TP53 variants in p53 signatures and the clonality of STICs in RRSO samples

ObjectivePrecursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer.MethodsWe analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease.Results TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer.ConclusionThe sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.     

Pancreatic Exocrine Insufficiency in Intraductal Papillary Mucinous Carcinoma Presenting with Leg Edema Treated with Pancreatic Exocrine Replacement Therapy

An 89-year-old woman underwent examinations for leg edema. Blood tests indicated low nutrition and low pancreatic enzymes, and a stool examination indicated fatty stool. Computed tomography showed pleural effusion, ascites, and cystic lesions in the pancreatic head and mural nodules within the cysts. Pancreatic juice cytology revealed adenocarcinoma. The diagnosis was pancreatic exocrine insufficiency caused by intraductal papillary mucinous carcinoma. The patient did not wish to undergo surgery. Therefore, diuretics, component nutrients, and pancreatic exocrine replacement therapy using pancrelipase were initiated. After starting treatment, her leg edema, pleural effusion, and ascites disappeared, and her activities of daily living improved markedly.     

Risk factors for postoperative pneumonia in elderly patients with colorectal cancer: a sub-analysis of a large,multicenter, case-control study in Japan

Surgery Today - Postoperative pneumonia affects the length of stay and mortality after surgery in elderly patients with colorectal cancer (CRC). We aimed to determine the risk factors of...     

Expression of parathyroid hormone/parathyroid hormone-related peptide receptor 1 in normal and diseased bladder detrusor muscles: a clinico-pathological study

Background

To investigate the expression of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor 1 (PTH1R) in clinical specimens of normal and diseased bladders. PTHrP is a unique stretch-induced endogenous detrusor relaxant that functions via PTH1R. We hypothesized that suppression of this axis could be involved in the pathogenesis of bladder disease.

Methods

PTH1R expression in clinical samples was examined by immunohistochemistry. Normal kidney tissue from a patient with renal cancer and bladder specimens from patients undergoing ureteral reimplantation for vesicoureteral reflux or partial cystectomy for urachal cyst were examined as normal control organs. These were compared with 13 diseased bladder specimens from patients undergoing bladder augmentation. The augmentation patients ranged from 8 to 31 years old (median 15 years), including 9 males and 4 females. Seven patients had spinal disorders, 3 had posterior urethral valves and 3 non-neurogenic neurogenic bladders (Hinman syndrome).

Results

Renal tubules, detrusor muscle and blood vessels in normal control bladders stained positive for PTH1R. According to preoperative urodynamic studies of augmentation patients, the median percent bladder capacity compared with the age-standard was 43.6% (range 1.5–86.6%), median intravesical pressure at maximal capacity was 30 cmH₂O (range 10–107 cmH₂O), and median compliance was 3.93 ml/cmH₂O (range 0.05–30.3 ml/cmH₂O). Detrusor overactivity was observed in five cases (38.5%). All augmented bladders showed negative stainings in PTH1R expression in the detrusor tissue, but positive staining of blood vessels in majority of the cases.

Conclusions

Downregulation of PTH1R may be involved in the pathogenesis of human end-stage bladder disease requiring augmentation.     

Influence of Underweight on Asthma Control

Background: Although the association between asthma control and body mass index (BMI) has been thoroughly investigated, most of this work has focused on the influence on asthma incidence or the effect of obesity on asthma control. To date, there have been no published studies on the influence of underweight on asthma control.Methods: The aim of this study was to investigate the influence of underweight, as defined by the Japan Society for the Study of Obesity (JASSO), on asthma control in Japanese asthmatic patients. Using data from questionnaire surveys administered by the Niigata Asthma Treatment Study Group, we compared asthma control, as measured by the Asthma Control Test (ACT), between a normal weight group (18.5 kg/m² =< BMI < 25 kg/ m²) and an underweight group (BMI < 18.5 kg/m²).Results: Of the asthmatic patients who completed the 2008 and 2010 surveys, 1464 and 1260 cases were classified as being in the normal weight group, and 174 and 155 cases were classified as being in the underweight group. The ACT score (median, [interquartile range]) in the underweight group in 2008 (22, [19-24]) and 2010 (23, [19-25]) was significantly lower than that in the normal group in 2008 (23, [20-25]) and in 2010 (24, [21-25]).Conclusions: This study is the first, large-scale investigation of the influence of underweight on asthma control, and we have confirmed an adverse influence in a clinical setting. A potential mechanism for this interaction was unknown. Further investigation will be required.     

Treatment of a patient with hemophilia A and hepatitis C virus-related cirrhosis by living-related liver transplantation from an obligate carrier donor

BACKGROUND: Decompensated hepatitis C virus (HCV)-related cirrhosis is the main indication for liver transplantation. We report the first successful living-related liver transplantation in a 49-year-old hemophilia A patient with end-stage HCV-related cirrhosis using a graft obtained from his 20-year-old daughter, an obligate carrier. METHODS: The donor's autologous fresh-frozen plasma rich in factor VIII (FVIII) by treatment with 1-deamino-8-D-arginine vasopressin was prepared before the operation. At induction, 1-deamino-8-D-arginine vasopressin was given to the donor to increase plasma FVIII level. In addition, autologous fresh-frozen plasma containing high FVIII concentrate was infused intraoperatively. The right lobe was harvested from the donor and transplanted orthotopically. The recipient was treated postoperatively with recombinant FVIII and immunosuppressive agents. RESULTS: The donor did not receive recombinant FVIII or allogenic blood during perioperative periods. No bleeding was encountered in the donor perioperatively. The recipient showed a steady increase in FVIII activity postoperatively and was discharged 40 days after transplantation. Ribavirin and interferon-alpha were provided for 3 months postoperatively to prevent potential recurrence of HCV infection. Serum HCV-RNA by RT-PCR became negative after such treatment. CONCLUSIONS: End-stage liver disease in patients with hemophilia A can be an indication for living-related liver transplantation. Furthermore, a graft from a living-related donor with hemophilia A carrier seems to be suitable provided such individuals receive adequate support for coagulopathies.     

CD1-dependent natural killer (NK1.1(+)) T cells are required for oral and portal venous tolerance induction

BACKGROUND: Local antigen presentation via either the oral (PO) or the portal venous (PV) routes results in suppression of systemic delayed-type hypersensitivity (DTH). The responsible cell populations are not well defined. Because NK1.1(+) T cells express the Fas ligand and produce high levels of the immunosuppressive cytokine, IL-4, they may play a role in both activated T-cell apoptosis and a Th1 to Th2 immune shift, thus promoting tolerance induction. METHODS: C57BL/6 mice were tolerized to BALB/c alloantigen by PV or PO spleen cells (25 x 10(6)) on Day 0. Subcutaneous (SQ) challenge with 10 x 10(6) BALB/c cells on Day 7 was followed by footpad injection of 10 x 10(6) BALB/c cells on Day 14. Footpad swelling was measured 24 h later. A single injection of the NK1.1(+) cell-depleting antibody, PK-136, was given IP (10 mg/kg) 2 days prior to PV or PO antigen. Flow cytometry evaluated NK1.1(+) cell depletion. CD1 knockout (KO) mice, lacking NK1.1(+) T cells, were also challenged with PV and PO Balb/c in parallel experiments. RESULTS: The DTH to BALB/c antigen was markedly suppressed in C57BL/6 mice when this alloantigen was given by either PO or PV routes (P < 0.001, P < 0.001). The maintenance of an unaltered response to third-party C3H/HeJ demonstrated alloantigenic specificity. Administration of the anti-NK1.1 T cell monoclonal antibody, PK-136, resulted in complete restoration of in vivo DTH responsiveness in PO tolerance (P < 0.01), and partial restoration in PV tolerance (P < 0.05) in C57BL/6 mice. FACS confirmed virtually complete depletion of liver, splenic, Peyer's patch, and mesenteric lymph node NK1.1(+) lymphocytes. Development of both PO and PV tolerance was prevented in CD1 KO mice. CONCLUSION: NK1.1(+) T cells play an essential role in antigen-specific suppression of the DTH response mediated by both oral and portal venous tolerance.     

Accessory mitral valve associated with aortic regurgitation in an elderly patient: report of a case

We encountered a 75-year-old man who complained of exertional dyspnea. An echocardiographic examination showed aortic regurgitation and a tumor in the left ventricular outflow tract. Under complete extracorporeal circulation, we surgically made an incision of the ascending aorta with a slight thickening of the aortic valve and an enlarged annulus. After excising the aortic valve, an examination of the subvalvular region revealed mitral valve-like tissue extending from the annular region of the right coronary cusp to the ventricular septum, while the chordae tendinae was attached to the septum. This issue was excised, and the aortic valve was replaced with a 27-mm SJM valve. The postoperative course was uneventful, and the patient was discharged in good condition on postoperative day 30. An accessory mitral valve is extremely rare. Since this indication for surgical treatment is associated with congenital heart disease or a left ventricular outflow tract obstruction, most patients are young. Our patient had no associated cardiac anomalies and no pressure gradient attributable to a left ventricular outflow tract obstruction. This accessory mitral valve was discovered during aortic valve replacement surgery. To our knowledge, our patient is the oldest reported with an accessory mitral valve to have undergone a surgical resection.     

Anesthetic management for pneumonectomy in a patient with cardiac amyloidosis

Cardiac amyloidosis may cause restrictive cardiomyopathy associated with heart failure, conduction disorder and ischemic heart disease. Therefore, patients with amyloidosis require careful hemodynamic monitoring in perioperative period. A 63-year-old man with cardiac amyloidosis was scheduled for pneumonectomy. His transthoracic echocardiography assessment showed a hypertrophic interventricular septum and slight decreased ejection fraction of 55%, but left ventricular (LV) diastolic function was decreased. Pulse Doppler for mitral valve inflow showed that the early peak velocity/atrial peak velocity (E/A) ratio was 0.9, the deceleration time (DT) was 163 msec and the early diastolic mitral annular tissue velocity (E') was 4 cm x sec(-1). These data suggested a pseudonormalization state. We performed careful monitoring using arterial pressure-based cardiac output (APCO), central venous oxygen saturation (ScvO2) and transesophageal echocardiography. There were no severe complications such as circulatory collapse and arrhythmia in the perioperative period.