Intraductal papillary mucinous neoplasms of the pancreas: an analysis of protein expression and clinical features

Background/Purpose The molecular pathology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has not been well characterized, and there are no reliable markers to predict the presence of associated invasive carcinoma in patients with IPMNs. We investigated the clinicopathologic characteristics of 37 IPMNs and the immunohistochemical findings of these tumors to investigate the malignancy of IPMNs. Methods Between May 1992 and September 2003, 37 patients with IPMNs, 24 with adenoma and 13 with carcinoma, underwent pancreatic resections at Sapporo Medical University Hospital, Japan. In tumor specimens from these patients, we immunohistochemically analyzed the expression of p53 protein, proliferating-cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), matrix metalloproteinase-7 (MMP-7), and E-cadherin. Clinical features and follow-up after resection were recorded. Results Aberrant expression of the proteins examined was frequently observed. Namely, there were significant differences in the expression of MMP-7 according to clinicopathological characteristics. Positive expression of MMP-7 was found in all of nine patients with infiltrating ductal pancreatic adenocarcinoma (IDC) and in all of seven patients with invasive intraductal papillary mucinous adenocarcinoma (IC-IPMC); however, 33.3% of patients with noninvasive IPMA, 58.3% of patients with intraductal papillary mucinous adenoma (IPMA), and all normal pancreatic tissues were negative for MMP-7; differences which were statistically significant (P < 0.05). Conclusions Our current results indicate that MMP-7 may play a significant role in the progression of noninvasive to invasive IPMC.     

Diagnostic and prognostic usefulness of N 1,N 8-diacetylspermidine and N 1,N 12-diacetylspermine in urine as novel markers of malignancy

Recently, we found N ¹,N ⁸-diacetylspermidine (Ac₂Spd) and N ¹,N ¹²-diacetylspermine (Ac₂Spm) in human urine, and noted that their amount increased significantly in patients with urogenital malignancies. Previous findings that simultaneous reference to these diacetylpolyamines is useful in distinguishing cancer patients from healthy persons were confirmed by more recent analytical data on urine samples from several cancer patients. Further examination revealed that urinary Ac₂Spm and Ac₂Spd tended to decrease when cancer patients were treated and entered partial remission. In cases where the Ac₂Spm and Ac₂Spd levels were normal or near-normal after treatments, the prognosis of the patients was generally good. In contrast, when their level remained far above the normal limits after apparently effective treatment, the prognosis of the patients was poor. When a patient is in remission for more than 3 years, urinary levels of both Ac₂Spm and Ac₂Spd are stabilized and stay below the normal limits, with rare exceptions. The recurrence of a cancer as well as the complication of a second one during the period of follow-up examination was accompanied by elevation of urinary diacetylpolyamines. These observations indicate that urinary Ac₂Spm and Ac₂Spd are useful as prognostic indicators after treatment and during follow-up examination of cancer patients. Received: 27 March 1997 / Accepted: 15 July 1997     

Identification of four novel mutations in F5 associated with congenital factor V deficiency

Coagulation factor V (FV) deficiency is a rare bleeding disorder characterized by low coagulant and antigen levels of FV with bleeding symptoms ranging from mild to severe. Only a limited number of mutations have been reported because of the large size of the factor V gene (F5) as well as the low prevalence. In this study, we have identified four novel mutations in F5 in five unrelated patients with congenital FV deficiency. All the patients, including two with undetectable FV activity, were asymptomatic and were found to have prolonged prothrombin time and activated partial thromboplastin time during preoperative screening or routine examinations. All four mutations found in this study are either missense or in-frame deletion. This is in contrast with previous reports of a high frequency of mutations introducing premature termination codons in inherited FV deficiency. Missense mutations of F5 might produce a mild phenotype and are not frequently diagnosed. Although FV deficiency is a very rare disorder with a predicted incidence of one in 1 million, this study suggests that the numbers of F5 mutations, especially missense mutations, are higher than estimated.     

Radical resection for pancreatic cancer

Ductal adenocarcinoma of the pancreas is still characterized by (1) poor prognosis after surgery and (2) extreme difficulty in early diagnosis, and we need a breakthrough. For the first problem, we have performed a wide range of lymphatic and connective tissue clearance (extended pancreatectomy) which has succeeded in improving the 5-year survival rate from 8% to 24% via decreasing the incidence of locoregional recurrence. When liver perfusion chemotherapy via the hepatic artery and the portal vein was added to the patients who had received extended pancreatectomy, the 5-year survival rate was further elevated to 40% via decreasing the incidence of hepatic metastasis. We conclude that pancreatic cancer should be treated by the better-balanced treatments between locoregional control and prevention of hepatic metastasis. For the second problem, we have more actively collected pancreatic juice to perform cytodiagnosis even though no obvious tumor was delineated by the conventional imaging diagnoses. When cancer cells were detected in the pancreatic juice, our method of intraoperative cytology was very useful in precisely locating the occult lesion indicating an appropriate range of pancreatectomy. The resected pancreas was proven to have included borderline malignancy and in situ or minimally-invasive carcinoma by the postoperative histology, and disease-free 5-year survival rate was 100%. In the future, we need to detect patients with a high risk of pancreatic cancer and develop a less-painful method to collect the pancreatic juice.     

Inflammatory paradental cyst (IPC) in the mandibular premolar region in children

OBJECTIVES: We investigated the occurrence of inflammatory paradental cysts (IPC) in the mandibular premolar, and demonstrated the points of difference with regard to diagnostic features between IPC and dentigerous cysts (DC). MATERIAL AND METHODS: We analyzed the radiographs and histology of 60 cases with a cystic lesion associated with inflammation in the mandibular premolar region based on diagnostic criteria as IPC. RESULTS: In 4 out of 60 cases, we diagnosed the 4 cysts as IPCs in the mandibular premolar region, and recognized that one form of IPC was similar to a mandibular infected buccal cyst. The other 56 non-IPC cases were diagnosed as DC. On the IPCs, the permanent tooth normally erupted in all 4 cases after treatment, but in one case, the IPC recurred. CONCLUSIONS: The present investigation suggested that we might have misdiagnosed IPCs in the mandibular premolar region as DC to date. It is important to consider the differences between IPC and DC with regard to the causes of recurrence during treatment of IPC.     

A pitfall in analyses of relevant factors concerning phenomena in the process of initiating dialysis: alterations in the characteristics of subjects diminish the significance of age

In our previous studies, relevant factors concerning the main phenomena related to the process of initiating dialysis were examined in elderly patients with chronic renal failure. Examined phenomena were as follows: (1) the acceptance of dialysis; (2) the urgency of initiating dialysis; (3) short-term outcome; (4) returning home. Multivariate logistic regression analysis was used to determine relevant factors. Although we speculated that age should be a relevant factor for each phenomenon, the phenomenon on which age had some impact was only the first. We suspected the existence of a pitfall, through which the relation of age was lost in the second, the third, or the fourth phenomenon. The fact that every phenomenon had its own relevant factors was thought to be an important clue to the discovery of pitfalls. Relevant factors were derived from both the number of dropout-patients and their demographic and clinical status. From the viewpoint of nondropout-patients, the progression of the process of initiating dialysis might alter the characteristics of subjects for successive phenomena In this study, we set out to investigate whether alterations in the characteristics of subjects were pitfalls. Alterations were regarded as a fall of the mean age, an increment of the rate of the patients with ability to walk, and an increment of the rate of the patients with normal cognitive function. In addition, the old-old patients tended to have limited numbers of those who had the ability to walk and normal cognitive function. In other words, aging changes in ambulatory and cognitive function were not brought to subjects. These alterations may cause the loss of the relation of age to each phenomenon. Thus, we presumed these alterations to be pitfalls. We must clarify whether aging changes are brought to subjects beforehand in analyses that include the old-old patients as subjects.     

Experimental myasthenia in mice. The role of the thymus and lymphoid cells

A possible function of the thymus gland with regard to developing neuromuscular block after immunization with thymus extract is discussed.

Inbred female C57BL/6 mice were immunized with thymus extract from female C57BL/6 (syngeneic), male C57BL/6 mice, AKR mice (allogeneic) and guinea-pigs and calves (xenogeneic). Two weeks later, the waning phenomenon was observed from the electromyography (EMG) in xenogeneically, allogeneically and syngeneically immunized mice. The waning reverted to a normal pattern following an intraperitoneal injection of neostigmine methylsulphate. EMG tracings revealed a decrease in the incidence of the waning phenomenon in those mice which were immunized after adult thymectomy.

The passive transfer of the waning phenomenon to non-thymectomized recipients could be achieved by the intravenous administration of lymph node cells obtained from the mice that had developed a myasthenic neuromuscular block after immunization. This finding was also observed in the recipients when the donors of lymph node cells had not developed the block.

On the other hand, administration of sera from mice with the waning phenomenon after immunization resulted in a neuromuscular block in both normal and adult-thymectomized mice. However, sera obtained from mice without waning did not have this feature.

     

Anaphylactoid reactions to radiocontrast media

Adverse reactions to contrast material are a concern because iodinated contrast materials are commonly used drugs. The risk for adverse reaction is 4% to 12% with ionic contrast materials and 1% to 3% with nonionic contrast materials. The risk for severe adverse reaction is 0.16% with ionic contrast materials and 0.03% with nonionic contrast materials. The death rate, one to three per 100,000 contrast administrations, is similar for both ionic and nonionic agents. More than 90% of adverse reactions with nonionic contrast materials are anaphylactoid. The types of severe reactions seen with nonionic contrast administration were initially predominantly anaphylactoid. With the advent of helical CT angiography, the reactions are now predominantly attributable to cardiopulmonary decompensation. With the widespread use of nonionic contrast materials, adverse reactions are now seen less frequently. Skills involved in evaluating and treating adverse reactions are not as frequently used. Periodic reviews and updates of specific treatment plans for various reactions with the physicians and staff who use contrast material are very important to ensure optimal preparedness. The key to successful treatment is preparation and early intervention.