Epstein–Barr virus positivity among surgically resected intramucosal gastric cancer

Epstein–Barr virus‐associated gastric cancer (EBV‐GC) accounts for approximately 8% of gastric cancers. However, little is known regarding intramucosal EBV‐GC. The present study aimed to evaluate endoscopic and clinicopathological characteristics of intramucosal EBV‐GC. Pathological data of 172 patients with 173 intramucosal gastric cancers who received gastrectomy with lymph node dissection were obtained for review. EBV‐encoded small RNA in situ hybridization (EBER‐ISH) was carried out using a tissue microarray block. Eight intramucosal early gastric cancers (4.6%) were EBER‐ISH positive in which no cases had any lymph node metastasis. Macroscopic types were either depressed or flat, dominant histology was mixed type of moderate and poorly differentiated adenocarcinoma. In detail, histological features of “lace pattern” or “lymphocyte infiltration into the stroma or cancer nests” were observed.     

Subtle CD20 positivity in the bone marrow of a patient who has a mucosa‐associated lymphoid tissue lymphoma should not be regarded as evidence of involvement in the bone marrow

Aims: Bone marrow (BM) biopsies of some mucosa‐associated lymphoid tissue (MALT) lymphoma patients show scattered or small clusters of CD20+ cells without definite lesions (subtle CD20 positivity). The aim of this study was to evaluate the clinical significance of BM involvement and subtle CD20 positivity in 122 patients diagnosed with MALT lymphoma. Methods and results: Patients were divided into three categories: BM involvement [BM(+)], subtle CD20 positivity, and no BM involvement [BM(?)]. Eleven (9%) showed BM involvement, and 17 (14%) showed subtle CD20 positivity. BM(+) patients had significantly worse progression‐free survival (PFS) than BM(?) patients [hazard ratio (HR) 6.25, P = 0.01], but there was no significant difference between subtle CD20 positivity and BM(?) patients. Patients with >30 CD3+ cells among 100 nucleated cells in the areas with increased numbers of CD3+ cells had significantly worse PFS than those with <15 CD3+ cells (HR 5.49, P = 0.02). BM(+) patients with >30 CD3+ cells had worse PFS than those with ≤30 CD3+ cells (P = 0.029), with an extent of BM(+) involvement of >10% positively correlating with >30 CD3+ cells (P = 0.015). Conclusions: Patients with BM(+) MALT lymphoma showed significantly worse PFS than those with subtle CD20 positivity and BM(?) MALT lymphoma, but the PFS of patients with subtle CD20 positivity MALT lymphoma was not significantly different from that of those with BM(?) MALT lymphoma. Increased numbers of BM T cells in MALT lymphoma patients might be suggestive of a worse prognosis.     

A Follow-Up Study with pH and Pressure Measurements in Patients Treated for Cardiospasm by Heller's Operation

A material of 52 patients operated upon for cardiospasm with a Heller myotomy is presented. The patients were re-examined in average 9 years after operation. Three patients were operated upon for a recur-rency. Sixty-five per cent had no symptoms at all. Of the remaining patients, 50% had mild and 50% distinct symptoms of stenosis. Fifteen per cent had symptoms of gastro-oesophageal reflux. Thirty-four patients were radio-logically re-examined. Eight of these patients had symptoms of regurgitation, which could only be confirmed by X-ray in 1 case. Twenty-nine of the 34 patients were investigated with simultaneous measurements of pH and pressure in the oesophagus and stomach. Five of these patients had symptoms of oesophagitis, but this could only be verified by the pH measurement in 1 patient. The pressure measurements showed great variations in the stomach-sphincter-gradient without any proved relation to the occurrence of reflux. The investigation supports the theory that more factors beyond the internal sphincter are of importance in keeping the cardia competent. However, it cannot support the theory that the distal fibres of the sphincter should be kept intact at operation in order to prevent the risk of refluxoesophagitis. It is stressed that a short incision will not solve the problem, as this procedure increases the tendency to recurrencies and will not prevent regurgitation (Malm, 1956).     

Benefits of maxillectomy with internal dissection of the masticator space by transmandibular approach in the surgical management of malignant tumours of the upper gingiva and hard palate: a clinical review of 10 cases

The aim of this study was to review patients with tumours extending to the posterior portion of the upper gingiva and hard palate, and to evaluate the postoperative outcomes. Ten consecutive patients with tumours in the upper gingiva and hard palate, who underwent maxillectomy with internal dissection of the masticator space by the transmandibular approach, were reviewed retrospectively. Among the 10 patients, the pathological diagnosis was squamous cell carcinoma in seven, adenoid cystic carcinoma in one, malignant melanoma in one, and osteosarcoma in one. Loco-regional control was achieved in eight of nine patients (88.9%). Three patients had residual moderate trismus. Cosmetic issues were not noted in any patient. En bloc resection of the maxilla with the internal portion of the masticator space and neck through the parapharyngeal space by the transmandibular approach is a useful and satisfactory technique for the excision of a tumour with involvement of the posterior portion of the upper gingiva and hard palate.     

Unusual scalp crusted scabies in an adult T-cell leukemia/lymphoma patient

A retrospective investigation was made of the occurrence of psychiatric symptoms among 441 patients operated on for primary hyperparathyroidism in Uppsala in 1956–79, and of the relationship between such symptoms and age, sex and degree of hypercalcaemia. A follow-up, using a mailed questionnaire, was carried out 4–27 years postoperatively.

Psychiatric symptoms were found in 23% of the patients (102/441). The patients with these symptoms had the same sex distribution and serum calcium levels as the other patients, but were significantly older. Severe symptoms occurred more frequently in older patients. Such symptoms were noted not only in patients with very high serum calcium values but also in association with mild or moderate hypercalcaemia.

The most common symptoms were depressive and anxiety states, which occurred in 78 patients. Psychosis with hallucinations and paranoid ideas was found in four patients. Eight patients had an organic brain syndrome and a further 12 patients had minor cerebral impairment.

At the follow-up half of the patients reported an improvement after the first postoperative year. Most of them considered that this improvement was sustained at the time of follow-up.

This study indicates that psychiatric symptoms are common among patients with hyperparathyroidism and can occur even with moderate hypercalcaemia. Elderly patients seem to be more vulnerable and more often develop severe symptoms such as psychosis or organic brain syndrome.     

Selective PI3Kδ inhibitors,a review of the patent literature

Introduction: Phosphatidylinositol 3-kinase (PI3K), a lipid kinase, is the first kinase involved in, and a key component of, the PI3K/Akt/mTOR signalling pathway, and is significantly upregulated in many cancers. However, four distinct isoforms of PI3K are known with different expression patterns and different pathophysiological roles. The PI3Kδ isoform is expressed in leukocytes and has been implicated as a potential target in the development of selective inhibitors for the treatment of haematological malignancies and various inflammatory diseases.

Areas covered: This review briefly covers the understanding of the four PI3K isoforms and their roles and the inhibitors selective for either one or two isoforms that have been identified to date. It then focuses upon progress in the identification of selective PI3Kδ inhibitors focusing upon the original efforts at ICOS/Calistoga that led to the initial clinical candidates such as CAL-101. After assessing the patent filings from these companies, it considers filings from other players and how they have sought to explore similar, and structurally distinct, scaffolds in their search for selective inhibitors, and how different companies appear focused on either oncological or anti-inflammatory uses for their inhibitors.

Expert opinion: The impact of the work at ICOS is highlighted by the fact that prior to their disclosure of selective leads, no patent applications claiming selective PI3Kδ inhibitors had been filed by other companies. This disclosure, followed by the first filings by Piramed, led to an upsurge in interest with a large cluster of filings published in 2008 while half the relevant applications were published in 2010 or 2011. These efforts, and the initial clinical data on CAL-101, the leading PI3Kδ inhibitors, have also prompted a number of commercially significant deals. In addition to an increasing number of filings, the entry into the clinical development of more selective PI3Kδ inhibitors should stimulate a better understanding of the role of this specific kinase isoform.