge, this is the first case of IE confirmed by 16S rRNA gene and groEL sequencing to have been caused by G. taiwanensis. The accurate diagnosis of rare or difficult-to-identify pathogens is a major challenge for clinical microbiological laboratories. The concurrent use of molecular methods could lead to the recognition of new or different pathogens.

Pseudo-SLE by human immunodeficiency virus infection.

A 61-year-old woman was admitted for long-lasting fever and recurrent opportunistic infections during the treatment of SLE. She had been diagnosed as SLE and type-IV nephritis based on a renal biopsy and serological findings. A colonoscopy and liver biopsy revealed disseminated Mycobacterium avium complex infection. Human immunodeficiency virus (HIV) infection status was then examined and found to be positive. From the clinical course, the first symptoms were inferred to have been those of HIV infection.

[A Case of Pathological Complete Response Following Neoadjuvant Chemotherapy with Gemcitabine plus Nab-Paclitaxel in Borderline Resectable Pancreatic Cancer].

We report a resected case with a pathological complete response(pCR)after neoadjuvant chemotherapy for borderline resectable pancreatic cancer(BRPC). A 67-year-old woman who had been treated for type 2 diabetes mellitus in our hospital presented with an exacerbation of diabetes. An abdominal CT scan confirmed a hypovascular mass in the pancreas body consistent with BRPC. After 3 courses of chemotherapy with gemcitabine plus nab-paclitaxel(GnP), her elevated DUPAN-2 level normalized. A follow up CT scan revealed that the tumor had decreased in size, and no distant metastasis was detected. Distal pancreatectomy with en-bloc celiac axis resection was performed. Histopathological examination of the resected specimens showed no evidence of residual cancer cells(pCR). The patient remains disease-free 8 months after surgery. Neoadjuvant GnP chemotherapy may be useful for BRPC.

Streptococcal toxic shock syndrome secondary to group A Streptococcus vaginitis.

Streptococcal toxic shock syndrome (TSS) is a systemic illness usually caused in the setting of infection by group A Streptococcus (GAS). The primary infections are often invasive infections of the respiratory tract or necrotizing infections of the skin and soft tissue, but some infections occur without relevant focus. GAS vaginitis is a rare condition among adult women and is accordingly thought to be uncommon as a cause of streptococcal TSS. Here we report the cases of two postmenopausal women with streptococcal TSS secondary to GAS vaginitis, one aged 55 and one aged 60. Both came to our emergency department with complaints or symptoms of abdominal pain, fever, hypotension, and multi-organ failure. In both cases, the relevant factor associated with streptococcal infection was a recent episode of GAS vaginitis. Both underwent fluid management and 14 days of antibiotic treatment and fully recovered without complications. Vaginitis was likely to be the primary infectious trigger of TSS in these two cases. Intrauterine device insertion, endometrial biopsy, and post-partum state have all been previously reported in TSS patients, and the female genital tract has been described as a portal of entry. GAS vaginitis warrants appropriate treatment as it may progress to severe systemic infection as described.

Anterior mediastinal abscess diagnosed in a young sumo wrestler after closed blunt chest trauma.

Most mediastinal abscesses result from infections after thoracotomy, esophageal perforation or pene- trating chest trauma. This disease is rarely caused by closed blunt chest trauma. All previously reported such cases after closed blunt chest trauma presented with hematoma and sternal osteomyelitis resulting from sternal fracture. Here we report a 15-year-old sumo wrestler who presented with an anterior mediastinal abscess without any mediastinal fracture. The mediastinal abscess resulted from the hematogenous spread of Staphylococcus aureus to a hematoma that might have been caused by a closed blunt chest trauma incurred during sumo wrestling exercises.

Leptospirosis in a Japanese urban area: a case report and literature review.

Leptospirosis is not a major disease in urban areas of Japan. We describe a 49-year-old man with leptospirosis, who lived in an urban area and had no history of living in endemic area of leptospirosis. As he worked at a fish market infested with rats, he was suspected of having contracted leptospirosis and received antimicrobial agent treatment. Serum and urinary tests confirmed the diagnosis of leptospirosis. Although it took six days from the onset until treatment initiation, the patient improved in response to receiving ceftriaxone for seven days. Analyzing past reports of Japanese patients with leptospirosis who had no history of overseas travel, we identified 90 patients with courses similar to that of our patient, and the period from onset to treatment initiation was about six days on average (described in 46 cases). Health care providers as well as patients need to recognize that even people with no history of being in an endemic area of leptospirosis may still be at risk of developing this disease depending on occupations and activities.

Treatment of Japanese patients with enteric fever using azithromycin and MIC levels for causative organisms.

In Japan azithromycin (AZM) has been used to treat enteric fever caused by bacteria with resistance to fluoroquinolones; however, the dose, length of treatment and effectiveness of AZM among Japanese patients with enteric fever is unclear. We studied 5 Japanese adults and 1 Japanese child with enteric fever (4 had typhoid fever and 2 had paratyphoid fever) who were treated with oral AZM. The treatment regimens were: 1,000 mg as a single or in 2 divided doses on the 1st day, followed by 500 mg as a single dose daily for 5-6 additional days, or 500 mg as a single dose daily for 10 days. The minimum inhibitory concentrations (MICs) for AZM against 5 causative organisms were investigated with an E-test. Good clinical results were observed in the 5 adult patients but treatment failure was seen in the 1 child patient with typhoid fever; no adverse reactions were found. MICs of AZM were 4 microg/ml against S. Typhi in 2 patients, 8 microg/ml against S. Typhi in 2 patients, and 32 microg/ml against S. Paratyphi A in 1 patient. Our findings indicate AZM may be a reasonable choice for treatment of Japanese adult patients with enteric fever.

[Results of a questionnaire survey on the use of gentamicin sulfate injection].

Unlike what has been approved overseas, only a low dose is approved in Japan for the use of Gentamicin Sulfate Injection (hereinafter referred to as GM Injection). A change in dose and administration was requested to the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs. As a consequence, high-dose GM Injection began to be developed in Japan. In order to assess the current use of GM Injection, a questionnaire survey was conducted among infectious disease specialists certified by the Japanese Association for Infectious Diseases, and physicians certified as specialists/instructors of antibiotic chemical treatment by the Japanese Society of Chemotherapy. Valid responses were obtained from as many as 38.0% of questionnaire recipients (719/1891 physicians). About 30% of the respondents used GM Injection in the year 2011. Major indications for adult patients included sepsis and infective endocarditis, and bacterial strains mainly included Pseudomonas aeruginosa, Staphylococcus, Enterococcus and Streptococcus species. Some diseases and bacterial strains domestically unapproved as indications were also treated with GM Injection. GM Injection is administered mainly as an intravenous infusion, usually once daily, which is not approved in Japan. Some physicians administered a fixed dose of GM (120 mg/day or less), not more than the upper limit approved in Japan. The majority of physicians, however, adopted a dosage of 3-5 mg/kgy/day, the standard dosage approved overseas. Physicians who implemented TDM outnumbered those who did not. The target blood level when administering 2-3 times a day was mostly 2 microg/mL or less as the trough level, and 4-10 microg/mL as the peak level. In particular, GM Injection was concurrently administered with other injectable antimicrobial agents to treat sepsis or infective endocarditis mainly in the following combinations: with penicillins or carbapenems for sepsis: with penicillins for infective endocarditis. Renal impairment was the most common adverse reaction requiring special care to be reported by the respondents. The survey revealed the current status of use, which is that GM Injection is used at the dose and administration approved in Japan, and that high-dose GM Injection, equivalent to the dosage approved overseas, is also used by quite a few physicians. The current use supports the request submitted to the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs. Therefore, the same dosage that is approved overseas is recommended to be approved as soon as possible in Japan.

Generation of a neutralizing human monoclonal antibody Fab fragment to surface antigen 1 of Toxoplasma gondii tachyzoites.

A combinatorial immunoglobulin gene library was constructed from lymphocytes in peripheral blood of a patient with toxoplasmosis and screened for production of human monoclonal antibody Fab fragments to recombinant surface antigen 1 (SAG1) of Toxoplasma gondii. Two Fab clones, Tox203 and Tox1403, which consisted of a common heavy chain and different light chains, showed positive staining on the entire surface of tachyzoites in confocal microscopy. Sequence analysis of the heavy-chain gene revealed that the closest germ line V segments were VH3-23. The germ line D segment was D1-7, and the closest germ line J segment was JH4. In the light-chain genes, the closest germ line V segment was Vκ1-17 with the Jκ1 or Jκ4 segments. The dissociation constants of these Fab fragments with recombinant SAG1 were 3.09 × 10(-9) M for Tox203 and 2.01 × 10(-8) M for Tox1403, indicating that the affinity of Tox203 was 7 times higher than that of Tox1403. Preincubation of T. gondii tachyzoites with Tox203 significantly inhibited their attachment to cultured MDBK cells. Passive immunization of mice with Tox203 also significantly reduced mortality after challenge with T. gondii tachyzoites. This is the first report of bacterial expression of human monoclonal antibody Fab fragments to SAG1 of T. gondii. These results also demonstrate that human Fab fragments to SAG1 might be applicable for immunoprophylaxis of toxoplasmosis.

[Notable imported infectious diseases].

Japanese doctors are somewhat unfamiliar with imported infectious diseases, however, the following imported infectious diseases are notable: cholera, which is currently endemic in Haiti and which there is a possibility of it being imported to Japan from endemic areas; typhoid fever and paratyphoid fever, whose causative organisms showing low sensitivity to fluoroquinolones have become predominant; rabies, which exhibits a high mortality; avian influenza H5N1, which has the possibility of changing into a new type of human influenza; chikungunya fever, in which the number of Japanese patients is increasing; and cyclosporiasis, which led to a number of food poisonings in the USA and Canada, and as a growing number of Japanese travel abroad, the number of infected Japanese patients returning from endemic areas will increase. It is thus important to identify the presence of these diseases on diagnosis.

[Albendazole in Japanese juvenile with enterobiasis in whom pyrantel pamoate is not effective].

A 18-year-old Japanese woman seen as an outpatient for refractory enterobiasis had been treated with pyrantel pamoate over 40 times since the age of 11. She washed her hands and cleaned house frequently, and all family members took pyrantel pamoate, but Enterobius vermicularis eggs remained. She was orally administered 400 mg of albendazole 3 times in clinic visits, after which eggs have not been seen for 1 year. Pyrantel pamoate is used widely against enterobiasis in Japan. Our case shows albendazole to also be effective against enterobiasis. Albendazole thus appears to be a useful anti-helminthic in enterobiasis patients in whom pyrantel pamoate is not effective. This is, to our knowledge, the first case of enterobiasis treated with albendazole in Japan.

Possible spontaneous regression of hepatocellular carcinoma with unique histopathological features confirmed by surgical resection: a case report.

BACKGROUND: Spontaneous regression of hepatocellular carcinoma (HCC) is a rare event, and its clinicopathological features and underlying mechanism are not fully understood. CASE PRESENTATION: An 84-year-old female with hepatitis C virus infection and diabetes mellitus was referred to our hospital for further examination. Abdominal ultrasonography showed a 3.4-cm solid tumor with a heterogeneous irregular center and no fibrous capsule in liver segment 8 (S8). An enhanced computed tomography (CT) scan revealed a tumor in S8 with heterogeneous enhancement in the arterial phase and washed out insufficiently in the portal and equilibrium phase. The enhanced pattern on magnetic resonance imaging was similar to that of CT. Although the imaging findings were not typical for HCC, liver resection (S8) was performed with HCC as the most probable diagnosis. Histopathological examination of the resected specimen showed that the tumor was well to moderately differentiated HCC with unique features. Approximately half of the tumor was composed of well-differentiated HCC that was focally accompanied by dense lymphocyte infiltration. The other half of the tumor was fibrotic tissue that resembled an inflammatory pseudotumor. Several foci of moderately differentiated HCC were scattered within the tumor with a nodule-in-nodule appearance, and the foci totally showed coagulative necrosis. On immunostaining, lymphocytes in the tumor stroma were positive for CD8 and programmed death 1. The expression of programmed death-ligand 1 was observed in carcinoma cells and macrophages specifically within the lymphocyte-rich area of HCC. CONCLUSIONS: We consider this case representative of spontaneous regression of HCC, and the immune response against HCC might contribute to tumor regression, leading to complex histopathological appearances. This case may provide insight into the mechanism of spontaneous regression of HCC.

Plasmid-mediated resistance to cephalosporins in Salmonella enterica serovar Typhi.

This study characterized a cephalosporin-resistant Salmonella enterica serovar Typhi isolate. The organism possessed a plasmid encoding the CTX-M-15 extended-spectrum-beta-lactamase. This plasmid is the determinant for the phenotype of cephalosporin resistance and is transferrable among Enterobacteriaceae.