Induction of apoptotic cell death by direct-current treatment in human leukemic cell lines

Exposure of human leukemic cell lines (HL-60, ML-1, U-937, MOLT-4, EOL-1) to short direct-current (d.c.) treatment induced apoptotic cell death, characterized by cell shrinkage and nuclear and internucleosomal DNA fragmentation. On the other hand, human peripheral blood lymphocytes and polymorphonuclear cells were relatively resistant to d.c treatment, and did not show any clear nuclear and DNA fragmentation. The effect of d.c. was slightly reduced by calcium depletion, but was not significantly affected by catalase or by superoxide dismutase. The present data suggest that previously reported tumor regression activities of d.c. treatment might be due, at least in part, to its apoptosis-inducing activity.     

Unusual variant of left paraduodenal hernia herniated into the mesocolic fossa leading to jejunal strangulation

Paraduodenal hernia is a rare condition in which the small bowel loops are herniated into an unusual fossa in the periduodenal area. We treated a patient with paraduodenal hernia diagnosed pre-operatively. A 28-year-old woman was admitted to our hospital because of intermittent abdominal pain. Abdominal ultrasonography revealed a large tumor adjacent to the pancreas. Provisional diagnosis made according to computed tomography (CT) findings was tumor of the pancreas tail. However, on a CT scan performed after the administration of diatrizoate meglumine/diatrizoate sodium (Gastrografin, Schering, Berlin, Germany) the mass was shown as a jejunum loop located between the stomach and the pancreas body. Subsequent laparotomy revealed that the jejunum loop was herniated into an unusually large mesocolic fossa and that the hernial orifice was covered by the adhesion between the transverse and descending colons. It seemed that the small intestine within the mesocolic fossa was strangulated by this adhesion. The patient's abdominal pain resolved postoperatively. These observations suggest that paraduodenal hernia should be suspected in patients with chronic, atypical abdominal pain, regardless of the findings for small bowel obstruction. (Received Oct. 6, 1997; accepted Jan. 23, 1998)     

Specificity of polymerase chain reaction-based clonality analysis of immunoglobulin heavy chain gene rearrangement for the detection of bone marrow infiltrate in B-cell lymphoma-associated haemophagocytic syndrome

As a wide range of disorders underlie haemophagocytic syndrome, a rapid distinction between benign polyclonal and malignant monoclonal lymphoid proliferations is critical. We investigated whether polymerase chain reaction (PCR) amplification of immunoglobulin heavy chain gene rearrangement could efficiently detect clonal B-cell populations in non-diagnostic marrow for B-cell lymphoma-associated haemophagocytic syndrome (B-LAHS). On amplifying two DNA samples per biopsy, no reproducible monoclonal PCR result was found in reactive haemophagocytic marrows. In contrast, four out of nine assessable B-LAHS patients with histomorphologically and immunohistochemically lymphoma-free bone marrow showed a reproducible monoclonal immunoglobulin heavy chain gene rearrangement. At the molecular level, two B-LAHS patients had lymphoma-free marrow as demonstrated by patient-specific PCR, suggesting that haemophagocytic marrow is not always associated with lymphoma involvement. PCR-based demonstration of clonal B-cell populations in marrow would add an extra dimension to B-LAHS diagnosis.     

Hilar cholangiocarcinoma associated with sarcoid reaction in the regional lymph nodes

A 74-year-old woman was admitted to our hospital with a 2-week history of jaundice. Percutaneous transhepatic cholangioscopy revealed a nodular tumor originating in the upper part of the common hepatic duct, which was invading the confluence of the right and left hepatic ducts. Microscopic examination of biopsy specimens revealed adenocarcinoma. Abdominal ultrasonography and computed tomography demonstrated multiple enlarged lymph nodes around the extrahepatic bile duct and the common hepatic artery. Laparotomy revealed lymph node enlargement in the hepatoduodenal ligament, behind the pancreatic head, and along the common hepatic and left gastric arteries. Extended left hepatic lobectomy, caudate lobectomy, and resection of extrahepatic bile duct with extended lymph node dissection were performed. The histology of permanent specimen revealed no tumor metastasis but a sarcoid reaction in the lymph nodes. The patient is in good health 21 months after the operation, without any evidence of recurrence. This is the first successfully resected case of hilar cholangiocarcinoma associated with sarcoid reaction in the regional lymph nodes.     

Mallory - weiss tear complicating intraoperative transesophageal echocardiography.

A Mallory - Weiss tear occurred as a complication of intraoperative transesophageal echocardiography carried out in a 62-year-old man who underwent coronary artery bypass grafting. Left ventricular function was monitored in the transgastric short-axis view. Postoperative esophagogastroscopy revealed a Mallory - Weiss tear at the gastroesophageal junction and erosions in the cardia, presumably secondary to contact pressure by the echoprobe and ultrasonic thermal injury. When not actively imaging, the echoprobe should be left free in the esophagus with the acoustic power off.     

Significant role of Psf3 expression in non‐small‐cell lung cancer

The GINS complex associates with cell division cycle (Cdc) protein 45 and mini‐chromosome maintenance (Mcm) proteins 2–7 to form the Cdc45–Mcm–GINS (CMG) complex, which is essential for DNA duplication. One member of the GINS complex is Psf3. We previously found that increased Psf3 expression was strongly associated with poor survival in lung adenocarcinoma. Here, we investigated the role of Psf3 expression in non‐small‐cell lung cancer (NSCLC). We verified Psf3 expression in human NSCLC tissues (180 patients) and cell lines. Immunohistochemical analysis revealed that the overexpression of Psf3 was significantly associated with vessel invasion (P = 0.016), lymphatic invasion (P = 0.002), and pleural invasion (P = 0.036). The overall survival rate in patients with Psf3 overexpression was significantly lower than that in patients without Psf3 overexpression (P = 0.006). Multivariate survival analysis revealed Psf3 expression to be an independent risk factor for an unfavorable outcome (P = 0.049). A proximal ligation assay showed interactions between Psf3 and other CMG components (such as Mcm2 and Cdc45) in both NSCLC specimens and cell lines, indicating that Psf3 acted as the CMG complex, which could lead to excessive proliferation. Knockdown of Psf3 inhibited the proliferation of both cell lines by delaying the S phase, which revealed that Psf3 played an important role in cancer proliferation. Thus, Psf3 acted as the CMG complex, promoting excessive proliferation. These results suggest that Psf3 inhibition might be a therapeutic target for NSCLC with Psf3 overexpression.     

Japanese Society of Medical Oncology Clinical Guidelines: RAS (KRAS/NRAS) mutation testing in colorectal cancer patients

The Japanese guidelines for the testing of KRAS mutations in colorectal cancer have been used for the past 5 years. However, new findings of RAS (KRAS/NRAS) mutations that can further predict the therapeutic effects of anti‐epidermal growth factor receptor (EGFR) antibody therapy necessitated a revision of the guidelines. The revised guidelines included the following five basic requirements for RAS mutation testing to highlight a patient group in which anti‐EGFR antibody therapy may be ineffective: First, anti‐EGFR antibody therapy may not offer survival benefit and/or tumor shrinkage to patients with expanded RAS mutations. Thus, current methods to detect KRAS exon 2 (codons 12 and 13) mutations are insufficient for selecting appropriate candidates for this therapy. Additional testing of extended KRAS/NRAS mutations is recommended. Second, repeated tests are not required for the detection; tissue materials of either primary or metastatic lesions are applicable for RAS mutation testing. Evaluating RAS mutations prior to anti‐EGFR antibody therapy is recommended. Third, direct sequencing with manual dissection or allele‐specific PCR‐based methods is currently applicable for RAS mutation testing. Fourth, thinly sliced sections of formalin‐fixed, paraffin‐embedded tissue blocks are applicable for RAS mutation testing. One section stained with H&E should be provided to histologically determine whether the tissue contains sufficient amount of tumor cells for testing. Finally, RAS mutation testing must be performed in laboratories with appropriate testing procedures and specimen management practices.     

Comparison of characteristic computed tomographic findings of gastrointestinal and non-gastrointestinal stromal tumors in the small intestine

Abdominal Radiology - We aimed to reveal specific findings of gastrointestinal stromal tumors (GISTs) in the small intestine on contrast-enhanced computed tomography (CT) by comparing GISTs with...