Intracholecystic Papillary Neoplasm Localized to the Cystic Duct: A Case Report.

Intracholecystic papillary neoplasm (ICPN) of the gallbladder is a premalignant lesion. An ICPN arising from the cystic duct is rare. A woman in her 60s exhibited dilatation of the common bile duct on computed tomography (CT) performed for screening of respiratory disease. The CT revealed an enhancing mass, 3.3 cm in diameter, in the cystic duct. Endoscopic ultrasonography showed a well-demarcated, hyperechoic mass in the dilated cystic duct. Endoscopic retrograde cholangiography showed that the common bile duct was slightly retracted by the dilated cystic duct. Cytological analysis of the bile juice did not show any evidence of malignancy. She was diagnosed with a cystic bile duct tumor suggestive of ICPN. Cholecystectomy, resection of the extrahepatic bile duct, and lymph node dissection were performed. Macroscopically, the papillary-proliferated tumor was localized to the cystic duct. No critical lesions were evident in the common bile duct. Histologically, the tumor in the cystic duct showed intraluminal growth with a papillary configuration without malignancy. Based on these findings, the tumor was diagnosed as an ICPN. We encountered a rare case of ICPN localized to the cystic duct of the gallbladder.

Alpha-fetoprotein-producing Colon Carcinoma with Rapidly Increasing Liver Metastases That Resulted in Death: A Case Report.

Alpha-fetoprotein (AFP) has been widely used as a tumor marker for detecting hepatocellular carcinoma and yolk sac tumors. Recently, cases of gastrointestinal cancer with elevated serum AFP levels have been reported. However, AFP-producing colon cancer is considered rarer than other AFP-producing gastrointestinal cancers. In this study, we report on a case of a 47-year-old woman who was diagnosed with sigmoid colon cancer and underwent sigmoidectomy and lymph node dissection. Postoperative adjuvant chemotherapy (AC) was performed after the curative surgery. After the seventh course of AC, multiple liver masses and enlarged systemic lymph nodes were detected; these were later diagnosed as liver metastases from sigmoid colon cancer. Laboratory examination revealed high AFP levels (14,657.8 ng/mL). After confirming the recurrence, her condition worsened rapidly, and she eventually died 8 months after the operation. Autopsy and histopathological findings showed that the liver mass was positive for AFP staining, but the sigmoid colon cancer tissue was not. We then determined that liver metastases of the colon cancer were more likely than germ cell carcinoma according to the clinical course and pathological findings. We assumed that colon cancer cells can rapidly expand by dedifferentiation, and we diagnosed AFP-producing colon cancer with liver metastases. Despite curative surgery and AC for AFP-producing colon cancer, the patient died of liver and systemic lymph node metastases.

Spontaneous regression of transverse colon cancer with high-frequency microsatellite instability: a case report and literature review.

BACKGROUND: Spontaneous regression (SR) of colorectal cancer (CRC) is extremely rare, and only few cases have been reported. Although it is not yet clarified, a plausible mechanism for SR of CRC is an immunological event. CASE PRESENTATION: In this report, we present the case of SR of primary CRC in a 78-year-old man. Preoperative colonoscopy was performed, and a type 2 tumor measuring 30 mm in diameter in the transverse colon was detected. The biopsy revealed a poorly differentiated adenocarcinoma. Colectomy was performed 2 months after initial colonoscopy. During the surgery, only a 10-mm ulcer harboring a polypoid lesion measuring 8.5 mm was detected in the resected tissue; no other masses or carcinoma cells were seen on histological examination. Afterwards, the biopsy specimens were reanalyzed, and immunohistological analysis verified this as adenocarcinoma with stroma-infiltrating lymphocytes. Further analysis revealed a loss of two mismatch repair proteins, suggesting sporadic high-frequency microsatellite instability (MSI-H). CONCLUSION: According to previous literature, a common site of SR in CRC is the proximal colon, which is a feature of MSI-H CRC. However, our report showed a rare case of SR of CRC, which was in the transverse colon, with MSI-H present. This report indicates a relationship between immunological features of MSI-H and the occurrence of SR of CRC. A better understanding of this phenomenon and the mechanisms involved will have significant preventive and therapeutic implications for CRC, including anti-PD-1 immune checkpoint inhibitor therapy.

[A case of advanced gastric cancer effectively treated with weekly paclitaxel as neoadjuvant chemotherapy].

We report a patient with advanced gastric cancer responding remarkably to neoadjuvant chemotherapy consisting of weekly paclitaxel. The patient was a 50-year-old male who had large advanced gastric cancer, suspected of invasion to the duodenum and pancreas and severe lymph node metastasis [cT4 (pancreas), cN2, cH0, cP0, cM0, cStage IV]. He was treated with weekly paclitaxel as neoadjuvant chemotherapy. According to gastroscope and CT findings, a significant tumor reduction was obtained after 3 courses. Therefore, distal gastrectomy with D2 nodal dissection were performed. The histological diagnosis was pT2, pN2, pStage IIIA, and the histological effect of the main tumor was judged to be Grade 2. The patient has now been in good health without recurrence for 3 years after surgery. This case suggests that neoadjuvant chemotherapy with weekly paclitaxel is a potentially effective regimen for advanced gastric cancer.

The importance of precise pT diagnosis for prognostic prediction of uterine cervical cancer--a single institutional report at a Japanese comprehensive cancer hospital.

We previously reported that the majority of Japanese pathologists misunderstand the International Union against Cancer-pT2 criteria for uterine cervical cancer (UCC). We compared the prognosis of originally diagnosed pT2 (ori-pT) UCC cases at our hospital with reclassified pT2 (re-pT) cases to assess the importance of making a correct pT diagnosis. There were 43 International Federation of Gynecology and Obstetrics (FIGO) II (i.e., cT2) and/or ori-pT2 UCC cases who received surgery without neoadjuvant chemotherapy at Shikoku Cancer Center from 1991 to 2003. The cases (seven ori-pT1 and 36 ori-pT2; 43 cN0 with six pN1) were reclassified as 22 re-pT1 and 21 re-pT2. Fifteen of the 23 ori-pT2a cases (65%) were re-pT1 because their vaginal extension had only been intraepithelial. The difference in the 5-year survival rate (5Y-SR) was not significant between the ori-pT1 and ori-pT2 cases using Fisher's exact test (F test): P = 0.236 > 0.05, whereas 5Y-SR of re-pT1 cases was significantly higher than re-pT2, including pN1 cases and excluding them (F test: P = 0.00164 < 0.01 and P = 0.0108 < 0.05, respectively). The 5Y-SR of ori-pT2-re-pT1 (overdiagnosed pT2) was significantly higher that of ori-pT2-re-pT2 (true pT2) including pN1 cases and excluding them (F test: P = 0.00694 < 0.01 and P = 0.0305 < 0.05, respectively). These results indicated that pT2 of UCC could be frequently misdiagnosed at an institutional level, and that misdiagnosed pT2 might impair the evidence-based medicine of UCC. Multi-institutional assessment of the accuracy of pTNM is recommended, because it is not likely that this is an endemic problem to our hospital.

Re-classification of pTNM staging for lung cancer: single-institution report at a Japanese comprehensive cancer hospital.

Among the major cancer sites, the lung has the most complicated pTNM description. Reclassification of International Union Against Cancer (UICC)-pTNM grading of 262 lung cancers resected at Shikoku Cancer Center was done using microscopy and audit of pathology reports. Of the 262 lung cancers, 222 were obtained at operation from 1999 to 2004 and 40 additional cases from 2006. Among 666 pTNM components of the former cases, 37 components (31T, 3N, 3M) in 35 cases were revised to different categories. The concordance rate (CR) of the original stage to the reclassified stage was 90% (210/222) in the five-group staging system (5GSS) without subdivisions and 84% (187/222) in the 8GSS with subdivisions such as IA and IB. It decreased in advanced cases. For example, the CR was higher in stage I (97%, 158/163) than in stage II-IV (88%, 51/59) in five-GSS (chi(2) test, P < 0.05). The CR in 8GSS of the additional 40 cases, which were diagnosed after the review of the former 222 cases, was 98% (39/40), indicating that the knowledge gained from the review improved the accuracy significantly (chi(2) test, P < 0.05). It is necessary to assess disparities in the accuracy of pTNM for lung cancer at each institution. This is also true for cancers at other sites.

Mutation of the epidermal growth factor receptor gene in the development of adenocarcinoma of the lung.

Recently, a mutation of the epidermal growth factor receptor (EGFR) gene has been reported to be implicated in the development of pulmonary adenocarcinoma. However, the involvement of the mutation in atypical adenomatous hyperplasia (AAH) and multiple adenocarcinomas still remains unclear. We herein examined the EGFR mutations in 9 AAH and 31 adenocarcinoma lesions obtained from 30 Japanese patients. Nine patients had synchronous or metachronous multiple adenocarcinomas and/or AAH. Mutations in exons 18-21 of EGFR gene were analysed using polymerase chain reaction and direct sequence methods. EGFR mutations were detected in 4 (44%) of 9 AAH and in 7 (23%) of 31 adenocarcinomas. A gefitinib-resistant point mutation (T790M) in exon 20 without gefitinib treatment was detected in 1 AAH and 1 adenocarcinoma. The patient with T790M mutated AAH, which also had an exon 19 mutation of D761Y, had synchronous adenocarcinoma, which had only an exon 19 mutation of D761Y. The other exon 19 mutations were all in-frame deletions. In the two patients with synchronous AAH and adenocarcinoma, AAH had mutations at exon 19 although adenocarcinoma did not have any mutations. In the patient with synchronous 2 adenocarcinomas, each had different mutations (exons 19 and 21). In two patients with double adenocarcinomas, 1 adenocarcinoma harbored exon 21 mutations, while the other demonstrated no mutations. Although EGFR mutations appeared to be partially associated with the early steps of adenocarcinoma development, such mutations may possibly occur randomly even in multiple lesions in a single patient.

The Vienna classification applied to colorectal adenomas.

BACKGROUND AND AIM: In 1999, a group of Western and Asian pathologists gathered in Vienna reached consensus regarding the classification of gastrointestinal epithelial neoplasia. In this study, that classification is applied to colorectal adenomas. METHODS: Colorectal adenomas from 1552 patients were histologically classified according to the categories listed in Vienna: category 3, low-grade dysplasia; 4.1, high-grade dysplasia; 4.2, carcinoma in situ; 4.3, suspicious of intramucosal carcinoma; 5.1, intramucosal carcinoma; and 5.2, submucosal carcinoma. The criteria used to diagnose these lesions are described in detail. Adenomas with dysplasia (categories 3 and 4.1) or with carcinoma (categories 4.2, 4.3, 5.1 and 5.2) were analyzed separately. On basis of their configuration, adenomas were classified into tubular, tubulovillous, villous, serrated, microtubular and combined phenotypes (i.e. other than tubulovillous). RESULTS: The highest percentage of adenomas with carcinoma was found amongst villous adenomas (29.6%), followed by combined adenomas (27.8%). Villous adenoma with carcinoma was the most frequent neoplasia at all ages; combined adenomas with carcinoma were more frequent among younger patients. In elderly patients (> or = 60 years of age) the highest percentage of adenomas with carcinoma was recorded in villous adenomas (28.1%), followed by serrated adenomas (19.2%). Villous adenomas and combined adenomas with carcinoma were more frequent in males. CONCLUSION: The Vienna classification of colorectal adenomas seems to be influenced by parameters inherent to the patient such as age and sex and by the histological phenotype of the adenoma. With the recent improvement in medical technology it is possible to laser-microdissect a defined group of neoplastic glands (such as with carcinoma in situ or with intramucosal carcinoma) for specific molecular analysis. This modern technology will permit in future the translation of histological structures into molecular terms.

A case of polyglandular autoimmune syndrome type III complicated with autoimmune hepatitis.

A 58-year-old woman complaining of finger tremor was referred to our hospital. The diagnosis of Graves' disease was made based on increased free triiodothyronine (18.88 pg/ml) and free thyroxine (7.47 ng/dl), low TSH (<0.005 microIU/ml) and increased TSH receptor binding antibody activity (70.9%). Serum level of AST (62 U/l) and ALT (93 U/l) were increased and liver biopsy revealed linkage of adjacent portal areas by lymphoplasmacytic infiltrates and fibrosis with piecemeal necrosis. Although antinuclear antibody was negative, these findings indicated that she had autoimmune hepatitis (AIH) according to the criteria of the International Autoimmune Hepatitis Scoring System. Slowly progressive type 1 diabetes mellitus (DM) was confirmed by a diabetic response pattern due to 75 g-oral glucose tolerance test, and seropositivity towards anti-glutamic acid decarboxylase (725 U/ml) and islet cell (80 JDF Units) antibodies. This case exhibited an extremely rare combination of three different autoimmune diseases, including Graves' disease, slowly progressive type 1 DM and AIH, and had no known sensitive human leukocyte antigen (HLA) typing or haplotype for these disorders. Although it is common for patients with Graves' disease to exhibit abnormal liver function, it is important to make an accurate diagnosis of AIH because of this life-threatening disorder.

A case of systemic sclerosis sine scleroderma associated with perforation of an afferent loop after subtotal gastrectomy with Billroth 2 anastomosis for its severe gastrointestinal involvement.

A 50-year-old man was admitted to hospital for dysphagia. The upper gastrointestinal series revealed esophageal stricture, pyloric stenosis, and hypomotile small intestine. He was diagnosed with systemic sclerosis sine scleroderma with gastrointestinal involvement. After subtotal gastrectomy with Billroth 2 anastomosis, he had recurrent intestinal pseudo-obstruction and perforation of the afferent loop. Our experience indicates that surgical procedures in bowel scleroderma, in which an afferent loop is reconstructed, could easily cause perforation of the afferent loop.

Occult breast carcinoma presenting with axillary lymph node metastases: follow-up of eleven patients.

BACKGROUND: Breast carcinoma presenting with axillary metastases and no clinically apparent primary tumor in the breast is an uncommon form of stage IIdisease. The methods of diagnosis and treatment of these patients are not established. We present our eleven treated cases of occult carcinoma and discuss the issues of evaluation and management. METHODS: Eleven patients with occult breast carcinoma (OBC) presenting between January, 1985 and April, 1998 at the National Shikoku Cancer Center were evaluated clinically and with immunohistochemical staining. Immunohistochemical staining was performed using the Envision method. The primary antibodies for gross cystic disease fluid protein-15 (GCDFP-15), estrogen receptor (ER) and progesterone receptor (PR) were used. RESULTS: Nine patients underwent mastectomy. Breast-conserving surgery was performed in one patient. One patient did not receive any operation for the breast. No primary tumor was found among three of nine cases receiving mastectomy. Some adjuvant therapies after the operation were performed in eight cases. Follow-up ranged from 5 to 310 months (median, 54 months), and the five-year disease free survival rate was 62.5%. There were eight GCDFP-15 positive cases (72.7%) and four ER and/or PR positive cases (36.4%). CONCLUSIONS: GCDFP-15 is useful for confirming the primary site of breast carcinoma. Ultrasonography, computed tomography, and magnetic resonance imaging are thought to be good for detecting occult primary tumors. The incidence of OBC is still unclear, but it is possible that these patients need to be treated as typical stage II patients.

Expression of cyclooxygenase-2, Fas and Fas ligand in pulmonary adenocarcinoma and atypical adenomatous hyperplasia.

BACKGROUND: Atypical adenomatous hyperplasia (AAH) has been reported to be a precancerous lesion of pulmonary adenocarcinoma. Cyclooxygenase-2 (COX-2), Fas and Fas ligand (FasL) are believed to be involved in the pathogenesis and progression of cancer. PATIENTS AND METHODS: We examined the expression of COX-2, Fas and FasL in 31 tissue specimens of adenocarcinoma and 9 of AAH using an immunohistochemical method. RESULTS: COX-2 staining was observed in 20 (65%) specimens of adenocarcinoma and 2 (22%) of AAH. There was a significant difference in incidence of expression between these two groups (p = 0.025). All tumor specimens obtained from three patients with simultaneous multiple adenocarcinoma showed positive COX-2 staining. In two patients having both adenocarcinoma and AAH, COX-2 expression was detected in adenocarcinoma but not in AAH. Fas was expressed in 5 (16%) adenocarcinoma and 2 (22%) AAH specimens. FasL was detected in 3 (9.7%) adenocarcinoma and 1 (11%) AAH specimen. CONCLUSION: These findings suggest that COX-2 might play a role in the progression from AAH to adenocarcinoma.

Measurement of localized ground-glass attenuation on thin-section computed tomography images: correlation with the progression of bronchioloalveolar carcinoma of the lung.

RATIONALE AND OBJECTIVE: This study was to measure localized ground-glass attenuation (GGA) in the peripheral lung on thin-section computed tomography (CT) and to assess any relationship between the attenuation and lesion. MATERIALS AND METHODS: Twenty-eight surgically resected tumors with localized GGA at thin-section CT were studied. The tumors were histologically diagnosed as 8 atypical adenomatous hyperplasia (AAH), 11 bronchioloalveolar carcinoma (BAC), and 9 BAC with fibrosis. We assumed three concentric circles, which were 0.8, 1.0, and 1.2 times the diameter of each tumor and measured the average CT values corresponding to inside each circle. We calculated a difference in CT value between 0.8 and 1.2 times the diameter of the tumor and defined as the contrast index. RESULTS: The contrast index for tumors with AAH, BAC, and BAC with fibrosis were 19.8 +/- 8.3, 42.5 +/- 16.0 (P < 0.05 vs. group with AAH), and 111.4 +/- 32.6 (P < 0.0001 vs. Group with BAC), respectively. The contrast index became greater in the stepwise progression from AAH to BAC and from BAC to BAC with fibrosis. CONCLUSION: The contrast index correlated histologic findings of the tumor growth in BAC. The contrast index may be a useful and objective measurement for determining surgical treatment for localized GGA in preoperative diagnosis.

Expression of eukaryotic initiation factor 4E in atypical adenomatous hyperplasia and adenocarcinoma of the human peripheral lung.

The overexpression of eukaryotic initiation factor 4E (eIF4E), a key regulator of protein synthesis, is involved in the malignant progression of various human cancers. We investigated eIF4E expression in atypical adenomatous hyperplasia (AAH) and adenocarcinomas of the human peripheral lung. On the basis of the WHO criteria with minor modifications, adenocarcinomas were classified as bronchioloalveolar carcinoma (BAC), mixed subtypes with a bronchioloalveolar pattern and minor invasion (early MX), and mixed subtypes with a papillary pattern and marked invasion (overt MX). eIF4E immunohistochemistry was performed in 143 tissue samples (31 AAH, 38 BAC, 43 early MX, and 31 overt MX). Both tumoral and stromal eIF4E levels were elevated from AAH, BAC, and early MX to overt MX and significantly associated with histological grade (P < 0.001 and P < 0.001, respectively). Tumoral and stromal eIF4E staining intensities were significantly correlated (P < 0.01). Immunoblot analysis of 51 tissue samples (2 AAH, 11 BAC, 18 early MX, and 20 overt MX) demonstrated that eIF4E expression in adenocarcinomas was 3.4-7.4-fold higher than in normal lung and that its expression progressively increased in the following order: AAH (lowest expression), BAC, early MX, and overt MX (highest expression). Multiple regression analysis revealed that both tumoral and stromal eIF4E expressions were significant independent factors for the histological subtype (P < 0.01 and P < 0.01, respectively). These results suggest that translational control is dysregulated during the development of peripheral lung adenocarcinoma and that progressive increases of tumoral and stromal eIF4E may be part of a positive feedback loop for malignant progression.

A case of recurrent metastatic thymoma showing a marked response to paclitaxel monotherapy.

We describe a case of recurrent metastatic thymoma showing an excellent response to salvage paclitaxel monotherapy. The patient had undergone a series of platinum-based chemotherapy treatments during the previous 20-month period and the patient's disease was considered resistant to such therapy at the start of treatment with paclitaxel. This is the first report to suggest that paclitaxel has anti-thymoma activity.

Focal ground-glass opacity detected by low-dose helical CT.

OBJECTIVE: Focal ground-glass opacity (GGO) has been detected increasingly by low-dose helical CT. Although focal GGO suggests in situ neoplastic lesion in the peripheral lung, it remains controversial how to manage these lesions. The purpose of this study was to evaluate the pathologic and radiologic characteristics of focal GGO in order to develop a standard of treatment for these lesions. PATIENTS: Forty-three patients with persistent focal GGO < or = 2 cm in size from January 1998 to September 2000 were studied. Thoracoscopic lung biopsy was performed consecutively for persistent focal GGO following a several-month observation period (mean, 3.7 months). RESULTS: The histologic diagnoses were bronchioloalveolar carcinoma (BAC) in 23 patients, adenocarcinoma with mixed subtypes in 11 patients, and atypical adenomatous hyperplasia (AAH) in 9 patients. None of 34 carcinoma patients had lymph node involvement. All of 17 lesions > or = 1 cm in size were malignant. GGO with solid components on high-resolution CT were highly associated with adenocarcinoma (malignant rate, 93.3%). CONCLUSIONS: Persistent focal GGO after observation for several months was a finding of early adenocarcinoma or its precursor. Especially, lesions > or = 1 cm in size or GGO with solid component were significant signs of malignancy. We concluded lung biopsy should be attempted for persistent focal GGO.

Preparation of purified, sterilized, and stable adenovirus vectors using albumin.

Cesium chloride ultracentrifugation combined with dialysis is a standard method for preparing a high titer of purified recombinant adenovirus. However, it was found that sterilization of the filter membrane after dialysis led to a complete loss of adenovirus activity. A virus pellet was visualized after centrifugation shortly and electron microscopy revealed an aggregation of recombinant virus within the filter membrane following dialysis with 10% (V/V) glycerol in phosphate buffered saline. The entrapment of aggregated adenovirus by the filter membrane explains why adenovirus activity is lost following sterilization. The addition of 1% albumin prevented viral aggregation and allowed the purified virus to retain its activity after filter sterilization. Furthermore, viral activity was retained within the 1% albumin solution for at least 1 week at 37 degrees C and for 2 weeks at 4 degrees C, whereas viral activity within the albumin-free solution was quickly lost.

Cardia carcinomas of intestinal type are associated with histologic changes in the gastric mucosa.

BACKGROUND: Previous studies of Japanese patients showed that distal gastric carcinomas (of the corpus or the antrum) were associated with histologic changes in the non-neoplastic gastric mucosa. These changes (cells with ciliated metaplasia, with large and small mucus-negative vacuoles, intramucosal glandular cysts, and extensive intestinal metaplasia) were often found in carcinomas of intestinal type.METHODS: In the present work, similar mucosal changes were searched for in surgical specimens carrying a carcinoma of the cardia. A total of 12 079 archival histologic sections, corresponding to 563 gastrectomies performed in Japanese patients, were analyzed.RESULTS: Of the specimens with cardia carcinoma of intestinal type seen in Tokyo ( n = 169) and in Matsuyama ( n = 168), 53.3% and 63.1% contained intramucosal cysts; 39.6% and 51.8%, ciliated metaplastic cells; 34.9% and 30.4%, large vacuolated cells; and 7.7% and 11.9%, small vacuolated cells; and 69.8% and 68.5% had high intestinal metaplasia scores, respectively. These percentages were significantly higher than those for cardia carcinomas of diffuse type in Tokyo ( n = 153) and in Matsuyama ( n = 73), in which 30.7% and 34.2% of the specimens had intramucosal cysts; 17.6% and 17.8%, ciliated metaplastic cells; 14.4% and 9.6%, large vacuolated cells; and 3.9% and 4.1%, small vacuolated cells; and 43.1% and 39.7% had high intestinal metaplasia scores, respectively.CONCLUSION: Thus, similarly to carcinomas of the corpus or the antrum, cardia carcinomas of intestinal type are associated with histologic changes in the gastric mucosa. The possibility that these changes are evoked by environmental factors was entertained.