Cronkhite-Canada syndrome with colon cancer, portal thrombosis, high titer of antinuclear antibodies, and membranous glomerulonephritis

A 64-year-old man, who came to us with diarrhea, presented with ectodermal changes such as hyperpigmentation, alopecia, and onychatrophy, and was affected by polyposis in the colorectum and stomach. The polyps were histologically consistent with those in Cronkhite-Canada syndrome (CCS). Interestingly, the patient also had colon cancer, as well as portal thrombosis and a high concentration of antinuclear antibody. Treatment with prednisolone ameliorated the symptoms and the gastrointestinal polyposis, while the cancer was successfully treated with a hemicolectomy. Six months after the surgery, the patient developed nephropathy, with nephrotic-range proteinuria, without recurrence of the cancer. The biopsied renal specimen showed membranous glomerulonephritis. This is a rare case of CCS associated with various complications such as colon cancer, portal vein thrombosis, a high titer of antinuclear antibodies, and membranous glomerulonephritis. Although the pathogenesis of CCS is essentially unknown, these complications might have been indicative of an underlying immunological abnormality.     

Removal of a chronically infected bipolar pacemaker electrode: a successful case report

A chronic infected bipolar pacemaker electrode with a fin tip was successfully removed 7 years and 9 months after its original implantation from a 72-year-old Japanese man, using the Cook pacemaker lead extraction system. The locking stylet could not advance to the lead tip over the positive pole because of firm adhesions. Because the scar tissue between the positive pole and myocardium could not be freed by the inner sheath, it was disrupted by the slanted end of the outer sheath. The firmest adhesion was on the positive pole, not on the fin tip. The complete extraction success rate of bipolar tined or fin leads is worse than for other types of leads. When extracting a bipolar pacemaker lead, dissection of the positive pole from scar tissue should be taken into account in addition to the lead tip. Rotating the slanted end of the outer sheath is a useful technique when dissecting firm adhesions.     

Epidemiological and bacteriological study on gonococcal infections]

Epidemiological and bacteriological studies on Neisseria gonorrhoeae isolated in Sapporo, Japan, in 1980 and 1991 performed and the following results were obtained. 1. The range of age in the patients infected with Neisseria gonorrhoeae tended to be younger than those in the whole country. 2. Male patients in the early 20s or younger with gonococcal urethritis were often infected by bon-professional females but those in their late 20s or older were often infected from professional females, for example prostitutes and hostesses. 3. The rate of professional females who were positive to gonococci reached 17.4% and young females in their teens with cervicitis had the highest morbidity rate of gonococci than those in the older females. 4. The latent period in gonococcal infections tended to become longer gradually. 5. The isolation rate of penicillinase producing Neisseria gonorrhoeae (PPNG) showed a peak of 23.9% (61/255) in 1985, but gradually declined thereafter and it was 3.7% (1/27) in 1991. 6. An investigation on auxotype showed a decline of proto and Pro-strains and an increase of AHU-strains in non-PPNG. And most of the PPNG belonged to proto or Pro-strains. 7. With the relationship between auxotype and sensitivity to AMPC, AHU-strains were more sensitive than proto or Pro-strains.     

Risk factors for early death in patients undergoing treatment for multiple myeloma

The survival time of myeloma patients improved from a few months to many years after treatment with melphalan. Perhaps chemotherapy more intensive than melphalan-prednisolone should be administered to patients at risk of early death. Therefore, early death must be accurately predicted. We analyzed 93 patients with recently diagnosed myeloma and found that 13 (14%) died within 6 months (early death). The most common cause of death was bacterial and fungal pneumonia when myeloma became uncontrollable. The response to conventional chemotherapy was poorer in patients at high risk of early death than the control group. Multivariate analysis showed that the serum level of beta-2 microglobulin was the only value that predicted early death.     

CCL2 is critical for immunosuppression to promote cancer metastasis

We previously found that cancer metastasis is accelerated by immunosuppression during Snail-induced epithelial-to-mesenchymal transition (EMT). However, the molecular mechanism still remained unclear. Here, we demonstrate that CCL2 is a critical determinant for both tumor metastasis and immunosuppression induced by Snail⁺ tumor cells. CCL2 is significantly upregulated in various human tumor cells accompanied by Snail expression induced by snail transduction or TGFβ treatment. The Snail⁺ tumor-derived CCL2 amplifies EMT events in other cells including Snail^? tumor cells and epithelial cells within tumor microenvironment. CCL2 secondarily induces Lipocalin 2 (LCN2) in the Snail⁺ tumor cells in an autocrine manner. CCL2 and LCN2 cooperatively generate immunoregulatory dendritic cells (DCreg) having suppressive activity accompanied by lowered expression of costimulatory molecules such as HLA-DR but increased expression of immunosuppressive molecules such as PD-L1 in human PBMCs. The CCL2/LCN2-induced DCreg cells subsequently induce immunosuppressive CD4⁺FOXP3⁺ Treg cells, and finally impair tumor-specific CTL induction. In murine established tumor model, however, CCL2 blockade utilizing the specific siRNA or neutralizing mAb significantly inhibits Snail⁺ tumor growth and metastasis following systemic induction of anti-tumor immune responses in host. These results suggest that CCL2 is more than a chemoattractant factor that is the significant effector molecule responsible for immune evasion of Snail⁺ tumor cells. CCL2 would be an attractive target for treatment to eliminate cancer cells via amelioration of tumor metastasis and immunosuppression.     

A rare case of clear cell sarcoma with 4 types of EWSR1-ATF1 fusions detected not in primary site but in metastatic site

Clear cell sarcoma is a unique tumor which has EWSR1-ATF1 or EWSR1-CREB1 fusion. Several patterns of EWSR1-ATF1 fusion are observed in clear cell sarcoma. Since type 5–7 fusions were reported recently, they are classified as type 1–7. We examined EWSR1-ATF1 and EWSR1-CREB1 fusions in a single case of clear cell sarcoma with lung metastasis in a 36-year-old Japanese man. As a result, we found only type 1 EWSR1-ATF1 fusion in the primary site, but 4 types of EWS-ATF1 fusion (type 1, 2, 5, 6) were detected in the metastatic site. These 4 types of fusion were completely identical to the recent report, but the case had the same fusion patterns in both primary and metastatic sites. In our case, increased splicing activity in the EWSR1-ATF1 fusion might be acquired at the metastatic site. There is another possibility that metastasis might develop through the increased splicing activity in the fusion.     

Induction of secondary metabolite production by fungal co-culture of Talaromyces pinophilus and Paraphaeosphaeria sp.

Fungal co-culture is a strategy to induce the production of secondary metabolites by activating cryptic genes. We discovered the production of a new compound, talarodone A (1), along with five known compounds 2–6 in co-culture of Talaromyces pinophilus and Paraphaeosphaeria sp. isolated from soil collected in Miyazaki Prefecture, Japan. Among them, the productions of penicidones C (2) and D (3) were enhanced 27- and sixfold, respectively, by the co-culture. The structure of 3 should be represented as a γ-pyridol form with the reported chemical shifts, but not as a γ-pyridone form, based on DFT calculation.     

Robotic-assisted lateral lymph node dissection for lower rectal cancer: short-term outcomes in 50 consecutive patients

Background

The goal of this study was to evaluate the short-term outcomes of robotic-assisted lateral lymph node dissection for patients with advanced lower rectal cancer.

Methods

Between 2012 and 2013, 50 consecutive patients underwent robotic-assisted lateral lymph node dissection for rectal cancer in Shizuoka Cancer Center Hospital. Perioperative outcomes including operative time, operative blood loss, length of stay, postoperative complications, and histopathological data were collected prospectively.

Results

Median patient age was 62 years (range 36–74 years). Operative procedures included low anterior resections (n = 27), intersphincteric resections (n = 16), and abdominoperineal resections (n = 7). Bilateral lymph node dissection was performed in 44 patients. The median operative time was 476 min (range 320–683 min), and the median time required for lateral lymph node dissection was 165 min (range 85–257 min). The median blood loss was 27 mL (range 5–690 mL). There were no cases of open surgery or laparoscopic conversion. The median duration of postoperative hospital stay was 8 days (range 6–13 days). Clavien–Dindo classification Grade III–IV complications occurred in only one patient (2.0 %). There were no cases of anastomotic leak. There was no perioperative mortality. The median number of harvested lateral lymph nodes was 19 (range 5–47).

Conclusions

Robotic-assisted lateral lymph node dissection is a safe, feasible, and useful approach for patients with advanced lower rectal cancer.