Ethical Issues faced by Home Care Physicians and Nurses in Japan and their Ethics Support Needs: a Nationwide Survey.

This study aimed to identify the ethical issues faced by home care physicians and nurses, and the support they require. It was conducted in collaboration with the Japanese Association for Home Care Medicine from November to December 2020. An e-mail was sent to 2785 physicians and 582 nurses who are members of the society, requesting their participation in a web-based survey targeting physicians and nurses with practical experience in home care; 152 physicians and 53 nurses responded. Home care physicians and nurses face ethical issues, some of which are that "the patient's wishes cannot be reliably understood owing to their impaired decision-making capacity" and "there is disagreement between the patient and their family members over the necessary healthcare." The respondents sought "experience with, and insight into, healthcare ethics" and "home care" from people with whom they would consult on ethical issues, but at the time of the actual consultation, those individuals were the main healthcare professionals involved with the patient. In addition, the respondents desired to have "multidisciplinary discussions in the community," "participation of healthcare ethics experts at meetings," and "meetings held by healthcare ethics experts" to discuss specific cases. Given these results and the history of healthcare ethics education in Japan-which has been implemented mostly for healthcare providers-we conclude that it is important for academic societies that offer healthcare ethics education to healthcare providers and regional core hospitals with ethics support resources to collaborate to provide ethics consultation services in the community.

Culturally Adapted Consensus Definition and Action Guideline: Japan's Advance Care Planning.

CONTEXT: A conceptual framework for advance care planning is lacking in societies like Japan's valuing family-centered decision-making. OBJECTIVES: A consensus definition of advance care planning with action guideline adapted to Japanese society. METHODS: We conducted a multidisciplinary modified Delphi study 2020-2022. Thirty physicians, 10 healthcare and bioethics researchers, six nurses, three patient care managers, three medical social workers, three law experts, and a chaplain evaluated, in 7 rounds (including two web-based surveys where the consensus level was defined as ratings by ≥70% of panelists of 7-9 on a nine-point Likert scale), brief sentences delineating the definition, scope, subjects, and action guideline for advance care planning in Japan. RESULTS: The resulting 29-item set attained the target consensus level, with 72%-96% of item ratings 7-9. Advance care planning was defined as "an individual's thinking about and discussing with their family and other people close to them, with the support as necessary of healthcare providers who have established a trusting relationship with them, preparations for the future, including the way of life and medical treatment and care that they wish to have in the future." This definition/action guideline specifically included support for individuals hesitant to express opinions to develop and express preparations for the future. CONCLUSION: Adaptation of advance care planning to Japanese culture by consciously enhancing and supporting individuals' autonomous decision-making may facilitate its spread and establishment in Japan and other societies with family-centered decision-making cultures.

Report on the Establishment of the Consortium for Hospital Ethics Committees in Japan and the First Collaboration Conference of Hospital Ethics Committees.

Hospital ethics committees (HECs) are expected to play extremely broad and pivotal roles such as case consultation, education of staffs on healthcare ethics, and institutional policy formation. Despite the growing importance of HECs, there are no standards for setup and operation of HECs, and composition and activities of HECs at each institution are rarely disclosed in Japan. In addition, there is also a lack of information sharing and collaboration among HECs. Therefore, the authors established the Consortium of Hospital Ethics Committees (CHEC) in October 2020, which has been regularly hosting a couple of core activities. One is the Healthcare Ethics Forum, held monthly online for CHEC members to freely discuss HECs and healthcare ethics consultation. The other is the Collaboration Conference of Hospital Ethics Committees, intended to provide a place for HEC members and administrative officers from across Japan to exchange information of their HECs, learn from each other, and cooperate to operate HECs appropriately. In this paper, the authors introduced CHEC as well as reported the results of a questionnaire survey conducted at the first conference among participating facilities, suggesting the diverse structures and activities of HECs in Japan.

Use of a 2-year continuing professional development programme to change Japanese physicians' attitudes to learning primary care: a qualitative study.

OBJECTIVE: To evaluate changes in the learning attitudes of primary care physicians. DESIGN: Qualitative study through one focus group interview with the programme's participants. Analysis of the focus group content using the Steps for Coding and Theorization method. SETTING: Japan. PARTICIPANTS: Eight primary care physicians who completed a 2-year continuing professional development (CPD) programme using a problem-based learning (PBL) approach, focused on acquiring the skills needed to practise as primary care physicians in the community. RESULTS: Participants described positive changes in their attitudes and behaviours as a result of the training programme. These changes were grouped into three main themes: 'changes in learning methods regarding medical practice', 'encounters with diverse perspectives and values, and confidence gained from those encounters', and 'showing one's attitude towards learning and its influence on others'. The experienced practitioners participating in this study reported that the programme helped them apply their skills more broadly; for example, searching the literature for psychosocial aspects of practice and engaging more comfortably with diverse perspectives. They reported the positive impact of their learning on their coworkers. CONCLUSION: A 2-year CPD programme using PBL can influence primary care physicians' attitudes and learning-related behaviours. Further research is needed to determine which specific aspects of the programme are the most effective and whether the changes in attitudes and behaviours described affect patient care.

How a problem-based learning approach could help Japanese primary care physicians: a qualitative study.

OBJECTIVES: This study aimed to identify training needs among primary care physicians in Japan who had no formal primary care training. METHODS:  We conducted a focus group interview with seven Japanese primary care physicians who had not previously undergone specialist training in primary care and had been recruited to a family medicine training program that used a problem-based learning approach. At the start of the program, the physicians attended the interview. The discussion was recorded, and the transcribed interview was analyzed using the Steps for Coding and Theorization method. RESULTS:  Three main themes emerged. First, there is a lack of standard re-education programs for physicians who move away from their specializations into primary care. Second, there is insufficient training on primary care in undergraduate and postgraduate medical education in Japan. Third, continuing professional development programs should cover the communication skills, attitudes, and behaviors necessary for primary care practice. CONCLUSIONS:  This study clarified the needs to be addressed in our training program for primary care physicians involved in retraining in primary care. It is important to consider how to best include the communication skills, attitudes, and behaviors necessary for primary care among the topics covered in the program. As the program undergoes further iteration, it will be important to check whether it meets the needs of primary care practitioners. It will be necessary to investigate the needs of re-education programs for more physicians in many areas, and to emphasize the importance of primary care re-education in these abilities in undergraduate and postgraduate medical education.

The impact of gender on medical visit communication and patient satisfaction within the Japanese primary care context.

OBJECTIVE: This study was designed to address significant gaps in the predominantly western-centric research literature by examining the influence of gender concordance in medical communication and patient satisfaction within the Japanese context. METHODS: New primary care patients (54 male and 49 female) were randomly assigned to study internists (6 males and 5 females). Recorded visits were coded with the Roter Interaction Analysis System (RIAS). Post-visit, patients completed a Japanese version of the Medical Interview Satisfaction Scale (MISS). 　 RESULTS: Female concordant visits showed higher levels of patient-centeredness than all other gender combinations. Female physicians substantially modified their communication based on patient gender while male physicians did not. Gender concordance was associated with higher female, but lower male patient satisfaction relative to gender discordant visits. CONCLUSION: Contrary to normative experience of medicine as a male dominated profession in Japan, and gender-based power differentials, male-gendered clinical communication is less likely to satisfy male than female patients, while female-gendered communication is positively associated with female patient satisfaction. PRACTICE IMPLICATIONS: Patient satisfaction ratings reflect greater gender flexibility in terms of acceptable physician behavior than Japanese norms would suggest.

Hepatocellular carcinoma incidentally detected at second hepatectomy for repeated colorectal liver metastasis in a patient with hepatitis C virus-related cirrhosis: a case report.

BACKGROUND: It has been reported that liver metastasis rarely occurs in a cirrhotic/hepatitic liver. Thus, coexistence of liver metastasis and hepatocellular carcinoma has been scarcely reported. To the best of our knowledge, there are no cases with hepatocellular carcinoma, which developed during an observational period after hepatectomy for colorectal liver metastasis, in the worldwide English literature. Here we present a case of hepatocellular carcinoma which occurred during a period between the first and second hepatectomy for repeated colorectal liver metastasis. CASE PRESENTATION: A 65-year-old Japanese woman underwent rectal resection for advanced rectal cancer. Hepatitis C cirrhosis was diagnosed at that time and antiviral therapy was offered but rejected because of socioeconomic reasons. At the age of 68, she developed two colorectal liver metastases originating from the rectal cancer, which were treated by local ablation and partial hepatectomy. At the age of 71, solitary recurrent colorectal liver metastasis was observed adjacent to the previously ablated lesion in segment 4, and thus segmentectomy 4 was performed. During surgery, a small tumor in segment 8 was incidentally identified. Taking into account her history, the tumor was considered to be recurrent colorectal liver metastasis and it was extirpated by partial hepatectomy. However, the segment 4 tumor was diagnosed as recurrent colorectal liver metastasis on the basis of histological findings and the segment 8 tumor was diagnosed as hepatocellular carcinoma. Although she had a cut surface abscess postoperatively, she was discharged from hospital 21 days after the surgery and is currently doing well 18 months after the second hepatectomy. She is currently receiving interferon and ribavirin therapy to eliminate hepatitis C virus. CONCLUSIONS: If antiviral therapy was performed earlier for the present case and viral elimination was achieved, hepatocellular carcinoma might not have developed. This case reemphasizes the importance of antiviral therapy for preventing carcinogenesis of hepatocellular carcinoma in patients with viral hepatitis even if they have other cancers.

Recognition of and intent to use gastrostomy or ventilator treatments in older patients with advanced dementia: differences between laypeople and healthcare professionals in Japan.

AIM: We compared differences between laypeople and healthcare professionals in the recognition of and intent to use gastrostomy and ventilator treatments in older patients with dementia. METHODS: Between November 2011 and January 2012, a questionnaire survey was carried out. People who underwent a general health check-up at Nomura Hospital Preventive Medical Center were recruited as the laypeople group. Physicians and nurses working in Mitaka, Tokyo, Japan, were recruited as the healthcare professional group. We assessed the recognition rate of ventilator and gastrostomy treatments. Then we provided two scenarios for participants to determine whether these methods represented life-sustaining treatments that will simply delay an inevitable death. Intentions were compared between cases with and without advance directives. RESULTS: Approximately 60% of laypeople did not know what gastrostomy is. Healthcare professionals were more likely to recognize a ventilator as a life-sustaining treatment; in contrast, there were no significant differences in judgments regarding gastrostomy. Both groups were more likely to have intent to use a gastrostomy and a ventilator for family members than themselves. Furthermore, healthcare professionals were more likely to want to use these items for patients than their family members. Advance directive for withholding life-sustaining treatment reduced the intention to use these treatments. CONCLUSION: It is necessary to increase our understanding regarding knowledge of end-of-life care options of both laypeople and healthcare professionals.

Blunt penetration technique for treatment of a completely obstructed anastomosis after rectal resection: a case report.

INTRODUCTION: We present a case of completely obstructed anastomosis after rectal resection which was nonsurgically and successfully treated with a blunt penetration technique using a commonly used device for transanal ileus drainage. The technique we used in this case has not been previously reported. CASE PRESENTATION: A 79-year-old Japanese man underwent redo rectal resection for completely separated anastomosis which was caused by anastomotic leakage after a sigmoidectomy performed 3 years previously that was remedied by diverging ileostomy. Immediately after the redo surgery, fluoroscopy showed good passage through the colorectal anastomosis but no anastomotic leakage. However, fluoroscopy and colonoscopy prior to the ileostomy takedown showed complete obstruction of the anastomosis. Unlike usual anastomotic strictures, the lumen between colon oral and rectum anal to the anastomosis was completely discontinued by a membranous structure. Therefore, a conventional balloon dilatation technique was unsuitable for this condition. We applied a blunt penetration technique using a commercially available device designed as a transanal drainage system for obstructing colorectal cancer to restore the continuity between the colon oral and rectum anal to the anastomosis. After restoring the continuity, we performed conventional balloon dilatation for the anastomosis and successfully treated the anastomotic obstruction. Subsequently, the patient underwent ileostomy takedown and is currently doing well 12 months after the ileostomy takedown. CONCLUSIONS: The penetration technique we applied is easy and less stressful to adopt because it does not require usage of materials specialized for other particular purposes. Furthermore, we believe that this technique is superior in safety to other reported methods for this condition even if applied in the wrong direction because this technique does not utilize electrocision or sharp needle puncture.

Small hepatocellular carcinoma with ring calcification: a case report and literature review.

Ring calcification in untreated hepatocellular carcinoma (HCC) is extremely rare, with only 3 previously reported cases in the English-language literature. A case of HCC with ring calcification was reported in this paper. Additionally, 3 previously reported cases of HCC with ring calcification were reviewed. In 3 of these 4 cases (including our case), surgery was performed. Although the size of the ring-calcified lesion ranged from 3.0-3.7 cm in previously reported cases, the size was only 1 cm in ours. The differentiation of the tumor was moderate in the 2 previously reported cases in the histological findings and poor in ours. In spite of their poor differentiation for their sizes, these tumors showed no early enhancement in dynamic computed tomography. All calcified tumors showed a thick fibrous capsule and extensive necrosis histologically. Ring calcification was considered to result from a circulatory disturbance caused by the imbalance between the less abundant arterial blood flow and high inner pressure induced by either the thick fibrous capsule or vigorous proliferation due to the poor differentiation. Ring calcification in untreated HCC may suggest a lower differentiation of the tumor. Even if its size is small, hepatic resection should be performed for any tumor with ring calcification because poor differentiation is considered to be one of the risk factors for recurrence after local ablation therapy, including radio frequency ablation.

Chylous ascites occurring after low anterior resection of the rectum successfully treated with an oral fat-free elemental diet (Elental(®)).

Chylous ascites occurring after abdominal surgery is rare. Despite being potentially critical, there is no definite treatment guideline because of its rarity. Here we present a case of massive chylous ascites occurring after rectal surgery which was successfully treated with an oral fat-free elemental diet (ED). A 67-year-old man underwent low anterior resection with para-aortic lymphadenectomy for advanced rectal cancer. Early postoperative course was uneventful and the patient was discharged from hospital 10 days after surgery; however, after discharge, abdominal distension rapidly developed. Abdominal computed tomography (CT) performed 3 weeks after surgery revealed massive ascites and laboratory findings showed remarkable hypoproteinemia and lymphopenia. Urgent diagnostic paracentesis showed the ascites to be a white milky fluid containing high levels of triglycerides (564 mg/dl), leading to a diagnosis of chyloperitoneum. Daily nutrition of the patient was entirely with a fat-free ED (30 kcal/kg/day of Elental(®), Ajinomoto Pharmaceutical Co. Ltd, Tokyo, Japan). After the initiation of oral Elental(®), abdominal distension, hypoproteinemia, and lymphopenia gradually improved. Abdominal CT performed 7 weeks after surgery showed no ascitic fluid in the abdomen, and thereafter a normal diet was initiated. Since then, no relapse of chyloperitoneum has been proven. As a result, the chylous ascites was successfully treated in the outpatient clinic.

[Sensory evaluation test: odor component analysis and endotoxin content of Krestin and Carbocrin (generic drug) to compare palatability].

We conducted a sensory evaluation test to demonstrate the difference in palatability between Krestin and Carbocrin (generic drugs). In addition,we analyzed the odorous components and endotoxin contents of the two products to clarify the difference in physicochemical properties. In the sensory evaluation test, questions were asked on the odor, taste, feeling on the tongue, and overall evaluation, to find out which is easier to swallow. Krestin is significantly superior to Carbocrin, showing a clear difference in palatability between the two products. In odor component analysis, chemicals estimated to be n-heptane and 4-methyl-3-penten-2-one or its isomer (ketone containing 6-carbon double bonding) were detected. In addition, endotoxin content was also different between the two products. According to the above results, Carbocrin is definitely different from Krestin. Prior to administration, it is necessary to give this information to patients and obtain consent before use.

[Interferon-alpha+cisplatin+5-FU therapy for gemcitabine-refractory unresectable and recurrent pancreatic cancer].

Interferon-alpha (IFN-Alpha) + cisplatin (CDDP) + 5-FU therapy was given to 10 patients with gemcitabine (GEM)-refractory unresectable or recurrent pancreatic cancer. CDDP (35 mg/m(2)) was administered intravenously on the first day, IFN-Alpha (5x10(6)IU) subcutaneously on day 2,4 and 6 of each week, and 5-FU (175 mg/m(2)/day) continuously infused every day for 4 weeks. The 10 patients consisted of 8 men and 2 women with a mean age of 56.2 years. As the main site of progression, 5 patients had liver metastases, 1 had lung metastases, 2 had peritoneal dissemination, and 2 had local recurrence. The objective response rate was 30%, including 1 complete response. Grade 3 anorexia, neutropenia and thrombocytopenia occurred in 60%, 40% and 40%, respectively. IFN-Alpha + CDDP + 5-FU therapy is an effective treatment for GEM-refractory pancreatic cancer, but with moderate toxicity.

Families' and physicians' predictions of dialysis patients' preferences regarding life-sustaining treatments in Japan.

BACKGROUND: Substituted judgment traditionally has been used often for patient care in Japan regardless of the patient's competency. It has been believed that patient preferences are understood intuitively by family and caregivers. However, there are no data to support this assumption. METHODS: A questionnaire survey was administered to 450 dialysis patients in 15 hospitals to determine their preferences for cardiopulmonary resuscitation (CPR) and dialysis therapy under various circumstances. Simultaneously, we asked family members and physicians of these patients about patient preferences to evaluate their ability to predict what their patients would want. The accuracy of families' and physicians' judgments was assessed by means of kappa coefficient. RESULTS: Three hundred ninety-eight pairs, consisting of a patient, 1 of his or her family members, and the physician in charge, participated from 15 hospitals in Japan, with a response rate of 88%. Sixty-eight percent of family members correctly predicted patients' current preferences for CPR, 67% predicted patients' preferences for dialysis when they were severely demented, and 69% predicted patients' preferences for dialysis when they had terminal cancer. Corresponding figures for physicians were 60%, 68%, and 66%. When using kappa coefficient analysis, those results indicated that neither family members nor physicians more accurately predicted their patients' wishes about life-sustaining treatments than expected by chance alone. (All kappa coefficients <0.4.) CONCLUSION: Our study suggests that patients who want to spend their end-of-life period as they want should leave better advance directives.

Usefulness of prophylactic transcatheter arterial infusion of anticancer agents with lipiodol to prevent recurrence of hepatocellular carcinoma after hepatic resection.

To improve the prognosis after hepatectomy for HCC, repeated postoperative transcatheter arterial infusions of anticancer drugs and lipiodol (TAI) were given. TAI may be effective as an adjuvant therapy for prevention of residual liver recurrence after hepatectomy, probably by suppression of the development of intrahepatic micrometastases rather than of multicentric carcinogenesis.

Two-stage hepatectomy for multiple bilobular liver metastases from colorectal cancer.

BACKGROUND/AIMS: To determine an appropriate surgical treatment for patients with multiple liver metastases, we evaluated the efficacy of two-stage hepatectomy in patients with multiple bilobular liver metastases from colorectal carcinoma. METHODOLOGY: Some patients with multiple liver metastases are not candidates for a complete resection by a single hepatectomy, even when downstaged by chemotherapy, after portal embolization. In two-stage hepatectomy, the highest possible number of tumors is resected in a first, noncurative intervention, and the remaining tumors are resected after a period of liver regeneration. Two-stage hepatectomy was performed in 11 patients. RESULTS: Two-stage hepatectomy was feasible in all of the 11 patients. In 3 of them, the first stage was a major resection (more extensive than a lobectomy). This first hepatectomy was uneventful in all patients. The second hepatectomy was also uneventful in nine patients, but in one of the other two, a perihepatic fluid infection occurred, and in the other, postoperative liver failure developed due to a right subphrenic abscess. However, all patients were discharged. The percentage of the expected resection volume at one time, calculated from CT volumetry, was 75.5+/-1.2% and the prognostic score as surgical risk was 56.6+/-4.5. In two-stage hepatectomy cases, the percentage of the resected volume and the prognostic score in the first hepatectomy were 25.4+/-6.4% and 6.7+/-7.3, and in the second, 45.7+/-4.5% and 28.5+/-5.8. During the follow-up procedures, a residual hepatic recurrence was observed in 6 patients, and pulmonary recurrence in 9. The 1- and 3-year survival rates after the first hepatectomy were 90% and 45%, with median survivals of 18 months from the first hepatectomy. CONCLUSIONS: Two-stage hepatectomy is a surgical modality intended for patients with initial unresectable metastases. However, following such surgery, protective treatment against residual liver recurrence and lung metastasis will be a most important issue.

Pharmacologic preconditioning effects: prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver.

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.

Usefulness of granular BCAA after hepatectomy for liver cancer complicated with liver cirrhosis.

OBJECTIVE: Nutritional disturbances such as ascites and hypoalbuminemia frequently arise after hepatectomy for liver cancer with liver cirrhosis. We examined the possibility of maintaining a favorable state of nutrition by outpatient administration of branched-chain amino acid (BCAA) granules. METHODS: Forty-three patients who had gross liver cirrhosis complicated by liver cancer and underwent surgery up to May 2002 were given BCAA granules (n = 21, BCAA group) or no granules (n = 22, control group). RESULTS: 1) Background details such as age, sex, surgical technique, blood loss, and duration of surgery showed no significant differences. 2) Among objective findings, improvement of ascites and edema tended to occur sooner in the BCAA group, but without a significant difference. 3) Although serum albumin recovered its preoperative value 9 mo after surgery in the control group, only 6 mo was required for recovery in the BCAA group. Total protein showed similar changes, but neither group showed any difference in changes of aspartate aminotransferase, alanine transferase, or platelets. 4) One year postoperatively, the change from the preoperative indocyanine green retention rate at 15 min after intravenous administration tended to be worse in the control group, but not significantly so. 5) In the BCAA group, hyaluronic acid and type IV collagen 7S improved significantly sooner than in the control group. CONCLUSIONS: BCAA supplementation after hepatectomy promotes rapid improvement in protein metabolism and inhibits progression to liver cirrhosis. Administration of BCAA after hepatectomy is considered beneficial to a patient's nutritional state.

Long-term physiologic changes of intraocular pressure: a 10-year longitudinal analysis in young and middle-aged Japanese men.

OBJECTIVE: Although the intraocular pressure (IOP) is the most important factor related to the onset and progression of glaucoma, there is little evidence on long-term aging effects on IOP. This article examines the changes of IOP over 10 years in normal eyes to assess physiologic changes related to aging. DESIGN: Population-based long-term longitudinal study. STUDY POPULATION AND OBSERVATION PROCEDURE: Two thousand nine hundred eighty-seven Japanese male aircraft crew members underwent IOP measurement by Goldmann apparatus and received physical and complete ophthalmologic examinations every year for 10 years. A total of 2330 healthy persons (21-49 years; mean age, 35.9+/-6.8 [standard deviation]) who had no history of treatment for ophthalmic diseases, current illnesses, and no missing data for 10 consecutive years were analyzed. MAIN OUTCOME MEASURES: For analysis of the longitudinal index (trend), the linear regression coefficients for 11 points of measurement were determined. Ophthalmologic and physiologic factors affecting the 10-year mean values and a trend of IOP were examined by multivariable linear regression analysis. RESULTS: Intraocular pressure tended to decrease with age in all age groups. The mean linear regression coefficient (right eye/left eye) = -0.076/-0.060 (95% confidence interval [CI]: (-0.094 to -0.057)/(-0.078 to -0.041), -0.073/-0.060 [95% CI: (-0.084 to -0.062)/(-0.071 to -0.049)], and -0.060/-0.050 [95%CI: (-0.075 to -0.046)/(-0.064 to -0.036)] (mmHg/year) in the 20s, 30s, and 40s, respectively). In investigating correlations between the 10-year mean values of IOP and factors examined in this study, multivariate analysis showed a significantly inverse correlation with spherical power (partial regression coefficient [B] = -0.155/-0.144) and positive correlation with esophoria (B = 0.536/0.521), systolic blood pressure (B = 0.021/0.022), heart rate (B = 0.024/0.024), and hematocrit (B = 0.041/0.043) with IOP. The trend of IOP was significantly positively associated with the trends of systemic factors: body mass index (BMI) (B = 0.117/0.119), blood pressure (systolic) (B = 0.020/0.020), and hematocrit (B = 0.057/0.045), but not with any ophthalmologic factor. CONCLUSIONS: The long-term observation clearly demonstrated that, in normal eyes, the IOP decreased with aging. The IOP value was negatively associated with spherical power and positively with esophoria, blood pressure, heart rate, and hematocrit. The change of IOP could be affected mainly by the change of body mas index, blood pressure, and hematocrit.

MUC1 overexpression is the most reliable marker of invasive carcinoma in intraductal papillary-mucinous tumor (IPMT).

BACKGROUND/AIMS: To clarify the development of pancreatic cancer we performed immunohistochemical analysis of the presence of the major apomucin and cell-cycle regulatory proteins using the tissues of IPMT and ductal adenocarcinoma (DC) of the pancreas. METHODOLOGY: Formalin-fixed and paraffin-embedded tissues of 24 IPMT and 21 DC cases were subjected to immunohistochemical staining for MUC1, MUC2, p16, p53 and DPC4. According to the WHO classification, there were 10 intraductal papillary-mucinous adenomas (IPMA); 3 borderline intraductal papillary-mucinous neoplasms (IPMB); 4 intraductal papillary-mucinous carcinomas (IPMC), non-invasive type (nIPMC); 4 IPMCs with invasive muci nous carcinoma (IPMC/muc); and 3 IPMCs with invasive tubular adenocarcinoma (IPMC/tub). RESULTS: MUC1 expression was seen in 6 of 7 invasive IPMCs (86%) and in all DCs (100%). MUC2 was only seen in non-invasive IPMT and in a part of IPMC/muc. p53 nuclear staining was positive only in 3 of 7 invasive IPMCs (43%) and 9 of 21 DCs (43%). DPC4 nuclear expression was positive in almost all cases of non-invasive IPMT, but negative or reduced in 4 of 7 invasive IPMCs (57%), and 14 of 21 DCs (67%). CONCLUSIONS: MUC1 overexpression is considered to be the most sensitive and specific marker of invasive carcinoma, followed by DPC4 and p53 with less sensitivity.