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A 62-year-old woman diagnosed with gallbladder cancer exhibiting broad liver invasion and metastasis to Couinaud's hepatic segments 4 and 8 (S4 and S8) consulted her regular doctor. Owing to the presence of liver metastases, she received treatment with gemcitabine plus S-1. After four cycles of chemotherapy, the size of the main lesion dramatically decreased and the two liver metastases disappeared. After six cycles of chemotherapy, the patient was referred to our hospital for surgical treatment. Upon admission, there was no evidence of any distant metastasis, based on a detailed radiological examination. Therefore, we performed cholecystectomy and central bisegmentectomy of the liver after obtaining the patient's informed consent. Pathological examination demonstrated viable cancer cells with granuloma formation and calcification in the gallbladder, as well as regenerative changes without viable cancer cells in S4 and S8 of the liver. Gemcitabine plus S-1 was again administered as postoperative adjuvant chemotherapy. One and a half years after the surgery, there were no signs of recurrence. In patients selected according to their response to chemotherapy, surgical treatment might therefore be effective against gallbladder cancer with metastasis.

Aims: Gastric gland mucin contains O-glycans exhibiting terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). Recently we demonstrated that mice deficient in αGlcNAc in gastric gland mucin develop gastric adenocarcinoma spontaneously, indicating that αGlcNAc is a tumour suppressor for gastric cancer. However, the role of αGlcNAc in Barrett's oesophagus (BO) remains unknown. In this study, we investigated whether reduced αGlcNAc expression in BO is associated with development of Barrett's adenocarcinoma (BAC)., Methods and Results: Thirty-five BO lesions adjacent to BAC were examined by immunohistochemistry for αGlcNAc, MUC6 and CDX2. As controls, 35 BO lesions without BAC obtained from patients with oesophageal squamous cell carcinoma were also analysed. Expression of αGlcNAc relative to its scaffold MUC6 in BO adjacent to BAC was reduced significantly compared to control BO. Decreased αGlcNAc expression in BO adjacent to BAC was particularly significant in patients with smaller tumour size (<20 mm) and minimal invasion of tumour cells to the superficial muscularis mucosae. There was also a significant inverse correlation between αGlcNAc and CDX2 expression in BO adjacent to BAC., Conclusions: Decreased expression of αGlcNAc compared with MUC6 in BO is a possible hallmark in predicting BAC development., (© 2013 John Wiley & Sons Ltd.)

Dedifferentiation (DD) is often encountered in gallbladder carcinoma (GBC) and poor prognosis with budding (BD) has been reported for other malignancies. However, the features of DD and BD in GBC remain unclear. The purpose of this study was to clarify the features and prognostic potential of DD and BD in GBC. A total of 80 patients with GBC (excluding intramucosal cancer) were enrolled. DD was histopathologically evaluated as tumors in which the grade of the invasive front is higher than the grade at the surface. BD was defined as an isolated single cancer cell or a cluster of fewer than five cancer cells at the invasive front. Of the 80 patients, 47 (58.8%) were positive for BD and 33 (41.2%) were positive for DD. Both BD and DD correlated significantly with disease-specific survival in univariate analysis (P < 0.0001 and P = 0.0013, respectively), but they were not identified as independent prognostic factors by multivariate analysis. In univariate analysis according to T stage, both BD and DD correlated significantly with survival in patients with T2 (n = 32) tumor (P = 0.0011 and P = 0.0018, respectively), whereas no prognostic impact in patients with T1b (n = 8), T3 (n = 34), or T4 (n = 6) tumor. Both DD and BD are frequently observed in GBC and reflect prognosis, particularly for T2 lesions. Therefore, the status of BD and DD should be taken into consideration in pathological reports on GBC.

Background: Pulmonary tumor thrombotic microangiopathy (PTTM) has been known as a rare and serious cancer-related pulmonary complication. However, the pathogenesis and pathophysiology of this debilitating condition still remains obscure and no effective management was recommended. The present study aims to elucidate the pathophysiology of PTTM., Methods: Autopsy records were searched to extract cases of pulmonary tumor embolism induced by metastasis of gastric carcinoma in the Toho University Omori Medical Center from 2000 to 2006. And then, tissue sections of extracted cases were prepared for not only light microscopic observation but morphometric analysis with the use of selected PTTM cases., Results: Six autopsies involved PTTM and clinicopathological data of them were summarized. There was a significant negative association between pulmonary arterial diameter and stenosis rate in four cases. Although all cases showed an increase of stenosis rate to some degree, the degree of stenosis rate varied from case to case. Significant differences were found for average stenosis rate between the under 100 micrometer group or the 100 to 300 micrometer group and the 300 micrometer group in four cases. However, no significant differences were found for average stenosis rate between the under 100 micrometer group and the 100 to 300 micrometer group in all cases. Meanwhile, all cases showed positive reactivity for tissue factor (TF), five showed positive reactivity for vascular endothelial growth factor (VEGF), and three showed positive reactivity for osteopontin (OPN)., Conclusions: In the present study, we revealed that the degree of luminal narrowing of the pulmonary arteries varied from case to case, and our results suggested that pulmonary hypertension in PTTM occurs in selected cases which have a widespread pulmonary lesion with severe luminal narrowing in the smaller arteries. Furthermore, our immunohistochemical examination indicated that gastric carcinoma indicating PTTM shows a higher TF-positive rate than typical gastric carcinoma. However, it remains still obscuring whether gastric carcinoma indicating PTTM shows a higher VEGF or OPN-positive rate as determined by immunohistochemistry.

A 19-year-old male was admitted to our hospital because of retroperitoneal tumor and metastases in the lung and liver. He underwent chemotherapy followed by retroperitoneal lymph node dissection and pathologic examination revealed mostly necrotic tissue with a small amount of teratomatous tissue. Two years later, a hyper echoic lesion was found in the left testis, and left high orchiectomy was performed. The resected specimen appeared to be a burned-out testicular tumor. Ten years later, CT scan detected lymph node swelling in the retroperitoneum, and excision of the tumor was performed. Pathologic examination revealed well-differentiated adenocarcinoma. Since no primary adenocarcinoma was found, this case was considered late relapse of a germ cell tumor.

A 72-year-old man with common bile duct cancer was treated by pylorus preserving pancreatoduodenectomy with D3 lymph node dissection and preventive radiotherapy at hepaticojejunostomy. At 4 months after surgery, CT demonstrated multiple liver metastatic tumors. Single drug chemotherapy, UFT 600 mg, was started. After 6 months, the liver metastatic tumor could not be seen by CT. UFT may be a first candidate for chemotherapy for recurrence of bile duct cancer.

A 67-year-old man with gallbladder cancer was treated by cholecystectomy and extrahepatic bile duct resection with regional lymph node dissection. At 10 months after surgery, CT demonstrated para-aortic lymph node recurrence. Single drug chemotherapy of UFT at 400 mg was started. After one month, the lymph node recurrence could not be detected by CT. UFT may be the primary candidate for chemotherapy for lymph node recurrence of gallbladder cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a widely known severe malignancy with a poor prognosis. Perineural invasion extending to the extra-pancreatic nerve plexus, a significant concern in the treatment is frequently present in this cancer. We analyzed immunohistochemical expression of neurotrophins (NGF, BDNF, NT-3) and the cognate receptors, Trk tyrosine kinase receptor family (TrkA, B, C) and p75NGFR in 28 surgically resected PDAC specimens. A comparative study between several clinicopathologic factors and Trk receptors revealed a significant correlation between increased expression of TrkA and cancer proliferation, as well as TrkC and cancer invasion, including venous and perineural invasion. The present findings revealed a novel mechanism in PDAC progression that is mediated via a NTs-Trk interaction.

Prostatic cancer is rarely diagnosed by detection of lung metastases. We report a case of prostatic cancer in a 73-year-old man detected by abnormalities in chest X-ray and serum prostate specific antigen (PSA) level. He was initially admitted to our hospital due to elevation of PSA level. On the first transperineal prostatic needle biopsy, prostatic cancer was not detected and he was followed. Seven months after the first biopsy, chest X-ray revealed multiple abnormal nodules in the lung fields bilaterally and PSA level was again elevated. A second prostatic biopsy and whole-body examination were performed, and he was diagnosed with moderately differentiated prostatic adenocarcinoma with multiple lung metastases. Complete androgen blockade therapy was performed immediately. Two months after the beginning of treatment, PSA level was normalized and the multiple lung metastases had completely disappeared. There has been no evidence of recurrence or PSA relapse 24 months after detection of the prostatic cancer. This is the 26th case of prostatic cancer diagnosed in Japan following detection of multiple lung metastases.

The effect of IFN-beta on cell growth and the mechanism of growth modulation was examined in human gastric carcinoma cell lines. IFN-beta inhibited the cell growth of TMK-1 cells, whereas it did not affect the growth of the other three cell lines (MKN-7, -28, and -45). The number of apoptotic cells in IFN-beta-treated TMK-1 cells was 2-fold the number of those in control TMK-1 cells, whereas the induction of apoptosis was not observed in IFN-beta-treated MKN-28 cells. IFN-beta enhanced the expression of cyclin-dependent kinase inhibitor p27Kip1 at mRNA and protein levels. The increased p27Kip1 bound preferentially to CDK6. The phosphorylation level of retinoblastoma protein in TMK-1 cells was reduced by IFN-beta treatment. IFN-beta did not affect the expression of cell cycle regulators in MKN-28 cells. These results suggest that the induction of p27Kip1 by IFN-beta might confer inhibition of cell growth, leading to subsequent apoptosis in TMK-1 cells.

p16MTS1/INK4A negatively regulates cell cycle progression by inhibiting the cyclin D/CDK4 complex that phosphorylates pRb. Frequent homozygous deletions of the p16 gene were recently found in various tumor cell lines. We examined the relationship between the genetic status of p16 and the expression of the cell cycle regulating molecules in human esophageal carcinoma cell lines. Out of eight human esophageal carcinoma cell lines, seven (67.5%) and six (75%) cell lines showed homozygous deletions of the p16 and p15 genes, respectively. All the p16-negative cell lines expressed high levels of cyclin D1, CDK4 and p27KIP1 proteins. Interestingly, the expression level of cyclin D1 was closely correlated to the levels of not only CDK4 but also p27KIP1 protein in p16-negative cell lines. Furthermore, all the p16-negative cell lines expressed Rb protein of approx 110 kDa which corresponds to the phosphorylated form, whereas the cell line with intact p15 and p16 genes did not express pRb. These results suggest that the expression of cyclin D1, CDK4, Rb and p27 is associated with the p16 gene status in esophageal carcinoma cell lines. Alternatively, loss of the p16 gene and subsequent over-expression of cyclin D1 and CDK4 might be involved in autonomous growth of esophageal carcinoma cells.