Bile cytology diagnosis in challenging cases: Validation of diagnostic bile cytology criteria and extensive study for immunocytochemical markers.

BACKGROUND: Bile cytology is useful in diagnosing biliary tract lesions, albeit often challenging due to equivocal findings. To achieve better diagnoses for clinical decisions, we conducted cytomorphological and immunocytochemical studies of bile cytology cases. MATERIALS AND METHODS: We re-evaluated 40 bile cytology cases with initial equivocal diagnoses, taken from the cytology records of Jichi Medical University Hospital, including 1778 bile cytology specimens. First, we assessed the cases by the diagnostic bile cytology criteria of the Japanese Society of Clinical Cytology. Second, we searched for useful immunocytochemical markers by extensive immunohistochemical analyses using tissue microarray for 10 antibodies: S100P, IMP3, GLUT1, p53, S100A4, Mapsin, MUC17, CD10, MDM2, and SMAD4. Microarrays were from 257 extrahepatic bile duct carcinoma cases. To elucidate the utility of immunocytochemistry, we applied selected markers to immunocytochemical evaluation of the equivocal cases after cell transfer. RESULTS: The criteria indicated a sensitivity 60%, specificity 87%, and accuracy 70%. Irregularly overlapping (88%), arranged (96%), and shaped (76%) nuclei were more common in malignant cases, while enlarged nuclei were more frequent in benign cases (67% vs. 28%). We applied S100P and IMP3, which showed higher accuracy (88% and 77%) in tissue microarray, to immunocytochemistry. The sensitivity of S100P and IMP3 were 69% and 70%, respectively. The specificity of S100P and IMP3 were 50% and 100%, respectively. CONCLUSION: The criteria showed a certain effectiveness even in challenging cases, and some pitfalls associated with reactive changes of benign cells. Although comprehensive diagnosis including cytomorphology seems preferable, S100P and IMP3 are promising immunocytochemical markers.

Histological evaluation of tumor differentiation score and prognosis of extrahepatic bile duct cancer: A proposal for a new histological grading system.

Extrahepatic bile duct (EHBD) cancer is a devastating cancer, and more common in Asian countries than in Western countries. Histological grading continues to be a highly relevant factor in prognosis and management of many kinds of cancer, however no uniform histological grading system exists for EHBD cancer. Histological heterogeneity within tumors is a problem in the evaluation of EHBD cancer. We developed an EHBD histological grading scheme to evaluate tumor differentiation pattern, and statistically analyzed its relationship with prognosis. In the present study, 257 surgically resected EHBD cancers were reviewed and their histological glandular differentiation (HGD) pattern was scored, and then we summed up the most and second most predominant scores. These scores were statistically analyzed for their relationship with patient prognosis. Patients showed a trend of shortening recurrence-free survival (RFS) and overall survival (OS) in association with higher HGD scores. In multivariate analyses, HGD score was determined to be an influential factor in RFS (P = 0.00041) and OS (P < 0.0001). In addition, combining HGD score and lymph node status correctly stratified patient prognosis in RFS. In conclusion, this new HGD scoring system is highly practical and has powerful prognostic value for EHBD cancer.

Overexpression of matriptase in tumor stroma is a poor prognostic indicator of extrahepatic bile duct cancer.

Bile duct cancer is known to contain numerous fibroblasts, and reported to recruit cancer- associated fibroblasts by secreting platelet-derived growth factor-D (PDGF-D) which needs serine proteases, such as matriptase, to behave as a ligand. However, their expression pattern, and prognostic value have not been clarified. In this study, we investigated the clinicopathological significance of PDGF-D and matriptase expression in patients with extrahepatic bile duct cancer. The samples were obtained from 256 patients who underwent the surgical resection between 1991 and 2015, and the expression levels of PDGF-D and matriptase were evaluated immunohistochemically. Staining intensities and distribution were scored, and finally classified into low and high expression groups in cancer cells and stroma respectively. High expression of matriptase in the cancer stroma was detected in 91 tumors (40%). The high stromal matriptase expression was significantly associated with shorter recurrence-free survival (RFS) and overall survival (OS) (P = 0.0027 and 0.0023, respectively). Multivariate analyses also demonstrated that the stromal matriptase expression level was an independent influential factor in RFS (P = 0.0050) and OS (P = 0.0093). Our findings suggest that the high stromal matriptase expression was strongly associated with tumor progression, recurrence and poor outcomes in patients with extrahepatic bile duct cancer.

Prognostic significance of the degree of lymphatic vessel invasion in locally advanced, surgically resectable pancreatic head cancer: A single center experience.

Little is known concerning the prognostic significance of the degree of lymphatic vessel invasion in pancreatic head cancer. To address this gap in knowledge, we retrospectively examined 60 patients with locally advanced, surgically resectable pancreatic head cancer who underwent pancreaticoduodenectomy and lymph node (LN) dissection.All cases were histopathologically diagnosed as ductal adenocarcinoma, stage II (25 pT3N0 cases, 35 pT3N1 cases). The following variables were investigated: age; sex; neoadjuvant therapy; adjuvant therapy; tumor size; tumor grade; invasion into the serosa, retropancreatic tissue, duodenum, bile duct, portal venous system and perineural area; cut margins; LN metastasis; and the number of invaded lymphatic vessels (LVI-score).Univariate analysis demonstrated that LN metastasis and an LVI-score ≥5 were significantly associated with poor disease-free survival. Multivariate Cox regression analysis confirmed that LN metastasis and an LVI-score ≥7 were significantly associated with poor disease-free survival. Additionally, LVI-scores ≥9 and ≥10 were comparable to or surpassed the significance of LN metastasis based on the hazard ratio. Univariate analysis demonstrated that tumor size >30 mm, duodenal invasion, LN metastasis and an LVI-score ≥2 were significantly associated with poor overall survival. Multivariate Cox regression analysis confirmed that LN metastasis and LVI-scores ≥9 and ≥10 were significantly associated with poor overall survival, and an LVI-score ≥10 was comparable to or surpassed the significance of LN metastasis based on the hazard ratio.Our study strongly suggests that a high degree of lymphatic vessel invasion is associated with a poor prognosis in patients with locally advanced, surgically resectable pancreatic head cancer.

An inguinal hernia with cryptorchidism with a Leydig cell tumor in an elderly man: A case report.

INTRODUCTION: Cryptorchidism is common in children but is rare in the elderly. It often presents with a constellation of signs and symptoms similar to routine inguinal hernias. We present the case of an elderly man with cryptorchidism containing a Leydig cell tumor and provide clinical insights. PRESENTATION OF CASE: An-84-year old man was admitted with an incarcerated right lower quadrant hernia. Both testes were absent on palpation of the scrotum. After reduction of the hernia, computed tomography scan revealed a round lesion in the hernia sac, which was suspected to be the ectopic testis. Laparoscopic exploration was performed in combination with an open anterior approach. The hernia orifice was the right internal inguinal ring, and the inguinal canal was obliterated by adhesions because the spermatic cord did not pass through it. The ectopic testis was resected with the hernia sac, and the hernia repaired with a KUGEL™ patch (Bard, USA). DISCUSSION: Laparoscopic exploration was useful to delineate the anatomy of this unusual inguinal hernia. The open anterior approach was necessary to dissect the ectopic testis and the hernia sac. Pathological findings revealed tumor cells with clear cytoplasm in the resected testis, diagnosed as a Leydig cell tumor. CONCLUSION: The combination of laparoscopic and anterior approaches facilitated the surgical treatment of an unusual inguinal hernia with cryptorchidism. The resected ectopic testis should undergo thorough histopathologic examination.

The management of gastric volvulus in elderly patients.

INTRODUCTION: Gastric volvulus is torsion of the stomach and requires immediate treatment. The optimal treatment strategy for patients with gastric volvulus is not established, because of significant variations in the cause and clinical course of this condition. PRESENTATION OF CASES: We describe our experience with six elderly patients with gastric volvulus caused by different conditions using various approaches. This includes two patients managed with endoscopic reduction, followed by endoscopic or laparoscopic gastropexy. DISCUSSION: Endoscopy is a necessary first step to determine the optimal treatment strategy, and endoscopic reduction is often effective. The indications for surgical repair of gastric volvulus depend on the patient's overall condition, and several options are available. In some elderly patients with severe comorbidities, major surgery may have an unacceptably high risk. We propose a novel treatment strategy for gastric volvulus in the elderly and a review of the literature. CONCLUSION: Early endoscopy is necessary in patients with gastric volvulus. Endoscopic or laparoscopic gastropexy may be adequate therapy in selected elderly patients.

[Treatment Using Self-Expandable Metal Stent for Ileus Associated with Colorectal Cancer in Our Hospital].

From September 2013 to February 2015, 14 patients with ileus associated with colorectal cancer underwent surgeryafter applying a self-expandable metal stent in our department. Twelve were left-side colon ileus patients and 2 were right-side colon ileus patients. The technical success rate of the stent insertion was 100%. One patient experienced complications(stent occlusion). All patients were able to eat, and 9 of them were able to leave the hospital temporarilybefore the operation. All patients with left-side colon ileus had their oral-side intestine evaluated before the operation. Ten patients received laparoscopic surgery, while those with unresectable metastases who needed to receive chemotherapy as a first choice underwent emergencysurgerywith stoma formation. In our department, patients with ileus caused bycolorectal cancer are treated according to a new flowchart based on the progress degree and background of each patient. The insertion of a self-expandable metal stent was useful for patients with ileus caused bycolorectal cancer in the immediate treatment period. On the other hand, the long-term outcomes in Japan remain to be analyzed.

Endocrine cell carcinomas of the colon and rectum: a clinicopathological evaluation.

PURPOSE: Endocrine cell carcinoma, according to the Japanese classification criteria for colorectal cancer, corresponds to neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC), as defined in the 2010 World Health Organization (WHO) classification. We retrospectively reviewed the clinical features of patients with these tumors diagnosed and treated at our institution. METHODS: The clinicopathological features of endocrine cell carcinomas of the colon and rectum diagnosed by neuroendocrine markers from January 2000 to December 2012 were retrospectively evaluated in 12 patients. RESULTS: Surgical specimens were obtained from eight of the 12 patients. MANEC was diagnosed in six patients and NEC in one. One tumor was unclassifiable. The tumors were not resected in four patients, and all died within 3 months. Of the eight patients who underwent resection, four received an R0 resection, two of whom underwent adjuvant chemotherapy and survived more than 5 years. One patient who underwent an R2 resection and continuous chemotherapy survived for 53 months. One patient with NEC underwent surgery and radiotherapy, and died 17 months later. CONCLUSION: Most endocrine cell carcinomas of the colon and rectum reviewed were MANECs. Though their prognosis was generally poor, chemotherapy may be effective in some patients.

Barrett's esophageal carcinoma consisting of undifferentiated carcinoma and differentiated adenocarcinoma: report of case.

We report on a 53-year-old male with esophageal cancer. He had no evidence of distant metastasis, and received a subtotal esophagectomy. Histopathologically, the tumors were contiguous with Barrett's epithelium. Undifferentiated carcinoma components existed independently of differentiated adenocarcinoma components. Undifferentiated carcinoma was present proximal to the esophagogastric junction. Both tumors had invaded the submucosa and were associated with a prominent lymphoid stroma. Metastasis from undifferentiated carcinoma was found in the paraesophageal lymph nodes. Immunohistochemically, both components were negative for 34bE12 and positive for CAM5.2 and showed nearly identical staining patterns for p53, indicating that the tumors were derived from Barrett's epithelium. Because the undifferentiated carcinoma did not express CK20 or carcinoembryonic antigen, the properties of adenocarcinoma had apparently been lost during the process of tumor cell progression. This is the first report of undifferentiated carcinoma associated with Barrett's esophagus with adenocarcinoma.