COVID-19 Effects on Income and Dental Visits: A Cross-sectional Study.

OBJECTIVES: In April 2020, the Japanese government declared a state of emergency owing to the outbreak of the novel coronavirus disease (COVID-19) pandemic, which resulted in reduced workforce and job losses. Furthermore, income is one of the most consistent predictors of dental visits. Therefore, this study examined the association between income changes and dental clinic visits during the COVID-19 state of emergency in Japan. METHODS: An online, self-reported cross-sectional survey about health activities including dental visits during the first COVID-19 state of emergency was conducted in Osaka, Japan (June 23 to July 12, 2020). Among participants with toothaches, the assessment for the association between "refrained from visiting a dentist despite wanting treatment for toothache during the state of emergency (refrained treatment)" and income changes before and after the state of emergency using a multivariate Poisson regression model adjusted for sex, age, self-rated health, frequency of regular dental visits, and employment status. RESULTS: Among 27,575 participants, 3,895 (14.1%) had toothaches, and 1,906 (6.9%) reported refrained treatment. Among people with decreased income (n = 8,152, 29.6% of overall participants), the proportions of the refrained treatment group were 8.0% (income decreased by 1%-49%), 9.9% (50%-99% decreased), and 9.1% (100% decreased). Among participants with toothache, after adjusting for all variables, compared with participants with no income change, we observed significantly higher prevalence ratios (PRs) for refrained treatment in those who experienced a decreased income owing to COVID-19 (1%-49% decrease: PR = 1.08; 95% confidence interval [CI], 1.005-1.17; 50%-99% decrease: PR = 1.18; 95% CI, 1.06-1.32; 100% decrease: PR = 1.18; 95% CI, 1.04-1.33). CONCLUSION: Decreased income was associated with refrained dental treatment during the COVID-19 state of emergency in Osaka, Japan. The economic damage related to the COVID-19 pandemic could lead to oral health inequalities. KNOWLEDGE TRANSFER STATEMENT: Our study found that individuals with decreased income owing to COVID-19 before and after the state of emergency showed significantly higher prevalence ratios for refraining from visiting a dentist despite wanting treatment for toothache. We believe that our study makes a significant contribution because it provides novel, basic data that economic damages related to the COVID-19 pandemic might expand to oral health inequalities.

Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer.

BACKGROUND: Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003). PATIENTS AND METHODS: Of 39 859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2111 patients who underwent surgery in 2003 were used as an external validation set. RESULTS: Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 versus 0.61; P < 0.001). Moreover, calibration was accurate. CONCLUSIONS: We have developed and externally validated an elaborative nomogram that predicts the 5-year OS of postoperative serosa-negative AGC. This nomogram would be helpful in the assessment of individual risks and in the consideration of additional therapy in clinical practice, and we have created freely available Web software to more easily and quickly predict OS and to draw a survival curve for these purposes.

Tobacco smoking and the risk of subsequent primary cancer among cancer survivors: a retrospective cohort study.

BACKGROUND: Smoking is a well-known risk factor for cancer; however, there is little evidence as to whether the smoking status of cancer survivors has any risk for subsequent primary cancer (SPC) incidence, regardless of the first cancer sites. PATIENTS AND METHODS: In total, 29,795 eligible patients with a first cancer between 1985 and 2004 were examined for SPC until the end of 2006, using a record linkage between hospital-based and population-based cancer registries. The association between smoking at the time of the first cancer diagnosis and three SPC groups (i.e. specific SPC, smoking-related SPCs, and all SPCs) was calculated by Poisson regression. RESULTS: Ever smokers had 59% and 102% higher risk for all SPCs and smoking-related SPCs, respectively, than never smokers. Cancer survivors who had recently stopped smoking had 18% and 26% less risk, respectively, for these SPCs than those who smoked at the diagnosis. We also found that, compared with those who had never smoked, cancer survivors who had ever smoked had a significantly elevated risk of oral/pharyngeal, esophageal, stomach, lung, and hematological SPCs, regardless of the first cancer sites. CONCLUSIONS: These findings indicate that smoking increases not only the first cancer but also a second or SPC. Moreover, the results from recent quitters versus current smokers suggest that smoking cessation may decrease the risk for SPC, especially for smoking-related SPCs in cancer survivors. Preventive measures are necessary to reduce not only SPC incidence but also tobacco use.

Prospective randomized trial of preoperative enteral immunonutrition followed by elective total gastrectomy for gastric cancer.

BACKGROUND: Perioperative enteral immunonutrition is thought to reduce postoperative morbidity in patients undergoing major gastrointestinal surgery. This study assessed the clinical effects of preoperative enteral immunonutrition in well nourished patients with gastric cancer undergoing total gastrectomy. METHODS: Well nourished patients with primary gastric cancer, fit for total gastrectomy, were randomized to either a control group with regular diet, or an immunonutrition group that received regular diet supplemented with 1000 ml/day of immunonutrients for 5 consecutive days before surgery. The primary endpoint was the incidence of surgical-site infection (SSI). Secondary endpoints were rates of infectious complications, overall postoperative morbidity and C-reactive protein (CRP) levels on 3-4 days after surgery. RESULTS: Of 244 randomized patients, 117 were allocated to the control group and 127 received immunonutrition. SSIs occurred in 27 patients in the immunonutrition group and 23 patients in the control group (risk ratio (RR) 1.09, 95 per cent confidence interval 0.66 to 1.78). Infectious complications were observed in 30 patients in the immunonutrition group and 27 in the control group (RR 1.11, 0.59 to 2.08). The overall postoperative morbidity rate was 30.8 and 26.1 per cent respectively (RR 1.18, 0.78 to 1.78). The median CRP value was 11.8 mg/dl in the immunonutrition group and 9.2 mg/dl in the control group (P = 0.113). CONCLUSION: Five-day preoperative enteral immunonutrition failed to demonstrate any clear advantage in terms of early clinical outcomes or modification of the systemic acute-phase response in well nourished patients with gastric cancer undergoing elective total gastrectomy. REGISTRATION NUMBER: ID 000000648 (University Hospital Medical Information Network (UMIN) database).

The significance of abdominal para-aortic lymph node metastasis in patients with lower thoracic esophageal cancer.

Para-aortic lymph node (PALN) recurrence is often seen in patients with lower thoracic esophageal cancer treated by esophagectomy with extended lymph node dissection. However, the clinicopathological characteristics of patients with PALN metastasis and the significance of PALN dissection are unknown. A total of 283 patients with lower thoracic esophageal cancer underwent esophagectomy with lymphadenectomy at our hospital between April 1984 and March 2007. Among these 283 patients, 60 patients were enrolled in this retrospective study according to following criteria: (i) clinical T2 to T4 tumor, (ii) no clinical PALN metastasis, and (iii) received PALN dissection. PALN dissection was indicated by a tumor depth of at least T2 and no severe complications. The clinicopathological data, recurrence pattern, and overall survival were compared between patients with PALN and without PALN metastasis. The mean length of surgery was 587 min and the mean blood loss was 1383 mL. The morbidity was 33.3% and mortality was 5% in this series. Sixteen patients (26.7%) had PALN metastasis; these showed significantly more lymph node metastases (15.8 ± 13.2 vs. 3.0 ± 3.2, P < 0.0001) and significantly worse survival rates (53.3% vs. 79.9% at 1 year, 6.7% vs. 62.0% at 3 years, P < 0.0001) than patients without PALN metastasis. The incidence of lymph node recurrence (P < 0.0001) and hematogenous recurrence (P= 0.0487) was also higher in patients with PALN metastasis than in patients without PALN metastasis. Among the 16 patients with PALN metastasis, a univariate analysis revealed total number of metastatic nodes < 8 (P= 0.0325) to be a significant prognostic factor. A multivariate logistic regression analysis of the regional lymph nodes identified the invasion of the lower mediastinal nodes (hazard ratio = 6.120) and retroperitoneal nodes (hazard ratio = 15.167) to be significantly correlated with PALN metastasis. PALN metastasis is suggested to be related to the systemic spread of lymphatic metastasis even in lower thoracic esophageal cancer. PALN dissection for pathological PALN(+) patients should not be performed. It remains to be determined in future prospective studies whether patients without pathological PALN metastasis, but showing PALN micrometastasis, could achieve improved survival with PALN dissection.

Prevention of gastroduodenal content reflux and delayed gastric emptying after esophagectomy: gastric tube reconstruction with duodenal diversion plus Roux-en-Y anastomosis.

Reflux of gastroduodenal contents and delayed gastric emptying are the most common and serious problems after esophagectomy with gastric reconstruction. However, attempts to reduce the above symptoms, surgically as well as non-surgically, had no or limited effect. To address this issue, we performed retrosternal gastric reconstruction with duodenal diversion plus Roux-en-Y anastomosis (RY) in eight patients with thoracic esophageal cancer and compared the outcomes with control patients who underwent standard reconstruction. The procedure is simple, safe, and not associated with any postoperative complications. The pancreatic amylase concentrations in the gastric juice samples on postoperative day 2 were slightly lower in the non-RY group than in the RY group (1884 ± 2152 vs. 25,790 ± 23,542IU/mL, respectively, P= 0.07). Postoperative endoscopic examination showed neither reflux esophagitis nor residual gastric content in the RY group. Quality of life assessed by the Dysfunction After Upper Gastrointestinal Surgery-32 questionnaire postoperatively was significantly better in the RY group than in the non-RY group for 'decreased physical activity,''symptoms of reflux,''nausea and vomiting,' and 'pain.' The results of this pilot study suggest that gastric reconstruction with duodenal diversion plus RY seems effective in improving both the reflux and delayed gastric emptying. The benefits of this procedure need to be further assessed in a large-scale, randomized controlled trial.

Clinical features and outcomes of delayed perforation after endoscopic submucosal dissection for early gastric cancer.

Perforation is a major complication of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). However, there have been no reports on delayed perforation after ESD for EGC. We aimed to elucidate the incidence and outcomes of delayed perforation after ESD. Clinical courses in 1159 consecutive patients with 1329 EGCs who underwent ESD were investigated. Delayed perforation occurred in six patients (0.45 %). All these patients had complete en bloc resection without intraoperative perforation during ESD. Five of six perforations were located in the upper third of the stomach, while one lesion was found in the middle third. Symptoms of peritoneal irritation with rebound tenderness presented within 24 h after ESD in all cases. One patient did not require surgery because the symptoms were localized, and recovered with conservative antibiotic therapy by nasogastric tube placement. The remaining five patients required emergency surgery. There was no mortality in this case series.

Correlation between pretherapeutic d-dimer levels and response to neoadjuvant chemotherapy in patients with advanced esophageal cancer.

Neoadjuvant chemotherapy may improve survival of responders in esophageal cancer patients but is useless and harmful in non-responders. Thus, it is important to predict the effect of the chemotherapy, and that any predictor must be applicable clinically. The aim of this study is to examine the correlation between pretherapeutic hypercoagulopathy as determined by plasma d-dimer levels and response to chemotherapy. In 71 patients with esophageal cancer who underwent neoadjuvant chemotherapy (cisplatin, adriamycin and 5-fluorouracil) followed by surgery, plasma d-dimer levels were measured before chemotherapy and the clinical and pathological responses to chemotherapy were assessed at 4 weeks after therapy (after surgery). Pretherapeutic plasma d-dimer level was significantly lower in clinical responders (complete response/partial response [CR/PR]; 0.62 +/- 1.10 microg/mL, mean +/- SD) than in non-responders (no change/progressive disease [NC/PD]; 1.15 +/- 1.08 microg/mL, P = 0.0491), and in pathological responders (Grade 1b-3; 0.62 +/- 1.11 microg/mL) and non-responders (Grade 0-1a; 1.15 +/- 1.05 microg/mL, P = 0.0107). The optimal cut-off level of the plasma d-dimer levels for predicting clinical and pathological responses was 0.6 microg/mL. Then, sensitivity and specificity for the prediction of CR/PR were 68% and 73%, and those for Grade 1b-3 were 91% and 69%, respectively. Our results suggested that pretherapeutic plasma d-dimer level correlated significantly with clinical and pathological responses to chemotherapy. Pretherapeutic plasma d-dimer level can be used as a predictor for chemosensitivity.

Suppression of tumorigenicity, but not anchorage independence, of human cancer cells by new candidate tumor suppressor gene CapG.

Previously, we isolated a series of cell lines from a human diploid fibroblast lineage as a model for multistep tumorigenesis in humans. After passaging a single LT-transfected fibroblast clone, differently progressed cell lines were obtained, including immortalized, anchorage-independent and tumorigenic cell lines. In the present paper, we analysed the gene expression profiles of these model cell lines, and observed that expression of the CapG protein was lost in the tumorigenic cell line. To examine the possibility that loss of CapG protein expression was required for tumorigenic progression, we transfected CapG cDNA into the tumorigenic cell line and tested for tumor-forming ability in nude mice. Results showed that ectopic expression of CapG suppressed tumorigenicity, but not growth in soft agar or liquid medium. We also found that certain cancer cell lines including stomach cancer, lung cancer and melanoma had also lost CapG expression. One such cancer cell line AZ521 also became non-tumorigenic after the introduction of CapG cDNA. Moreover, we showed that CapG expression was repressed in small-cell lung cancer tissues. Together, our findings indicated that CapG is a new tumor suppressor gene involved in the tumorigenic progression of certain cancers.

Preoperative chemotherapy for clinically node-positive patients with squamous cell carcinoma of the esophagus.

Lymph node metastasis is one of the strongest prognostic factors for patients with esophageal cancer. Whether neoadjuvant chemotherapy is effective for metastatic nodes and improves the prognosis of clinically node-positive patients is unknown. Seventy-seven patients with clinically node-positive esophageal cancer, who were given preoperative chemotherapy (5-fluorouracil, cisplatin and adriamycin) followed by surgery, were retrospectively analysed. The histological effectiveness of the chemotherapy against the main tumor in the resected specimen was correlated with nodal status and prognosis. Of the 77 patients, the histological effects in the main tumors were grade 3 in one patient (1.3%), grade 2 in 10 (13.0%), grade 1b in seven (9.1%), grade 1a in 50 (64.9%) and grade 0 in nine (11.7%). Eleven patients (14.3%) were found to be pathologically node-negative. The pathological stages were significantly earlier in responders (grades 3-1b) than in non-responders (grades 1a-0) (P = 0.0001). The responders showed a significantly lesser degree of lymph node metastasis (P = 0.0005), fewer metastatic nodes (2.2 +/- 3.1 vs. 12.0 +/- 20.5, P = 0.0482) and better survival (P = 0.002) than the non-responders. The most common failure pattern for the non-responders was lymphatic recurrence, with an incidence of 47.5% (28/59), while that for the responders was 16.7%. Responders to neoadjuvant chemotherapy show fewer metastatic nodes and better prognosis than non-responders. Neoadjuvant chemotherapy may offer clinical benefit to responders.

Prognosis of patients who develop cervical lymph node recurrence following curative resection for thoracic esophageal cancer.

Patients with esophageal cancer often display relapse at cervical nodes after surgery, but their prognosis and a suitable therapy remains unknown. We retrospectively reviewed the records for 35 patients who underwent esophagectomy with lymphadenectomy who then displayed relapse at the cervical lymph nodes alone between 1985 and 2003 in order to observe the prognostic factors for such patients. Median survival time from the date of recurrence for all 35 patients was 12 months with 1-year, 2-year, 3-year and 5-year survival rate of 47.2%, 26.5%, 17.7% and 8.8%, respectively. With regard to the initial treatment against cervical node recurrence, 15 patients were treated by radiotherapy alone, eight by chemoradiotherapy, 11 by surgery and one by chemotherapy alone. Univariate analysis revealed that cervical node dissection at the prior esophagectomy (yes/no, P = 0.0178), time to recurrence (> 9 months or < 9 months, P = 0.0497) and the number of relapsed nodes (solitary/multiple, P = 0.0029) were significant prognostic factors. Among these factors, the number of relapsed nodes (solitary/multiple) was found to be the only significant prognostic factor with an odds ratio of 2.409 and 95% confidence interval of 1.033-5.619 by multivariate analysis. In conclusion, cervical node metastasis is generally considered to be distant organ metastasis. However, if it is a solitary node recurrence, substantial survival can be attained by appropriate loco-regional therapy.

Does pleural lavage cytology before thoracic closure predict both patient's prognosis and site of cancer recurrence after resection of esophageal cancer?

BACKGROUND: Operative manipulation occasionally exfoliates and spreads cancer cells in the surgical field, and it is a matter of concern whether the exfoliated cancer cells actually affect the patient's prognosis and sites of cancer recurrence. METHODS: In 240 patients with esophageal cancers, lavage cytology (LC) of the right pleural cavity was performed before and after esophageal resection combined with regional lymphadenectomy. The cytologic results were compared with the pathologic factors associated with cancer extension, postoperative survival, and cause of surgical failure. RESULTS: Only 3 patients (1.3%) were LC positive before resection. Of the 237 LC-negative patients, LC was also negative after resection in 215 patients (90.7%) (LC-/-), but LC became positive after resection in 22 patients (9.3%) (LC-/+). The 3-year survival rate was 0% in the LC-/+ group versus 65% in the LC-/- group, and the median survival rates were 10.9 months and 25.0 months, respectively (P <.0001). Multivariate analysis revealed that LC-/+ was an independent prognostic factor (P =.0331), along with nodal involvement and depth of cancer invasion. However, there were no significant differences in the sites of cancer recurrence between the 2 groups. Only 1 patient was found to develop the first recurrence in the pleural cavity. The LC-/+ group had a higher incidence of bulky lymph-node metastasis (P =.0009). CONCLUSIONS: Pleural LC after resection of esophageal cancer seems to be a prognostic indicator of overall recurrence, but not necessarily in the pleural cavity. Patients with a positive LC after resection may benefit most by effective systemic adjuvant chemotherapy.

Application of sentinel node biopsy to gastric cancer surgery.

BACKGROUND: Sentinel node (SN) biopsy has been tried in the management of a variety of cancers with the hope that it would eliminate many unnecessary lymph node dissections, resulting in less morbidity. This important technique, however, has not been tried in gastric cancer surgery. The feasibility of SN biopsy and its accuracy in predicting the lymph node status in patients with gastric cancer were examined in the current study. PATIENTS AND METHODS: SN biopsy was performed in patients with T1 (n = 44) or T2 (n = 30) gastric cancers (ie, immediately after laparotomy, indocyanine green was injected around the primary tumor, and the green-stained nodes [SNs: 2.6 +/- 1.7 nodes per patient] were removed). Then, gastrectomy with extended lymphadenectomy was performed. The unstained nodes (non-SNs: 39 +/- 18 nodes per patient) were obtained from the resected specimens. Both SNs and non-SNs were subjected to histologic examination with hematoxylin-eosin. RESULTS: SNs could be identified in 73 of 74 patients (success rate, 99%). Of these 73 patients, 10 had lymph node metastases in SNs or non-SNs, or both; 6 in both SNs and non-SNs; 3 in SNs alone; and 1 in non-SNs alone. The sensitivity of the SN status in the diagnosis of the lymph node status of the patient was 90% (9/10) and specificity was 100% (63/63). Sensitivity was 100% in the T1 group (n = 44) and 88% in the T2 group (n = 29). CONCLUSIONS: SN biopsy using indocyanine green can be performed with a high success rate, and the SN status can predict the lymph node status with a high degree of accuracy, especially in patients with T1 gastric cancer.

Molecular strategy for detecting metastatic cancers with use of multiple tumor-specific MAGE-A genes.

BACKGROUND: The human melanoma-associated antigen family A (MAGE-A) has high specificity and expression in various malignancies, but individual family members are expressed at low frequency in any one particular type of cancer. We therefore developed a method to detect mRNAs from multiple MAGE-A genes in a single reaction. METHODS: Universal MAGE-A (uMAGE-A) primers and probe were designed to reverse-transcribe, amplify, and detect by electrochemiluminescence (ECL) MAGE-A mRNAs on the Origen Analyzer. The assay was performed on total RNA of melanoma (n = 9 cell lines and 24 tumors), breast cancer (n = 7 and 26), and colorectal cancer (CRC; n = 5 and 12). We also evaluated blood from melanoma (n = 50), breast cancer (n = 16), and CRC (n = 21) patients. RESULTS: The uMAGE-A mRNA was detectable in 0.01-1 ng of cell line RNA. The identity of the uMAGE-A cDNA products was confirmed by sequencing and polyacrylamide gel electrophoresis. The uMAGE-A assay increased detection of melanoma, breast cancer, and CRC tumor by 13%, 31%, and 25%, respectively, compared with a MAGE-A1 assay, and by 17%, 19%, and 25%, respectively, compared with a MAGE-A3 assay. The uMAGE-A assay detected circulating tumor cells in the blood of melanoma (24%), breast cancer (25%), and CRC (29%) patients. CONCLUSIONS: The uMAGE-A reverse transcription-PCR/ECL assay provides a practical and sensitive approach for detection of various metastatic cancers in tissues and blood.

Synchronous esophageal and renal cell carcinoma.

Multiple cancer associated with esophageal cancer is not uncommon; however, synchronous esophageal and renal cell carcinoma is very rare. Only three cases have been reported to date, and one of these patients was treated in our institution. We have since successfully treated another patient. Here, we report the two cases treated in our institution. In the first case, esophagectomy, nephrectomy, and reconstruction using a gastric tube were carried out in one stage. Post-operative renal function was temporarily impaired by the complications of anastomotic leakage and pyothorax but no hemodialysis was needed. In the second case, as the patient had undergone distal gastrectomy because of gastric cancer, we chose a two-stage operation, i.e. esophagectomy and nephrectomy as the first stage, followed by reconstruction using a colon substitute after 4 weeks, resulting in only slight renal dysfunction. Patients 1 and 2 are alive and well 7 years and 2 years after the operations respectively.

p21(Waf1/Cip1) and p53 protein expression in breast cancer.

p21/Cip1/Waf1 (wild-type p53 activated fragment 1/cyclin-dependent kinase [Cdk]-interacting protein 1) is a prominent Cdk inhibitor and has been shown to be a downstream mediator of p53. In this study, we sought to clarify the clinical significance of Waf1 and the relationship between Waf1 and p53 in breast cancer. For this purpose, the expressions of Waf1 and p53 were evaluated immunohistochemically in a series of 104 patients. Waf1 was expressed in 51 (49%) of 104 tumors tested, and p53 in 33 tumors (32%). Inverse expression of these two proteins was seen in 76 cases (73%); 47 were Waf1-positive and p53-negative, and 29 were Waf1-negative and p53-positive. A comparison with clinicopathologic parameters showed that Waf1 expression correlated with negative lymph nodes (P<.01), a low histologic grade (P<.0001), and positive estrogen receptor status (P<.01). Recurrence-free survival was lower for patients with Waf1-negative tumors than for those with Waf1-positive tumors (P<.0001). In multivariate analysis, Waf1 expression and low histologic grade (1 or 2) tumors had an independent prognostic significance for recurrence-free survival. These results suggest that Waf1 is induced mainly by a p53-dependent pathway and could be a reliable indicator of recurrence in breast cancer.

Analysis of phosphorylation of pRB and its regulatory proteins in breast cancer.

AIM: In order to study the role of retinoblastoma protein (pRB) in breast cancer, the phosphorylation of pRB and the expression of its related proteins-such as cyclin E, cyclin dependent kinase 2 (Cdk2), and p21/Cdk interacting protein 1 (Cip1)-were examined in 30 breast cancers in which pRB overexpression was confirmed immunohistochemically. METHODS: The phosphorylation of pRB for 30 tumours was investigated with western blotting. The expression of pRB, Cdk2/Cdc2, cyclin E, and p21/Cip1 was identified by immunohistochemistry and western blotting. RESULTS: The expression of pRB was confirmed in 52 of 70 tumours (74%) by immunostaining. Western blotting for pRB showed that 25 of 30 representative cancers (83%) were underphosphorylated, while only five tumours showed the hyperphosphorylated form of pRB. However, cyclin E and Cdk2-which promote phosphorylation of pRB-were expressed in all tumours. On the other hand p21/Cip1, a Cdk2 inhibitor, was expressed in 18 of 25 tumours with underphosphorylated pRB, while four of the five tumours with hyperphosphorylated pRB showed no expression of p21/Cip1. Examination of the relation between pRB phosphorylation and clinicopathological variables showed that the underphosphorylated group was characterised by low risk of lymph node metastasis (p < 0.01). CONCLUSIONS: The phosphorylation of pRB appears to be regulated mainly by p21/Cip1 through the suppression of cyclin E and Cdk2 in breast cancer. The underphosphorylated form of pRB may be useful as a prognostic factor.

Midkine expression in human breast cancers: expression of truncated form.

The expression of midkine (MK), a growth/differentiation factor, was assessed in 34 surgically resected specimens of primary breast cancer or mastopathy. Using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, all of the non-cancerous and cancerous tissues were found to express MK except for one breast cancer specimen. Northern blot analysis revealed that MK mRNA was also expressed in the normal breast tissues examined. Immunohistochemical analysis of the MK protein was performed on a limited number of the specimens, showing that some cancerous tissues were immunoreactive with anti-MK antibodies. Furthermore, using RT-PCR analysis, expression of not only the wild-type but also a truncated form of MK, which was recently found in various human tumor cell lines, was detected in 6 of 26 cancerous tissues but not in non-cancerous tissues.

Nonpalpable breast cancer with nipple discharge: how should it be treated?

In this study, 26 cases of nonpalpable breast cancer with nipple discharge treated at our department were reviewed. Their discharge was either bloody or serous with a positive hematest, but all except for one were negative for cytology, while CEA value of the discharge was high in 72.7%. Mammograms were found to be unreliable for diagnosis, while abnormal findings were observed in 84.6% by ductography. However, final diagnosis was determined histopathologically from surgical specimens, showing 14 intraductal and 12 invasive ductal cancers, none with components of comedo carcinomas. Seventeen patients underwent mastectomy following duct-lobular segmentectomy and a small remnant of intraductal carcinoma was found microscopically in only one patient. All patients except for one have survived for 98 months on average with no symptoms of metastasis. These findings suggest that duct-lobular segmentectomy with an adequate surgical margin should be adopted as the final operation for selected patients with nonpalpable breast cancer involving nipple discharge.

Expression of truncated midkine in human colorectal cancers.

Midkine (MK) is a growth differentiation factor originally found as the product of a retinoic acid-responsive gene. The expression of MK was examined in 35 surgically resected specimens of primary colorectal cancer using the reverse transcription-polymerase chain reaction (RT-PCR). All of the cancerous tissues expressed MK. In 5/25 cancerous tissues a truncated form of MK, which was recently found in various human tumor cell lines, was detected in addition to the full-size MK. In contrast, the truncated from of MK could not be detected in non-cancerous tissues, whereas the wild-type form was detected in 8/10 non-cancerous tissues. These results suggest that the expression of the truncated form of MK may be associated with tumorigenesis.