Terminal deletion of the long arm of chromosome 3 [46,XX,del(3)(q27→qter)]

We report on a terminal deletion of the long arm of chromosome 3 [46,XX,del(3)(q27→qter)] in a female newborn infant who died 45 hours after delivery and had multiple congenital abnormalities including bilateral anophthalmia, congenital heart disease, and abnormal genitalia. The findings are compared to those of four previously reported cases with terminal del (3q). © 1996 Wiley-Liss, Inc.     

Definite familial multiple system atrophy with unknown genetics

Multiple system atrophy (MSA) is an oligodendrogliopathy of presumably sporadic origin, characterized by prominent α‐synuclein inclusions with neuronal multisystem degeneration, although a few Mendelian pedigrees have been reported. Here we report two familial cases of MSA of unknown genetic background. One patient was diagnosed as a possible MSA‐C (cerebellar dysfuntion) case, and the other as clinically possible MSA‐P (parkinsonism), which turned out to be definite MSA, based on a detailed autopsy. The neuropathology showed extensive deposition of α‐synuclein in the glia as well as in the neurons located in the cerebral cortices and hippocampal systems, although neither multiplication of the SNCA gene or mutations in COQ2 gene were identified in the family concerned.     

Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia

Recently, somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, have been reported in acute myeloid leukemia (AML). We analyzed the clinical significance of NPM1 mutations in comparison with cytogenetics, FLT3, NRAS, and TP53 mutations, and a partial tandem duplication of the MLL gene (MLL-TD) in 257 patients with AML. We found NPM1 mutations, including 4 novel sequence variants, in 64 of 257 (24.9%) patients. NPM1 mutations were associated with normal karyotype and with internal tandem duplication (ITD) and D835 mutations in FLT3, but not with other mutations. In 190 patients without the M3 French-American-British (FAB) subtype who were treated with the protocol of the Japan Adult Leukemia Study Group, multivariate analyses showed that the NPM1 mutation was a favorable factor for achieving complete remission but was associated with a high relapse rate. Sequential analysis using 39 paired samples obtained at diagnosis and relapse showed that NPM1 mutations were lost at relapse in 2 of the 17 patients who had NPM1 mutations at diagnosis. These results suggest that the NPM1 mutation is not necessarily an early event during leukemogenesis or that leukemia clones with NPM1 mutations are sensitive to chemotherapy.     

The topoisomerase II alpha gene status in primary breast cancer is a predictive marker of the response to anthracycline-based neoadjuvant chemotherapy

This study aimed at evaluating the usefulness of topoisomerase II alpha (TOP2A) for predicting the effect of anthracycline-based neoadjuvant chemotherapy in breast cancer. The TOP2A status was examined using fluorescent in situ hybridization (FISH) in 14 pre-chemotherapeutic breast cancer tissues, and was also assessed by immunohistochemistry (IHC) in 14 pairs of pre- and post-chemotherapeutic breast cancer specimens. TOP2A gene aberration by IHC tended to show a correlation with pathological responses but this was not statistically significant (p=0.060). On the other hand, the low TOP2A/CEP17 ratio correlated with good pathological responses (p=0.012). TOP2A overexpression was not significantly associated with response (p=0.580). Our results thus suggest that the TOP2A/CEP17 ratio may be a useful predictor of the effects of anthracycline-based neoadjuvant chemotherapy in breast cancer.     

Multiple system atrophy variant with severe hippocampal pathology

The striatonigral and olivopontocerebellar systems are known to be vulnerable in multiple system atrophy (MSA), showing neuronal loss, astrogliosis, and alpha-synuclein-immunoreactive inclusions. MSA patients who displayed abundant neuronal cytoplasmic inclusions (NCIs) in the regions other than the striatonigral or olivopontocerebellar system have occasionally been diagnosed with variants of MSA. In this study, we report clinical and pathologic findings of MSA patients characterized by prominent pathologic involvement of the hippocampus. We assessed 146 consecutively autopsied MSA patients. Semi-quantitative analysis of anti-alpha-synuclein immunohistochemistry revealed that 12 of 146 patients (8.2%) had severe NCIs in two or more of the following areas: the hippocampal granule cells, cornu ammonis areas, parahippocampal gyrus, and amygdala. In contrast, the remaining 134 patients did not show severe NCIs in any of these regions. Patients with severe hippocampal involvement showed a higher representation of women (nine women/three men; Fisher's exact test, p = 0.0324), longer disease duration (13.1 ± 5.9 years; Mann–Whitney U-test, p = 0.000157), higher prevalence of cognitive impairment (four patients; Fisher's exact test, p = 0.0222), and lower brain weight (1070.3 ± 168.6 g; Mann–Whitney U-test, p = 0.00911) than other patients. The hippocampal granule cells and cornu ammonis area 1/subiculum almost always showed severe NCIs. The NCIs appeared to be ring-shaped or neurofibrillary tangle-like, fibrous configurations. Three of 12 patients also had dense, round-shaped NCIs that were morphologically similar to pick bodies. The patients with Pick body-like inclusions showed more severe atrophy of the medial temporal lobes and broader spreading of NCIs than those without. Immunohistochemistry for hyperphosphorylated tau and phosphorylated TDP-43 revealed minimal aggregations in the hippocampus of the hippocampal MSA patients. Our observations suggest a pathological variant of MSA that is characterized by severe involvement of hippocampal neurons. This phenotype may reinforce the importance of neuronal alpha-synucleinopathy in the pathogenesis of MSA.     

Serum soluble interleukin‐2 receptor level is more sensitive than angiotensin‐converting enzyme or lysozyme for diagnosis of sarcoidosis and may be a marker of multiple organ involvement

Skin lesions in sarcoidosis are often the initial symptoms that enable the dermatologist to be the first to diagnose this granulomatosis. However, diagnosis is sometimes very problematic. In 2015, the diagnostic criteria for sarcoidosis were updated in Japan, with elevated serum soluble interleukin‐2 receptor (sIL‐2R) replacing negative tuberculin reaction. Therefore, we assessed the clinical utility of sIL‐2R compared with two other common markers, angiotensin‐converting enzyme (ACE) and lysozyme, in patients who visited the dermatology clinic. Data from 72 patients showed that sIL‐2R was more sensitive than both ACE and lysozyme in supporting a diagnosis of sarcoidosis (52.8%) compared with ACE (29%) and lysozyme (26.4%). Additionally, the sIL‐2R level was significantly higher in patients with multiple organ involvement and parenchymal infiltration. Patients with elevated sIL‐2R levels had higher serum ACE and lysozyme levels, a higher incidence of pulmonary involvement, more severe chest radiographic stage and a high incidence of expression‐specific signs by imaging analysis. Receiver–operator curve analysis showed that sIL‐2R was a better marker at the threshold cut‐off point compared with ACE and lysozyme for identifying patients with multiple organ involvement, detecting patients with pulmonary disease and parenchymal infiltration as well as predicting the presence of specific signs in the diagnosis of sarcoidosis. Moreover, the kinetics of sIL‐2R levels correlated closely with clinical manifestations, in contrast to the modest changes of ACE and lysozyme levels during the follow‐up period. In conclusion, sIL‐2R may be considered a good marker for diagnosis and a potential indicator of disease activity.     

Comparison of laparoscopy-assisted and open pylorus-preserving pancreaticoduodenectomy for periampullary disease

Background

Although many reports have described laparoscopic pancreatic surgery, pancreaticoduodenectomy (PD) has not been widely accepted. The present study aimed to compare laparoscopy-assisted and open pylorus-preserving pancreaticoduodenectomy (PPPD) to investigate the feasibility, safety, and tumor clearance.

Methods

Fifteen patients with periampullary disease underwent laparoscopy-assisted PPPD, in which resection was performed laparoscopically and the reconstruction was performed through a small midline incision. These patients were compared with 15 patients who, during the same period, underwent conventional open PPPD.

Results

Mean operative time and mean blood loss were similar between groups. No significant differences in the incidence of complications or hospital stay were noted between groups. Surgical margin and number of lymph nodes found in the resected specimen did not differ between groups.

Conclusions

Laparoscopy-assisted PPPD is on the same level with conventional open surgery in terms of perioperative outcomes or treatment efficacy.